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

Ye, J.; Tan, J.; Lin, Y.; Guo, M.; Duan, H.; Zhang, F.; Yang, X.

2025-06-17 pharmacology and toxicology
10.1101/2025.06.12.659390 bioRxiv
Show abstract

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, {middle dot}OH, O2-{middle dot}, and FRAP value versus individual components post-gastrointestinal digestion. In ethanol-injured BRL-3A hepatocytes, SR-CP (60 g/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 mol/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 ({downarrow} 51.97%/80.52%) to prevent excessive ROS production and activating the AMPK/SIRT1 axis ({uparrow} 30.70%/6.99%); 2) Potentiation of Nrf2 nuclear translocation ({uparrow} 0.48-fold) and HO-1 induction ({uparrow} 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.

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