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Network pharmacology analysis identified 29 core overlapping targets between bioactive components and ALI\u2010related targets. Co\u2010fermentation 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\u2010fermented extract (PHF) ameliorated alcohol intoxication, activated alcohol\u2010metabolizing enzymes, reduced blood ethanol and acetaldehyde levels; mitigated hepatotoxicity, hepatosteatosis, and fibrosis. PHF exhibited dual immunomodulatory effects via TLR4\/MyD88\/NF\u2010\u03baB pathway by balancing inflammatory cytokines and regulating macrophage polarization. Its natural origin and dual immune properties boost translational potential for ALI.\n                  <\/jats:p>","DOI":"10.1002\/fsn3.71829","type":"journal-article","created":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T08:20:58Z","timestamp":1777105258000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Enhanced Bioactivity of\n                    <i>Puerariae<\/i>\n                    Radix\u2010\n                    <i>Hovenia<\/i>\n                    Seed Extracts Through\n                    <i>Lactiplantibacillus plantarum<\/i>\n                    and\n                    <i>Lacticaseibacillus paracasei<\/i>\n                    Co\u2010Fermentation: Impact on Alcoholic Liver Injury and Macrophage Polarization"],"prefix":"10.1002","volume":"14","author":[{"given":"Yunpeng","family":"Sun","sequence":"first","affiliation":[{"name":"Northeast Asia Research Institute of Traditional Chinese Medicine 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