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.