Hepatoprotective effects of Persicaria capitata against alcoholic liver injury by regulating the gut-liver axis via PI3K-Akt and TLR4/NF-κB signaling pathways.
ETHNOPHARMACOLOGICAL RELEVANCE Persicaria capitata, a vital Miao medicine, is traditionally employed to "clear heat and promote diuresis" and "detoxify". In traditional theory, alcoholic liver injury (ALI) is categorized as a "Damp-Heat accumulation" syndrome, often manifesting as damp-heat jaundice. The traditional application of P. capitata in treating jaundice and inflammatory conditions provides a rationale for its hepatoprotective use. AIM OF THE STUDY To provide a scientific basis for the traditional use of P. capitata by systematically investigating the protective effects of its water extract (WP) on ALI and exploring the associated molecular mechanisms. MATERIALS AND METHODS An ALI mouse model was established by alcohol feeding for 28 days. Mice were orally administered with WP (175, 350, 700 mg/kg/day). Liver and intestinal functions were assessed by biochemical assays, histology, transcriptomics, 16S rRNA sequencing, and Western blotting. RESULTS WP significantly reduced serum ALT, AST, and hepatic lipid levels while alleviating oxidative stress. Mechanistically, WP regulated the gut-liver axis by maintaining intestinal barrier integrity (increased ZO-1 and Occludin expression) and enriching beneficial Akkermansia bacteria. This restoration of the intestinal barrier subsequently suppressed hepatic inflammatory responses and hepatocyte apoptosis by blocking the LPS-TLR4/NF-κB signaling cascade while simultaneously promoting the PI3K-Akt survival pathway. CONCLUSIONS By modulating the gut-liver axis-specifically through the restoration of intestinal barrier integrity and the regulation of TLR4/NF-κB and PI3K-Akt signaling-P. capitata effectively mitigates ALI. This study provides a mechanistic rationale for its traditional use and supports its development as a promising intervention for alcoholic liver-related pathologies.