Bridging herb and needle: shared hepatoprotective mechanisms of saikosaponins and acupuncture and the rationale for combined therapy.

Liver disease remains a major global health burden, and treatments that directly reverse established fibrosis remain limited and indication-specific. Radix Bupleuri was selected for this review because it is widely used in traditional East Asian liver-directed formulas and because its principal triterpenoid constituents, saikosaponins, have a substantial but predominantly preclinical hepatology literature. This review critically synthesizes saikosaponin evidence across chemical, immune-mediated, alcohol-related, cholestatic, fibrotic, and metabolic injury, emphasizing congener-specific actions, experimental-model limitations, poor bioavailability, dose-dependent hepatotoxicity, and potential cytochrome-mediated interactions. We separately appraise manual acupuncture, electroacupuncture, moxibustion, and acupoint catgut embedding. Human evidence is strongest for metabolic liver disease and is concentrated in electroacupuncture and embedding studies; evidence for fibrosis and cirrhosis is weaker, while most mechanistic data derive from electroacupuncture or moxibustion in rodents. The two evidence streams show partial functional overlap in fibrogenic cell state and matrix turnover, redox control, innate-inflammatory signaling, and metabolic-autophagic regulation. This overlap is asymmetric: vagus-dependent hepatic Nrf2 activation is supported for electroacupuncture, whereas direct evidence for canonical hepatic Nrf2 activation by saikosaponins remains limited. Gut microbiota, bile-acid metabolism, intestinal-barrier integrity, and gut-brain signaling form an additional systems-level interface, but their causal role in a combined intervention is untested. No direct co-administration study was identified. The proposed combination should therefore be treated as a falsifiable research hypothesis, not as demonstrated synergy or an established therapy.