Efficacy and Hepatotoxicity of Psoralea corylifolia L.: A Meta-Analysis and Machine Learning Assessment in Postmenopausal Osteoporosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Psoralea corylifolia L. (P. corylifolia, also known as Cullen corylifolium (L.) Medik.) is a traditional medicinal herb used for bone-related disorders. Its broader application is constrained by concerns about hepatotoxicity, creating a challenge in balancing efficacy and safety. AIM OF THE STUDY: To systematically evaluate the osteoprotective efficacy of P. corylifolia in postmenopausal osteoporosis and to explore a preliminary preclinical therapeutic window within a benefit-risk assessment framework. MATERIALS AND METHODS: Following a comprehensive search of major databases, we performed a meta-analysis coupled with Bayesian Gaussian process regression modeling. Efficacy was primarily assessed using bone mineral density, whereas alanine aminotransferase and aspartate aminotransferase, derived from separate toxicity datasets, were evaluated as safety outcomes. Mouse and rat doses were standardized to human equivalent doses (HED) for cross-species harmonization. RESULTS: A total of 23 efficacy studies and 7 toxicity studies were included. Meta-analysis showed that P. corylifolia significantly improved bone mineral density (standardized mean difference = 4.32, p < 0.001, I2 = 89%) and generally improved trabecular microarchitecture outcomes. Model integration suggested a favorable benefit-risk profile within a restricted range. After dose standardization of psoralen to HED for cross-species harmonization, 4.5 mg/kg for 7.0 weeks was estimated as a model-informed investigational reference pending further validation. CONCLUSIONS: This study provides meta-analytic evidence supporting the efficacy of P. corylifolia and uses Bayesian modeling to identify a preliminary, non-clinically validated investigational dose window that requires further validation in human studies.