The anti-hepatitis B virus therapeutic potential of anthraquinones derived from Aloe vera.

ABSTRACT

Although the approved hepatitis B virus (HBV)-polymerase inhibitors (e.g., lamivudine) often lead to drug-resistance, several natural products have shown promising efficacies. Though Aloe vera (AV) gel and its constituents are shown inhibitors of many viruses, their anti-HBV activity still remains elusive. We therefore, tested the anti-HBV potential of AV extract and its anthraquinones in hepatoma cells, including molecular docking, high-performance thin layer chromatography (HPTLC), and cytochrome P450 (CYP3A4) activation analyses. Our anti-HBV assays (HBsAg/HBeAg Elisa) showed maximal inhibition of viral antigens production by aloe-emodin (~83%) > chrysophanol (~62%) > aloin B (~61%) > AV extract (~37%) in HepG2.2.15 cells. Interestingly, the effect of aloe-emodin was comparable with lamivudine (~86%). Moreover, sequential treatment with lamivudine (pulse) followed by aloe-emodin (chase) enhanced the efficacy of monotherapy by ~12%. Docking (AutoDock Vina) of the anthraquinones indicated strong interactions with HBV-polymerase residues that formed stable complexes with high Gibbs's free energy. Further, identification of aloe-emodin and aloin B by validated HPTLC in AV extract strongly endorsed its anti-HBV potential. In addition, our luciferase-reporter gene assay of transfected HepG2 cells showed moderate induction of CYP3A4 by aloe-emodin. In conclusion, this is the first report on anti-HBV potential of AV-derived anthraquinones, possibly via HBV-polymerase inhibition. Of these, although aloin B exhibits novel antiviral effect, aloe-emodin appears as the most promising anti-HBV natural drug with CYP3A4 activating property towards its enhanced therapeutic efficacy.