Fructus Psoraleae (FP), widely used in traditional medicine, is increasingly reported to cause serious hepatotoxicity in recent years. However, the main toxic constituents responsible for hepatotoxicity and the underlying mechanisms are poorly understood. In the present study, psoralen, a main and quality-control constituent of FP, was intragastrically administered to Sprague-Dawley rats at a dose of 60 mg/kg for 1, 3 and 7 days. Blood and selected tissue samples were collected and analyzed for biochemistry and histopathology to evaluate hepatotoxicity. The results showed that psoralen could induce hepatotoxicity by enhanced liver-to-body weight ratio and alterations of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total cholesterol after administration for 3 days. In addition, histopathological examinations also indicated the hepatotoxicity induced by psoralen. Furthermore, the mRNA and protein levels of hepatic bile acid transporters were significantly changed, in which MRP4, ABCG5 and ABCG8 were repressed, while the protein level of NTCP tended to increase in the rat liver. Taken together, psoralen caused liver injury possibly through affecting bile acid transporters, leading to the disorder of bile acid transport and accumulation in hepatocytes.

近年来，在传统医学中广泛使用的补骨脂（FP）越来越多地被报道会引起严重的肝毒性。然而，导致肝毒性的主要毒性成分及其潜在机制知之甚少。在本研究中，补骨脂素是 FP 的主要和质量控制成分，以 60 mg/kg 的剂量给 Sprague-Dawley 大鼠灌胃，持续 1、3 和 7 天。收集血液和选定的组织样本并分析其生物化学和组织病理学以评估肝毒性。结果表明补骨脂素可通过增加肝体重比和血清丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）和总胆固醇在给药 3 天后引起肝毒性。此外，组织病理学检查还表明补骨脂素引起的肝毒性。此外，肝脏胆汁酸转运蛋白的 mRNA 和蛋白质水平发生显着变化，其中 MRP4、ABCG5 和 ABCG8 受到抑制，而 NTCP 的蛋白质水平在大鼠肝脏中趋于增加。综上所述，补骨脂素可能通过影响胆汁酸转运蛋白引起肝损伤，导致胆汁酸转运和肝细胞积聚障碍。