Bakuchiol, a potentially toxic component in Fructus psoraleae, causes liver damage in vitro by affecting the homeostasis of the liver GABA signalling system.

ETHNOPHARMACOLOGICAL RELEVANCE: Fructus Psoraleae (FP) is an herbal medicine widely used in East Asia. Nevertheless, numerous reports have documented its toxicity, including adverse reactions involving the liver, kidney, and skin. The underlying toxic components and mechanisms remain unclear, which severely limits its clinical application.

AIM OF THE STUDY: This study aimed to identify potentially toxic components in FP and to further elucidate their mechanism of toxicity.

MATERIALS AND METHODS: Potentially toxic components in FP were rapidly screened using a zebrafish model. Potential hepatotoxicity-related targets and pathways were identified by integrating network toxicology with molecular docking, and the candidate targets were subsequently validated.

RESULTS: Fifteen components of FP were evaluated for acute toxicity in zebrafish. Bakuchiol, bavachinin and corylifolinin - the three compounds exhibiting the highest c/LC50 values - adversely affected normal hepatic function in zebrafish and induced oxidative stress responses. Bakuchiol was further identified as the component with the greatest hepatotoxic potential and was demonstrated to disrupt the homeostasis of the γ-aminobutyric acid (GABA) signalling system in the liver at 1, 5 and 10 μM by altering Cl- levels and upregulating GABAA receptor expression. Moreover, the GABAA receptor antagonist flumazenil was able to counteract bakuchiol-induced hepatotoxicity.

CONCLUSION: Bakuchiol, by virtue of its high content and potent toxicity, is a potential hepatotoxic component of FP. It disrupts hepatic GABA system homeostasis by affecting Cl- channel and GABAA receptor expression.