Innovative analysis and future prospects of Bupleuri Radix's pharmacology and toxicity based on the gut-liver axis

Bupleuri Radix (BR) is a traditional Chinese medicine, which has a significant protective effect on hepatic and intestinal diseases, but its potential hepatotoxicity is still worrying. The bi-directional effects of BR are systematically summarized in this review, with a primary focus on the gut-liver axis. Saikosaponins, as the main bioactive components of BR, are converted by the gut microbiota into metabolites with enhanced bioavailability, thereby regulating the intestinal flora, strengthening the intestinal barrier, and alleviating inflammation through pathways such as NF-κB, PI3K/Akt/mTOR, and STAT3. Concurrently, BR and its components exert hepatoprotective effects through antioxidant, anti-inflammatory, and metabolic regulation mechanisms. However, saikosaponin and volatile oil may induce hepatotoxicity via oxidative stress and apoptosis. Critical evidence gaps persist regarding the systematic interplay between BR's multi-component actions and the gut-liver axis, the toxicity of metabolites, and clinical hepatotoxicity risk. Future research should prioritize these areas to optimize the safe and effective application of BR.