Review Article |
Corresponding author: Sophi Damayanti ( sophi.damayanti@gmail.com ) Academic editor: Paraskev Nedialkov
© 2022 Anjar Hermadi Saputro, Aluicia Anita Artarini, Daryono Hadi Tjahjono, Sophi Damayanti.
This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Citation:
Saputro AH, Artarini AA, Tjahjono DH, Damayanti S (2022) The long and stumble way to find potential active compounds from plants for defeating hepatitis B and C: review. Pharmacia 69(3): 699-708. https://doi.org/10.3897/pharmacia.69.e85160
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Hepatitis is a liver illness caused by virus such as hepatitis A virus, hepatitis B virus and hepatitis C virus. Hepatitis B and C are considerably more usual and induce more cirrhosis and dead worldwide than hepatitis A. Although drugs that are currently often used in the medication of hepatitis B and C, the finding of recent drug from various resources including herbal has been intensively developed. Therefore, the purpose of this review is to consider the possibility of plant’s compounds as anti-HBV and anti-HCV. From the results of a review of several articles, several plant’s compound have shown effectiveness againts HBV and HCV by in silico, in vitro and in vivo studies. In conclusion, several plant’s active compounds are possibility to be developed as anti-hepatitis B and C.
plant’s active compound, anti-HBV, anti-HCV
Hepatitis is an inflammatory liver disease which is a solemn infectious illness in the world. Hepatitis can progress to liver cancer and cirrhosis. Hepatitis B and C are types of hepatitis that can usually develop into chronic hepatitis, cirrhosis or liver cancer. The cause of hepatitis A is the picornaviridae family virus that is hepatitis A virus (HAV) while the cause of hepatitis B is the hepatitis B virus (HBV) including the DNA virus of the hepadnavirus family and the cause of hepatitis C is the hepatitis C virus (HCV) which belongs to the flaviviridae family that is an enveloped virus (
Based on WHO data, the case of hepatitis B is quite elevated in the worldwide. Some places in Asia, Africa and the Pacific shave the highest prevalence of HBV. Drugs that are presently often used in the medication of hepatitis B are the nucleoside or nucleotide group and the interferon group (
Hepatitis C also has been spread over the globe, approximately beyond than 180 million humans have been infected by hepatitis virus C (
This review article is supposed to provide scientific explanation about the active compounds in plants that have the potential as antiviral of hepatitis B or C using in silico, in vivo and also in vitro testing methods.
In this review article the data presented is based on data collection in the form of journals and scientific articles both national and international journals or scientific articles obtained from search results online by entering the keywords “anti-HBV”, “anti-HCV”, “anti-hepatitis B virus” and “anti-hepatitis C virus” in Science Direct, Elsevier, Research Gate, and Google Scholar, then after scientific journals are collected, conducted screening of scientific journals that have relevance to the antiviral of plants compounds for the last 10 years (2012–2022).
It is guess that beyond than 350 million humans with hepatitis B are caused by infection with the HBV in the world, where it is estimated that deaths from HBV infection reach more than 750,000 deaths per year so that hepatitis B is a top priority to be overcome in the world. Although there is a vaccine to prevent HBV, the role of the community is very important in preventing the transmission of hepatitis B. In addition, the use of interferon alpha drugs has been widely applied to treat hepatitis B, the usage of this drugs has unwanted side effects for patients (
Hepatitis C virus (family flaviviridae) is one of RNA virus. The proteins involved in the existence cycle of HCV are non-structural proteins (NS2, NS3, NS4A, NS4B, NS5A, NS5B), proteins C, E (1 and 2), and p7. The proteins C, E1, E2, and p7are used to infect host cells so commonly called with infectious particles in viruses, while non-structural proteins are used in the multiply process. Non-structural proteins and RNA of the virus are found in the liver because replication of the virus occurs in there (
About 80% of humans with acute hepatitis C will develop into chronic. Sex factors, age, asymptomatic, obesity, ethnics, HIV disease, immunosuppression conditions, alcohol, and diabetes being points that can escalate the risk of becoming chronic (
Detection of acute hepatitis C can be made if anti-HCV of patient is positive, due to the absence of serological markers that can indicate acute infection of hepatitis C virus. Although 80% of acute hepatitis C infections are symptom-free, if a person with appropriate symptoms for example alanine aminotransferase (ALT) higher than 10 times from the normal limit value without a history of hepatitis, it can be suspected as hepatitis C acute (
Hepatitis C patients should check the amount of hepatitis C virus RNA before receiving drug therapy in IU/mL units using real-time PCR technique. Genotype examination is needed to assign the duration of medication, therapeutic regimen and determine various techniques such as sequence analysis, hybrization and PCR. Currently the examination of 6 genotypes in chronic hepatitis C infection can be accurately identified (
Treatment of HBV infection uses various drugs, one of which is tenofovir which is commonly prescribed to pregnant women infected with HBV (
Recuperation of hepatitis C is often focus on the chronic condition. In chronic hepatitis C therapy can be given antivirals in order to avoid the emergence of complications of cancer in the liver, death, and HCC (hepatocellular carcinoma). The target of antiviral therapy is SVR (Sustained Virological Response) so that the presence of RNA of hepatitis C virus should be checked. Antiviral administration of hepatitis C using an amalgam of DAA regimen (Direct Acting Antiviral) can achieve SVR12 more than 90% in all genotypes in people with chronic hepatitis C and consumption of Peg-IFN and ribavirin (
Most of hepatitis C treatments using DAA drugs nowdays. The first generation DAA is boceprevir. There are many new generations of DAA such as simeprevir, sofosbuvir, elbasvir, ledipasvir, daclatasvir, and grazoprevir. This new generations of DAA has several advantages, such as give higher SVR12 number than interferon drugs, available in oral preparations and has minimal side effects with shorter duration of treatment (
The mechanism of work of each drug in hepatitis C therapy varies with the drug itself. The mechanisms of drugs in hepatitis C therapy are:
Patients who have chronic cirrhosis liver may be given antiviral as long as there are no contraindications. This aims to achieve SVR12 and reduce the incidence of various complications due to liver cancer (cirrhosis of the liver). Some existing studies show the achievement of SVR12 in patients with compensatory liver cirrhosis decreases the incidence of hepatocellular carcinoma and decompensated liver cancer. However, people with hepatitis C with cirrhosis have a lower chance of achieving SVR12 (
Because of cirrhosis patient usually have hypertension, hypersplenism, low platelet, low leucocyte level and also side effects of drugs so that intense monitoring should be done during therapy (
The following is a table (Table
Active compounds present in plants that have been studied to have anti-HBV and anti-HCV activity.
Active Compounds | Plant’s Name | Test Method | Anti-HBV / Anti-HCV | References |
---|---|---|---|---|
1,2,3,4,6-Pentagalloyl glucose | Terminalia Chebula | in silico | Anti-HCV | ( |
3-hydroxy caruilignan C | Swietenia Macrophylla | in vitro | Anti-HCV | ( |
4-pyridone glucoside and polyacetylene glucoside | Artemisia scoparia | in vitro | Anti-HBV | ( |
8-epi-kingiside (8-Epik) | Jasminum officinale var. grandiflorum | in vitro, in vivo | Anti-HBV | ( |
Alkaloids and polysaccharides (SFP-100) | Sophora flavescens | in vitro, in vivo | Anti-HBV | ( |
Alkaloids, lectins and polysaccharides | Viscum coloratum | in vitro | Anti-HBV | ( |
Apigenin | Plants that contain apigenin compound | in vitro | Anti-HCV | ( |
APS | Maytrenus ilicifolia | in vitro | Anti-HCV | ( |
Azadirachtin | Plants that contain azadirachtin compound | in silico | Anti-HBV | ( |
Baccatin III | Plants that contain baccatin III compound | in silico | Anti-HBV | ( |
Caffeine | Plants that contain caffeine compound | in vitro | Anti-HCV | ( |
Chebulagic Acid | Terminalia Chebula | in silico | Anti-HCV | ( |
Curcumin | Plants that contain curcumin compound | in vitro | Anti-HBV | ( |
Delphinidin | Plants that contain delphinidin compound | in vitro | Anti-HCV | ( |
Detarium microcarpum stem extract | Detarium microcarpum (Caesalpinaceae) | in vitro | Anti-HCV | ( |
Dimocarpus longan extract | Dimocarpus longan (Sapindaceae) | in vitro | Anti-HCV | ( |
Embelia ribes root extract | Embelia ribes (Primulaceae) | in vitro | Anti-HCV | ( |
Embelin | Plants that contain embelin compound | in silico | Anti-HBV | ( |
Ent-cauranoid (1 and 2) and ent-cauranoid type diterpenoids | Rabdosia japonica | in vitro | Anti-HBV | ( |
Epigallocatechin-3-gallate | Camellia sinensis | in vitro | Anti-HCV | ( |
Epigallocatechin gallate (EGCG) | Plants that contain EGCG compound | in silico | Anti-HCV | ( |
Ficus fistula leaves extract | Ficus fistula (Moraceae) | in vitro | Anti-HCV | ( |
Flavonoid | Cudrania cochinchinensis or C. tricuspidata, Acanthus ilicifolius, Phyllodium pulchellum | in vitro and in vivo | Anti-HBV | ( |
Gallic Acid | Limonium sinense | in vitro | Anti-HCV | ( |
Garcinia mangostana L fruit peels extract | Garcinia mangostana L (Clusiaceae) | in vitro | Anti-HCV | ( |
Glycosides longumoside A and B | Piper longum | in vitro | Anti-HBV | ( |
Glycyrrhiza uralensis root extract | Glycyrrhiza uralensis (Fabaceae) | in vitro | Anti-HCV | ( |
Griffithsin | Griffithsia sp | in vitro | Anti-HCV | ( |
Hesperidin | Plants that contain hesperidin compound | in silico | Anti-HBV | ( |
Honokiol | Magnolia Officiais | in vitro | Anti-HCV | ( |
Ladanein | Marrubium peregrinum L | in vitro | Anti-HCV | ( |
Ladanein | Plants that contain ladanein compound | in silico | Anti-HCV | ( |
Ligustrum lucidum fruit extract | Ligustrum lucidum (Oleaceae) | in vitro | Anti-HCV | ( |
Limonium sinense root extract | Limonium sinense (Plumbaginaceae) | in vitro | Anti-HCV | ( |
Lupeol | Plants that contain lupeol compound | in silico | Anti-HBV | ( |
LPRP-Et-97543 | Liriope platyphylla | in vitro | Anti-HBV | ( |
Melanolepis multiglandulosa stem extract | Melanolepis multiglandulosa (Euphorbiaceae) | in vitro | Anti-HCV | ( |
Melicope latifolia leaves extract | Melicope latifolia (Rutaceae) | in vitro | Anti-HCV | ( |
Menisdaurin | Plants that contain menisdaurin compound | in silico | Anti-HBV | ( |
Monoterpenes, (japopenoid A, B, C, and caffeoliquinic acid derivatives | Lonicera japonica | in vitro | Anti-HBV | ( |
Morinda citrifolia leaves extract | Morinda citrifolia (Rubiaceae) | in vitro | Anti-HCV | ( |
Naringenin | Plants that contain naringenin compound | in silico | Anti-HCV | ( |
Niranthin and nirtetralin B | Phyllanthus niruri. L | in vitro and in vivo | Anti-HBV | ( |
Norbisabolan sesquiterpenes | Phyllantus acidus | in vitro | Anti-HBV | ( |
Oxymatrine (OMT) | Sophora tonkinensis Gagnep | in vivo | Anti-HBV | ( |
Phenolic compound, organic acid and terpenoids | Boehmeria nivea | in vitro | Anti-HBV | ( |
Phyllanthin, ellagic acid and hypophyllanthin | Phyllanthus rheedei | in vitro | Anti-HBV | ( |
Pinus massoniana bark extract | Pinus massoniana (Pinaceae) | in vitro | Anti-HCV | ( |
Platycodon grandiflorum root extract | Platycodon grandiflorum (Campanulaceae) | in vitro | Anti-HCV | ( |
Plumbagin | Plumbago indica L. | in vitro | Anti-HCV | ( |
Polysaccharides | Isatis indigotica Fortune | in vitro | Anti-HBV | ( |
Polysaccharides | Saussurea laniceps | in vitro | Anti-HBV | ( |
Pragmanthera capitata leaves extract | Pragmanthera capitata (Loranthaceae) | in vitro | Anti-HCV | ( |
Psoralen | Plants that contain Psoralen compound | in silico | Anti-HBV | ( |
Quercetin | Embelia ribes | in vitro | Anti-HCV | ( |
Quercetin | Plants that contain quercetin compound | in silico | Anti-HBV | ( |
Quercetin and myricetin-3-O-rhamnoside | Guiera senegalensis | in vitro | Anti-HBV | ( |
Ruta angustifolia leaves extract | Ruta angustifolia (Rutaceae) | in vitro | Anti-HCV | ( |
Rutin | Plants that contain rutin compound | in silico | Anti-HBV | ( |
Saikosaponin b2 | Bupleurum kao | in vitro | Anti-HCV | ( |
Saponin | Abrus cantoniensis | in vitro and in vivo | Anti-HBV | ( |
Saponins (asiaticoside) | Hydrocotyle sibthorpioides Lam | in vitro and in vivo | Anti-HBV | ( |
Scytovirin | Scytonema varium | in vitro | Anti-HCV | ( |
Secoiridoid glycosides | Swertia cincta | in vitro | Anti-HBV | ( |
Sesquiterpenes | Cyperus rotundus | in vitro | Anti-HBV | ( |
Silibinin | Silybum marianum | in vitro | Anti-HCV | ( |
Silybin | Plants that contain Silybin compound | in silico | Anti-HCV |
|
Silymarin Extract | Silybum marianum | in vitro | Anti-HCV | ( |
Swertisin | Iris tectorum Maxim | in vitro, in vivo | Anti-HBV | ( |
Toona sureni leaves extract | Toona sureni (Meliaceae) | in vitro | Anti-HCV | ( |
Trichilia dregeana root extract | Trichilia dregeana (Meliaceae) | in vitro | Anti-HCV | ( |
Triterpenoid | Iris confusa | in vitro | Anti-HBV | ( |
Ursolic acid | Cynomorium Songaricium | in vitro | Anti-HCV | ( |
Xanthohumol | Humulus lupulus L | in vitro | Anti-HCV | ( |
β Sitosterol | Plants that contain β Sitosterol compound | in silico | Anti-HBV | ( |
From the table it can see that there are many plants that have anti-hepatitis B and C by in silico, in vivo and in vitro studies. The following are an explanation of the plant’s active compounds that have anti-hepatitis B and C activity.
4-pyridone glucoside and polyacetylene glucoside compounds contained in Artemisia scoparia extract in a experimentation run by
The compound 8-epi-kingiside (8-Epik) contained in Jasminum officinale var. Grandiflorum based on research by
Based on anti-hepatitis B research conducted by
The lectin compounds, polysaccharides and alkaloids contained in Viscum coloratum (Kom.) Nakai have anti-hepatitis B activity by in vitro test based on the research of
The curcumin compound has anti-hepatitis B activity based on a journal reported by
Based on experiment run by
Based on research conducted by
Several glycoside and alkaloid compounds contained in the 90% ethanol extract of Piper longum have anti-hepatitis B activity in vitro according to the research of
The compound LPRP-Et-97543 contained in 95% ethanol extract of Liriope platyphylla has anti-hepatitis B action based on research conducted by
Monoterpene group compounds, namely caffeoliquinic acid derivatives, japopenoids (Types A, B and C) contained in Lonicera japonica have anti-hepatitis B activity in vitro based on research conducted by
Niranthin and nirtetralin B compounds contained in Phyllanthus niruri have anti-hepatitis B action based on research conducted by
Based on experiment run by
Oxymatrine compounds contained in Sophora tonkinensis Gagnep have anti-hepatitis B activity in vivo based on research by
Based on the in vitro research of
Based on the in vitro research conducted by
Based on the in vitro research by
The polysaccharide compound SL-4 compounds in the 95% ethanol extract of Saussurea laniceps has anti-hepatitis B activity by in vitro test according to Chen et al. (2015) using Lamivudine as a control. In this study Saussurea laniceps can inhibit HBsAg by 32.81% and HBeAg by 60.75% at 500 μg/mL.
Quercetin and myrisetin-3-O-ramnoside compounds contained in the 96% ethanol extract of Guiera senegalensis have anti-hepatitis B activity by inhibiting HBsAg by 60% at 50 µg/mL based on research conducted by
The presence of soyasaponin Bb and soyasaponin Be compounds in Abrus cantoniensis Hance have anti-hepatitis B activity. Experiment run by
Based on research by
In vitro test, Secoiridoid glycosides group compounds, namely swertiasida, 9-epi swertiamarin, swericinctoside, swertianoside E contained in 90% ethanol extract of Swertia cincta have anti-hepatitis B activity based on research of
Another study reported by
The Swertisin compound contained in the 95% ethanol extract of Iris tectorum has anti-hepatitis B activity according to the research of
Based on the research of
There are many of plants active compound as anti-HCV have been reported. Griffithsin, Scytovirin, Saikosaponin b2, Ladanein, Delphinidin, Silibinin, root extract of Trichilia dregeana, stem extract of Detarium microcarpum, Embelia ribes root extract and Pragmanthera capitate leaves extract work as anti-HCV by inhibiting viral entry of hepatitis C virus. Then epigallocatechin-3-gallate, xanthone extract, 3-hydroxy caruilignan C, plumbagin, xanthohumol, apigenin, caffeine, APS, quercetin, ursolic acid, honokiol, silymarin extract have anti-HCV activity by inhibiting replication of HCV. On the other hand several plants extract also can inhibit HCV J6/JFH1 specifically such as Melanolepis multiglandulosa stem extract, Ruta angustifolia leaves extract, Glycyrrhiza uralensis root extract, leaves extract of Toona sureni, leaves extract of Melicope latifolia, leaves extract of Ficus fistula, Morinda citrifolia leaves extract with IC50 between 2.0 μg/mL to 17.1 μg/mL. (
Ligustrum lucidum fruit extract, Platycodon grandiflorum root extract, Garcinia mangostana L fruit peels extract, and Pinus massoniana bark extract can inhibit HCV replication. Limonium sinense root extract can also inhibit viral entry of HCV to the cell. Extract of Dimocarpus longan can also inhibit HCV (
In silico studies, experiment run by
Another study reported by
Based on research by
From the results of a review of several articles, it can be concluded that there are many active compounds in plants that potentially can be developed as anti-hepatitis B and C. Although there is a need for further research related to the anti-hepatitis B and C activities of plant’s active compounds, the development and discovery of active compounds from plants as an alternative to anti-hepatitis B and C must always be explored.
We are thankful for the financial support by Ganesha Talent Assistantship-Research Group Scholarship ITB, School of Pharmacy ITB and University Center of Excellence on Artificial Intelligence for Vision, Natural Language Processing & Big Data Analytics (U-CoE AI-VLB) ITB.
This study has no conflict of interest.