Unlocking the Hepatoprotective Potential of <i>Cyperus rotundus</i> Through Edible Vinegar Processing: A Study on Functional Ingredient Enhancement

L. (CR), a globally pervasive weed with dual agricultural and medicinal significance, undergoes vinegar-processed (VCR) to enhance its hepatoprotective properties. This study investigated the phytochemical and functional changes induced by vinegar processing and elucidated the role of α-cyperone, a key bioactive sesquiterpene, in modulating gut-liver axis homeostasis. UPLC-Q-Exactive Orbitrap MS and HPLC analyses revealed a significant increase in α-cyperone content post-vinegar processing. In thioacetamide-induced acute and chronic liver injury models, VCR significantly outperformed CR in reducing serum ALT and AST, hepatic TNF-α and IL-6, and oxidative stress, while restoring gut barrier integrity via up-regulation of ZO-1 and occludin. Molecular docking supported α-cyperone's high-affinity binding to the TLR4/NF-κB pathway, corroborated by western blot and immunofluorescence. Gut microbiota analysis demonstrated VCR's capacity to reverse dysbiosis, notably enriching Bacteroidetes and improving microbial diversity. These findings highlight edible vinegar processing as a sustainable strategy to transform agricultural waste into a functional food-grade intervention for liver health, mediated by α-cyperone-driven modulation of the gut-liver axis.