ABSTRACT Cyperus rotundus 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.
Jia‐He et al. (Fri,) studied this question.