Procyanidin B2 Ameliorates Acute Alcoholic Liver Injury by Suppressing the PI3K-Akt/NF-κB Signaling Pathway to Regulate Oxidative Stress and Inflammatory Response.

Acute alcoholic liver injury is a significant clinical challenge with complex pathogenesis. This study systematically investigated the hepatoprotective effect of procyanidin B2 (PB2) using an integrated approach combining network pharmacology, molecular docking, molecular dynamics simulations, and in vivo/in vitro validation. Network analysis identified 161 common targets and highlighted the PI3K-Akt/NF-κB pathway as central. PB2 demonstrated high binding affinity to core targets such as SRC. In a mouse model, PB2 intervention significantly attenuated histopathological damage, reduced oxidative stress markers, improved lipid profiles, and suppressed pro-inflammatory cytokines while enhancing IL-10 expression. Western blot analysis confirmed PB2 dose-dependently inhibited phosphorylation of key proteins in the PI3K-Akt and NF-κB pathways. Cellular experiments further validated that PB2 alleviated ethanol-induced injury, apoptosis, and inflammatory response. These findings reveal that PB2 exerts protective effects against acute alcoholic liver injury primarily by modulating the PI3K-Akt/NF-κB signaling axis, offering a promising natural therapeutic candidate.