Antioxidants are natural or chemical compounds that can prevent oxidative stress and scavenge free radicals. Oxidative stress arises from an imbalance between free radicals and antioxidants in our bodies (Islam 2006). While our bodies can produce natural antioxidants, they may not be sufficient to inactivate all free radicals. Therefore, additional antioxidants from external sources, such as plants and vegetables that are rich in antioxidants, are necessary. Allium cepa is one such plant known to possess compounds with antioxidant activity, which has attracted the interest of many researchers.

Commonly used antioxidant testing methods include 2,2’-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH), Fe²⁺ chelating activity, ferric-reducing antioxidant power assay (FRAP), H2O2 radical scavenging activity, and Trolox equivalent antioxidant activity (TEAC) method. Each method has its own advantages and disadvantages, and the choice of method depends on the study objectives, availability of resources, physical and chemical properties of the samples, sample size, and other relevant factors.

Kumar et al. (2013) reported that the aqueous extract of A. cepa exhibited antioxidant potency with an IC₅₀ value of 195.2 ± 0.2 µg/mL. Another study by Fredotovic et al. (2017) investigated the methanolic extract of A. cepa and reported a DPPH scavenging percentage of 64.82% at a sample concentration of 100 µg/mL. Antioxidant activity was also tested on the essential oil derived from A. cepa, with a reported IC₅₀ value of 630 µg/mL for DPPH (Ye et al. 2013). Furthermore, the IC₅₀ value of total polyphenols in onions for DPPH testing was found to be 43.24 µg/mL (Ouyang et al. 2018).

Essential oils are typically found in nonpolar extracts, while polyphenols are usually present in semi-polar extracts. Previous research has reported that semi-polar to polar solvent extracts exhibited lower IC₅₀ values compared to nonpolar solvent extracts.

Sidhu et al. (2019) conducted a study to investigate the antioxidant activity of various layers of A. cepa (Egyptian red onion) bulbs, including the outer, middle, and inner layers. The results showed that the outermost layer had the highest concentration of antioxidant compounds compared to the other layers, with a Trolox equivalent antioxidant activity (TEAC) value of 2457.0 mmol/100 g. This may be attributed to the outermost layer being more exposed to external factors such as plant pests and climate changes, which stimulate the production of secondary metabolites in plants.

While the bulb of A. cepa is commonly used, the peel of A. cepa also has potential as a medicinal component. Although the peel is not typically consumed by humans and is often discarded as waste, Masood et al. (2023) were interested in studying the antioxidant activity of the peel in comparison to the bulb of A. cepa. The results showed that the ethanolic extract of the peel exhibited higher antioxidant activity than the ethanolic extract of the bulb, as determined by ABTS, DPPH, FRAP, Fe²⁺ chelating activity, and H2O2 radical scavenging activity. Therefore, it can be concluded that all parts of A. cepa have the potential to serve as a source of antioxidants.

Antioxidant activity is often associated with phenolic compounds, which contain a hydroxyl group (OH) directly bonded to a phenyl group. A. cepa is known to contain quercetin, iso-quercitrin, and gallic acid. Correlation analysis between antioxidant activity and total phenolic content (TPC) has shown a statistically positive relationship. Higher TPC values correspond to increased antioxidant activity (Muflihah et al. 2021). Antioxidant activity is also influenced by the flavonoid group. Higher total flavonoid content (TFC) leads to increased antioxidant activity, which can be attributed to the position of the OH groups on the flavonoid structure. The presence of a hydroxyl group at the 3-OH position on ring B, as well as ortho-hydroxy groups on rings A and B, positively affect the activity (Treml and Smejkal 2016; Fitriansyah et al. 2022).

Based on the data presented in Table 2, it appears that the polyphenol compounds responsible for this activity include quercetin 3-glucoside, quercetin 4’-glucoside, quercetin 3,4’-diglucoside, quercetin 7,4’-diglucoside, isorhamnetin 4’-galactoside, quercetin 3,7,4’-triglucoside, isorhamnetin 3,4’-diglucoside, isorhamnetin 4’-glucoside, and iso-quercitrin.

Erukainure et al. (2021) demonstrated the cytotoxic effects of the ethyl acetate extract of A. cepa yellow var. on normal human embryonic kidney cells (HEK293). The GC-MS analysis of the ethyl acetate extract revealed the presence of phytol acetate, pentadecanoic acid, and allyl ionone as the predominant fatty acids, while campesterol, cycloartenol-3β acetate, ergost-7-en-3β-ol, fucosterol, and sitosterol were identified as the predominant sterols.

Diabetes mellitus is a major health problem worldwide. Several researchers have reported an association between phenolic compounds in herbs and plants and their α-glucosidase inhibitory activity and antioxidant activity (Kwon et al. 2006). Diabetes is characterized by hyperglycemia, increased production of free radicals, and predisposition to oxidative stress, leading to diabetes complications (Masood et al. 2023).

Supplementation of bread with 1% and 3% peel extract of A. cepa powder and 7% onion has been shown to reduce blood sugar and malondialdehyde (MDA) levels in diabetic rats after eight weeks of treatment. Moreover, A. cepa supplementation significantly improved antioxidant enzyme activity in treated diabetic rats (Masood et al. 2021). Another study investigated the α-glucosidase inhibitory activity of the ethanolic extract of A. cepa bulbs and peels, which demonstrated a reduction in blood glucose levels by decreasing glucose absorption rate. The ethanolic extract of A. cepa peels exhibited 80% inhibition of α-glucosidase activity (Masood et al. 2023).

Obesity is defined as a significant increase in body weight or body mass index (BMI) (Novelli et al. 2007; Amin and Nagy 2009). A. cepa contains flavonoids and saponins that are associated with a pancreatic lipase inhibitory effect (Marelli et al. 2022). According to the study by Marelli et al. (2022), A. cepa inhibits the hydrolysis of lipid esters and exhibits a protective effect against phospholipases through the action of active intermolecular molecules. A. cepa also contains secondary metabolites such as squalene, which inhibits cholesterol biosynthesis by inhibiting 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase in the liver (Ibrahim et al. 2020). Administration of 10% and 20% A. cepa leaf extracts resulted in decreased levels of triglycerides, total cholesterol, VLDL cholesterol, and LDL cholesterol (Momoh et al. 2022). Li et al. (2020) reported that A. cepa extract at a dose of 4.5 g/kg body weight showed potential as an antihyperlipidemic agent. A. cepa is rich in quercetin and isoquercitrin, which are known to be responsible for the antihyperlipidemic effect.

Tyrosinase inhibitory activity was tested using L-DOPA or L-tyrosinase, with IC₅₀ values of 52.7 μM and 4.3 μM, respectively (Arung et al. 2011a). The study reported that quercetin 4’-O-β-D-glucopyranoside, isolated from the dry skin of A. cepa, is responsible for this activity. The results indicate that dried red onion peel contains skin-whitening ingredients with anti-tyrosinase activity. Arung et al. (2011b) also reported that the methanol extract of dry skin from A. cepa contains quercetin-3’-O-β-D-glucoside, which can inhibit melanogenesis in B16 melanoma cells with an IC₅₀ value of 38.8 μM.

Bacterial pathogens, such as Bacillus cereus, Escherichia coli, Klebsiella pneumoniae, Mycobacterium tuberculosis, Pseudomonas aeruginosa, Salmonella typimurium, Staphylococcus aureus, and Streptococcus pneumoniae, are microorganisms that can cause mild to severe infections and are responsible for numerous deaths (GBD 2019 Antimicrobial Resistance Collaborator 2022). Antibacterial agents are substances that can kill or inhibit the growth of bacterial pathogens, thereby minimizing their pathogenic effects (Kenawy 2001). Antibacterial testing can be conducted using various methods, including agar diffusion and dilution/microdilution methods. The diffusion method can utilize disk paper or well method to determine the capability of a sample to inhibit bacterial growth by comparing the results with existing antibiotics. On the other hand, the dilution/microdilution method is used to assess the potency of a sample as an antibacterial agent (Balouiri et al. 2016).

Methanol skin extract of various A. cepa variants, obtained through sonication-assisted extraction, has shown potential as an antimicrobial agent, particularly against Gram-negative bacteria such as S. typimurium and Gram-positive bacteria such as B. cereus (Sagar and Pareek 2020). These findings align with the results reported by Fredotović et al. (2021), who demonstrated the antimicrobial activity of waste extract from A. cepa L, with MIC values of 500 µg/mL against MRSA (multidrug-resistant S. aureus), S. pyogenes, and B. cereus . In a study by Yousufi (2012), the antibacterial activity of ethanol, chloroform, and aqueous extracts of A. cepa was evaluated using the Kirby-Bauer method, which showed inhibition zone diameters of more than 11 mm against E. coli and K. pneumoniae.

Ethanol extract of A. cepa at a concentration of 150 mg/mL exhibited antibacterial activity, inhibiting E. coli, S. aureus, and P. aeruginosa with inhibition zone diameters of 10 mm, 14 mm, and 9 mm, respectively (Oyawoye et al. 2022). Another study demonstrated that the extract of fresh A. cepa resulted in inhibition zone diameters of 20 mm, 17 mm, and 15 mm against S. pyogenes, S. aureus, and E. coli, respectively (Shinkafi et al. 2013).

In a study by Heidary et al. (2022), A. cepa exhibited potential as a phytomedicine capable of inhibiting C. albicans and suppressing major fungal virulence factors. Sittisart et al. (2017) demonstrated that an A. cepa extract from Thailand, at a concentration of 80%, had antifungal activity against the mycelial growth of the pathogenic fungus, Phomopsis spp.

Furthermore, other research reported that A. cepa extract exhibited inhibitory effects against multidrug-resistant bacteria, including multi-drug resistant S. aureus (MRSA) (Fredotović et al. 2021). Kyung (2012) conducted a study showing that A. cepa extract possessed antibacterial activity against multi-drug resistant M. tuberculosis. In addition, Ahmadi et al. (2018) reported that A. cepa showed potential as an antiviral agent against avian influenza subtype H9N2, reducing mortality and possibly inhibiting the propagation of the virus in chicken egg embryos.

Sato et al. (2015) was reported that A. cepa have a potency as a antiallergic activity for type I hypersensitive, with IC₅₀ value is a 20.8 µg/mL. From the correlation coeffecient between antiallergic activities and HPLC chromatogram constituent from A. cepa noted that quercetin 4’-glucoside has a highly-positive correlation with the antiallergic activities.

The effect of anti-inflammatory testing was done by carrageenan-induced with experimental animals. Oyewusi et al. (2021) were reported that 200 mg/kg methanol extract of A. cepa bulb, showed inhibition of inflammatory activity 62.50% on 30 min, which significantly higher than indomethacin (15.63%) at 10 mg/kg.

Ghorani et al. (2018) reported that the activity of the water-ethanol extract of A. cepa (with three concentrations of 0.175, 0.35, and 0.7 mg/mL) on tracheal response, pneumonia cells and levels phospholipase A2 (PLA2) levels in bronchoalveolar fluid (BALF) of rats with asthma have been tested. A. cepa at any concentration was able to reduce the total white blood cell count (WBC) and PLA2 levels compared with the asthmatic group. Decreased tracheal reactivity has been shown with extracts of A. cepa at concentrations of 0.35 and 0.7 mg/mL. Meanwhile, the effect of reducing the number of monocytes compared with the asthmatic group was demonstrated by the A. cepa extract with the highest concentration (0.7 mg/mL). So, from this report A. cepa was potential for asthma treatment.

Sato et al. (2015) reported that A. cepa exhibits potential as an antiallergic agent for type I hypersensitivity, with an IC₅₀ value of 20.8 µg/mL. The correlation coefficient analysis between antiallergic activities and HPLC chromatogram constituents from A. cepa indicated a highly positive correlation between quercetin 4’-glucoside and the antiallergic activities.

The anti-inflammatory effect was evaluated using carrageenan-induced inflammation in experimental animals. Oyewusi et al. (2021) reported that the methanol extract of A. cepa bulb at a dose of 200 mg/kg showed a 62.50% inhibition of inflammatory activity after 30 minutes, which was significantly higher than that of indomethacin (15.63%) at a dose of 10 mg/kg.

Ghorani et al. (2018) conducted a study to evaluate the activity of a water-ethanol extract of A. cepa (at concentrations of 0.175, 0.35, and 0.7 mg/mL) on tracheal response, pulmonary cells, and phospholipase A2 (PLA2) levels in bronchoalveolar fluid (BALF) of rats with asthma. The A. cepa extract at all concentrations was able to reduce the total white blood cell count (WBC) and PLA2 levels compared to the asthmatic group. Decreased tracheal reactivity was observed with A. cepa extracts at concentrations of 0.35 and 0.7 mg/mL. Moreover, the highest concentration of A. cepa extract (0.7 mg/mL) demonstrated a significant reduction in the number of monocytes compared to the asthmatic group. Therefore, based on this report, A. cepa shows potential for the treatment of asthma.

The antiplatelet activity was assessed using a turbidimetric assay, and the extent of aggregation was measured using the Lumi-aggregatometer. The methanol extract of A. cepa bulb demonstrated potency as an antiplatelet agent. Ko et al. (2018) reported that the activity of antiplatelet agents is affected by flavonols such as quercetin and quercetin glucosides. Quercetin showed a significant effect against platelet aggregation compared to its glucosides. However, the combination of quercetin and its glucosides was found to be more effective than quercetin alone. The exact mechanism of this synergistic effect is still unknown (Ko et al. 2018).