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INFECTIOUS DISEASES / RESEARCH PAPER
Antiviral flavonoids- and polyphenols-driven novel anti-HBV efficacy of Ilex paraguariensis
1
School of Biotechnology, IFTM University, Moradabad, India
2
Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
Submission date: 2024-01-11
Final revision date: 2024-03-28
Acceptance date: 2024-05-16
Online publication date: 2024-06-06
Corresponding author
Mohammad K. Parvez
Department of Pharmacognosy College of Pharmacy King Saud University Riyadh 11451, Saudi Arabia
Department of Pharmacognosy College of Pharmacy King Saud University Riyadh 11451, Saudi Arabia
KEYWORDS
TOPICS
ABSTRACT
Introduction:
Antiviral natural products have shown great promise as alternatives to conventional therapies to address drug resistance in hepatitis B virus (HBV). The abundance of bioactive flavonoids and polyphenolic contents in leaves of Ilex paraguariensis (yerba mate) warrants assessment of its anti-HBV activity.
Material and methods:
The total ethanol extract of I. paraguariensis leaves (IP-Ext), including its n-hexane (IP-Hex), chloroform (IP-Chl), ethyl acetate (IP-EtAc) and ethanol (IP-EtOH) fractions, was tested for non-hepatocytotoxicity on HepG2 cells (MTT assay) and anti-HBV efficacy on HepG2.2.15 cells (ELISA). Further, quantitative high-performance liquid chromatography (HPLC) was employed to identify the antiviral compounds in the extract. In addition, in silico molecular docking was performed to delineate the possible mechanism of anti-HBV activity of the identified compounds.
Results:
All samples showed non-cytotoxicity except IP-EtAc, with mild toxicity at 200 g/ml. Their anti-HBV assessment showed dose-dependent inhibitions of HBV antigens (HBsAg and HBeAg). At the selected optimal dose (50 g/ml), while IP-Ext showed mild (HBsAg: 24.2% and HBeAg: 20.6%) and IP-Chl showed moderate (HBsAg: 42.3% and 40.1%) activity, IP-Hex (HBsAg: 55.6% and HBeAg: 52.4%) and IP-EtOH (HBsAg: 53.2% and HBeAg: 50.2%) exhibited high activity. HPLC revealed known anti-HBV flavonoids (rutin: 18.98, quercetin: 6.52 and kaempferol: 9.10 g/g) and polyphenols (caffeic acid: 11.43 and chlorogenic acid: 3.22 g/g) in the extract. Their (10 g/ml, each) anti-HBV activities were: quercetin (HBsAg: 67.8% and HBeAg: 64.4%), kaempferol (HBsAg: 63.5% and HBeAg: 61.6%), chlorogenic acid (HBsAg: 55.2% and HBeAg: 53.8%), rutin (HBsAg: 51.2% and HBeAg: 48.4%) and caffeic acid (HBsAg: 42.2% and HBeAg: 39.5%). Notably, while our previous molecular docking had shown strong interactions of these flavonoids with HBV polymerase, here, we observed good binding affinity of the polyphenols with both drug-sensitive (wild-type) and drug-resistant (mutant) polymerases.
Conclusions:
This is the first study suggesting the anti-HBV therapeutic efficacy of I. paraguariensis attributed to its antiviral flavonoids and polyphenols.
Antiviral natural products have shown great promise as alternatives to conventional therapies to address drug resistance in hepatitis B virus (HBV). The abundance of bioactive flavonoids and polyphenolic contents in leaves of Ilex paraguariensis (yerba mate) warrants assessment of its anti-HBV activity.
Material and methods:
The total ethanol extract of I. paraguariensis leaves (IP-Ext), including its n-hexane (IP-Hex), chloroform (IP-Chl), ethyl acetate (IP-EtAc) and ethanol (IP-EtOH) fractions, was tested for non-hepatocytotoxicity on HepG2 cells (MTT assay) and anti-HBV efficacy on HepG2.2.15 cells (ELISA). Further, quantitative high-performance liquid chromatography (HPLC) was employed to identify the antiviral compounds in the extract. In addition, in silico molecular docking was performed to delineate the possible mechanism of anti-HBV activity of the identified compounds.
Results:
All samples showed non-cytotoxicity except IP-EtAc, with mild toxicity at 200 g/ml. Their anti-HBV assessment showed dose-dependent inhibitions of HBV antigens (HBsAg and HBeAg). At the selected optimal dose (50 g/ml), while IP-Ext showed mild (HBsAg: 24.2% and HBeAg: 20.6%) and IP-Chl showed moderate (HBsAg: 42.3% and 40.1%) activity, IP-Hex (HBsAg: 55.6% and HBeAg: 52.4%) and IP-EtOH (HBsAg: 53.2% and HBeAg: 50.2%) exhibited high activity. HPLC revealed known anti-HBV flavonoids (rutin: 18.98, quercetin: 6.52 and kaempferol: 9.10 g/g) and polyphenols (caffeic acid: 11.43 and chlorogenic acid: 3.22 g/g) in the extract. Their (10 g/ml, each) anti-HBV activities were: quercetin (HBsAg: 67.8% and HBeAg: 64.4%), kaempferol (HBsAg: 63.5% and HBeAg: 61.6%), chlorogenic acid (HBsAg: 55.2% and HBeAg: 53.8%), rutin (HBsAg: 51.2% and HBeAg: 48.4%) and caffeic acid (HBsAg: 42.2% and HBeAg: 39.5%). Notably, while our previous molecular docking had shown strong interactions of these flavonoids with HBV polymerase, here, we observed good binding affinity of the polyphenols with both drug-sensitive (wild-type) and drug-resistant (mutant) polymerases.
Conclusions:
This is the first study suggesting the anti-HBV therapeutic efficacy of I. paraguariensis attributed to its antiviral flavonoids and polyphenols.
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