School of Integrative Medicine, 58301Tianjin University of Traditional Chinese Medicine, Tianjin, China.
Institute of Traditional Chinese Medicine, 58301Tianjin University of Traditional Chinese Medicine, Tianjin, China.
Hum Exp Toxicol. 2021 Jun;40(6):1012-1021. doi: 10.1177/0960327120979346. Epub 2020 Dec 15.
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.
补骨脂（FP）作为一种传统药物，在医学领域被广泛应用，但近年来其严重的肝毒性问题也越发受到关注。然而，导致肝毒性的主要毒性成分及其潜在作用机制尚未完全明确。在本研究中，补骨脂素（FP 的主要成分和质量控制成分之一）以 60mg/kg 的剂量连续灌胃给予 Sprague-Dawley 大鼠 1、3 和 7 天。收集血液和选定的组织样本进行生化和组织病理学分析，以评估肝毒性。结果表明，补骨脂素在给药 3 天后可通过增加肝体比和血清丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）和总胆固醇的变化来诱导肝毒性。此外，组织病理学检查也表明补骨脂素可导致肝毒性。此外，肝内胆汁酸转运体的 mRNA 和蛋白水平也发生了显著变化，其中 MRP4、ABCG5 和 ABCG8 被抑制，而 NTCP 的蛋白水平在大鼠肝脏中则趋于增加。综上所述，补骨脂素可能通过影响胆汁酸转运体导致肝损伤，从而导致胆汁酸在肝细胞内的转运和积累紊乱。
