Enhanced Bioactivity of Puerariae Radix- Hovenia Seed Extracts Through Lactiplantibacillus plantarum and Lacticaseibacillus paracasei Co-Fermentation: Impact on Alcoholic Liver Injury and Macrophage Polarization.

This study investigated the hepatoprotective potential of Puerariae Radix-Hovenia Seed extracts co-fermented with Lactiplantibacillus plantarum and Lacticaseibacillus paracasei in alleviating alcoholic liver injury (ALI) and regulating macrophage polarization. Network pharmacology analysis identified 29 core overlapping targets between bioactive components and ALI-related targets. Co-fermentation elevated total flavonoids, polysaccharides, and saponins, and altered the flavonoid profile: puerarin (+20%), daidzin (+695%), and myricetin (+84%) increased, while daidzein decreased by 48%. Optimized structural degradation and reduced impurity fragments indicated advantages in enhancing bioavailability and reducing adverse reactions. Co-fermented extract (PHF) ameliorated alcohol intoxication, activated alcohol-metabolizing enzymes, reduced blood ethanol and acetaldehyde levels; mitigated hepatotoxicity, hepatosteatosis, and fibrosis. PHF exhibited dual immunomodulatory effects via TLR4/MyD88/NF-κB pathway by balancing inflammatory cytokines and regulating macrophage polarization. Its natural origin and dual immune properties boost translational potential for ALI.