Compound Abrus cantoniensis Extract Alleviates AFB1-Induced Liver Injury by Regulating PI3K-AKT Pathway and Gut Microbiota/Butyrate Metabolism.

Aflatoxin B1 (AFB1) 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 AFB1-induced hepatic injury remains to be elucidated. Here, network pharmacology combined with molecular docking suggested that the compound Abrus cantoniensis extract (ACCE) attenuates AFB1-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 AFB1-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 AFB1-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 AFB1-induced liver injury by regulating the PI3K-AKT pathway and the gut microbiota and its metabolite butyrate.