Compound Abrus cantoniensis Extract Alleviates AFB 1 ‐Induced Liver Injury by Regulating PI3K‐AKT Pathway and Gut Microbiota/Butyrate Metabolism

ABSTRACT Aflatoxin B 1 (AFB 1 ) is a potent hepatotoxin commonly ingested through contaminated food. Abrus cantoniensis Hance, a traditional Chinese medicinal herb, is commonly included in hepatoprotective compound prescriptions, yet its protective role against AFB 1 ‐induced hepatic injury remains to be elucidated. Here, network pharmacology combined with molecular docking suggested that the compound Abrus cantoniensis extract (ACCE) attenuates AFB 1 ‐induced hepatotoxicity via modulation of the PI3K‐AKT signaling pathway. This was validated through integrated transcriptomic, microbiomic, metabolomic, and in vivo/in vitro analyses. In vivo, ACCE ameliorated hepatic and intestinal damage in AFB 1 ‐exposed mice, modulated PI3K‐AKT and TLR4/NF‐κB pathways, reshaped gut microbiota by enriching Lachnospiraceae_NK4A136_group , and increased short‐chain fatty acids (SCFAs), particularly butyrate. In vitro, ACCE activated PI3K‐AKT and suppressed TLR4/NF‐κB signaling in HepG2 cells, effects diminished by pathway inhibitors. Butyrate alone also protected against AFB 1 ‐induced injury via TLR4/NF‐κB inhibition, an effect similarly reversed by inhibitors. Notably, combined treatment with ACCE or its main components and butyrate yielded superior protection. Collectively, these findings suggest that ACCE can alleviate AFB 1 ‐induced liver injury by regulating the PI3K‐AKT pathway and the gut microbiota and its metabolite butyrate.