Latest Articles from Pharmacia Latest 100 Articles from Pharmacia https://pharmacia.pensoft.net/ Fri, 29 Mar 2024 14:04:41 +0200 Pensoft FeedCreator https://pharmacia.pensoft.net/i/logo.jpg Latest Articles from Pharmacia https://pharmacia.pensoft.net/ Effect of Equisetum ramosissimum Desf. on body weight and Leptin/Ghrelin in standard and high-fat diet https://pharmacia.pensoft.net/article/117823/ Pharmacia 71: 1-7

DOI: 10.3897/pharmacia.71.e117823

Authors: Reem Issa, Mahmoud Abu Samak, Manal M. Abbas, Talal Al-Qaisi, Razan Obeidat, Bayan Ghanim, Nidal Qinna

Abstract: The necessity of maintaining healthy habits, diet and minimal medical complications is challenging. The current study investigates Equisetum ramosissimum on levels of leptin, ghrelin, and their ratio in association with body weight changes in animals receiving standard and high-fat diet. Ethanolic extract was prepared by maceration and total phenols and flavonoids contents were determined using Folin-cicalto and AlCl3 methods. Study animals were fed with either standard or high-fat diets prior treatment with E. ramosissimum extract (500mg/kg). Body weights were monitored and serum concentrations of leptin, ghrelin and their ratios were determined. The plant extract comprised total phenols and flavonoids of 0.03 ± 0.01 mg/mg as Gallic acid, and 0.04 ± 0.03 mg/mg as quercetin, respectively. Findings revealed significant decrease in body weights of standard-diet animals and restoration of weight to normal after treatment with extract along with significant increase in serum ghrelin concentrations with strong correlation R and R2 values in respect to body weight. As well, significant reduction in serum leptin/ghrelin ratio was positively correlated with body weight and serum leptin levels. E. ramosissimum extract possessed promising characteristics on being introduced in dietary supplements and weight control regimens. The current study presented the influence of extract in decreasing body weight in animals fed with standard diet. Moreover, it restored the weights of obese animals which received the extract after gaining weight and being on high-fat diet. Further preclinical studies are warranted to reveal the translational potentials of E. ramosissimum extract and its vital effect on adipokines.

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Research Article Tue, 26 Mar 2024 19:27:04 +0200
Intake of anticonvulsant drugs by women with epilepsy during pregnancy and breastfeeding: advantages and disadvantages https://pharmacia.pensoft.net/article/120686/ Pharmacia 71: 1-8

DOI: 10.3897/pharmacia.71.e120686

Authors: Irina Vaneva, Ibryam Ibryam, Rumyana Kuzmanova

Abstract: Anti-epileptic drugs (AED) are being widely used in neurological practice. These are being prescribed as standard treatment not only of epilepsy, but also in various non-epileptic conditions, such as psychic illnesses and chronic pain. The main issue for women with epilepsy and their doctors during the AED administration is child and mother’s safety during pregnancy and breastfeeding. Anti-epileptic treatment during these periods could have an unfavourable impact on the frequency of mother’s seizures and child’s psychomotor development. Breastfeeding-related risks during the AED administration remain theoretical, bearing in mind the insufficient data from the limited previously undertaken research. In view of the established benefits from breastfeeding for babies’ long-term health in the general population, breastfeeding is to be promoted, with discretion on whether this should be balanced, individual, with monitoring of AED concentration in mother’s milk and mother and breastfed child’s serum.

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Review Article Tue, 26 Mar 2024 19:26:37 +0200
Mapping the research on healthcare students’ empathy: Insights from a bibliometric analysis https://pharmacia.pensoft.net/article/120826/ Pharmacia 71: 1-8

DOI: 10.3897/pharmacia.71.e120826

Authors: Hening Pratiwi, Susi Ari Kristina, Anna Wahyuni Widayanti, Yayi Suryo Prabandari

Abstract: Empathy is required not only by healthcare professionals but also by students as healthcare professionals’ candidates. The research into the development of empathy in healthcare students is essential in the field of health education. This study aimed to investigate research trends in the topic of healthcare students’ empathy using bibliometric analysis. We used the Scopus database on June 17, 2023, and “empathy” AND “students” AND “pharmacy” OR “medical” OR “dentist” OR “nurse” OR “nutritionist” are the search keywords. The remaining articles were examined using VOSviewer software. The results demonstrated a rapid increase in research on the topic of healthcare students’ empathy between 2014 and 2023. The most prolific authors were Hojat, M., and Diaz-Narváez. The United States has the most publications and citations in this discipline. The keywords used in the current study were grouped into 7 clusters, and the term “human” is most frequently used. Our study contributes significantly to the developing literature on empathy for healthcare students.

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Review Article Tue, 26 Mar 2024 19:26:21 +0200
Oral acute toxicity study of ethanol extract of Mobe leaves (Artocarpus lacucha Buch-Ham) in Wistar rats https://pharmacia.pensoft.net/article/117500/ Pharmacia 71: 1-8

DOI: 10.3897/pharmacia.71.e117500

Authors: Denny Satria, Panal Sitorus, Aminah Dalimunthe, Syukur Berkat Waruwu, Vivi Asfianti

Abstract: Many medicinal plants are now being chosen because the treatment is safer and cheaper. Artocarpus lacucha Buch-Ham is a plant with many pharmacological activities and is efficacious; its safety has not been studied. Acute oral toxicity evaluation followed Organization for Economic Co-operation and Development guidelines using the fixed dose method. The evaluation began with a preliminary test, then a primary test with three groups: a 2000 mg/Kg BW dose test group, a 5000 mg/Kg BW dose test group, and a control group. The results of visual observations, haematological and clinical examinations, and histological examination of organs (liver, spleen, kidneys, lungs and heart) showed no toxicity in the animals, and they did not die during testing. The findings of this study support the safety of Artocarpus lacucha Buch-Ham leaf ethanol extract, which did not produce harmful results in acute toxicity tests.

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Research Article Mon, 25 Mar 2024 19:06:08 +0200
Testosterone, estradiol and their ratio in male patients with acute coronary syndrome https://pharmacia.pensoft.net/article/113755/ Pharmacia 71: 1-5

DOI: 10.3897/pharmacia.71.e113755

Authors: Savi Shishkov, Kiril Hristozov, Atanas Angelov, Svetoslava Slavcheva, Yana Bocheva, Mila Boyadzhieva

Abstract: The role of androgens and estrogens in cardiovascular disease is a subject of ongoing studies. Therefore, we aim to explore the association of testosterone (T), estradiol and their ratio with cardiovascular risk factors and severity of cardiac ischemia in male patients with acute coronary syndrome. (ACS) n = 72 and controls (n = 35) Lower values of both total and free T were found in the ACS group compared to controls (8.97 vs. 10.98 nmol/l, p = 0.001 for total T and 0.189 vs. 0.223 nmol/l, p = 0.006 for free T). Patients with myocardial infarction with ST-elevation had significantly lower T fractions compared to ACS without ST-elevation. The T to estradiol ratio was significantly lower in the ACS group compared to controls and is lowest in those with STEMI. Also, all testosterone fractions – free, bioavailable, and free T, are lower in patients with ACS compared to controls. Based on these observations a conclusion can be drawn that amore estrogenic environment is associated with ST-elevation and correlates with the severity of ACS in male patients.

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Research Article Mon, 25 Mar 2024 19:04:23 +0200
Pharmacists’ burnout and motivation for pharmaceutical care in chronically ill patients – a pilot study for the north-eastern region of Bulgaria https://pharmacia.pensoft.net/article/120566/ Pharmacia 71: 1-7

DOI: 10.3897/pharmacia.71.e120566

Authors: Anna Todorova, Mariya Ivanova, Valentina Petkova

Abstract: Medical professionals are the most susceptible to professional burnout. An anonymous survey of master pharmacists was conducted to assess burnout with the MBI-HSS-MP tool and analyse the challenges of working in community pharmacies. Burnout affected 53% of the 127 pharmacists surveyed. Factors influencing the scales forming burnout emotional exhaustion (EE) depersonalisation (DP), and personal accomplishment (PA) were: administrative difficulties in servicing the prescriptions of chronically ill patients: affected 57% of respondents and influenced EE (p = 0.036); lack of precise instructions at work (38% of respondents, influenced DP, p = 0.007) and (EE, p = 0.000); lack of prior information about innovations 38% (EE p = 0.002). Lack of time to carry out pharmaceutical care (PhC) influenced EE (p = 0.019) and DP (p = 0.006) and DP was associated with lower empathy for patients, Lack of perceived professional satisfaction (PA; p = 0.042) was increased. The increased administrative duties shifted the focus away from PhC and decreased pharmacists’ motivation.

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Research Article Mon, 25 Mar 2024 10:05:27 +0200
Microwave-assisted organic synthesis of pyrroles (Review) https://pharmacia.pensoft.net/article/119866/ Pharmacia 71: 1-10

DOI: 10.3897/pharmacia.71.e119866

Authors: Emilio Mateev, Ali Irfan, Alexandrina Mateeva, Maya Georgieva, Alexander Zlatkov

Abstract: The detection of pyrrole rings in numerous organic compounds with various pharmacological activities, emphasizes its huge importance in medicinal chemistry. Thus, the synthesis of pyrroles continues to arouse interest and Paal-Knorr condensation is considered to be the main synthetic route. A significant advance has been made since the MW activation was introduced in the organic synthesis which can be confirmed with the rapid growth of the published papers on that topic. Microwave irradiation is gaining popularity since faster reaction time, higher yields, easier work-up and reduced energy input can be achieved. Furthermore, it appears in numerous green chemistry protocols. The aim of the current article was to provide insights into the microwave syntheses of pyrrole derivatives, focusing on the most used synthetic approaches - Paal-Knorr, Clauson-Kaas, Barton-Zard, Hantzsch and others. The article was divided into several sections starting with the principles of the microwave organic synthesis. Thereafter the structure and the main pharmacological effects of the pyrrole derivatives were examined. Subsequently, articles describing the synthesis of pyrroles via Paal-Knorr, Hantzsch, Clauson-Kaas and Barton– Zard were discussed. All the reviewed papers conclude a significant reduction of the reaction times after MW irradiation compared to conventional heating.

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Review Article Mon, 25 Mar 2024 10:04:49 +0200
Dietary intake of vitamin D in adult outpatients with different degrees of obesity coming from an urban community https://pharmacia.pensoft.net/article/121860/ Pharmacia 71: 1-6

DOI: 10.3897/pharmacia.71.e121860

Authors: Maria Georgieva Nikolova, Kristina Pavlova Kilova, Valentina Boyanova Petkova, Adolf Ali Alakidi

Abstract: The aim of the present study was to investigate in-depth the dietary intake of vitamin D of subjects with different BMI in relation to serum vitamin D status. The survey covered 264 individuals, aged 19 to 60 years. Vitamin D deficiency was found in 33.3% of the participants and 40.2% showed evidence of insufficient vitamin D intake. It was established that the daily average dietary intake of vitamin D among the whole group of subjects was 6.6 μg/day (women – 5.6 μg/day, men – 10.4 μg/day). We found significant correlations between daily average dietary intake of vitamin D and weight, % body fat, fat mass, visceral fat (in women), muscle and fat-free mass, and height-adjusted indices: fat mass index and fat-free mass index, total body water and some metabolic variables (basal insulin and high sensitivity C-reactive protein). The survey revealed that the dietary intake of vitamin D of the respondents was insufficient.

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Research Article Thu, 21 Mar 2024 15:22:20 +0200
Effects of the EM CYP2C19 type and MDR1 3435CC gene on Helicobacter pylori eradication rate in patients with duodenal ulcer by the four-drug regimen of rabeprazole, bismuth, tetracycline, and tinidazole https://pharmacia.pensoft.net/article/108090/ Pharmacia 71: 1-9

DOI: 10.3897/pharmacia.71.e108090

Authors: Liem T. Nguyen, Vuong B. Nguyen, Tu V. Tran, Loan T. T. Le, Mai H. T. Phuong, Thang Nguyen

Abstract: Background: The MDR1 genotype and the CYP2C19 phenotype determine how much PPI is absorbed from the gut and how much is processed in the liver. Objective: To assess the impact of CYP2C19 and MDR1 C3435T gene polymorphisms on the efficiency of H. pylori eradication treatment with a 4-drug regimen of rabeprazole, bismuth, tetracycline, and tinidazole (RBTT) in patients with duodenal ulcers. Methods: The study was conducted at Can Tho University of Medicine and Pharmacy. Gene polymorphisms for CYP2C19 and MDR1 C3435T were detected through a blood test. The RBTT 4-drug regimen was used to eradicate H. pylori. Results: The success rate of the RBTT regimen for eradicating H. pylori in female patients with the CYP2C19 EM phenotype + MDR1 3435CC genotype was 20.0% lower than the rate of 91.7% for the group without both phenotype and genotype (p = 0.01, OR = 0.02, 95%CI: 0.00–0.45). Conclusion: Compared to the group lacking both phenotypes and genotypes, female patients with the CYP2C19 EM phenotype + MDR1 3435CC genotype had a lower rate of H. pylori eradication by RBTT regimen.

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Research Article Thu, 21 Mar 2024 15:20:11 +0200
Formulation and validation of Candesartan cilexetil-loaded nanosuspension to enhance solubility https://pharmacia.pensoft.net/article/114943/ Pharmacia 71: 1-13

DOI: 10.3897/pharmacia.71.e114943

Authors: Sarmad Al-Edresi, Karrar Albo Hamrah, Abulfadhel Al-Shaibani

Abstract: The following research aimed to enhance solubility by loading candesartan cilexetil into nanosuspension. Candesartan cilexetil-loaded nanosuspension was prepared with the aid of Design-Expert® software. A technique of solvent evaporation was employed to produce nanosuspensions from hydroxyl propyl methyl cellulose (HPMC E5), polyvinyl pyrrolidone (PVP K-30), and poloxamer (PXM 188). The optimised nanosuspensions’ particle size and polydispersity index (PDI) were 64.65 nm and 0.059, respectively. The entrapment efficacy (EE %) and drug loading (DL %) were 86.75 and 10.17%, respectively. The atomic force microscopy (AFM) revealed spherical and smooth nanoparticles. The Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) revealed pure, crystalline and conjugated drugs inside the nanosuspension. The release study confirmed 90% release within 10 min. No significant changes in particle sizes over three months were found, indicating stable nanoparticles. Saturated solubility of the candesartan cilexetil powder and loaded nanosuspension was 63.3 ± 6 and 344.7 ± 16 µg.ml-1, respectively, revealing more than five times increase in solubility. Candesartan cilexetil-loaded nanosuspensions were successfully prepared using different combinations of PVP K-30, HPMC E-5 and PXM 188 in various concentrations. Solubility was enhanced by loading the payload into nanosuspensions.

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Research Article Tue, 19 Mar 2024 09:49:36 +0200
Simultaneous HPLC determination of remdesivir and dexamethasone in the presence of metformin, sitagliptin, and glimepiride in a synthetic mixture and spiked human plasma https://pharmacia.pensoft.net/article/120463/ Pharmacia 71: 1-10

DOI: 10.3897/pharmacia.71.e120463

Authors: Stanislav Bozhanov, Miglena Smerikarova, Vania Maslarska

Abstract: The COVID-19 pandemic has raised many questions regarding the control and therapy of type 2 diabetes and the higher risk of severe disease progression. One of the therapeutic regimens used in moderate and severe cases of COVID-19, endorsed by the World Health Organization, involves the administration of an antiviral medicinal product and a corticosteroid. The present study describes the development of a liquid chromatographic method for the simultaneous separation and quantification of Remdesivir and Dexamethasone in the presence of Metformin, Sitagliptin, and Glimepiride in a synthetic mixture. The developed method also allows determination of Remdesivir, Dexamethasone, and Glimepiride in spiked plasma samples, using Sitagliptin as internal standard. A mixture of acetonitrile and potassium dihydrogen phosphate buffer (pH 3) in a ratio of 45:55 v/v was used as а mobile phase on a C18 column. The recovery percentages from plasma ranged from 85.1 to 108.5%. The developed method can serve in routine quality control and clinical laboratory practice.

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Research Article Fri, 15 Mar 2024 07:34:10 +0200
The impact of DME treatment on diabetic patients https://pharmacia.pensoft.net/article/119594/ Pharmacia 71: 1-7

DOI: 10.3897/pharmacia.71.e119594

Authors: Valeria Draganova, Petya Goycheva, Dimityr Dzhelebov

Abstract: Background: Both type 1 and type 2 diabetics can potentially develop nephropathy, neuropathy, and retinopathy. Diabetic macular edema(DME) is associated with the severity of diabetic retinopathy (DR). DME results from chronic damage to the microvascular structures of the retina, and together with HbA1C is a clinically proven risk factor for the progression of retinopathy. The duration of diabetes in patients affects both the prevalence and incidence of macular edema, progression of retinopathy, and other complications of the disease. Patients with type 2 diabetes may exhibit signs of diabetes at a significantly late stage of the disease, most often in the presence of macular edema. It is even possible to report no presence of reduced vision. Screening diabetic patients for early detection of retinal abnormalities is essential to prevent the development of DR/DME and avoid vision loss. Aims: To find and analyze treatment options for DME for diabetic patients. Methods: This literature review was based on an extensive search of medical databases, including PubMed, Web of Science, and Scopus, by keywords: ,,diabetic retinopathy’’, ,,visual loss’’, ,,treatment’’. The publication time span included articles that appeared between December 01, 2015 and January 01. 2023. Forty-four original works selected for inclusion in the review . It had two main goals: (1) To examine systematically, in the context of DR, existing therapies for DME. (2) To work towards improved therapeutic outcomes for DME among individuals with DR. Results: Traditional diabetes therapy involves photocoagulation or laser treatment. Recently developed pharmacotherapies use anti-VEGF products or corticosteroids. They are designed to attack specific molecular pathways associated with the development of DR. Gene therapies could be a prospective treatment option for some patients. They target those genes that appear involved in generating vascular abnormalities or trigger an inflammatory response and attempt to neutralize their activity. Conclusion: This literature review examines the advantages and disadvantages of all treatment options for diabetic retinopathy patients’. It could provide all practitioners with important and in-depth information on the current aspects of diabetic retinopathy treatment.

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Research Article Wed, 13 Mar 2024 14:47:16 +0200
Study of the antitumor activity of the combination baicalin and epigallocatechin gallate in a murine model of vincristine-resistant breast cancer https://pharmacia.pensoft.net/article/113446/ Pharmacia 71: 1-20

DOI: 10.3897/pharmacia.71.e113446

Authors: Dima Awajan, Anas H. A. Abu-Humaidan, Wamidh H. Talib

Abstract: Background: Breast cancer is one of the primary causes of death in women worldwide. Yearly, a quarter of cancer cases in women are breast cancer. The problem is aggravated by the emergence of chemotherapeutic resistance. One of the practices to overcome this problem is using natural products along with chemotherapy. Epigallocatechin Gallate (EGCG) is the main efficient catechin in green tea. Baicalin is the main active chemical constituent of Scutellaria baicalensis. Both natural products have anti-cancer and improving resistance activities. Therefore, a combination of EGCG and baicalin may afford a possible way out to overcome chemotherapeutic resistance. Methods: EGCG and baicalin were tested on Vincristine-sensitive (EMT-6/P) and Vincristine-resistant (EMT-6/V) mouse mammary cell lines. Antiproliferative and apoptotic effects were assessed for EGCG, baicalin, their combination, and Vincristine in vitro using MTT and caspase-3 assays. An in vivo study was conducted to assess the effect of EGCG, baicalin, their combination, vincristine, vincristine along with the combination in both EMT-6/P and EMT-6/V mouse mammary cell lines. The safety profile was also considered using liver enzymes and creatinine assays. Results: in vitro, EGCG and baicalin had synergistic effects in both cell lines. The combination of baicalin and EGCG as 140 and 100 µM respectively, caused an apoptotic effect higher than the single treatment of baicalin 175 µM or EGCG 125 µM, in vincristine-resistant cell lines. In vivo, the combination along with vincristine significantly enhanced the reduction of tumour size in mice implanted with EMT-6/P and EMT-6/V cell lines. According to the safety profile, the combinations of EGCG and baicalin are safe. Conclusion: The combination of baicalin and EGCG can be optimistic in improving vincristine-resistant cells to treatments.

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Research Article Tue, 12 Mar 2024 09:56:33 +0200
Preparation and characterization of vemurafenib microemulsion based hydrogel using surface active ionic liquid https://pharmacia.pensoft.net/article/111178/ Pharmacia 71: 1-9

DOI: 10.3897/pharmacia.71.e111178

Authors: Mohammed Jasim Neamah, Entidhar Jasim Muhammed Al-Akkam

Abstract: Cancer is considered the second leading cause of death worldwide. Skin melanomas account for the highest mortality rate amongst all types of skin cancer. Systemic treatment with vemurafenib has a high rate of adverse effects, so attempts have been made to prepare a topical form of this drug. Microemulsions have been used to improve drug delivery to the skin. The microemulsions were prepared by dissolving vemurafenib in a mixture of peppermint oil and Smix, followed by the addition of water. The characteristics and effectiveness of surface-active ionic liquid-based vemurafenib microemulsions were characterised and evaluated in vitro. The vemurafenib microemulsions (CP5, CP7 and CP8) had droplet sizes in the microemulsion range (less than 200 nm), and they were used to prepare microemulsion-based hydrogels using HPMC K15M via the hot and cold method. The prepared microemulsion-based hydrogels were then evaluated. The microemulsion-based hydrogel GP5 exhibited higher skin deposition (45.4%) than the other hydrogels; thus, GP5 is a promising candidate for the topical treatment of melanoma by vemurafenib.

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Research Article Tue, 12 Mar 2024 09:56:33 +0200
Nanostructured lipid carriers: A prospective dermal drug delivery system for natural active ingredients https://pharmacia.pensoft.net/article/115849/ Pharmacia 71: 1-15

DOI: 10.3897/pharmacia.71.e115849

Authors: Endang Wahyu Fitriani, Christina Avanti, Yeva Rosana, Silvia Surini

Abstract: Nanostructured lipid carriers (NLCs) are versatile tools used for several purposes, including drug release modification, adhesion to the skin, film-forming ability followed by hydration of the superficial layers of the skin, as well as high penetration with permeation into and across deeper skin layers. During the formulation of active ingredients sourced from nature into dosage forms, NLCs play a crucial role in overcoming challenges associated with the process. These challenges include poor solubility and skin permeability, sensitivity to light, heat, and oxygen, leading to degraded quality, reduced potency, and probable risks of skin irritation or allergic reactions. Therefore, this review aimed to provide a comprehensive overview of NLCs as effective delivery system through the skin for natural active ingredients. The extensive discussion covers the advantages and disadvantages of a dermal delivery system for these ingredients, focusing on various types, lipids, and surfactants used in the formulation, preparation, and characterization process. Additionally, the recent developments in NLCs technology are explored. The result showed that NLCs would advance into a more efficient, precise, and safe system to transport natural active ingredients dermally.

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Review Article Tue, 12 Mar 2024 09:56:33 +0200
Pharmacological correction of the activity of bone remodelling markers in the oral fluid of patients with generalised periodontitis depending on blood type https://pharmacia.pensoft.net/article/114268/ Pharmacia 71: 1-6

DOI: 10.3897/pharmacia.71.e114268

Authors: Yurii Bandrivsky, Andrii Bambuliak, Orysia Bandrivska, Iryna Maika, Khrystyna Dutko, Lesia Kuchyrka

Abstract: This article presents the data on the effectiveness of the treatment complex we developed on the activity of bone remodelling markers in the oral fluid during the treatment of generalized periodontitis, depending on the blood group. The use of our proposed drugs of general and local action in patients with generalized periodontitis of different blood groups allowed to reduce the average content of TRACP in the oral fluid by 18.25%, while increasing the level of BSALP by 27.64% in comparison with the corresponding data before treatment, p, р1<0.05, 0.01, which indicates the predominance of bone remodelling processes over osteoresorption processes in patients of the main group. The tactics of treatment of patients with generalized periodontitis of different blood groups, which we propose, is more effective than the conventional therapy and contributes to a faster achievement of remission of generalized periodontitis.

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Research Article Fri, 8 Mar 2024 16:28:58 +0200
Analysis of non-compliances identified in GMP inspections between 2013 and 2022 https://pharmacia.pensoft.net/article/120053/ Pharmacia 71: 1-6

DOI: 10.3897/pharmacia.71.e120053

Authors: Hristina Lebanova, Svetoslav Stoev, Galina Petrova

Abstract: Ensuring the quality and safety of medicinal products is of paramount importance to the pharmaceutical industry. Good manufacturing practice (GMP) regulations are part of a pharmaceutical manufacturer’s quality management system and ensure that medicinal products are manufactured, imported and controlled consistently to quality standards appropriate to their intended use. The aim of the present study is to analyze the non-compliant operations identified during GMP inspections carried out by national competent authorities (NCA) in the EU/EEC between 2013 and 2022. A retrospective analysis of non-compliance reports published in the EudraGMDP database between 2013 and 2022 was performed. Overall, 99 reports by 21 national competent authorities were analyzed presenting the results of inspections in 19 countries. A total of 1458 deficiencies were identified, of which 544 (37%) were classified as major and 127 (9%) as critical. The most common non-compliant operations were the manufacturing of active substances (49 deficiencies) and the preparation of non-sterile products (47 deficiencies). In 41 cases, the NCA recommended suspension or voiding of the certificate of suitability (CEP) and in 36 cases revocation of the GMP certificates. The observed deficiencies highlight the importance and need for continuous monitoring and improvement of manufacturers’ production processes and quality management systems.

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Research Article Fri, 8 Mar 2024 11:21:44 +0200
Targeting cisplatin resistance in breast cancer using a combination of Thymoquinone and Silymarin: an in vitro and in vivo study https://pharmacia.pensoft.net/article/117997/ Pharmacia 71: 1-19

DOI: 10.3897/pharmacia.71.e117997

Authors: Reem Ali Hamed, Wamidh H. Talib

Abstract: Background: Breast cancer (BC) is considered the most diagnosed cancer among women globally. This is because of its high possibility of metastasis and high resistance to chemotherapy. Cisplatin is a platinum-based antitumor agent that is used to treat various types of cancer. However, the main obstacle to using this drug is drug resistance. Drug resistance is a cause of most relapses of cancer which eventually lead to death. Nowadays, combining natural products is a trend to overcome drug resistance. Thymoquinone (TQ) is a natural phytochemical that exists mainly in blackseed. It has been used in medicine for decades, especially as an anticancer agent. Silymarin is a milk thistle compound that exhibits anticancer, hepatoprotective, and neuroprotective activity. Hence, the combination of TQ and silymarin could be a probable solution to treat cancer and reduce chemoresistance. Methods: This study tested this combination on cisplatin-sensitive (EMT6/P) and cisplatin-resistant (EMT6/CPR) mouse mammary cell lines. Apoptotic and antiproliferative activity was assessed for TQ and silymarin in vitro using caspase-3 and [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide] (MTT) assays, respectively. An in vivo study was performed to evaluate the effect of TQ and silymarin combination in mice inoculated with EMT6/P and EMT6/CPR cells. The safety profile was also examined using creatinine and liver enzyme assays. Results: In vitro, the TQ and silymarin combination synergized in both cell lines. Also, this combination caused apoptosis induction at a higher rate than the single treatment in both cell lines. In vivo, TQ and silymarin combination resulted in a remarkable reduction in tumor size and enhanced the cure rate in mice implanted with EMT6/P and EMT6/CPR cell lines. According to the safety profile results, TQ and silymarin combination was safe. Conclusion: In conclusion, the combination of TQ and silymarin provides a promising solution in treating BC resistant to cisplatin by inducing apoptosis. Further studies are needed to define the exact anticancer mechanisms of this combination.

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Research Article Wed, 6 Mar 2024 07:56:05 +0200
Antihypertensive activity of spray-dried nanoemulsion containing Asiatic acid-Palm oil in high salt diet-fed rats https://pharmacia.pensoft.net/article/115091/ Pharmacia 71: 1-10

DOI: 10.3897/pharmacia.71.e115091

Authors: Aditya Trias Pradana, Garnpimol C. Ritthidej, Vudhiporn Limprasutr, Ausana Wongtayan, Vimolmas Lipipun, Iksen

Abstract: Asiatic acid (AA) is a compound isolated from Centella asiatica, which possesses significant antihypertensive activity. Several studies have shown that its hypertensive activity can be attributed to various mechanisms, such as Angiotensin-Converting-Enzyme (ACE) inhibition in the renin-angiotensin-aldosterone system (RAAS) pathway. Meanwhile, palm oil (PO) is an antioxidant, which has proven to have synergistic effects with the compound by preventing arterial thrombosis and atherosclerosis. Despite these synergistic effects, AA dosage in antihypertensive therapy has been reported to be relatively high compared to the common synthetic drug captopril. Therefore, this study aimed to produce spray-dried powder of nanoemulsion to enhance the solubility of AA, decrease the possibility of oxidation, and increase its activity. Redispersed AA nanoparticles were also successfully obtained during the synthesis process. Several evaluations were carried out, including particle size, particle distribution, zeta potential, cell viability, and antihypertensive activity in rats to ensure the improvement of physicochemical characteristics and activity as antihypertensive agent. The results showed that AA succeeded in forming nanoemulsion with excipients. In addition, it was encapsulated in a maltodextrin carrier, exhibiting good physicochemical characteristics and safety to the Caco-2 cells. The redispersion of the spray-dried powder yielded nanoparticles with a size of 217.4 ± 10.196 nm. The spray-dried nanoemulsion of AA also had faster effect than non-formulated AA (raw powder) in lowering the blood pressure of hypertensive Sprague-Dawley (SD) rats. Graphical abstract:

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Research Article Tue, 5 Mar 2024 13:56:02 +0200
Qualitative chemical compounds analysis and in vitro estimation of antiproliferative, antidiabetic and anti-Alzheimer’s disease effects of Ononis natrix (L.) family Fabaceae https://pharmacia.pensoft.net/article/119755/ Pharmacia 71: 1-11

DOI: 10.3897/pharmacia.71.e119755

Authors: Ahmed Mohamed Mohamed Youssef, Doaa Ahmed Mohamed Maaty, Yousef Mohammad Al-Saraireh

Abstract: The O. natrix belongs to the family Fabaceae and is distributed in Jordan. Different species of the family Fabaceae contain chemical compounds that may have potential antiproliferative, antidiabetic, and anti-Alzheimer’s disease. High-performance liquid chromatography (HPLC) was applied to analyse the phenolic compounds found in O. natrix methanolic extract. Using the MTT assay, the antiproliferative action was studied. The enzymes α-glucosidase and butyrylcholinesterase inhibition assays were used to study the antidiabetic and anti-Alzheimer’s disease actions, respectively, of methanolic extract of O. natrix. Eleven phenolics and seven flavonoids were identified in the methanolic extract of O. natrix by HPLC. The highest phenolics and flavonoids were gallic acid (1.25 mg/100 g dry weight) and rutin (1.44 mg/100 g dry weight), respectively. The most cancer cell lines influenced by the extract of O. natrix were PC-3 (IC50 = 55 ± 2 µg/mL) and HepG-2 (IC50 = 68 ± 2 µg/mL) compared to positive control cisplatin. However, the cancer cell lines CaCo-2, MCF-7, and HeLa showed IC50 values of 109 ± 2 µg/mL, 123 ± 2 µg/mL, and 79 ± 1 µg/mL, respectively, related to cisplatin. The O. natrix extract inhibited the α-glucosidase enzyme and butyrylcholinesterase enzyme by 84% and 86%, respectively compared to positive controls acarbose and rivastigmine. The O. natrix may possess antiproliferative effects against prostate cancer and hepatocellular carcinoma. It also may have antidiabetic and anti-Alzheimer’s disease effects.

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Research Article Fri, 1 Mar 2024 18:34:26 +0200
Aqueous black rice (Oryza sativa L. indica) extract enhanced the activation of CD4+ and CD8+ T cells in mouse breast cancer model https://pharmacia.pensoft.net/article/113442/ Pharmacia 71: 1-7

DOI: 10.3897/pharmacia.71.e113442

Authors: Fadjar Kurnia Hartati, Wirdatun Nafisah, Adi Sutanto, Elfi Anis Saati, Miftahul Khairoh, Sjamsiah

Abstract: Black rice is a functional food of Indonesia that has several pharmaceutical activities including anti-cancer. This study aimed to evaluate the immunomodulatory potential of aqueous black rice (ABR) extract on mouse breast cancer model. A carcinogen, 7,12-dimethylbenz[a]anthracene (DMBA), was applied for breast cancer induction in mice. The study was designed to be seven groups (six mice in each group), including Normal or control group (N), a Cancer (C; DMBA-induced mice) group, Cisplatin (Cis; DMBA-induced mice + Cisplatin) treatment group, and DMBA-induced mice + ABR extract (ABR1; dose 1 or 0.2 g/kg, ABR2; dose 2 or 0.3 g/kg, ABR3; dose 3 or 0.4 g/kg, and ABR4; dose 4 or 0.5 g/kg) treatment group. The cancer-bearing mice were given ABR extract for two weeks, and flow cytometry was used to assess the numbers of CD4+ and CD8+ T cells, as well as the production of inflammatory cytokines IL-17, TNFα, and IFNγ. The histopathology of breast tissue in mice was analyzed using hematoxylin and eosin staining and microscope observation. The induction of DMBA in mice lower the activation of CD4+ and CD8+ T cells, and induced IL-17, TNFα, and IFNγ production. The histology of the mammary tissue of the untreated mice demonstrated an infiltration of cancer cells toward stroma, whereas that of the treated groups, especially those under high doses of ABR extract, showed a better prognosis, exhibiting a reduction in cancer cells surrounded by a relatively larger number of adipose tissues. The activation of CD4+ and CD8+ T cells, as well as the reduction of cytokines (IL-17, TNFα, and IFNγ), were thought to be influenced by ABR extract. The activation of T cells optimized the elimination of cancer cells activity; moreover, the production of pro-tumor cytokines was inhibited.

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Research Article Thu, 29 Feb 2024 19:01:17 +0200
Chrysin’s dose-dependent effects on steroidogenesis in female BALB/c mice: In vivo study of adrenal, ovarian, and uterine hormone regulation https://pharmacia.pensoft.net/article/114547/ Pharmacia 71: 1-9

DOI: 10.3897/pharmacia.71.e114547

Authors: Khalid M. Alqaisi, Manal A. Abbas, Rand Alshawawreh

Abstract: Background: Chrysin is known for its pharmacological effects and structural resemblance to estrogen. The study explores the impact of chrysin on steroidogenesis focusing on adrenal and ovarian steroidogenic enzymes. Materials and methods: Thirty female BALB/c mice were divided into three groups: a control group and two chrysin-treated groups (50 mg and 100 mg). Gene expression of key steroidogenic enzymes was assessed in adrenal glands and ovaries using RT-qPCR. Uterine expression of estrogen receptor alpha (ERα) was also examined. Histological analysis of adrenal glands and ovaries was performed. Results: High-dose chrysin downregulated CYP17A1 expression in adrenal glands compared to control and low-dose groups. In contrast, 3β-HSD was significantly downregulated in the high-dose group. In ovaries, high dose chrysin reduced aromatase expression. Conclusion: Our findings revealed that chrysin’s impact on steroidogenesis is dose-dependent. By downregulating CYP17A1 in adrenal glands, potentially affecting androgen and estrogen synthesis, and enhancing aromatase expression in ovaries at lower doses.

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Research Article Thu, 29 Feb 2024 19:00:30 +0200
The effects of meloxicam, lornoxicam, ketoprofen, and dexketoprofen on human cervical, colorectal, and mammary carcinoma cell lines https://pharmacia.pensoft.net/article/113677/ Pharmacia 71: 1-12

DOI: 10.3897/pharmacia.71.e113677

Authors: Lyubomir Marinov, Ani Georgieva, Reneta Toshkova, Ivanka Kostadinova, Iliya Mangarov, Tanya Toshkova-Yotova, Irina Nikolova

Abstract: Targeting the inflammation-related molecules with nonsteroidal anti-inflammatory drugs (NSAIDs) represents a promising approach for cancer prevention/therapy. We evaluated the in vitro anticancer effects of meloxicam, lornoxicam, ketoprofen, and dexketoprofen on the proliferation, migration, and apoptosis of human cervical, colorectal, and mammary carcinoma cells. The antiproliferative activity and cytotoxicity of tested NSAIDs on HeLa, HT-29, and MCF-7 cell lines were assessed by the MTT test. The apoptosis-inducing potential was analyzed by fluorescent staining with acridine orange/ethidium bromide and DAPI. Migration activity was assessed by a wound-healing scratch assay. The tested NSAIDs reduced the viability of the used tumor cell lines. The cytomorphological analysis revealed reduced cell density and mitotic activity and the presence of cells with morphological features of early and late apoptosis. Significant inhibition of the migration capacity was established as well. In conclusion, NSAIDs could be candidates for the development of new pharmacological strategies for the treatment and prevention of cancer.

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Research Article Thu, 29 Feb 2024 18:59:49 +0200
Malaria’s molecular dance: Mechanism, therapies, and emerging insights https://pharmacia.pensoft.net/article/117145/ Pharmacia 71: 1-12

DOI: 10.3897/pharmacia.71.e117145

Authors: Nabila Ananda, Athaya Sabina, Ulfa Rahmadani, Ali Syahrizal, Nabillah Deskya, Sinta Maria, Muhammad Riza, Lusi Rahmadia, Anni Holila, Dwi Putri, Kevin Gabriel, Ratna Sari Zai, Mega Carensia, Princella Halim, Naomi Regina, Dinda Rizka, Aulia Syahfitri, Tessa Rotua, Maria Belen, Fahmy Nanda, Rizzanda Pramuditya, Khairunnisa Khairunnisa, Emil Salim, Fahrul Nurkolis, Chindy Umaya, Rony Abdi Syahputra

Abstract: Malaria, caused by Plasmodium parasites and transmitted through Anopheles mosquitoes, remains a formidable global health challenge. This abstract provides an overview of the intricate molecular mechanisms underlying malaria pathogenesis, explores current therapeutic approaches, and highlights emerging insights that may shape future strategies for malaria control. The intricate dance between Plasmodium parasites and their human hosts begins with the mosquito’s bite, leading to the invasion of erythrocytes by Plasmodium species. We delve into the molecular mechanisms governing parasite entry and subsequent replication within host cells, shedding light on key factors such as erythrocyte surface receptors and parasite-encoded proteins critical to invasion and survival. While malaria treatment has relied heavily on antimalarial drugs, the emergence of drug resistance necessitates ongoing exploration of novel therapeutic strategies. This abstract reviews current antimalarial drug classes, their mechanisms of action, and the challenges posed by drug resistance. We also highlight promising drug candidates and innovative approaches in the pipeline, including the use of advanced molecular techniques and immunotherapies. Emerging insights from genomics, proteomics, and transcriptomics have deepened our understanding of Plasmodium biology and host-parasite interactions. We discuss the potential of these omics approaches in identifying new drug targets, understanding drug resistance mechanisms, and developing vaccines. Additionally, we examine the role of human genetics in influencing susceptibility to malaria and response to treatment. Vector control remains a critical component of malaria prevention. We touch upon emerging strategies, such as genetically modified mosquitoes and novel insecticides, in the context of integrated vector management programs. Finally, we emphasize the importance of a multifaceted approach to malaria control, combining advances in molecular biology, drug development, vector control, and public health interventions.

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Review Article Wed, 28 Feb 2024 11:40:43 +0200
Curcumin is comparable to metformin for the treatment of PCOS in rats: a preclinical study https://pharmacia.pensoft.net/article/119708/ Pharmacia 71: 1-10

DOI: 10.3897/pharmacia.71.e119708

Authors: Salam Shannag, Khawla Nuseir, Linda Tahaineh, Wael Hananeh

Abstract: Background: Ploy cystic ovary syndrome (PCOS) is a common gynecological disorder affecting between 4–20% of females worldwide. Curcumin, the active ingredient in turmeric (Curcuma longa Zingiberaceae) is a yellow polyphenol with a wide range of pharmacological activities such as antioxidant, anti-inflammatory, anti-tumor, neuroprotective and cardioprotective properties. Methods: Letrozole was used to induce PCOS in female Wistar rats. Curcumin, metformin, or a combination of both was given to assess their therapeutic effects. Body weight, estrogen, progesterone, testosterone, and glucose levels were measured after disease induction and at the conclusion of treatment. Additionally ovarian histomorphology was examined after sacrificing the animals and removal of the ovaries. Results and conclusion: Weight was significantly reduced in the curcumin, metformin and curcumin and metformin combination groups. Testosterone was decreased, progesterone was increased, and normal ovarian morphology was restored in the three groups. Conclusions: curcumin is therapeutically effective for PCOS and is comparable to metformin.

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Research Article Tue, 27 Feb 2024 16:54:00 +0200
Kidney protective effect of sitagliptin in 5-fluorouracil-challenged rats https://pharmacia.pensoft.net/article/114441/ Pharmacia 71: 1-5

DOI: 10.3897/pharmacia.71.e114441

Authors: Ahmed Hassan Al-Ghamdi, Mervat Z. Mohamed, Rabei M. Elbadry, Amr A. Fouad

Abstract: The possible protective effect of sitagliptin (SIT) against nephrotoxicity induced by a single dose 5-fluorouracil (5-FU) (150 mg/kg, i.p.) was investigated in rats. SIT treatment (5 and 10 mg/kg/day, p.o.) was given for 7 days, starting 5 days before 5-FU administration. Both SIT doses caused significant reductions of serum creatinine and neutrophil gelatinase-associated lipocalin levels in rats received 5-FU. Both doses of SIT also significantly decreased malondialdehyde, tumor necrosis factor-α, interleukin-1β, nuclear factor-κB p65 (NF-κB p65), Bax/Bcl-2 ratio, and cleaved caspase-3 in kidneys of 5-FU-challenged rats. Additionally, SIT, at both doses, significantly increased renal total antioxidant capacity and nuclear factor erythroid 2related factor 2 (Nrf2) in rats received 5-FU. Besides, SIT markedly attenuated the 5-FU-induced histopathological kidney tissue injury in rats. It was concluded that SIT, at both doses, provided a significant nephroprotective effect in 5-FU-challenged rats, through its antioxidant, antiinflammatory, and antiapoptotic activities, and by modulating Nrf2 and NF-κB pathways.

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Research Article Tue, 27 Feb 2024 16:53:17 +0200
Association of the rs1801133 and rs1801131 polymorphisms in the MTHFR gene and the adverse drug reaction of methotrexate treatment in a sample of Iraqi rheumatoid arthritis patients https://pharmacia.pensoft.net/article/113597/ Pharmacia 71: 1-8

DOI: 10.3897/pharmacia.71.e113597

Authors: Qassim Mahdi Mutlak, Ali Abdulhussain Kasim

Abstract: Background: Methotrexate is one of the mainstays for treating rheumatoid arthritis (RA) with a wide range of adverse drug reactions, however, it’s the relationship between adverse drug reactions and genetic polymorphism remains to be highlighted, and there is a lack of studies concerning Arabic Iraqi population regarding this aspect. Objective: Evaluate the association between genetic mutations in the MTHFR gene in SNPs (rs1801133G>A and rs1801131T>G) on the adverse drug reaction for RA Iraqi patients. Methods: An observational study, that involved 95 Iraqi RA patients with established RA. Patients were divided according to the occurrence of adverse drug reactions. A polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was being utilized for MTHFR variants (rs1801133 and rs1801131). The Macrogen Company (Korea) provided the forward and reverse primers in lyophilized form. All PCR procedures are carried out using a PCR thermal cycler (Germany). Results: The study included 95 patients with RA, with a mean age of 43.1 ± 10.6 years, most of the patients were female (85.3%), about 35.8% were smokers, most of the patients had disease low activity (45.2%), followed by moderate (41.1%), high (9.5%), and remission (4.2%). No significant association between individual genetic polymorphism with adverse drug reactions. AG haplotype for rs1801133 rs1801131 polymorphism is associated with reducing the risk of overall adverse drug reactions, meanwhile, GT haplotype for rs1801133, and rs1801131 polymorphism were marginally associated with increased risk of adverse drug reactions. Conclusion: In conclusion, we have successfully found a panel of pharmacogenetic indicators that have the potential to be valuable in predicting the response to methotrexate treatment in patients with rheumatoid arthritis. Haplotypes for rs1801133 rs1801131 polymorphism are associated with reducing or increasing the risk of MTX adverse drug reactions. It is very important to evaluate patients’ haplotypes before starting the therapy program so that we can expect the treatment outcome with the most suitable dose and most tolerable one at the same time.

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Research Article Tue, 27 Feb 2024 10:42:35 +0200
HPLC method for the determination of nifedipine in rat plasma: development, validation, and application to pharmacokinetic drug-herb interaction study https://pharmacia.pensoft.net/article/119198/ Pharmacia 71: 1-6

DOI: 10.3897/pharmacia.71.e119198

Authors: Devy N. A. Hasanuddin, Afrillia Nuryanti Garmana, Lucy Sasongko

Abstract: A simple and rapid high-performance liquid chromatography (HPLC) was developed to determine the plasma level of nifedipine in rats after its single administration and combination with herbs. Nifedipine was extracted with acetonitrile to precipitate protein from plasma samples. The separation was implemented on a C18 column with a mobile phase of acetonitrile: water (63:37, v/v). The calibration curve displayed good linearity in the 30–1000 ng/mL range. The lower limit of quantification (LLOQ) was 30 ng/mL. The intraday and interday assay accuracy and precision met the criteria of validation and study sample analysis. The recovery was found to be 101.89%. Stability studies showed that nifedipine was stable after 12 h at room temperature and 21 days at -20 °C. No significant difference was examined between the pharmacokinetic parameters of nifedipine with or without Gynura procumbens leaf extract. The proposed method was helpful for the pharmacokinetic interaction study of nifedipine combined with herbal in rats.

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Research Article Mon, 26 Feb 2024 16:53:20 +0200
Gallates – toxicological data and a pilot study on the prevalence of contact sensitization https://pharmacia.pensoft.net/article/120507/ Pharmacia 71: 1-6

DOI: 10.3897/pharmacia.71.e120507

Authors: Maya G. Lyapina, Silvia P. Tsanova-Savova, Maria G. Nikolova, Maia L. Vizeva, Georgi Ts. Momekov

Abstract: Propyl, octy- and dodecyl gallates are largely used in food, cosmetic and pharmaceutical industry as additives – preservatives. The main source of exposure non-related with food consumption is their use of cosmetic products. Gallates are classified as skin sensitization human health hazard. This research aims to evaluate the prevalence of contact sensitization to gallates and to estimate the possible cross/concomitant sensitization to gallate mix and other cosmetics ingredients among cosmeticians and cosmetology students. Skin patch testing with Gallate mix along with 19 other haptens was performed among 109 participants – 37 cosmetology students, 26 cosmeticians, and 46 controls. The study established high prevalence of contact sensitization to gallates, with higher risk for students (45.9%) and cosmeticians (38.5%). A significantly higher (р = 0.008) prevalence of co-sensitization to decyl glucoside was established for the control group. Proper risk information, with complex programs for prevention of occupational skin diseases should be provided.

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Research Article Fri, 23 Feb 2024 15:14:01 +0200
Fenugreek galactomannan: High-Performance Thin-Layer Chromatography (HPTLC) method for identification and quantification of galactose and mannose https://pharmacia.pensoft.net/article/118029/ Pharmacia 71: 1-8

DOI: 10.3897/pharmacia.71.e118029

Authors: Vanya Nalbantova, Velislava Todorova, Niko Benbassat, Cedric Delattre

Abstract: Fenugreek (Trigonella foenum-graecum L.) is a leguminous, medicinal plant that finds applications in traditional medicine and as an agent in pharmaceutical and nutraceutical products. Its seeds contain various compounds to which numerous beneficial effects are attributed, such as soluble polysaccharides, in particular galactomannan. There are limited data reporting the determination of Bulgarian fenugreek galactomannan composition by HPTLC. The analysis was successful in separating galactose and mannose, each demonstrating different Rf values 0.36, 0.48, respectively. After developing the method with the appropriate conditions, it was validated for linearity, accuracy and precision, range, limits of detection (LD) and quantification (LQ), and robustness. The LD of galactose and mannose was found at 91.34 ng/band and 85.26 ng/band, respectively. The method confirmed the composition of hydrolyzed galactomannan from fenugreek, revealing a ratio of galactose to mannose closed to 1:1, and this capability can be of significant value in both the pharmaceutical and food industries.

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Research Article Fri, 23 Feb 2024 15:13:37 +0200
The prognostic role of markers of systemic inflammation in patients with metastatic lung cancer receiving immunotherapy: A comprehensive review of the literature https://pharmacia.pensoft.net/article/115558/ Pharmacia 71: 1-7

DOI: 10.3897/pharmacia.71.e115558

Authors: Tanya Zlatanova, Jeliazko Arabadjiev

Abstract: Lung carcinoma stands as a prevalent malignancy characterized by a distressingly elevated fatality rate. Immunotherapy, administered either as a monotherapy or together with chemotherapy, represents the primary therapeutic approach for the majority of individuals grappling with advanced non-small cell lung cancer. The influence of systemic inflammation in fostering cancer dissemination and progression is a well-documented phenomenon. This literature review examines contemporary indices and scoring systems, which have emerged as informative indicators of systemic inflammation in recent years. These indices and scores are valuable prognostic and predictive elements in assessing treatment response among patients with metastatic lung cancer undergoing immunotherapeutic treatment.

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Research Article Thu, 22 Feb 2024 18:26:57 +0200
Comparative analysis of newer classes of antidiabetics and the concept of pharmaceutical care – dealing with therapeutic problems https://pharmacia.pensoft.net/article/120141/ Pharmacia 71: 1-8

DOI: 10.3897/pharmacia.71.e120141

Authors: Anna Peneva, Milen Dimitrov, Valentina Petkova

Abstract: The prevalence of obesity is increasing rapidly. The latest World Health Organization – WHO report declares the disease as an epidemic. After pharmacodynamic, pharmacokinetic, clinical and pharmacoepidemiologic data analysis and comparison of the three classes of antidiabetic medicinal products: GLP-1 receptor agonists, DPP-4 inhibitors and SGLT2 inhibitors, a literature review of the topic, patient education and the concept of pharmaceutical care emerged as methods for dealing with the most common adverse drug reactions, safety concerns, and drug interactions.

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Research Article Thu, 22 Feb 2024 18:26:36 +0200
Analysis of regulatory implementation of regulation 536/2014 by European Union countries and Ukraine regarding the examination of clinical trials data and information https://pharmacia.pensoft.net/article/109829/ Pharmacia 71: 1-11

DOI: 10.3897/pharmacia.71.e109829

Authors: Liliia Hala, Oleksandr Nabok

Abstract: The article presents the results of a comparative analysis of regulatory requirements for expertise of clinical trials documentation, submitted for regulatory authority and ethic committees’ approval in EU member countries and Ukraine, outlining the main trends, considering the updated Regulation (EU) No 536/2014, which came into effect on January 31, 2023. Among the positive changes are simplification of safety reporting requirements, use of artificial intelligence in the process of clinical trials documentation examination for obtaining regulatory authority and ethic commission approval, introduction of a single portal for submitting materials for clinical trials, and functioning of database for the submission and review of initial Clinical Trial Application documents and obtaining authorization within the EU to facilitate the interaction between applicants and regulatory authority are highlighted. To harmonize Ukraine’s regulatory requirements with EU legislation, it is advisable to use a single portal for data exchange and document submission for applicants in regards to clinical trials, regulatory authority and local ethics committees. This will expedite the examination process of clinical trial documentation and simplify the monitoring of document review progress.

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Research Article Tue, 20 Feb 2024 18:11:02 +0200
Effects of topical Ivermectin on imiquimod-induced Psoriasis in mouse model – Novel findings https://pharmacia.pensoft.net/article/114753/ Pharmacia 71: 1-14

DOI: 10.3897/pharmacia.71.e114753

Authors: Sally Ayad Almudaris, Fouad Kadhim Gatea

Abstract: Aim: investigate the possible anti-psoriatic effect of ivermectin in mice based on observational and histopathological outcomes and biomarkers. Methods: Sixty male Swiss Albino Mice were divided into six groups (Groups I–VI); each group contained ten mice with shaved dorsal skin. The clinical, pathological, and laboratory effects were measured. Results: Topical Ivermectin significantly decreased vascular endothelial growth factor levels. At the same time, the combination of ivermectin plus Clobetasol showed a more significant reduction in tumor necrosis factor-alpha (TNF-α) and Interleukin-17 (IL-17) levels. Regarding the Interleukin-10 (IL-10) level, the Ivermectin and Ivermectin/Clobetasol combination groups showed a significant increase in IL-10. Conclusion: Topical Ivermectin’s anti-psoriasis activity increases IL-10 levels and could be used efficiently to alleviate psoriatic symptoms. Its combination treatment with Clobetasol holds promise for the management of psoriasis.

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Research Article Tue, 20 Feb 2024 10:33:01 +0200
Potential of 10% propolis-based toothpaste on the inhibition of biofilm-forming bacteria growth in vitro https://pharmacia.pensoft.net/article/118072/ Pharmacia 71: 1-7

DOI: 10.3897/pharmacia.71.e118072

Authors: Suryono Suryono, Prayudha Benni Setiawan, Nur Rahman Ahmad Seno Aji, Christia Aye Waindy Vega, Budi Rodestawati, Endang Lukitaningsih, Friska Ani Rahman, Sherlina Devina, Sholiha Sarah Tsabita, Selcaria Istna Datau, Ananto Ali Alhasyimi

Abstract: Aim of the study: To investigate the potential of 10% propolis-based toothpaste on inhibiting biofilm-forming bacteria growth in vitro. Material and method: Organoleptic properties are evaluated, considering color, odor, and taste. Antibacterial tests use a disc diffusion method against Streptococcus mutans, Staphylococcus aureus and Porphyromonas gingivalis bacteria, while cytotoxicity is assessed using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay on fibroblast cells. Statistical analysis involves mean ± standard deviation. The data were then tested using a one-way analysis of variance and Kruskal-Wallis, followed by post-hoc test (p < 0.05). Results: The organoleptic evaluation of 10% propolis toothpaste reveals a visually clear appearance, consistent orange flavor, and aroma lasting 30 days. Based on the antibacterial results, a 10% level of propolis toothpaste sample inhibited the growth of Streptococcus mutans, Staphylococcus aureus and Porphyromonas gingivalis bacteria. The post-hoc test showed that toothpaste demonstrated significant inhibition on S. mutans and S. aureus compared to the negative control (p < 0.05). The toothpaste showed a larger inhibitory zone towards P. gingivalis compared to the adverse control; however, no significant differences were observed (p > 0.05). Cytotoxicity assessment on fibroblast cells shows a high percentage (85.31%) of viable cells. The findings highlight the 10% of propolis toothpaste’s potential and non-toxic as oral care product. Conclusions: 10% propolis toothpaste inhibits S. mutans, S. aureus, P. gingivalis growth, and not toxic on fibroblast.

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Research Article Tue, 20 Feb 2024 10:32:39 +0200
Phytoconstituents, antioxidant, and cholinesterase inhibitory activities of the leaves and stem extracts of Artocarpus sericicarpus https://pharmacia.pensoft.net/article/112499/ Pharmacia 71: 1-8

DOI: 10.3897/pharmacia.71.e112499

Authors: Suciati Suciati, Erlinda Rhohmatul Laili, Hamizah Haula, Lidya Tumewu, Nitra Nuengchamnong, Nungruthai Suphrom, Aty Widyawaruyanti

Abstract: The study aimed to investigate the antioxidant and cholinesterase inhibitory activities of the leaves and stems of Artocarpus sericicarpus and to analyse the phenolic compounds in the extracts. The modified Ellman’s method was used to determine the cholinesterase inhibitory activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. The antioxidant properties were evaluated using DPPH and ABTS methods. The total phenolic content (TPC) was measured by spectrometric assay, and compound identification was carried out by LC-MS/MS analysis. The results showed that the leaf and stem extracts of A. sericicarpus exerted significant inhibitory effects against AChE and BChE, as well as antioxidant activities. The stem ethanolic extract exhibited the highest potency against AChE and BChE with IC50 values of 5.81 and 11.46 µg/mL, respectively. The leaf and stem ethanolic extracts gave higher antioxidant activities and TPC compared to the water-based extracts. The LC-MS/MS analysis indicated the presence of phenolic compounds, such as flavones, flavonols, flavanones, prenylated chalcones, and xanthones in the extracts.

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Research Article Mon, 19 Feb 2024 16:32:21 +0200
Adherence to disease-modifying therapies among patients with multiple sclerosis in Bulgaria – A real world study https://pharmacia.pensoft.net/article/117681/ Pharmacia 71: 1-7

DOI: 10.3897/pharmacia.71.e117681

Authors: Yoana Seitaridou, Teodora Chamova, Maria Kamusheva

Abstract: Introduction: The purpose was to assess the level of medication adherence (MA) and related factors among individuals with multiple sclerosis (MS) in Bulgaria. Materials and methods: A prospective one-year study was conducted among 54 patients with MS diagnosed, treated, and monitored in Clinic of Neurology, University Hospital “Alexandrovska”, Sofia in 2022/2023. Clinical data, patients reported outcomes, patients’ characteristics such as age, gender and reduced work capacity, and other data were collected to define the predictors of non-adherence to medicines. MA level was assessed through a free Morisky–Green 4-item questionnaire. Results: Мost of the observed patients were rated with high and moderate adherence to MS therapy (n = 44; 81.48%). The remaining 18.52% of the patients with poor adherence to therapy were women. There was no statistical basis for asserting differences in adherence levels among the various factors considered. Conclusion: The current study demonstrates the importance of MA assessment and provides insights into MA among patients with MS in Bulgaria. Still, there are low-adherent patients, and the responsible factors should be further investigated.

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Research Article Thu, 15 Feb 2024 15:17:10 +0200
Malaria in Indonesia: current treatment approaches, future strategies, and potential herbal interventions https://pharmacia.pensoft.net/article/116095/ Pharmacia 71: 1-14

DOI: 10.3897/pharmacia.71.e116095

Authors: Tina Christina L. Tobing, Wahrianto, Eka Saputri, Nasywa Inayah Wafa, Putri Daffa Zulfianti, Lidwina Iswari Sihaloho, Annisa Rabbiatul Husna, Devia Salsabila, Fito Hansen Hotasi Silalahi, Alex Insandus Sitohang, Aysiah Sabrina, Atika Darayani Hasyati Harianja, Silvyani Agustilova Barus, Salwa Sabina, Annisa Aulia Rahma, Adrian Joshua Velaro, Khairunnisa Khairunnnisa, Emil Salim, Fahrul Nurkolis, Rony Abdi Syahputra

Abstract: Malaria remains a significant public health challenge in Indonesia, with varying prevalence across regions, particularly in eastern provinces like Papua and West Papua. This parasitic disease, transmitted by Plasmodium-infected Anopheles mosquitoes, continues to burden affected populations. Contemporary treatment approaches predominantly rely on Artemisinin-based Combination Therapy (ACT). However, the emergence of drug resistance, coupled with environmental and demographic factors, presents ongoing challenges. This paper explores current malaria treatment strategies in Indonesia, emphasizing the importance of vigilance in the face of drug resistance and the need for innovative approaches. Additionally, it discusses the potential of herbal interventions, drawing from the rich traditional knowledge of medicinal plants in Indonesia. Secondary metabolites found in herbs, including flavonoids, terpenoids, and alkaloids, show promise as antimalarial agents. As Indonesia and the global community strive to combat malaria, research, surveillance, and healthcare infrastructure development must remain at the forefront of strategies. Despite the complex nature of malaria control, continued dedication and collaboration offer hope for reducing the disease’s impact and progressing towards its eventual elimination. Graphical abstract:

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Review Article Thu, 15 Feb 2024 12:29:16 +0200
Health Emergency Preparedness and Response Authority’s (HERA) role in dealing with the monkeypox emergency in the European Union https://pharmacia.pensoft.net/article/117944/ Pharmacia 71: 1-6

DOI: 10.3897/pharmacia.71.e117944

Authors: Atanas Toshev, Elina Petkova-Gueorguieva, Anna Mihaylova, Galinka Pavlova, Nikoleta Parahuleva, Stefan Balkanski, Lily Peikova, Violeta Getova, Vasil Madzharov, Stanislav Gueorguiev

Abstract: The current article examines and analyzes the actions taken by the European Commission, specifically through the Directorate-General Health Emergency Preparedness and Response Authority (HERA) – an organization that anticipates threats and potential health crises, through intelligence gathering and building the necessary response capacities), aimed at supporting member states in limiting the spread of MPOX (monkeypox – an infectious disease caused by the monkeypox virus). It explores specific pharmaceutical products and vaccines procured by HERA and how they have been distributed among member states. The article raises questions about the compliance in purchasing pharmaceutical products and vaccines lacking approval for use within the European Union, highlighting the potential new regulatory challenges for Bulgaria if it needs to secure medications for treatment of human smallpox disease such as Jynneos and TPOXX (Tecovirimat) for its citizens. In conclusion, the article notes the swift response of HERA through the procurement of the Jynneos vaccine and TPOXX medicinal product. This swift response may have contributed to the decline of MPOX cases in the European region, potentially due to collaborative efforts among health authorities at both European and national levels. This success underscores the importance of cooperation among health authorities at various levels in combating infectious diseases.

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Review Article Wed, 14 Feb 2024 17:36:34 +0200
Arylnaphthalene lignans with a focus Linum species: a review on phytochemical, biotechnological and pharmacological potential https://pharmacia.pensoft.net/article/117690/ Pharmacia 71: 1-10

DOI: 10.3897/pharmacia.71.e117690

Authors: Rada Nedelcheva, Yancho Zarev, Rositsa Mihaylova, Ekaterina Kozuharova, Georgi Momekov, Iliana Ionkova

Abstract: Lignans are a large group of dimeric phenylpropanoids with a long and distinguished history of medicinal use in the ancient cultures of many peoples. The two main groups, -aryltetralin and arylnaphthalene lignans, are leading compounds with important pharmacological properties and a wide range of biological activities. While the first group is well studied mainly for the production of podophyllotoxin, for arylnaphthalene lignans, the data on the availability of a sustainable resource for their production is are still insufficient. The Linum genus, comprising approximately 180 species, is notable for its arylnaphthalene lignans production like justicidin B and isojusticidin B. The pharmacological potential of arylnaphthalene lignans includes cytotoxic, antiviral, anti-inflammatory and antiprotozoal effects. The review highlights the use of biotechnology by in vitro cultures for optimising lignan production. Structural elucidation of novel lignans underscores the ongoing diversity and potential discoveries in this botanical domain, providing an important additional information of arylnaphthalene lignans.

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Review Article Wed, 14 Feb 2024 12:10:09 +0200
The effect of L-Arginine from Giant Snake Head fish (Channa micropeltes) on neuroinflammation and neuron damage in traumatic brain injury in rats https://pharmacia.pensoft.net/article/111239/ Pharmacia 71: 1-9

DOI: 10.3897/pharmacia.71.e111239

Authors: Andy Nugroho, Didik G. Tamtomo, Dono Indarto, Risya Cilmiaty, Soetrisno

Abstract: Backgrounds: Traumatic brain injury has high mortality and morbidity. The involvement of neuroinflammatory responses and neuronal damage in traumatic brain injury is the basis for the development of renewable neuroprotective agents, one of which is the amino acid L-Arginine. The amino acid L-Arginine which can be found in Giant Snake Head fish (Channa micropeltes) is thought to inhibit anti-inflammatory effects through the Arg-1 signaling pathway. Aims: To prove and analyze the effect of giving L-Arginine Giant Snake Head fish on neuroinflammation and neuronal damage in a rat model of traumatic brain injury. Methods: This randomized controlled trial (RCT) study used a posttest-only control group design. Thirty-five male rats (Rattus norvegicus) with the Wistar strain were randomly divided into five treatment groups, namely the normal control group (N), negative control (KN), and 3 treatment groups (A-C). The KN and A-C groups were modeled after traumatic brain injury and given L-Arginine at a dose of 0.5; 1.5; and 3 g/kgBW/day for 7 days specifically A-C. Brain tissue samples were used for the examination of TLR4, TNF-α, GSDMD, Caspase-3, and histopathological features. All data were analyzed using the Kruskall-Wallis test, except for GSDMD expression with a significance <0.05. Results: The mean TLR4 expression in A (15.7 ± 5.35), B (12.9 ± 5.67), and C (11.4 ± 6.27) were lower and significant compared to KN, but higher and significant compared to N. The same pattern appears in the decrease in TNF-α expression, Caspase-3 expression, and histopathology of brain tissue damage. The mean relative expression of GSDMD to N in A (1.3 ± 0.53), B (1.2 ± 0.52), and C (1.2 ± 0.60) was higher than in KN, but not significant. Relative expression of GSDMD to Beta Actin, A and B have the same higher expression than C, KN, and N. Conclusion: Expression of TLR-4, TNF-α, Caspase-3 and histopathology of brain tissue damage in traumatic brain injury model rats given Giant Snake Head fish L-Arginine were lower than without L-Arginine. Meanwhile, the expression of GSDMD in traumatic brain injury model rats when given Giant Snake Head fish L-Arginine was slightly higher than without L-Arginine.

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Research Article Tue, 13 Feb 2024 16:34:14 +0200
Evaluation of types and concentration of bile salts impact on physical properties of nisoldipine-loaded bilosomes https://pharmacia.pensoft.net/article/116917/ Pharmacia 71: 1-7

DOI: 10.3897/pharmacia.71.e116917

Authors: Ghada Hamid Naji, Fatima J. Al Gawhari

Abstract: Background: Bilosomes are lipid vesicles that exhibit flexibility and deformability. They consist of phospholipids and amphiphilic bile salts. Compared to the normal vesicular systems such as liposomes and niosomes, bilosomes provide several notable advantages, including simplified manufacturing, cost-effectiveness, and enhanced stability. Aim: The main objective of the present work was to evaluate the effect of different bile salts on the physical properties that include entrapment efficiency, vesicle size, and polydispersity index(PDI). In addition, in vitro drug release for nisoldipine (NSD) loaded bilosomes was evaluated. Methods: Nisoldipine-loaded bilosomes were made using a thin film hydration technique. Cholesterol along with surfactant (span 60) was employed, and the formulation also contained several different bile salts, including sodium deoxycholate (SDC), sodium glycocholate (SGC), and sodium taurocholate (STC). Results: The developed NSD bilosomes exhibited an entrapment efficiency ranging from 44.2 ± 0.3 to 82.36 ± 0.80% and a vesicle size diameter in the nanometric dimensions (166 ± 1.83 to 237.8 ± 3.3 nm). An in-vitro release study revealed that formulas prepared with SDC bile salts showed higher drug release than SGC and STC formulas. Increasing the bile salt amount from 5 mg to 10 mg increases entrapment efficiency with increasing vesicle size. Further increase in bile salt led to decreased entrapment efficiency with increased vesicle size. SDC gives the best result in terms of entrapment efficiency and acceptable size. STC provides the largest particle size due to its high molecular weight compared to SGC and SDC. Conclusion: The SDC bile salt component is better suited for manufacturing NSD bilosomes. This is because this component yields the best results regarding high entrapment efficiency, nano size, and prolonged drug release.

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Research Article Fri, 9 Feb 2024 09:53:39 +0200
Assessment of anxiety and depression among professional healthcare workers during the COVID-19 pandemic – observational cross-sectional study https://pharmacia.pensoft.net/article/115198/ Pharmacia 71: 1-6

DOI: 10.3897/pharmacia.71.e115198

Authors: Mohammed Mahmood Mohammed, Hayder Adnan Fawzi

Abstract: Aim: Evaluate the prevalence of depression among professional healthcare workers (PHCW) during the COVID-19 pandemic. Methods: A cross-sectional study was conducted during the fourth wave of COVID-19 infection in Iraq. A semi-structured questionnaire in English was used to obtain information about the study variables. Results: The study included 314 participants, with a mean age of 34.3 years, slightly higher male to female sex (55.1 to 44.9%), doctors represent (26.1%), pharmacist represent (26.4%) while 36.9% includes other PHCW (nurse, laboratory technician, doctor assistance, and paramedics). There was a high prevalence of depression in the current study (98.4%). There was no significant association between total HADS with sex, specialty, and duration of working in COVID-19 isolation wards. Meanwhile, age above 50 years appears to be associated with higher HADS scores compared to younger PHCW. Conclusion: Healthcare practitioners faced a heightened susceptibility to experiencing depression throughout the COVID-19 pandemic.

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Research Article Thu, 8 Feb 2024 10:41:45 +0200
Cost-effectiveness of cardiomyopathy ambulatory care with sacubitril/valsartan vs standard therapy after COVID-19 in Kazakhstan https://pharmacia.pensoft.net/article/115952/ Pharmacia 71: 1-6

DOI: 10.3897/pharmacia.71.e115952

Authors: Dana Dadanbekova, Kairat Zhakipbekov, Almat Kodasbayev, Ubaidilla Datkhayev, Guenka Petrova, Konstantin Tachkov

Abstract: The aim of this study is to evaluate the cost-effectiveness of 2 different therapies of cardiomyopathy (CM) after COVID -19. The focus of the study is fixed dose combination (FDC) of sacubitril/valsartan and standard therapy in Kazakhstan. This is written from the point of view of the health insurance institution. Information for the age, gender, CM therapy, number of hospitalizations, COVID-19 infection, and past cardiovascular surgeries of 237 patients with incidents of CM which required a hospitalization after a COVID-19 infection was collected. Selected patients were divided into two groups: the cost of FDC and standard therapy and the annual cost of their therapy was calculated. The incremental cost-effectiveness ratio was calculated by dividing the cost of medication therapy by the number of hospitalizations between the two compared groups. Robustness of the results was tested with deterministic and probabilistic sensitivity analyses. The study was performed in City cardiology centre of Almaty in Kazakhstan during 2020–2022. Results show that FDC is more costly but more effective, leading to fewer hospitalizations. ICER accounts for €-2,743.08 per hospitalization saved in the group on FDC vs standard of therapy. Sacubitril/valsartan is cost-effective in ambulatory conditions in comparison with standard therapy of cardiomyopathy after COVID-19 leading to savings due to the decrease in the number of hospitalizations.

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Research Article Thu, 8 Feb 2024 10:41:45 +0200
Potent antioxidant activity of black grass jelly (Mesona palustris BL) leaf extract and fractions https://pharmacia.pensoft.net/article/117435/ Pharmacia 71: 1-5

DOI: 10.3897/pharmacia.71.e117435

Authors: Dytha Andri Deswati, Kusnandar Anggadiredja, Afrillia Nuryanti Garmana

Abstract: Black grass jelly (Mesona palustris BL) is an Indonesian traditional food that is rich in antioxidants and believed to have potential for treating various diseases such as diabetes, hypertension, and cancer. The present study aimed to determine the antioxidant activity of black grass jelly leaf extract as well as fractions using ABTS, DPPH and FRAP methods. Following ethanol extraction and subsequent fractionations, total flavonoid level was determined, followed by antioxidant activity tests using the ABTS, DPPH and FRAP with vitamin C as references. The tests revealed the following order of antioxidant activities, ethyl acetate fraction>extract>water fraction>n-hexane fraction. All test substances had IC50 of <50 ppm, which categorized them as having very high antioxidant activities. In line with this data, on the basis of reducing power, ethyl acetate extract was shown to be the most potent antioxidant, having a value of 20.24 mgAAE/g sample. Overall, results of the present study suggest the potential use of black grass jelly as a part of the therapeutic armamentarium for oxidative stress-related diseases.

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Research Article Thu, 8 Feb 2024 10:41:45 +0200
In silico and in vitro screening of pyrrole-based Hydrazide-Hydrazones as novel acetylcholinesterase inhibitors https://pharmacia.pensoft.net/article/114120/ Pharmacia 71: 1-7

DOI: 10.3897/pharmacia.71.e114120

Authors: Emilio Mateev, Ali Irfan, Alexandrina Mateeva, Magdalena Kondeva-Burdina, Maya Georgieva, Alexander Zlatkov

Abstract: Virtual screening is emerging as a highly applied technique and gained prominence as widely used method for the search and identification of potential hits, significantly reducing the time needed to discover novel and effective compounds compared to high-throughput screening. Recently, the superiority of simulations with multiple programs compared to a single software docking has been discussed. The aim of this work was to apply consensus docking, molecular mechanics/generalized Born surface area (MM/GBSA) free binding energy recalculations, and in vitro evaluations on an in-house dataset of recently synthesized pyrrole-based hydrazide-hydrazones in the search for novel acetylcholinesterase (AChE) inhibitors. Two licensed softwares – GOLD 5.3 and Glide, were employed for the virtual screenings, and several chemotherapeutic potential hits were identified. Furthermore, MM/GBSA free binding energy recalculations were provided to enhance the robustness of the in silico results. The MM/GBSA scores of the top ten pyrrole-based hydrazide-hydrazones were ranging from -60.44 to -70.93 Kcal/mol. Subsequent, in vitro evaluations of the top ranked compounds revealed that 12d exhibited the highest AChE inhibitory activity, with a 55% inhibition rate at a concentration of 10 μM. Moreover, this prominent pyrrole-based AChE inhibitor formed stable complex with the active site of the enzyme. Interactions with the active amino residues Tyr72 and Tyr286 indicated that 12d was located near the peripheral anionic site of the enzyme. Additionally, in silico ADME investigations using QikProp demonstrated that 12d possesses optimal pharmacokinetic properties. In conclusion, this study identified a novel pyrrole-based AChE inhibitor 12d through a combination of computational and experimental findings.

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Research Article Mon, 5 Feb 2024 10:58:25 +0200
Effectiveness of combination therapy of magnesium, vitamin B2 and Co-enzyme 10 supplementation on vestibular migraine: a retrospective cohort study https://pharmacia.pensoft.net/article/112909/ Pharmacia 71: 1-7

DOI: 10.3897/pharmacia.71.e112909

Authors: Ala Abu-Zaid, Sawsan Abu-Zaid, Muna Barakat, Rashed Al-Huniti, Hamzeh Khair

Abstract: Vestibular migraine (VM) has conventionally been treated through acute migraine-aborting therapeutic interventions and prevention to reduce migraines’ occurrence, length and intensity. There is growing attention to the development of non-pharmaceutical prophylactic interventions for migraines in the search for effective treatments, such as through mineral, vitamin and other supplementation. This research aims to examine the effectiveness of magnesium, vitamin B2 and Co-enzyme 10 supplementation to decrease vestibular migraines’ frequency, duration and severity. Method: This retrospective cohort study was conducted in a Jordanian context over 57- VM patients, each patient attending the outpatient dizziness clinic between August 2022 and February 2023. Patients were treated for six months with a combined supplementation of magnesium, vitamin B2, and Co-enzyme Q10. Assessments were made of three measures of VM attack, namely frequency, duration and severity, both before and after intervention. Result: Supplements administration demonstrated a significant reduction (by 81.1%) in VM-symptoms frequency (p < 0.001). Moreover, reductions in symptom duration in minutes occurred progressively as the treatment period continued and showed statistical significance, with impacts upon over 80% of the sample and a reduction from 763.9 minutes to 122.5 minutes (p < 0.001). The mean of pre-intervention severity was 7.2/10, with a significant decrease shown following treatment, at 2.1/10, and very positive results for over 71% of the sample (p < 0.001). Conclusion: The preliminary findings of this study showed a promising potential for such supplements in the treatment and prevention of VM; however, more research and a prospective trial are recommended.

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Research Article Fri, 2 Feb 2024 17:53:32 +0200
The promise and challenges of ChatGPT in community pharmacy: A comparative analysis of response accuracy https://pharmacia.pensoft.net/article/116927/ Pharmacia 71: 1-5

DOI: 10.3897/pharmacia.71.e116927

Authors: Ali H. Salama

Abstract: This study evaluates ChatGPT, an AI-based language model, in addressing common pharmacist inquiries in community pharmacies. The assessment encompasses Drug-Drug Interactions, Adverse Drug Effects, Drug Dosage, and Alternative Therapies, each comprising 20 questions, totaling 80 questions. Responses from ChatGPT were compared against standard answers, generating textual and chart scores. Textual score was computed by relating correct answers to the total questions within each category, while chart score involved the total correct answers multiplied by the chart-type questions. ChatGPT exhibited distinct performance rates: 30% for Drug-Drug Interactions, 65% for Adverse Drug Effects, 35% for Drug Dosage, and an impressive 85% for Alternative Therapies. While Alternative Therapies displayed high accuracy, challenges arose in accurately addressing Drug Dosage and Drug-Drug Interactions. Conclusion: The study underscores the complexity of pharmacy-related inquiries and the necessity for AI model enhancement. Despite promising accuracy in certain categories, like Alternative Therapies, improvements are crucial for Drug Dosage and Drug-Drug Interactions. The findings emphasize the need for ongoing AI model development to optimize integration into community pharmacy settings.

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Research Article Tue, 30 Jan 2024 16:38:34 +0200
Propranolol nanoemulgel: Preparation, in-vitro and ex-vivo characterization for a potential local hemangioma therapy https://pharmacia.pensoft.net/article/115330/ Pharmacia 71: 1-12

DOI: 10.3897/pharmacia.71.e115330

Authors: Taif Abdullah, Khalid Al-Kinani

Abstract: A lack of safe and effective topical alternatives to oral propranolol HCl (PHCl) hampers optimal management of infantile hemangioma (IH), particularly in complex cases with severe side effects or treatment failures. This study aimed to develop a nanoemulsion gel (NEG) for topical PHCl delivery. A meticulously formulated nanoemulsion (NE) encapsulated with clove oil, Tween 20, and polyethylene glycol 400 emerged as the standout candidate (NE3) due to its exceptional stability, resilience, and favorable drug loading. NE3 exhibited a remarkable globule size of 14.57 nm, a low polydispersity index (PDI) of 0.282, and a stabilizing zeta potential of −19.89 mV. The subsequent formulation of PHCl-NEG displayed desired rheological and spreadability properties for topical application. Ex-vivo skin retention and permeation studies revealed effective PHCl deposition within the dermal layer with minimal systemic exposure. This promising approach offers a potential alternative to oral PHCl, potentially mitigating severe side effects and improving outcomes in complex IH cases.

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Research Article Tue, 30 Jan 2024 16:38:16 +0200
Synthesis, in silico and in vitro antimicrobial activity of N-(benzyl)-5-methyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidine-6-carboxamides https://pharmacia.pensoft.net/article/110013/ Pharmacia 71: 1-9

DOI: 10.3897/pharmacia.71.e110013

Authors: Sergiy V. Vlasov, Oleksandr V. Borysov, Hanna I. Severina, Vitaliy S. Vlasov, Amjad Ibrahim M. Abu Sharkh, Victoriya A. Georgiyants

Abstract: According to the recent studies bezylcarboxamide fragment attached to the thiophene ring of thieno[2,3-d]pyrimidine is beneficial for antimicrobial activity of the compounds. Therefore we focused our efforts on constructing of the simple molecules such as N-(benzyl)-5-methyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidine-6-carboxamides to get deeper insight into their antimicrobial activity. As the optimal procedure for preparation of target compounds we choose 1,1’-carbonyldiimidazole promoted interaction of 5-methyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidine-6-carboxylic acid with the series of substituted benzyl amines. The obtained amides showed good activity against the strains of S. aureus and B. subtilis, which was higher for the derivative without substituents in benzene ring or the compounds with small substituents like methyl or methoxyl groups in the para-position of the benzene ring. Docking studies showed that despite the good values of the scoring functions, the conformational analysis of the ligands’ poses in the active site revealed their ability for only partial inhibition of TrmD of P. aeruginosa.

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Research Article Mon, 29 Jan 2024 16:26:22 +0200
Association study between D2 receptor A-241G, rs1799978 genetic variation and olanzapine efficacy in Iraqi schizophrenic patients https://pharmacia.pensoft.net/article/111984/ Pharmacia 71: 1-6

DOI: 10.3897/pharmacia.71.e111984

Authors: Zahra Jawd Mohammed Ali Al-Musawi, Atheer Majid Rashid Al-Juhaishi

Abstract: This study aimed to assess the role of D2 receptor A-241G (rs1799978) genetic polymorphism and olanzapine response and safety in Iraqi schizophrenic patients. The case-control study composed of 100 schizophrenic patients consisting of both genders were recruited from the Psychiatry Outpatient Department and 50 apparently healthy volunteers, served as a control group. Patient response to olanzapine was evaluated with the aiding of the PANSS and genotyping of D2 receptor A-241G (rs1799978) polymorphisms was detected using the nested PCR method. The heterozygous (AG) and mutant (GG) alleles of D2 receptor A-241G (rs1799978) were significantly predominated in schizophrenic patients and absent in healthy volunteers. Schizophrenic patients with the G allele of D2 receptor A-241G (rs1799978) and who were administered olanzapine exhibited a notable resistance to olanzapine. In conclusion, the genetic polymorphism of D2 receptor A-241G (rs1799978) was significantly associated with resistance to olanzapine in Iraqi schizophrenic patients.

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Research Article Mon, 29 Jan 2024 08:16:53 +0200
Preparation and evaluation of biological activity of ZSM-5 nanoparticles loaded with gefitinib for the treatment of non-small cell lung carcinoma https://pharmacia.pensoft.net/article/112449/ Pharmacia 71: 1-12

DOI: 10.3897/pharmacia.71.e112449

Authors: Farah Al-Sahlawi, Israa Al-Ani, Mohamed El-Tanani, Hafiz Aadil Farooq

Abstract: Background: Gefitinib (GEF) is a tyrosine kinase inhibitor that has proven good efficacy against Non-small cell Lung Carcinoma (NSCLC). It has low solubility and dissolution rate and low oral bioavailability. This work aimed to improve efficacy by loading on ZSM-5 silica nanoparticles and testing the prepared delivery system on A-549 lung cancer cells. Methods: ZSM-5 was synthesized in the laboratory and different methods of loading GEF on the nanoparticles were used, then the system was characterized by X-ray diffraction, Fourier Transport Infra-Red (FTIR), and drug release and dissolution. Results and conclusion: GEF-loaded nanoparticles (NPs) showed prolonged release of GEF over 12 hours with an improved biological efficacy expressed by the decrease in IC50 compared to free GEF (P < 0.001) using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay. Also, there was a significant decrease in migration and colony formation ability of the GEF-loaded NPs on A-549 lung cancer cells. In conclusion, loading GEF onto ZSM-5 NPs resulted in a lower IC50 and improved biological action toward A-549 cells.

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Research Article Thu, 25 Jan 2024 14:58:43 +0200
Novel anticoagulants in the management of atrial fibrillation: A comprehensive comparative analysis https://pharmacia.pensoft.net/article/113097/ Pharmacia 71: 1-6

DOI: 10.3897/pharmacia.555.e113097

Authors: Mazen M. Jwaid, Mohammed J. Alwan, Isam Ihsan, Maher M. Jwaid, Yasir F. Muhsin, Hany A. Al-hussaniy, Mohammed K. Al iraqi

Abstract: Background: Atrial fibrillation (AF) stands as the most prevalent cardiac arrhythmia, with associated risks of stroke and systemic thromboembolism. While vitamin K antagonists, specifically warfarin, have historically been the mainstay for stroke prevention in AF, they come with inherent limitations. Aim: This review seeks to offer a comprehensive analysis of the efficacy, safety, and clinical advantages of novel oral anticoagulants (NOACs) compared to traditional warfarin in AF management. Method: A meticulous examination of pivotal clinical trials, meta-analyses, and recent research publications was conducted. Four NOACs, namely Dabigatran, Rivaroxaban, Apixaban, and Edoxaban, were compared against warfarin, focusing on parameters like stroke prevention, risk of bleeding, patient compliance, and drug interactions. Results: NOACs, as a collective group, demonstrated a comparable or superior efficacy profile in stroke prevention compared to warfarin. They also showcased a more predictable therapeutic range, fewer drug and food interactions, and, in certain cases, a better safety profile. The challenges associated with frequent monitoring and dose adjustments inherent to warfarin therapy were notably absent with NOACs. Conclusion: NOACs present a robust alternative to warfarin for AF management, demonstrating comparable efficacy and, in certain aspects, heightened safety and practicality. However, the choice of anticoagulant should remain individualized, taking into account patient-specific factors and clinician expertise.

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Review Article Wed, 24 Jan 2024 14:45:25 +0200
Physicochemical characterization of novel toothpaste from Caulerpa racemosa and Thunnus fish bone: Antibacterial potency against colonization of selected cariogenic-periodontal bacteria https://pharmacia.pensoft.net/article/118021/ Pharmacia 71: 1-8

DOI: 10.3897/pharmacia.71.e118021

Authors: Citra Fragrantia Theodorea, Fahrul Nurkolis, Erik Idrus, Timotius William Yusuf, Christopherous Diva Vivo, Dionysius Subali, Nurpudji Astuti Taslim, Alexander Patera Nugraha

Abstract: This study evaluated the physicochemical properties of toothpaste from combined Caulerpa racemosa and Thunnus fish bone (Toothpaste Caulerpa and Thunnus or TCT) and its antibacterial activity towards the colonization of selected cariogenic and periodontal bacterias. Four forms of toothpaste which contained C. racemosa extract and calcium carbonate or bone isolates of tuna and control (F1 (1.5:45); F2 (3:45); F3 (4.5:45); F4 (0:45)) were compared and analyzed for antioxidant activity (DPPH assay), organoleptic (sensory), homogeneity, viscosity, pH, and foamability. Antibacterial activity tests were conducted on Streptococcus mutans, Staphylococcus aureus, and Porphyromonas gingivalis. The antioxidant activity of the group’s (F1, F2, F3, F4) p=0.0001 differed considerably (CI 95%). F3 was the most antioxidant-active formula, with 27.46 ± 3.09%. F3 also had good sensory tests, adequate homogeneity, optimal pH 7.64 ± 0.68, an increased viscosity level of 443.07 ± 0.12, and the least foam formations of 19.28 ± 0.07, all of which are significantly different (p<0.05) from other variations of TCT formulas. Interestingly, F3 has greater inhibition against the activity of selected bacterias. In conclusion, formula 3 (F3) is a recommended toothpaste, made from combined C. racemosa and Thunnus fish bone, and has promising physicochemical and antibacterial properties. A further clinical study is urgently needed.

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Research Article Wed, 24 Jan 2024 14:36:07 +0200
Activity of an oleanane-type tritrepenoid saponin from A. glycyphyllos on human recombinant MAO enzymes https://pharmacia.pensoft.net/article/114786/ Pharmacia 71: 1-6

DOI: 10.3897/pharmacia.71.e114786

Authors: Aleksandar Shkondrov, Magdalena Kondeva-Burdina, Ivan Stambolov, Ilina Krasteva

Abstract: For centuries, plants have been a leading point in the identification of potential therapeutic agents. Monoamine oxidase inhibition is a key mechanism in the treatment of various neurological and psychiatric diseases. Some triterpenoid saponins are reported to inhibit this enzyme. An extract from the aerial parts of Astragalus glycyphyllos was purified and separated by chromatographic techniques, which led to the isolation of one triterpene saponin. Its structure was analysed by ultra-high-performance liquid chromatography coupled with high-resolution electrospray ionisation mass spectrometry. The compound was subjected to a pharmacological study where human recombinant monoamine oxidase enzymes type A and B (hMAOA and hMAOB) were used. On the activity of hMAOA, the saponin had no effect, but on hMAOB, it exhibited statistically significant inhibition in comparison to the control, Selegiline. The compound could have potential in other models, so further investigations are required.

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Research Article Wed, 24 Jan 2024 14:35:39 +0200
Phytochemical analysis, antioxidant, and antitumor activity of Ligustrum ovalifolium leaves grown in Jordan: an in vitro and in vivo study https://pharmacia.pensoft.net/article/111517/ Pharmacia 71: 1-10

DOI: 10.3897/pharmacia.71.e111517

Authors: Asma Ismail Mahmod, Muna Oqal, Ali Muharrif Khalid, Fatma U. Afifi, Wamidh H. Talib

Abstract: Ligustrum ovalifolium (family Oleaceae) is a flowering plant with reported anti-inflammatory, antioxidant, hypotensive, and hypoglycemic activities. The present study investigated the phytochemical components and biological activities of L. ovalifolium leaves. Results showed that ethyl acetate extract has the highest potential to reduce cell growth in HeLa, T47D, and MDA-MB-231 cell lines with IC₅₀ values of 0.047, 0.07, and 0.072 mg/mL, respectively. Based on the LD50 value, the tumor-bearing mice were IP injected with 12.5 mg/kg of ethyl acetate extract. Tumor growth was significantly reduced (-43.1%) compared to the control group. According to the LC-MS analysis, Apigenin-7-O-glucoside was the flavonoid with the highest percentage value in L. ovalifolium leaves. DPPH assay exhibited antioxidant activity of ethanol and water extracts with the percentage of scavenging around 91% at a concentration of 200 µg/mL. As well, the assessment of liver and kidney functions of the experimented animals showed no toxicity effect compared to the control result. All things considered, the outcomes of this study revealed an antitumor potential of L. ovalifolium leaves extracts, hence this activity may arise from the presence of different potent flavonoids and the antioxidant potential. Nevertheless, further investigations are needed to determine the targets and signaling pathways that are affected by L. ovalifolium leaves extracts.

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Research Article Wed, 24 Jan 2024 14:32:24 +0200
Anticancer and antioxidant activities of essential oils of Chiliadenus iphionoides from Jordan: in vitro and in vivo study https://pharmacia.pensoft.net/article/116195/ Pharmacia 71: 1-7

DOI: 10.3897/pharmacia.71.e116195

Authors: Sumayah AlNaimat, Ala’ Abu-Odeh, Wamidh H. Talib

Abstract: Medicinal plants have been used since ancient times and may even be considered the origin of modern medicine. Natural products are a potential source for drug discovery and development of cancer treatments. Several pharmacological therapeutic activities were reported for Chiliadenus iphionoides. This research was designed to evaluate the essential oil of Chiliadenus iphionoides antioxidant potential and antiproliferative activity both in vitro and in vivo. The essential oil of Chiliadenus iphionoides was extracted by hydrodistillation. The chemical composition analysis was performed using gas chromatography. The main compounds identified in Chiliadenus iphionoides essential oil were oxygenated monoterpenes, such as eucalyptol (36.08%). A dose-dependent inhibition of cell proliferation was observed after the treatment of various cell lines (A549 (human lung cancer adenocarcinoma), MDA-MB-231 (triple-negative breast cancer cell line), T47 (human breast cancer cell line), EMT6/P (mouse mammary sarcoma cell line)) with increasing concentrations of the essential oil (0.02–2.5 mg/mL). The essential oil of Chiliadenus iphionoides was more cytotoxic against EMT6 and T47 cells with IC₅₀ values of 0.03±0.03 and 0.08± 0.009 mg/mL, respectively. The essential oil exhibited low cytotoxicity against a normal VERO cell line (IC₅₀ value > 4 mg/ml). Balb/C mice were inoculated with EMT6/p breast cancer cells and then treated with (60 mg/kg/day intraperitoneal injection) of essential extract for ten days. Interestingly, a significant (p < 0.05) reduction occurred in the tumor size of the treated group compared to the control group. Treatment toxicity was evaluated by measuring liver and kidney parameters. The tumor-bearing mice treated with the Chiliadenus iphionoides extract showed normal serum levels of AST, creatinine, and slight elevation in ALT level. The results indicated that Chiliadenus iphionoides have anticancer properties both in vitro and in vivo. We suggest that eucalyptol, a major active component, is a promising candidate for use as an anticancer agent. However, further molecular investigation is required to understand the molecular bearings of Chiliadenus iphionoides activity.

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Research Article Wed, 24 Jan 2024 14:30:07 +0200
Anticancer potential of garlic bioactive constituents: Allicin, Z-ajoene, and organosulfur compounds https://pharmacia.pensoft.net/article/114556/ Pharmacia 71: 1-23

DOI: 10.3897/pharmacia.71.e114556

Authors: Wamidh H. Talib, Sally Atawneh, Areen Nabil Shakhatreh, Ghyda’a Nabil Shakhatreh, Islam Subhi Rasheed aljarrah, Reem Ali Hamed, Doaa Adel banyyounes, Intisar Hadi Al-Yasari

Abstract: Cancer, a formidable disease with a significant mortality rate, continues to claim the lives of thousands of individuals annually in contemporary society. Conventional cancer therapies are notorious for their substantial adverse effects and lack of specificity. Within the context of neoplastic development, cancer hallmarks represent fundamental biological properties that cancer cells progressively acquire. A promising approach for combating cancer involves the simultaneous targeting of multiple cancer hallmarks. Plant-derived natural compounds stand out as a promising reservoir for the development of novel and more efficacious anticancer therapeutics due to their structural diversity and minimal toxicity profiles. Garlic (Allium sativum) has garnered considerable attention for its established anti-cancer properties over the years. Within garlic, a myriad of bioactive constituents, including organosulfur compounds, flavonoids, and phenolic compounds, exhibit distinct effects on cancer cells. The objective of this review paper is to furnish a comprehensive elucidation of the mechanisms underpinning the anticancer actions of garlic. The elucidated findings from the studies encompassed within this review not only contribute to a more profound comprehension of the anti-cancer properties of garlic but also serve as a robust foundation upon which researchers and healthcare practitioners can formulate enhanced anticancer pharmaceuticals grounded in natural garlic compounds.

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Review Article Wed, 24 Jan 2024 14:27:39 +0200
Evaluation of factors related to entrepreneurial intentions among young pharmacists in the Mekong Delta region: a cross - sectional study in Vietnam https://pharmacia.pensoft.net/article/116771/ Pharmacia 71: 1-13

DOI: 10.3897/pharmacia.71.e116771

Authors: Vo Thi My Huong, Nguyen Phuc Hung, Nguyen Thi Trang Dai, Vo Pham Trinh Thu, Tang Nghiep Minh, Phan Anh Tu, Mai Thu Suong

Abstract: At present, a new wave of entrepreneurship has emerged and made a significant impact in Vietnam despite challenges. The study aims to assess the factors related to the entrepreneurial intentions of young pharmacists in 2023 in the Mekong Delta region. A cross-sectional descriptive method was conducted, involving interviews with 815 young pharmacists living in the Mekong Delta region, via a pre-designed research questionnaire. Results showed that 6 out of 43 variables were eliminated after Cronbach’s alpha was run. The Kaiser-Meyer-Olkin coefficient (0.5–0.923) indicated statistical significance and suitable conditions for Exploratory Factor Analysis. Confirmatory Factor Analysis and Structural Equation Modeling results were consistent with market data. With the impact of difficulties, attitude, perception of behavioral control, subjective norms, achievement needs on knowledge, and knowledge on entrepreneurial intentions (p < 0.05). In conclusion, the study successfully collected samples and gained a deeper understanding of the factors influencing the entrepreneurial intentions of young pharmacists.

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Research Article Wed, 17 Jan 2024 17:41:25 +0200
Evaluation of empagliflozin efficacy as a promising anti-aging treatment in mice: In-vivo study https://pharmacia.pensoft.net/article/116184/ Pharmacia 71: 1-9

DOI: 10.3897/pharmacia.71.e116184

Authors: Khalid Ali Obaid, Hayder Adnan Fawzi

Abstract: Aim: Evaluation of the anti-aging properties of Empagliflozin (EMP) associated with the aging process in mice. Methods: The mice were allocated into four groups: negative control received normal saline without receiving D-galactose (DGA); all the three other groups received DGA (200 mg/kg/day orally) for eight weeks; the second group received normal saline; the third group received vitamin C, the final group received EMP and continued for another eight weeks. Results: Treatment with EMP reduced the levels of TNF-α, IL-1β, and MDA levels significantly compared to induction group (91.7±9.6 ng/ml, 30.6±5.5 pg/ml, and 66.7±8.3 ng/ml vs. 304.0±102.9 ng/ml, 70.2±6.8 pg/ml, and 204.7±56.9 ng/ml; respectively), while levels of GSH-Px were significantly increased (3.3±0.6 ng/ml vs. 0.3±0.2 ng/ml). In addition, EMP increases the level of both COL-1 and COL-3 compared to the induction group (1,783.6±186.9, and 1,583.6±186.9, vs. 885.7±242.5, and 685.7±242.5 pg/ml; respectively). Conclusion: EMP positively affects several aging parameters in mice.

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Research Article Wed, 17 Jan 2024 16:06:50 +0200
The endogenous cannabinoid and the adrenergic systems in modulation of stress-response https://pharmacia.pensoft.net/article/115659/ Pharmacia 71: 1-8

DOI: 10.3897/pharmacia.71.e115659

Authors: Yilmaz Suleymanoglu, Dimitar Bakalov, Zafer Sabit, Vlayko Vodenicharov, Radka Tafradjiiska-Hadjiolova, Hristina Nocheva

Abstract: In our modern, fast-paced society, excessive stress (or distress) is a major risk factor for developing a plethora of diseases. There are several neuromediatory systems in the brain that regulate the response to stress, including the adrenergic and endocannabinoid systems. In our experiments, we study the effects of the endocannabinoid system on the restrain stress-induced analgesia (r-SIA). The experiments were done on male Wistar rats. The animals were confined in special restrainers for a period of one hour. The animals were treated with Clonidine (at 4 mg/kg) – a prototypical α2-agonist; Yohimbine – an α2-adrenergic receptor antagonist; Desipramine – a NE reuptake blocker; CB1r agonist anandamide (AEA); CB1r antagonist АМ251 in different combinations. r-SIA was investigated by means of the paw pressure test in order to get a better understanding of the role that the neurotransmitter anandamide plays in the process. The degree to which the levels of r-SIA fluctuated served as an indicator of the degree to which the cannabinoid system and the adrenergic system interacted with one another. Cannabinoids that are administered exogenously were found to reduce levels of r-SIA and modulate the effects of the adrenergic system. These conclusions were reached based on the findings of our research.

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Research Article Wed, 17 Jan 2024 14:04:53 +0200
Head and neck cancer pain https://pharmacia.pensoft.net/article/113077/ Pharmacia 71: 1-6

DOI: 10.3897/pharmacia.71.e113077

Authors: Venny Tiursani Sarumpaet, Yussy Afriani Dewi, Sally Mahdiani

Abstract: Background: Pain is a condition that often occurs in patients with head and neck cancer. Pain in patients with malignancy occurs mostly due to metastatic processes. Method: This research is a cross-sectional descriptive study to measure variables using the VAS, BPI, HADS, and LANSS questionnaires. Result: 127 subjects met the inclusion and exclusion criteria. Most patients with were male (63.8%), with the most ages being in the 46–55 year group (33.9%). Most patients were in stage III (48%), with the most diagnosed being nasopharyngeal malignancy (42.5%). About 60.6% of patients have received pain management according to WHO Step 2 and most suffered from neuropathic pain (65.8%) with the most pain intensity being moderate pain (53.5%). Pain interfered most with activities (91.3%) and as many as 64.6% experienced depression. Conclusion: A description of pain in head and neck patients is needed for good management of malignancy and pain management.

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Research Article Tue, 16 Jan 2024 16:32:37 +0200
Docking, synthesis, and anticancer assessment of novel quinoline-amidrazone hybrids https://pharmacia.pensoft.net/article/117192/ Pharmacia 71: 1-12

DOI: 10.3897/pharmacia.71.e117192

Authors: Ahmad H. Abdullah, Ahmad K. Alarareh, Mahmoud A. Al-Sha’er, Almeqdad Y. Habashneh, Firas F. Awwadi, Sanaa K. Bardaweel

Abstract: A group of new amidrazone compounds that include a quinoline component was produced through the reaction of hydrazonyl chloride, derived from 6-aminoquinoline, with appropriate secondary cyclic amines. The new compounds were confirmed through 1H-NMR, 13C-NMR, FTIR, and HRMS, and further verified by single-crystal X-ray diffraction. The antitumor potential of the synthesized compounds was tested against lung cancer (A549) and breast cancer (MCF-7) cell lines. Among the compounds, the ethyl carboxylate and o-hydroxy phenyl piperazine derivatives (10d and 10g) exhibited the strongest activity against both cell lines, with IC50 values of 43.1 and 59.1 μM for the lung and breast cancer cell lines, respectively. Moreover, the most potent compounds were subsequently docked into the c-Abl kinase binding site (PDB code: 1IEP) as a possible anticancer mechanism. In-silico ADMET study shows acceptable pharmacokinetic properties, and the toxicity profile for the most potent compounds is non-carcinogenic.

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Research Article Mon, 15 Jan 2024 10:38:26 +0200
Interplay of adiponectin and resistin in type 2 diabetes: Implications for insulin resistance and atherosclerosis https://pharmacia.pensoft.net/article/114863/ Pharmacia 71: 1-8

DOI: 10.3897/pharmacia.71.e114863

Authors: Rawan Abudalo, Abdelrahim Alqudah, Esam Qnais, Rabaa Y. Athamneh, Muna Oqal, Roaa Alnajjar

Abstract: Aim: The study aims to investigate the association between type 2 diabetes and adipokines, particularly resistin and adiponectin, in insulin resistance. It also explores the potential of the resistin to adiponectin ratio as an indicator for these conditions Methods: This research involved 198 participants, including 100 patients with type 2 diabetes and 98 controls. It focused on measuring various biochemical parameters like HbA1c, fasting plasma glucose, lipid profiles (low-density lipoprotein, oxidized low-density lipoprotein, triglyceride, total cholesterol), and adipokines (resistin and adiponectin). The study utilized the Homeostasis Model Assessment of Insulin Resistance and Triglyceride-Glucose index to evaluate insulin resistance. Results: Type 2 diabetic patients exhibited higher levels of HbA1c, fasting plasma glucose, lipid profiles, and resistin, but lower adiponectin levels compared to controls. Adiponectin showed a negative correlation with insulin resistance, while resistin demonstrated a positive correlation. Both adipokines significantly related to atherogenic markers, with adiponectin offering protection against atherosclerosis and resistin augmenting it. Conclusion: The findings underscore the complex roles of resistin and adiponectin in the pathophysiology of type 2 diabetes, insulin resistance. The resistin to adiponectin ratio could be a useful biomarker for insulin resistance. These insights suggest potential therapeutic strategies for treating diabetes and preventing its complications.

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Research Article Mon, 15 Jan 2024 10:31:47 +0200
Molecular docking study of ginger (Zingiber officinale) on Immunoglobulin A for smoking cessation https://pharmacia.pensoft.net/article/116751/ Pharmacia 71: 1-6

DOI: 10.3897/pharmacia.71.e116751

Authors: Rika Mayasari Alamsyah, Mieke Hemiawati Satari, Sondang Pintauli, Shelly Iskandar

Abstract: Smoking is a big problem that can cause death throughout the world. The main ingredient in cigarettes, nicotine, is toxic to humans in several ways. Quitting smoking with the help of medication is associated with adverse side effects such as drowsiness, dry mouth, and nausea. The option of quitting smoking with herbal concoctions such as Zingiber officinale is the recommended choice. The active components of ginger are gingerol and shogaol, which are responsible for their pharmacological effects on immunoglobulin A, which can improve the immune system. The method used is molecular docking, which looks at the stability of human secretory immunoglobulin A when interacting with gingerol and bupropion, which are used as comparison compounds. Molecular docking findings of all herbal material samples revealed that almost all bioactive substances had lower binding energies than immunoglobulin A, especially proteins with PDB IDs 6UE7 and 6UEA. However, only a few ginger-derived bioactive compounds interacting with the 6UEA protein show binding energy values smaller than -7 ± 0.5 kcal/mol. The compounds 8-Gingerol, 8-Shogaol, 6-Shogaol, 6-Gingerol, 5-Shogaol, and 4-Shogaol were able to target the immunoglobulin A receptor protein better than the control, although not as good as the native ligand. Gingerol and Bupropion compounds have stable RMSD and RMSF values compared to human secretory immunoglobulin A without the ligand.

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Research Article Fri, 12 Jan 2024 11:27:08 +0200
Attitude of medical doctors to adverse drug reactions reporting in Bulgaria https://pharmacia.pensoft.net/article/115559/ Pharmacia 71: 1-7

DOI: 10.3897/pharmacia.71.e115559

Authors: Dobriana Sidjimova, Tatyana Benisheva, Vili Topalova, Valentina Petkova

Abstract: Adverse Drug Reactions (ADRs) pose a challenge for medical doctors (MDs) and other healthcare professionals (HCPs). Serious ADRs increase patient morbidity and mortality and generate a large financial footprint on healthcare costs. Statistics show that about 6% of hospitalizations are due to ADRs and over 50% of them could be avoided. Two years after introducing the pharmacovigilance (PhV) requirements in the European Union, national regulatory PhV requirements were published in the Bulgarian pharmaceutical legislation. Nonetheless, MDs‘ awareness of the PhV topic still remains extremely important due to patient safety. Spontaneous reporting of ADRs is essential to the success of a pharmacovigilance program. Underreporting of ADRs is common, especially among MDs and HCPs. This study aims to analyse the attitude and the knowledge of graduated MDs towards the reporting of ADRs and drug safety in general. In addition, the study aims to examine their opinion, attitude, and recommendations so that reporting of ADRs becomes more regular.

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Research Article Fri, 12 Jan 2024 11:26:36 +0200
Role of D2 receptor (–141 C Ins/Del) genetic polymorphism on olanzapine-induced adverse drug reaction in schizophrenic patients https://pharmacia.pensoft.net/article/112064/ Pharmacia 71: 1-8

DOI: 10.3897/pharmacia.71.e112064

Authors: Zahra Jawd Mohammed Ali, Atheer Majid Rashid Al-juhiashi

Abstract: Olanzapine is commonly prescribed for the management of schizophrenia and is associated with many adverse effects like weight gain, hyperglycemia, and hyperprolactinemia, which may increase the risk of other diseases like diabetes mellitus and cardiovascular diseases. Genetic polymorphism of the D2 receptor may be responsible for the incidence of such adverse effects. This study aimed to assess the role of D2 receptor–141 C Ins/Del (rs1799732) genetic polymorphism and olanzapine-induced adverse effects in Iraqi schizophrenic patients. The case-control study was performed from October 2022 to April 2023 in Al-Hassan Al-Mojtaba Hospital. A total of 100 schizophrenic patients consisting of both genders, aged between 20 and 65 years, were recruited from the Psychiatry Outpatient Department, and 50 apparently healthy without any disease comprising both genders aged 20 to 63 years, served as a control group and were also enrolled in this study. Plasma level of FBS, HbA1c, lipid profile, and prolactin were measured, and genotyping of D2 Receptor–141 C Ins/Del (rs1799732) Polymorphisms was detected using the RFLP method. The heterozygous (Ins/Del) and mutant (Del/Del) alleles of D2 receptor–141 C Ins/Del (rs1799732) was significantly predominated in schizophrenic patient and absent in healthy volunteers. Schizophrenic patients with the deletion allele of D2 receptor–141 C Ins/Del and who were administered olanzapine (rs1799732) exhibited notably higher susceptibility to metabolic adverse effects induced by olanzapine, such as weight gain, hyperglycemia, dyslipidemia, and hyperprolactinemia. In conclusion, the genetic polymorphism of D2 receptor–141 C Ins/Del (rs1799732) was significantly associated with olanzapine induce metabolic adverse effects in Iraqi schizophrenic patients.

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Research Article Fri, 12 Jan 2024 11:22:19 +0200
Morphological, teratogenic and behavioral evaluations of Gelidium spinosum methanol extract on zebrafish embryos https://pharmacia.pensoft.net/article/109918/ Pharmacia 71: 1-10

DOI: 10.3897/pharmacia.71.e109918

Authors: Warsi Warsi, Irwandi Jaswir, Qamar Uddin Ahmed, Nurkhasanah Mahfudh, Mohamed Sufian bin Mohd. Nawi, Abdul Rohman, Alfi Khatib

Abstract: Gelidium spinosum is an edible red seaweed from the family Gelidiaceae with possibility to be developed. The potential medical benefits of G. spinosum have been established, yet adequate empirical research on its toxicity is still lacking. Hence, the present work was aimed to examine the toxicity of G. spinosum methanol extract (GsME) on zebrafish (Danio rerio) embryos and to identify the phytoconstituents using gas chromatography-mass spectrometry (GC-MS) analysis. Results of this study showed that GsME induced morphological defects in zebrafish embryos, including reduction in eye size and body length. Moreover, yolk sac size and mortality were increased in zebrafish embryos exposed to GsME in a dose-dependent manner. GsME at high concentrations triggered teratogenic effects in zebrafish embryos such as decrease in heartbeat/minute, lack of pigmentation, lack of somite, structural deformity, pericardial oedema, and yolk oedema. The LC50 and EC50 of GsME were < 100 mg/L, which classified as a harmful category. The teratogenic index of GsME was found to be > 1, indicating its teratogenic attribute. Additionally, GsME exerted behavioral effects i.e. significantly lower total distance of movement and slower swimming speed of zebrafish embryos. GC-MS analysis of GsME was confirmed the presence of amino acid, phenolics, carboxylic acids, reducing sugars, saturated fatty acids and brominated saturated fatty acid in the extract. It suggesting that compounds of 13-bromotetradecanoic acid, palmitic acid, and stearic acid containing in GsME were contributed to the toxic effects.

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Research Article Thu, 11 Jan 2024 18:56:15 +0200
Tempe as superior functional antioxidant food: From biomechanism to future development of soybean-based functional food https://pharmacia.pensoft.net/article/116748/ Pharmacia 71: 1-7

DOI: 10.3897/pharmacia.71.e116748

Authors: Reggie Surya, Nurlinah Amalia, William Ben Gunawan, Nurpudji Astuti Taslim, Marwan Ghafoor, Nelly Mayulu, Hardinsyah Hardinsyah, Rony Abdi Syahputra, Felicia Kartawidjajaputra, Gianluca Rizzo, Raymond Rubianto Tjandrawinata, Dionysius Subali, Rudy Kurniawan, Fahrul Nurkolis

Abstract: Foods that have nutritional value along with additional health advantages are referred to as functional foods. Fruits, vegetables, and spices are rich sources of antioxidants, which can help prevent damage from free radicals and environmental stress. It has been demonstrated that consuming foods high in antioxidants lowers the risk of degenerative diseases such as cancer, emphysema, immunological deficiencies, respiratory disorders, heart disease, and stroke. It also lowers the risk of Parkinson’s disease and other inflammatory conditions. Traditional Indonesian fermented soybean-based food products, or soybeans and known as “tempe”, have been associated with a host of health benefits, including a lower risk of cardiovascular disease, a lower risk of cancer, improved bone health, and enhanced immunological function. This article investigates tempe’s potential as a meal with antioxidant properties and suggests a mechanism via which it can trigger the Nrf2-mediated antioxidant response. The study offers insights into the potential applications, development, and potentiation of tempe by synthesizing potential biomolecular pathways for its antioxidant actions at the cellular level.

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Review Article Thu, 11 Jan 2024 14:36:50 +0200
Optimization of ultrasound-assisted extraction using response surface methodology and quantification of polyphenol compounds in Avicennia officinalis L. from Vietnam https://pharmacia.pensoft.net/article/115528/ Pharmacia 71: 1-9

DOI: 10.3897/pharmacia.71.e115528

Authors: Ngoc-Van Thi Nguyen, Cuong Van Nguyen, Ngan Tuyet Duong, Xuan-Trang Thi Dai, Kien Trung Nguyen, Cam-Thuy Thi Le

Abstract: Response surface methodology was used to estimate the optimum extraction parameters, for which the total phenolic content and total flavonoid content of Avicennia officinalis L. extract were the highest. Based on the 3D surface plots and regression analysis of the independent variables, the optimal conditions for the ultrasound-assisted extraction were as follows: methanol content, 55.27%; liquid-to-solid ratio, 14:1 (mL/g, v/w); temperature, 48.8 °C, and time, 9.66 min. Optimal extraction conditions were applied to validate the quantification. The bioactive compounds from the Avicennia officinalis L. extract were identified through ultra-fast liquid chromatography coupled to diode array detector for the first time. These methods were applied to quantify phenolic acids and flavonoids from A. officinalis extracts collected at six different locations in Vietnam. The results showed that the concentrations of these compounds varied from 0.319 ± 0.022 to 3.524 ± 0.125 mg/g in the methanol extract. The result showed that cinnamic acid is the major compound in A. officinalis collected in Vietnam. In the present study, an optimized ultrasound-assisted extraction was first designed to improve the content of phenolic acids and flavonoid compounds from A. officinalis. Additionally, the bioactive compounds from the A. officinalis extract were identified through UFLC-DAD for the first time.

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Research Article Thu, 11 Jan 2024 14:36:24 +0200
Microneedle and drug delivery across the skin: An overview https://pharmacia.pensoft.net/article/112503/ Pharmacia 71: 1-12

DOI: 10.3897/pharmacia.71.e112503

Authors: Iman Hamdan

Abstract: The skin offers a route of administration with numerous advantages. However, one of the major limitations of this route is the limited number of drugs that possess the ideal physicochemical properties to passively diffuse through the skin barrier. Today, microneedle (MN) technology proved to be superior in the field of drug delivery. MN arrays are devices that consist of micron-sized projections which pierce the stratum corneum (SC), the main barrier for drug delivery across the skin. MN technology has the potential to provide a localised drug delivery with minimal toxicity and expand the range of drugs for transdermal and intradermal delivery. In this comprehensive review, MN technology was thoroughly discussed. Meeting regulatory standards and large-scale production is essential to advance MN technology into a cost-effectiveness commercial scale.

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Review Article Wed, 10 Jan 2024 14:31:43 +0200
Nephroprotective effects of Equisetum ramosissimum L. extract in streptozotocin-induced diabetic rats https://pharmacia.pensoft.net/article/113659/ Pharmacia 71: 1-11

DOI: 10.3897/pharmacia.71.e113659

Authors: Raheeq Khairy Abdullah, Reem A. Issa, Mahmoud Abu-Samak, Beisan A. Mohammad, Manal A. Abbas, Shady Helmi Awwad

Abstract: Diabetes is a widespread health issue that impacts people all over the globe. The Equisetum ramosissimum L. plant has numerous traditional uses and pharmacological properties, including antidiabetic effects.The objective of this study was to thoroughly examine the advantages of incorporating extracts from the aerial components of E. ramosissimum to control diabetic nephropathy. The phytochemical constituents of E. ramosissimum extract were explored using phytochemical and HPLC analysis, focusing on phenols and flavonoid content. The effect of plant extract was evaluated on different kidney function parameters linked to diabetic nephropathy (fasting blood glucose, creatinine, uric acid, and urea) in streptozotocin induced-diabetic rats. Histopathological changes in the liver were also examined. The results showed methanol and ethanol extracts of E. ramosissimum have a total content of phenols (equivalent to gallic acid, 7.62 and 8.97 mg/g) and flavonoids (equivalent to quercetin, 8.87 and 12.86 mg/g), respectively. After conducting the UHPLC-MS/MS analysis, it was found that both the methanol and ethanol extracts contained isoferulic acid, ISO-Orientin, myristic acid, linoelaidic acid, rutin, and 3-Glu-7-Rha quercetin. Additionally, isoferulic acid, myristic acid, linoelaidic acid, rutin, and 3-Glu-7-Rha quercetin were present in the extracts. The ethanol extract of E. ramosissimum significantly impacted STZ-induced diabetic mice by reducing their fasting blood glucose levels, and their creatinine and urea levels (P < 0.005). In conclusion, E. ramosissimum ethanol extract has shown potential effects to counteract some diabetes consequences on kidney function. Therefore, further studies are required to investigate its effect on other diabetes-related complications.

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Research Article Tue, 9 Jan 2024 09:34:36 +0200
Spectroscopic and thermodynamic characterization of the interaction of a new synthesized antitumor drug candidate 2H4MBBH with human serum albumin https://pharmacia.pensoft.net/article/112385/ Pharmacia 71: 1-5

DOI: 10.3897/pharmacia.71.e112385

Authors: Silviya Abarova, Katerina Stoitchkova, Svetlin Tzonev, Maria Argirova, Denitsa Yancheva, Neda Anastassova, Boris Tenchov

Abstract: In the present work we studied the interactions of a newly synthesized drug candidate, 2-(2-hydroxy-4-methoxybenzylidene)-1-(1H-benzimidazol-2-yl)hydrazine (2H4MBBH), with human serum albumin (HSA) by fluorescence spectroscopy. 2H4MBBH-HSA binding parameters were assessed by fluorescence quenching strategy. As made clear by the concentration data, 2H4MBBH unequivocally quenched the instrinsic HSA fluorescence. The calculated Stern-Volmer quenching constant Ksv, the Ka of 2H4MBBH-HSA complexes, as well as the thermodynamic parameters ∆H°, ∆S° and ∆G°, showed that the H-bonding forces play major part in the interaction of 2H4MBBH with HSA. These calculations point to a quenching component based on 2H4MBBH-HSA static complex formation rather than energetic collisions.

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Research Article Tue, 9 Jan 2024 09:32:29 +0200
Effect of tobacco smoking and alcohol consumption on semen quality and hormone reproductive levels in infertile males: A systematic review and meta analysis https://pharmacia.pensoft.net/article/113854/ Pharmacia 71: 1-14

DOI: 10.3897/pharmacia.71.e113854

Authors: Ryan Ramon, Syah Mirsya Warli, Nur Rasyid, Widi Atmoko

Abstract: Aim: This study compared semen quality, FSH, LH, and Testosterone levels in infertile males among smokers and non-smokers and semen quality among alcoholics and non alcoholics. Methods: A literature search was conducted across five databases in December 2021. The search for this article uses specific keywords tailored to each search database’s specifications. Results: A total of 15 studies with 12,503 infertile male participants included in this study. 8,025 were non-smokers, 4,477 were smokers, 210 were alcoholics and 407 were non alcoholics. The effect of tobacco smoking on sperm were more significant in smokers than in non-smokers. Alcohol consumption affects the quality and quantity of semen. Both tobacco smoking and alcohol consumption combined may amplify their negative effects toward semen parameters. Conclusion: Smoking and alcohol has a detrimental impact on conventional semen characteristics. Due to the harmful effects of both factors, men seeking reproduction should be advised to avoid these habits.

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Review Article Thu, 4 Jan 2024 11:26:06 +0200
Amstirdam coffee ameliorates Lp-PLA2 and the inflammatory response in an atherosclerosis mice https://pharmacia.pensoft.net/article/106817/ Pharmacia 71: 1-8

DOI: 10.3897/pharmacia.71.e106817

Authors: Wirdatun Nafisah, Annia Zhafarina Dalilati, Yuyun Ika Christina, Mochammad Fitri Atho’illah, Muhaimin Rifa’i, Tengku Natasha Eleena Tengku Ahmad Noor, Alexander Patera Nugraha

Abstract: Coffee is a kind of daily beverage, and its correlation with cardiovascular disease and atherosclerosis is still debatable. The aim of this study is to investigate the effects of Amstirdam coffee extract (ACE) on lipoprotein-associated phospholipase A2 (Lp-PLA2) and the inflammatory response in atherosclerosis mouse models. The study used 25 Swiss male mice for five groups (n = 5): healthy mice fed a normal diet (N); mice fed a high-fat, high-fructose diet (HFFD); mice fed HFFD and treated with ACE at doses of 104 (D1), 520 (D2), and 5200 mg/kg BW (D3). The levels of Lp-PLA2, regulatory T cells (Tregs) (CD4+CD25+CD62L+, CD4+CD25+IL-10+, CD4+CD25+TGF-+), IL-10 (CD4+IL-10+), and TGF-B (CD4+TGF+) were analyzed using a flow cytometer. Histological analysis of the mouse aorta was done by hematoxylin and eosin (HE) staining. This study indicated a significant increase in total cholesterol (TC), triglyceride (TG), LDL, and Lp-PLA2 levels in the HFFD group. HFFD also reduced HDL, IL-10, and TGF produced by CD4 and Tregs compared with the normal group. ACE at all doses significantly reduced Lp-PLA2 levels compared with the HFFD group (p < 0.05). Interestingly, the administration of 520 mg/kg BW ACE (D2) increased the production of IL-10 significantly compared to other doses (p < 0.05). The D3 group possessed a high TGF- production and Treg expression level significantly different between groups (p < 0.05). Foam cells were mostly found in the aorta of the HFFD group compared to the normal and ACE treatment groups. This study suggested that ACE could reduce Lp-PLA2 enzyme activity and foam cell formation through the immunosuppressive activity of IL-10 and TGF cytokines.

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Research Article Thu, 4 Jan 2024 11:26:06 +0200
A 36-year-old woman with a parathyroid cyst https://pharmacia.pensoft.net/article/115504/ Pharmacia 71: 1-3

DOI: 10.3897/pharmacia.71.e115504

Authors: Iveta Nedeva, Vlayko Vodenicharov, Vera Karamfilova, Yavor Assyov

Abstract: Background: Parathyroid cysts are rare entities. They account for less than 0.5% of parathyroid lesions. They are divided into two main groups: functioning and non-functioning. Case description: We present a 36- year-old woman with complaints of palpitations, sweating, and nervousness of about 2 months’ duration. From an ultrasound of the thyroid gland with data on anechoic formation under the lower pole of the left lobe of the thyroid gland with dimension 14/16/24 mm. Fine needle aspiration (FNA) of the formation was performed with aspiration of about 5 ml of clear liquid and examination of washout. PTH from the washout of the extrathyroidal lesion-1040 pg/ml. A month later with ultrasound data on recurrence of the formation; repeated aspiration of about 5 ml of blood fluid was performed with subsequent application of 1 ml of absolute alcohol intranodal. Conclusion: Thirty days after the procedure with ultrasound data of slight regression in the dimension: 10/11/20 mm.

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Short Communication Thu, 4 Jan 2024 11:26:06 +0200
Molecular docking screening, dynamics simulations, ADMET, and semi-synthesis prediction of flavones and flavonols from the COCONUT database as potent bifunctional neuraminidase inhibitors https://pharmacia.pensoft.net/article/114967/ Pharmacia 71: 1-10

DOI: 10.3897/pharmacia.71.e114967

Authors: Thi-Kim-Quy Ha, Nguyen-Huan Pham-Khanh, Thanh-Khiet Nguyen

Abstract: Finding new neuraminidase (N) inhibitors to improve anti-influenza treatment is necessary because of the high mutation rates of N protein. Over 3,000 flavones/flavonols and their synthesized products from the COCONUT database were performed in silico docking screening with N1-H274Y-oseltamivir protein (PDB ID: 3CL0). Several derivatives containing nitrogen heterocyclic groups or aromatic rings showed higher anti-neuraminidase potential than that of laninamivir. Especially, the linker groups between the flavone aglycone and nitrogen heterocyclic group created the interactions with the triad of arginine residues Arg118-Arg292-Arg371, which suggested these compounds could become bifunctional inhibitors against the influenza virus strains at the sialic acid binding site and the adjacent 430-cavity position through triad of arginine residues binding. ADMET indicators and the synthesis design strategy of the most suitable compound, ethyl 4-{2-[(5-hydroxy-4-oxo-2-phenyl-4H-chromen-7-yl)oxy]acetyl}piperazine-1-carboxylate, were also successfully predicted and it could be a concerned candidate for further wet-lab synthesis, in vivo and clinical study.

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Research Article Wed, 3 Jan 2024 12:23:56 +0200
Lead drug discovery from imidazolinone derivatives with Aurora kinase inhibitors https://pharmacia.pensoft.net/article/114935/ Pharmacia 70(4): 1529-1540

DOI: 10.3897/pharmacia.70.e114935

Authors: Bathula Sivakumar, Ilango Kaliappan

Abstract: Cancer is the second leading cause of death worldwide, and breast cancer accounts for 6.27 million cases in the year 2022. In the present study, Quantitative Structural Activity Relationship (QSAR) studies were performed on a dataset of 39 molecules of Imidazolinone analogues using in random selection using QSARINS Software. The statistically validated (R2 = 0.8429 Q2loo = 0.7558) MLR model was used to predict the bioactivity of novel leads. Moreover, high-scoring compounds were exposed to molecular docking and molecular dynamic modeling study. Intended derivatives 1–23 exhibited the anticipated bioactivity using a QSAR model. Aforementioned molecules were tested for binding affinities with the target protein and the majority of them demonstrated excellent interactions with binding pocket residues. Molecular dynamics simulations using Desmond for 100 ns of top complexes 1, 7, 9, 13 and 19 showed critical structural data concerning Aurora kinase inhibition. There were stable hydrophobic and hydrophilic interfaces in the dynamic site of compounds with a leading chemical structure. The chemical interacts to the (PDB: 1MQ4) structure in a stable way, according to RMSD, RMSF, RoG, H-bond, and SASA analysis. Furthermore, the docking results have been confirmed by MM-PBSA and MM-GBSA. Based on our findings, we reported the inclusion of the necessary structural features of imidazolinone derivatives leads to the development of the potent candidates for further development.

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Research Article Mon, 18 Dec 2023 17:34:56 +0200
UHPLC-Orbitrap screening of oleraindoles in hydromethanolic extracts of Portulaca oleracea https://pharmacia.pensoft.net/article/113577/ Pharmacia 70(4): 1521-1527

DOI: 10.3897/pharmacia.70.e113577

Authors: Yulian Voynikov, Reneta Gevrenova, Dimitrina Zheleva-Dimitrova, Vessela Balabanova, Irina Nikolova, Lyubomir Marinov, Iossif Benbassat, Georgi Momekov

Abstract: Purslane (Portulaca oleracea L., Portulacaceae) is a widespread edible plant with significant ethnobotanical and ethnopharmacological importance. The plant is characteristic for the presence of a class of indoline amide glucoside alkaloids, called cyclo-dopa amides, or oleraceins. Additionally, a new, structurally similar to oleraceins, class of indole amides have been discovered recently, called oleraindoles. These compounds have been evaluated to possess antiinflammatory and anticholinesterase activities. Herein, utilizing UHPLC-Orbitrap-MS with MS2 filtering by diagnostic ion filtering (DIF), and diagnostic difference filtering (DDF) using different data analysis tools, eight compounds with oleraindole structure were tentatively identified.

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Research Article Mon, 18 Dec 2023 17:18:54 +0200
Molecular dynamic of omega-3 compounds as an anti-obesity agent into GPR-120 receptor https://pharmacia.pensoft.net/article/115501/ Pharmacia 70(4): 1541-1548

DOI: 10.3897/pharmacia.70.e115501

Authors: Ida Musfiroh, Ginna Megawati, Dewi Marhaeni Diah Herawati, Okta Nama Putra, Evi Sylvia Nurrasjid

Abstract: Obesity is a cause of comorbid diseases such as type 2 diabetes mellitus, dyslipidemia, hypertension which is based on low-level chronic inflammation. The GPR-120 receptor plays a role in insulin sensitization which is related to diabetes mellitus which is a comorbid obesity. Omega-3 fatty acids are believed to possess anti-inflammatory properties, hence potentially serving as a preventive measure against obesity-related comorbidities. The aim of this study is to do a stability analysis of the binding affinity between nine specific chemicals derived from omega-3 and the active site of the human GPR120 receptor using molecular dynamics simulations. Docking analysis was performed using Discovery Studio Visualizer, AutoDock Tools 1.5.6, and molecular dynamic simulation with AMBER 16. In this study, we used neurotensin 8–13 as a natural ligand to bind with the neurotensin receptor. Based on the neurotensin receptor docking results, the ΔG values for the following compounds are close to the values for neurotensin 8–13 -6.41 kcal/mol; docosahexaenoic acid -8.96 kcal/mol; eicosapentaenoic acid -7.41 kcal/mol; and heneicosapentaenoic acid -6.34 kcal/mol. Neurotensin 8–13 forms hydrogen bonds with TYR146, ARG213, and PHE344 of the neurotensin receptor, whereas docosahexaenoic acid forms hydrogen bonds with TYR146. Meanwhile, the average RMSD fluctuations for each system, namely docosahexaenoic acid, eicosapentaenoic acid, and heneicosapentaenoic acid, were 0.672, 0.437, and 0.650, respectively. The SASA of the neurotensin receptor-ligand complex showed similar fluctuations, with the average values for docosahexaenoic acid, eicosapentaenoic acid, and heneicosapentaenoic acid being 230.40, 229.89, and 230.20 nm2.

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Research Article Mon, 18 Dec 2023 09:33:19 +0200
Metabolic syndrome: comparison of three diet-induced experimental models https://pharmacia.pensoft.net/article/109965/ Pharmacia 70(4): 1539-1548

DOI: 10.3897/pharmacia.70.e109965

Authors: Alexandra Petrova, Rumyana Simeonova, Christina Voycheva, Yonko Savov, Lyubomir Marinov, Vessela Balabanova, Reneta Gevrenova, Dimitrina Zheleva-Dimitrova

Abstract: The high-fat (HF) diets can be used to generate a valid rodent model for metabolic syndrome (METS). The aim of this study was to compare three different diets, namely a high-fat, high-carbohydrate diet (HF-HCD), a high-fat lard-based diet (HFD), and a cafeteria diet (CFD), in terms of the ability to induce METS. The next step was to characterize the syndrome according to the biochemical and histopathological changes in the liver and pancreas, and to determine the optimal animal model. As a result, all diets disturbed significantly the serum biochemical parameters. HF-HCD and CFD increased the uric acid levels and reduced the weight gain in comparison with the standard chow diet (SCD) and HFD. The HFD and CFD induced the highest fasting glycemia levels. Although the animals fed with HF-HCD had the lowest body weight, the most serious histopathological changes in the pancreas, hypertension, and oxidative stress were noted in them.

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Research Article Tue, 12 Dec 2023 10:55:12 +0200
Simulated microgravity affects carrageenan-induced inflammation process in rats https://pharmacia.pensoft.net/article/107698/ Pharmacia 70(4): 1531-1538

DOI: 10.3897/pharmacia.70.e107698

Authors: Viktor Yotov, Raina Ardasheva, Anita Mihaylova, Nina Doncheva, Ilia Kostadinov, Valentin Turiyski

Abstract: Weightlessness significantly impacts physiological systems. In the current study, we investigate the effects of 7 days exposure of rats to simulated microgravity (using a modified rat-modeled random positioning machine, working with four experimental animals simultaneously) on local carrageenan-induced inflammation and serum levels of liver enzymes, metabolites (glucose, urea, creatinine), and metabolic hormones (thyroid-stimulating hormone – TSH, aldosterone, cortisol). Male Wistar rats (n=12, m=200 ± 20 g) were evenly divided into RPM (experimental) and RPM-K (control) groups. The RPM rats showed a notable mass decrease compared to the controls. A significant increase in the carrageenan-induced inflammatory response was reached on the 24th hour in the RPM group compared to the RPM-K. Simulated microgravity resulted in lower serum glucose, creatinine, cortisol, and elevated urea levels. In conclusion, 7 days of exposure to random positioning machine-simulated microgravity promotes a pro-inflammatory state, potentially affecting insulin sensitivity, glucose utilization, and muscle catabolism.

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Research Article Tue, 12 Dec 2023 10:55:12 +0200
A comprehensive in vivo study of the antihypertensive properties and toxicity of roselle (Hibiscus sabdariffa L.) https://pharmacia.pensoft.net/article/109119/ Pharmacia 70(4): 1521-1530

DOI: 10.3897/pharmacia.70.e109119

Authors: Yasmiwar Susilawati, Raden Maya Febriyanti, Ellin Febrina, Anis Chaerunisaa, Sri A. Sumiwi

Abstract: Background: Roselle (Hibiscus sabdariffa L.) calyces have been used in traditional medicine as diuretics, mild laxatives, and antihypertensive agents but to date, a comprehensive study of its pharmacological activity and safety has not been conducted. Aims of the study: The current study aims to provide a comprehensive evaluation of the antihypertensive efficacy and toxicity profile of Roselle (H. sabdariffa L.) calyces extract. Utilizing animal models, the investigation assessed the dose-dependent pharmacological effects and safety of H. sabdariffa L. Results: The findings indicate that the extract exerts a significant antihypertensive effect at a dose of 250 mg/kg body weight (BW), lowering systolic and diastolic blood pressures by 10.12% and 11.63%, respectively. Ethyl acetate fractions administered at 112.5 mg/kg BW demonstrated greater efficacy than n-hexane and aqueous fractions, suggesting that the active compounds likely possess semi-polar properties. Acute toxicity testing yielded an LD50 of 8.75 g/kg BW for male rats and 7.5 g/kg BW for female rats, classifying the extract as slightly toxic. The sub-chronic toxicity study shows that H. sabdariffa L. demonstrates an effect on bodyweight and urea levels in male and female rats, while the change in the blood parameters, creatinine level, and the liver index was only observed in female rats. Conclusions: These data suggest that H. sabdariffa L. extract exhibits therapeutic promise but should be administered cautiously, preferably at doses lower than 250 mg/kg BW, due to potential toxicity.

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Research Article Tue, 12 Dec 2023 10:55:12 +0200
Facile, sensitive and reagent-saving smartphone-based digital image colorimetric assay of captopril tablets enabled by long-pathlength RGB acquisition https://pharmacia.pensoft.net/article/114927/ Pharmacia 70(4): 1511-1519

DOI: 10.3897/pharmacia.70.e114927

Authors: Thana Thanayutsiri, Thapakorn Charoenying, Prasopchai Patrojanasophon, Boonnada Pamornpathomkul, Praneet Opanasopit, Tanasait Ngawhirunpat, Theerasak Rojanarata

Abstract: A new assay of captopril (CTP) tablets was developed based on digital image colorimetry using Ellman’s reagent. For the first time, a facile technique of increasing the analytical path was applied in this work to enhance the sensitivity. For this purpose, the reaction solutions were photographed using a smartphone while they were contained in two 1-cm pathlength cuvettes which were placed side by side. The Red-Green-Blue (RGB) in term of [B/(R+G+B)] was used to plot a standard curve. Compared to using a single cuvette, double cuvettes resulted in more precise analytical signals and better linearity (r2 of 0.9992). Additionally, CTP could be analyzed at low concentrations (2.5–25 µM) with LOD of 0.70 µM and LOQ of 2.13 µM, thus lowering the reagent consumption. The assay was proven to be valid, and it was greener, faster, and more affordable than the pharmacopeial chromatographic method, thereby suitable for pharmaceutical quality control.

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Research Article Mon, 11 Dec 2023 20:19:09 +0200
Serotonin production of the developing gastrointestinal tract of human embryos in 6th gestation week https://pharmacia.pensoft.net/article/114080/ Pharmacia 70(4): 1499-1509

DOI: 10.3897/pharmacia.70.e114080

Authors: Nadya Penkova, Pepa Atanasova, Radoslav Penkov, Petar Hrischev, Lyudmil Peychev, Zhivko Peychev

Abstract: Background: Local regulation of gastrointestinal tract digestion is performed by a large number of hormones produced by the mucosal enteroendocrine cells. Some of the earliest differentiating cells in the gastrointestinal tract are enteroendocrine cells. Serotonin-producing cells - EC cells are found mostly in the stomach and duodenum. Aim: The aim of our study is to establish the presence and to make morphological and morphofunctional characteristic of ЕС cells in the developing gastrointestinal tract of a human. Materials and methods: Our study was performed with biopsy specimen from human stomach and duodenum and fragments of gastrointestinal tract of human embryos 6th gestation week, studied by immunohistochemical, electron microscopy and morphometric methods. Results: EC cells have already been differentiated in the 6th gestation week. Embryonic EC cells had identical characteristics with those of adults. They were in two morphofunctional conditions: stage of increased synthesis and stage of relative secretory rest. Conclusion: In the early embryonic period - 6th gestation week EC cells have already been differentiated. The occurrence of EC cells with hormonal production prior to the definitive differentiation of tissues presupposes participation of serotonin in the digestive tube histogenetic processes.

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Research Article Mon, 11 Dec 2023 20:18:39 +0200
Interleukin-6: Unravelling its role in sarcopenia pathogenesis and exploring therapeutic avenues https://pharmacia.pensoft.net/article/115762/ Pharmacia 70(4): 1493-1498

DOI: 10.3897/pharmacia.70.e115762

Authors: Yavor Assyov, Iliana Ganeva, Stefan Ikonomov, Iveta Nedeva, Toni Velikov, Zdravko Kamenov, Tsvetelina Velikova

Abstract: This review explores the intricate relationship between interleukin-6 (IL-6) and sarcopenia, a prevalent condition characterized by progressive skeletal muscle loss, particularly in aging populations. Emphasizing the rising prevalence and health challenges posed by sarcopenia, the paper delves into the multifunctional roles of IL-6 in immune response, inflammation and inflammaging associated with sarcopenia. Significantly elevated in sarcopenic individuals, IL-6 prompts an exploration of its molecular impact on muscle wasting. The review critically assesses IL-6 as a potential biomarker for sarcopenia diagnosis and prognosis while also examining therapeutic interventions targeting IL-6 signaling pathways, offering a foundation for future research and the development of targeted therapeutic strategies to alleviate the impact of this debilitating condition.

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Review Article Fri, 8 Dec 2023 12:21:06 +0200
Design, synthesis and molecular docking study of coumarin pyrazoline derivatives against MCF-7 breast cancer cell line https://pharmacia.pensoft.net/article/108670/ Pharmacia 70(4): 1487-1492

DOI: 10.3897/pharmacia.70.e108670

Authors: Wafaa Yusuf Khalaf, Rita Sabah Elias, Leaqaa Abdulredha Raheem

Abstract: A new eight series of 3-(2-oxo-2H-chromen-3-yl)-5-(substituted phenyl)-1H-pyrazole-1-carbaldehyde derivatives (9–16) were designed and created from coumarin-chalcone derivatives (1–8). The structures of the derivatives were established by using melting point, mass spectrum, IR, 1HNMR, and 13C NMR spectroscopic methods. In vitro antiproliferative activities were evaluated against MCF-7 breast cancer cell line using Microculture Tetrazolium (MTT) assay. The results showed that the compounds 9, 12- 14 has a moderate activity against MCF-7 breast cancer cell line with IC50 61.44, 70.11, 22.6 and 25.99 µg/mL respectively, while the compounds 10,11, 15 and 16 were found to be inactive against studied cell line within IC50 > 100 µg/mL. The possible binding interaction between studied compounds (9–16) and human ER-α (PDB ID: 1ERR) were studied by molecular docking. The results revealed that only the compounds 11 and 16 form π -H interaction with ER-α (PDB ID: 1ERR) within the highest negative values of binding affinity -7.04260 and -7.17308 kcal.mol-1 respectively than the other compounds, while Raloxifene used here as a positive control form a strong ionic bonding with Asp 351 within the binding affinity -9.61928 kcal/mol which is more negative value than the studied compounds.

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Research Article Fri, 8 Dec 2023 12:18:24 +0200
Solubility enhancement of carvedilol by multicomponent crystal approach using glycine and arginine as coformers https://pharmacia.pensoft.net/article/112271/ Pharmacia 70(4): 1479-1486

DOI: 10.3897/pharmacia.70.e112271

Authors: Iyan Sopyan, Wuri Ariestika Sari, Sandra Megantara, Taofik Rusdiana

Abstract: A Carvedilol is a member of BCS class II, it has a low solubility and bioavailability. This work intends to increase the solubility of carvedilol using a multicomponent crystal method. Based on in silico investigations showed that carvedilol-arginine formed one hydrogen bond and carvedilol-glycine formed two hydrogen bonds. Compared to the solubility of pure carvedilol, CVD: GLY multicomponent crystal ratios of 1:1, 1:2, and 2:1 resulted in increases in solubility of 1.9 times, 2.6 times, and 2.5 times respectively. The solubility of the multicomponent crystals in the CVD:ARG however, did not increase. The best dissolution profile was provided by multicomponent crystal CVD: GLY (1:2), with a % dissolution of 86.03% in HCl medium pH 1.45 and 29.5% in phosphate buffer medium pH 6.8. The results of characterization included FTIR, DSC, PXRD, and SEM evaluation of CVD: GLY multicomponent crystal (1:2) indicated the formation of a new solid crystalin phase. CVD: GLY multicomponent crystal (1:2) showing the best solubility and dissolution profile as compared to pure carvedilol.

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Research Article Thu, 7 Dec 2023 15:29:26 +0200
Pharmacological methods for weight reduction and their connection with the human gut microbiota https://pharmacia.pensoft.net/article/114567/ Pharmacia 70(4): 1471-1477

DOI: 10.3897/pharmacia.70.e114567

Authors: Venelin Dimitrov Denchev, Teodora Svetoslavova Handjieva-Darlenska

Abstract: In the beginning of the twenty-first century, obesity has become a concerning world-wide issue due to its high prevalence in modern society. It is a metabolic disorder, caused by excessive accumulation of adipose tissue in the human organism – the main reason for which is increased caloric intake and decreased caloric expenditure in combination with dysregulation of hunger. It is a chronic systematic disease that leads to the development of a large number of health complications, the most common of which are: diabetes mellitus type 2, arterial hypertension, atherosclerosis, sleep apnea, different types of cancer and more. During the last decade, significant advancements have been made in regard to treatment of many endocrine and metabolic conditions, using pharmacological means, and some of these novel medications have proven to be an effective therapy for obesity. There is emerging evidence that such drugs can exhibit an effect over the human gut microbiota – the complex system of commensal bacteria located in the gastrointestinal tract, which could affect appetite, mucosal integrity, nutrient absorption, and that interaction can be the key to understanding the pathogenesis of obesity and its treatment.

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Review Article Mon, 4 Dec 2023 09:24:17 +0200
Polyscias scutellaria: An emerging source of natural antioxidants and anti-inflammatory compounds for health https://pharmacia.pensoft.net/article/112502/ Pharmacia 70(4): 1463-1470

DOI: 10.3897/pharmacia.70.e112502

Authors: Adi Muradi Muhar, Adrian Joshua Velaro, Arya Tjipta Prananda, Sony Eka Nugraha, Gamze Çamlik, Siddhanshu Wasnik, Satirah Zainal Abidin, Osfar Sjofjan, Muhammad Andika Yudha Harahap, Muhammad Faridz Syahrian, Nurpudji Astuti Taslim, Nelly Mayulu, Happy Kurnia Permatasari, Fahrul Nurkolis, Putri Cahaya Situmorang, Rony Abdi Syahputra

Abstract: Polyscias scutellaria (PS), an increasingly recognized botanical marvel, has emerged as a remarkable reservoir of natural antioxidants and anti-inflammatory compounds, holding immense potential for enhancing health and promoting overall well-being. In this comprehensive investigation, we meticulously examined the multifaceted properties of PS through various parameters, including DPPH scavenging activity, total phenol, and total flavonoid content in its ethanol extract (EEPS), ethyl acetate extract (EAPS), and n-hexane extract (nhPS). Additionally, we conducted in-depth assessments of cellular responses to EEPS and EAPS, encompassing cell viability, nitric oxide (NO) production, and the modulation of pivotal pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), and interleukin-12 (IL-12), utilizing the RAW 264.7 cell line as a model system.Our findings illuminate the exceptional antioxidant prowess of PS extracts, with EEPS, EAPS, and nhPS displaying noteworthy DPPH scavenging activities. These results underscore their potential in quenching harmful free radicals and mitigating oxidative stress. Furthermore, our investigation unveils the promising anti-inflammatory attributes of EEPS and EAPS, as evidenced by their capacity to preserve cellular viability, dampen NO production, and suppress the secretion of critical pro-inflammatory mediators (TNF-α, IL-6, IL-1β, and IL-12) in RAW 264.7 cells. These remarkable anti-inflammatory effects hint at the therapeutic potential of PS in ameliorating chronic inflammatory conditions and bolstering the body’s immune response.In conclusion, Polyscias scutellaria stands as an emerging botanical champion, offering a wealth of natural antioxidants and anti-inflammatory compounds that hold great promise for optimizing health and well-being. This study opens exciting avenues for future research to elucidate the precise bioactive constituents within PS and unravel their intricate mechanisms of action, paving the way for the development of innovative therapeutic interventions and wellness-enhancing products. The remarkable properties of PS underscore its potential as a cornerstone of holistic health and a valuable asset in the pursuit of a vibrant and balanced life. Graphical abstract

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Research Article Mon, 4 Dec 2023 09:24:17 +0200
Relationship of serum Fetuin-A with metabolic and vascular parameters in patients with prediabetes and type 2 diabetes mellitus https://pharmacia.pensoft.net/article/115795/ Pharmacia 70(4): 1455-1461

DOI: 10.3897/pharmacia.70.e115795

Authors: Vera Karamfilova, Iveta Nedeva, Tsvetan Gatev, Antoaneta Gateva, Yavor Assyov, Antonina Gerganova, Dobrin Popov, Tsvetelina Velikova, Zdravko Kamenov

Abstract: Background: Fetuin-A is a multifunctional liver-derived glycoprotein that is associated with insulin resistance and might play a role in the pathogenesis of prediabetes and type 2 diabetes (T2DM). Objective: This study evaluated the relationship of Fetuin-A with metabolic and vascular parameters in patients with prediabetes and T2DM. Materials and methods: total 120 obese patients were included. They were divided into three groups: group 1 – without carbohydrate disturbances, group 2 – with prediabetes and group 3 – with type 2 diabetes mellitus. Results: Higher Fetuin-A serum levels were observed in patients with prediabetes and T2DM compared to those with normoglycemia. Fetuin-A ≥821 mcg/ml increased the risk for T2DM 32-fold. Additionally, we found positive correlations between Fetuin-A, vibration perception threshold and toe-brachial index and a negative correlation with neuropathy disability score. Conclusion: Fetuin-A could be predictive for incidents of prediabetes and T2DM.

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Research Article Mon, 4 Dec 2023 09:24:17 +0200
Biotechnological approaches for sustainable production of astragaloside I, II and IV from endemic species of Astracantha aitosensis (Ivan.) and Astragalus membranaceus (fisch.) by in vitro cultures https://pharmacia.pensoft.net/article/114989/ Pharmacia 70(4): 1449-1453

DOI: 10.3897/pharmacia.70.e114989

Authors: Preslav Enchev, Yancho Zarev, Iliana Ionkova

Abstract: This study investigates the bioproduction of astragalosides I, II and IV from endemic Astracantha aitosensis (arnacantha) and Astragalus membranaceus species, and the biotechnological methods for increased efficiency. The extracts from established in vitro cultures, including A. aitosensis callus, shoots and roots and A. membranaceus hairy roots, showed higher astragaloside concentrations than native roots. Specifically, in vitro A. aitosensis cultures produced astragaloside I and II at 0.06 and 0.10 mg/g DW, which were absent in native roots. The production of A. membranaceuss hairy roots exceeds 8 to 15 times astragaloside I and II (0.80 and 0.90 mg/g DW) production when compared to native roots (0.10 and 0.05 mg/g DW), and around 3 times high amount related to astragaloside IV. Addressing astragaloside production challenges, this research also reveals biotechnology approaches as an alternative for sustainable production of this rare cycloartane saponins, conserving the natural habitats. A pilot reproducible in vitro cellular platform has been created, and protocol for specific, unconventional induction of the biosynthesis of the desired target compounds, exploiting the enzymatic system of plant cells from the unexplored plant species A. aitosensis has been established. Our findings clearly show the possibility of using in vitro cultures of A. aitosensis and A. membranaceus for biotechnology production of cycloartane type saponins.

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Research Article Thu, 30 Nov 2023 19:16:57 +0200
Neurodegenerative diseases associated antibody repertoire signatures in mimotope arrays based on cyclic versus linear peptides https://pharmacia.pensoft.net/article/115179/ Pharmacia 70(4): 1439-1447

DOI: 10.3897/pharmacia.70.e115179

Authors: Shina Pashova-Dimova, Peter Petrov, Sena Karachanak-Yankova, Anastas Pashov

Abstract: The role of peptide probes’ conformational flexibility in extracting immunosignatures has not been sufficiently studied. Immunosignatures profile the antibody diversity and prove promising for early cancer detection and multi-disease diagnostics. A novel tool for modeling antibody repertoires, the concept of antibody reactivity graphs, proved instrumental in this respect. Serum samples from patients with Alzheimer’s disease (AD), frontotemporal dementia (FTD), dementia of unknown etiology (DUE), and healthy controls were probed using a set of 130 7-mer peptides relevant to neurodegenerative diseases. Results show that linear peptides probed with IgM yielded higher graph density compared to IgG, indicating different levels of polyspecificities. Additionally, the impact of peptide topology and antibody isotype on feature selection was studied using recursive feature elimination. Findings reveal that IgM assays on linear peptides offer superior diagnostic differentiation of neurodegenerative diseases and define the degree of agreement between IgG and IgM immunosignatures with linear or cyclic peptides.

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Research Article Thu, 30 Nov 2023 19:10:01 +0200
A novel formulation of ketoconazole entrapped in alginate with anionic polymer beads for solubility enhancement: Preparation and characterization https://pharmacia.pensoft.net/article/108120/ Pharmacia 70(4): 1423-1438

DOI: 10.3897/pharmacia.70.e108120

Authors: Viviane Annisa, Teuku Nanda Saifullah Sulaiman, Akhmad Kharis Nugroho, Agung Endro Nugroho

Abstract: Ketoconazole has low solubility in intestinal pH, whereas drug absorption is largest in the small intestine, which can reduce the bioavailability of the drug. Alginate can be combined with a suitable polymer and cross-linked with divalent ions and another polymer to enhance the solubility of the drug. Ketoconazole could be loaded into a matrix polymer consisting of alginate and anionic polymer through hydrogen bonds formed with the N atom of the ketoconazole. The method employed to produce ketoconazole beads involved ionic gelation with CaCl2 as a cross- linking agent, and various polymer combinations were used: alginate 100:0 (AL100), alginate:pectin 75:25 (AP75) and 50:50 (AP50), alginate:gum acacia 75:25 (AG75) and 50:50 (AG50), and alginate:carrageenan 75:25 (AK75) and 50:50 (AK50). The beads were characterized by using differential scanning calorimetry (DSC), scanning electron microscopy (SEM), Fourier transform infrared (FT-IR), X-ray diffraction (XRD), swelling study, in vitro drug release study, and solubility determination. The incorporation of ketoconazole into combination matrices of AL100, AG75, AP75, AP50, and AK75 resulted in significantly higher solubility in FaSSIF-2X (Fasted State Simulated Intestinal Fluid) at pH 6.5 compared to pure ketoconazole.

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Research Article Thu, 30 Nov 2023 19:05:49 +0200
Combination of ketogenic diet and probiotics inhibits breast cancer in mice by immune system modulation and reduction of Insulin growth factor-1 https://pharmacia.pensoft.net/article/111822/ Pharmacia 70(4): 1411-1422

DOI: 10.3897/pharmacia.70.e111822

Authors: Ayah Kamel Saeed Kamal, Wamidh H. Talib

Abstract: Breast cancer (BC) is the most prevalent malignancy in women and the first tumor type in the world. Ketogenic diets (KD), which are high in fat, low in carbohydrates, and sufficient in protein, can be used alone or as adjuvants with cancer drug medication as cancer therapy or prevention methods. Probiotics are nonpathogenic microorganisms or groups of bacteria that live in the gut and nourish the host body. In this work, we tested a new KD-probiotic combination against breast cancer implanted in mice. Several combination of probiotics (1×109 CFU/0.5ml) and KD (14.1 kcal/2g) reduced tumor size and enhanced cure rate. KD and combination therapy groups increased beta-hydroxybutyrate (β-OHB) while decrease blood glucose, and IGF-1.IFN-γ, IL-2, IL-4, and IL-10 serum levels were measured to assess immune reaction to various therapies. Combination and probiotics therapy raised IFN-γ, and IL-4 levels, however IL-10 level did decrease in all treated group with highest decrease in combination group. In the safety profile, probiotics, ketogenic diet, and their combination were safe. Overall, the combination of a ketogenic diet and probiotics has the potential to be utilized in the future development of anti-cancer nutrition to augment conventional therapies. Graphical abstract. Summary of the effect of Ketogenic diet, Probiotics and its combination on EMP-6 breast cancer cell and in vivo:

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Research Article Thu, 30 Nov 2023 18:55:03 +0200
Hepatoprotective activity of QBD-based optimized N-acetyl cysteine solid lipid nanoparticles against CCL4-induced liver injury in mice https://pharmacia.pensoft.net/article/113287/ Pharmacia 70(4): 1397-1410

DOI: 10.3897/pharmacia.70.e113287

Authors: Bhavana Madupoju, Subhakar Raju Rapaka, Narender Malothu, Prasanna Kumar Desu, Ankarao Areti

Abstract: Purpose: In the present study, N-acetyl cysteine (NAC)-Solid Lipid Nanoparticles (SLNs) were developed employing the Quality by Design (QBD) approach for the application of hepatoprotective activity. Methods: Using Box-Behnken Design (BBD) three independent variables (Soya lecithin, polysorbate content, and homogenization speed) and four dependent variables (% entrapment efficiency (EE), % drug release (DR), zeta potential (ZP), and particle size (PS)) were chosen for the study. The formulations were prepared by the hot homogenization method and characterized with SEM, FTIR, DSC, and XRD and evaluated their % EE, % DR, PS, and ZP. Developed SLNs were tested for their hepatoprotective activity by an in vivo mice model and compared the effectiveness with free NAC and Silymarin. Results: The optimized NAC-SLNs were found optimum with spherical and intact chemical structure (88.95% EE, 97.15% DR, -43.01 mv ZP, < 200 nm of PS) exhibiting Higuchi model of drug release. In terms of MDA levels, NAC-SLNs had a strong protective impact MDA level (23.09±0.01–21.84±0.01 u mole/mg protein) and were efficient in increasing GPx (16.89±0.01–20.71±0.02 unit/mg protein), GSH (18.94±0.57–24.21±1.00 unit/mg protein), which were reduced in the CCl4-intoxicated group. NAC-SLNs were more effective than NAC at inhibiting the liver enzymes SGOT (150.01±1.5–132.01±0.6 mg/dL), SGPT (100.73±1.1–91.98±2.8 mg/dL), ALP (147.07±0.8–124.79±0.5 mg/dL), and LDH (290.37±3.04–228.25±2.03U/L). Conclusion: The study concludes that NAC-SLNs therapy was not only substantially more effective than NAC, but it also had effects equivalent to a well-known hepatoprotective and antioxidant drug Silymarin.

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Research Article Thu, 30 Nov 2023 18:50:58 +0200
Regulation and control of the use of Cannabis and Cannabidiol in „novel foods” https://pharmacia.pensoft.net/article/114938/ Pharmacia 70(4): 1385-1395

DOI: 10.3897/pharmacia.70.e114938

Authors: Dobrina Tsvetkova, Lily Peykova, Lily Andonova-Dimitrova, Ivanka Pencheva

Abstract: Cannabis sativa L. is a medicinal plant from family Cannabaceae with many pharmacological activities. The recent appearance of a number of cannabis products in the pharmaceutical market has led to increased requirements for regulation and quality control. The control of Cannabis sativa L. is subject to the Psychotropic Substances Convention, which includes the addictive psychoactive delta-9-tetrahydrocannabinol (THC), and to the Narcotic Drugs Convention, which includes the illicit products: herbal and liquid cannabis, resin, extracts and tinctures of flowering or fruiting tops containing THC. Approved by the FDA for use in chemotherapy are Marinol caps. (THC) and Cesamet caps., containing the synthetic THC-derivative Nabilon. There is no harmonized European Union legislation on the use of cannabis and Cannabidiol (CBD), which antagonizes the THC-psychotropic effect. Legitimate products include seeds, oil, extracts, and seed tinctures of the industrial cannabis chemotype, containing primarily Cannabidiol and less than 0.2% THC. Sativex oral spray (THC/CBD = 1:1) is approved for muscle spasticity in multiple sclerosis. Cannabidiol was not used as a food ingredient in the European Union before 15.05.1997 and is a „novel food” according to Regulation 2015/2283. Flour; protein powder and cannabis seed oil are not „novel foods”. Cannabidiol as Epidiolex is FDA approved for epilepsy forms Lennox-Gastaut and Dravet.

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Review Article Thu, 30 Nov 2023 18:45:31 +0200
Formulation and development of a body gel scrub using Areca catechu L. seed extract and microbeads https://pharmacia.pensoft.net/article/106321/ Pharmacia 70(4): 1373-1383

DOI: 10.3897/pharmacia.70.e106321

Authors: Jiraporn Chingunpitak, Attawadee Sae Yoon, Katanyoo Pannoi, Kittipoom Horkul, Noppakrit Tungtongsakul

Abstract: The purpose of this study was to develop and evaluate an antioxidant body gel scrub formulation including Areca seed extract and Areca beads. The Areca seed ethanol extract had an IC50 of 183.30 µg/ml, a radical scavenging activity of 49.196%, and a total phenolic content of 21.21 ± 2.32 µg/ml. With a pH of 6.98 at 25 °C and a viscosity of 5,590.457 cP, the optimized formulation contained 1% w/w Areca seed extract, 5% w/w polyvinyl alcohol, 0.5% w/w Carbomer Ultrez 21, and 5% w/w Areca microbeads. The formulation had a radical scavenging efficiency of 68.66%. Stability tests were carried out under accelerated heating cooling conditions at 40 ± 2 °C, 75 % RH for 48 hours, followed by 4 °C for 48 hours each cycle for 24 days (6 cycles) and 30 days for 4 °C and 30 ± 2 °C, 75% RH, and no significant changes in physical or chemical properties were observed. This body gel scrub formulation shows potential for use in skincare applications due to its antioxidant activity and stability.

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Research Article Tue, 21 Nov 2023 10:27:47 +0200
A comparative study of oral diacerein and transdermal diacerein as Novasomal gel in a model of MIA induced Osteoarthritis in rats https://pharmacia.pensoft.net/article/111097/ Pharmacia 70(4): 1363-1371

DOI: 10.3897/pharmacia.70.e111097

Authors: Noor Yousif Fareed, Hanan Jalal Kassab

Abstract: Background: Osteoarthritis is a chronic pathology of the joints causing disability and morbidity. Diacerein is a disease-modifying agent indicated for osteoarthritis management with enhanced performance and have much lower side effects profile than conventional non-steroidal anti-inflammatory drugs. Oral administration of Diacerein is associated with a laxative effect , thus causing treatment discontinuation. Aim: This study aimed to evaluate the activity of Diacerein novasome-based transdermal gel compared with standard oral treatment in the management of induced osteoarthritis in a rat model. Materials and methods: A single intra-articular injection of monosodium iodoacetate was administered to the left knee joint, resulting in the development of Osteoarthritis. Disease progression and the effect of both routes of Diacerein treatment were evaluated by morphological, biochemical, histological, and radiological studies. Results: Osteoarthritis was successfully induced in rats’ knee joints. Morphological studies revealed that both Diacerein treatments significantly reduced joint swelling as compared to the untreated group. The serum TNF-α and IL-1β levels were significantly lower in both Diacerein treatment groups as compared to the untreated group throughout the course of the study. Histological and radiological findings confirmed that transdermal Diacerein treatment protects against cartilage degradation like oral treatment. Conclusion: Novasomal technology proved its efficacy as a carrier for the transdermal delivery of Diacerein. The in-vivo study on an animal model of osteoarthritis showed that Diacerein transdermal gels provided sufficient pharmacological activity for the attenuation of the disease. This finding could support its use as an alternative to the standard oral treatment to avoid side effects.

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Research Article Tue, 21 Nov 2023 10:25:55 +0200
Analysis of the pharmacotherapeutic effectiveness of the tyrosine kinase inhibitors therapy in patients with Chronic Myeloid Leukemia in a single hematology center in Plovdiv, Bulgaria https://pharmacia.pensoft.net/article/111923/ Pharmacia 70(4): 1355-1362

DOI: 10.3897/pharmacia.70.e111923

Authors: Veselina Goranova-Marinova, Daniela Grekova, Vania Georgieva, Kalina Andreevska, Yana Gvozdeva, Margarita Kassarova, Zhanet Grudeva-Popova

Abstract: Aim. The aim of this study is to evaluate treatment retrospectively, response to the therapy and outcomes in patients with chronic myeloid leukemia (CML) and to what extent the European recommendations of LeukemiaNET (ELN) are followed at the Hematology Clinic, University Hospital “St. Georgi”, MU Plovdiv. Methods. All patients with Ph+, BCR-ABL1+ CML who were treated and observed between 01.01.2018 and 12.31.2022 at the clinic were included in the study and were analyzed retrospectively. Results. One hundred and eighty-eight patients with a mean age of 61.26 (21–91) years were analyzed. 151 (80.3%) were in chronic phase (CP), 27 (14.4%) in accelerating one and 10 (5.3%) in blast crisis. The actual overall survival rate was 79.26%, while for CP it is very high – 86.75%, and the mortality rate is 20.74%. All patients received some form of tyrosine kinase inhibitors therapy (TKIs-therapy). The first line TKI was imatinib in 120 patients (64%), and 68 (36%) received a second-generation TKI. Treatment response was monitored with TKIs by RT-qPCR. Conclusion. CML patients treated in the hematology clinic receive standard care in accordance with ELN and BMSH recommendations. Overall survival (OS) in routine care is comparable to published data from international studies. Molecular monitoring provides a good basis for disease control in CP. There are unmet needs in the treatment of patients in advanced stages.

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Research Article Tue, 21 Nov 2023 10:24:08 +0200