Preparation of Scutellariae Radix and Corn-Soy Peptides Complex and Its Hepatoprotective Mechanisms

Amidst the growing global burden of alcohol-associated liver disease (ALD) and the limited clinical interventions, this study innovatively developed a complex of Scutellariae Radix and corn-soy composite peptides (SR-CP). SR-CP exhibited significantly enhanced bioaccessible antioxidant capacity, demonstrating a 0.84-2.89-fold increase in DPPH, ABTS⁺, ·OH, O2⁻·, and FRAP value versus individual components post-gastrointestinal digestion. In ethanol-injured BRL-3A hepatocytes, SR-CP (60 μg/mL) significantly ameliorated cellular viability by 38.28% (vs. ethanol model), normalized ALT/AST leakage by 19.92%/87.35%, restored SOD/GSH antioxidant reserves to 24.74 ± 1.71 U/mg prot and 55.35 ± 1.64 μmol/g prot respectively, while suppressing lipid peroxidation through 65.93% reduction in MDA production (vs. ethanol model). Mechanistic profiling revealed dual regulatory effects: 1) Inhibiting CYP2E1/NADPH-OX (↓ 51.97%/80.52%) to prevent excessive ROS production and activating the AMPK/SIRT1 axis (↑ 30.70%/6.99%); 2) Potentiation of Nrf2 nuclear translocation (↑ 0.48-fold) and HO-1 induction (↑ 1.63-fold) through AMPK-mediated antioxidant signaling. The superior hepatoprotection of SR-CP over single constituents establishes a novel paradigm for functional food development, bridging traditional herbal wisdom with molecular-targeted ALD intervention via the AMPK/Nrf2/HO-1 axis.