Resveratrol mitigates oxidative stress and suppresses HBV replication via modulation of the SIRT1-Nrf2 pathway in liver cells

Hepatitis B virus (HBV) infection induces oxidative stress, contributing to liver injury and promoting viral replication through elevated reactive oxygen species (ROS). Resveratrol (RES), a polyphenolic antioxidant, has shown antioxidant and antiviral properties, but its role in modulating the SIRT1-Nrf2 axis under oxidative stress remains unclear. This study investigates RES’s effects on oxidative stress pathways and HBV replication, emphasizing SIRT1-Nrf2 regulation as a potential therapeutic target. LO-2 and HepG2 cells were treated with H₂O₂ (300–1000 μM) with or without RES (50 μM). Cell viability (MTT), SIRT1/pNrf2 expression, ROS/MDA levels, and HBV markers (HBc protein, HBV DNA) were analyzed. Confocal microscopy assessed SIRT1 and pNrf2 localization. RES improved cell viability, upregulated SIRT1, promoted Nrf2 phosphorylation/nuclear translocation, and enhanced antioxidant defenses. It significantly reduced ROS/MDA levels and suppressed HBV replication by decreasing HBc protein and HBV DNA (<i>p</i> &lt; 0.05), indicating an oxidative stress-dependent antiviral effect. RES mitigates oxidative stress and suppresses HBV replication via SIRT1-Nrf2 modulation, offering a novel therapeutic strategy for HBV-related liver damage.