Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
Phase 1 clinical trial laboratory, Wuhan Jinyintan Hospital, Wuhan, China.
Phytother Res. 2023 Jun;37(6):2280-2289. doi: 10.1002/ptr.7739. Epub 2023 Feb 1.
Psoralen is a major component of Fructus Psoraleae that could induce liver injury. In this study, C57BL/6J mice were administered with psoralen at doses of 80 mg/kg for 3, 7 and 14 days. Blood and liver samples were collected for serum biochemistry and histopathology examinations, respectively. Psoralen led to liver injury with significantly increased liver weight and liver coefficient and up regulated serum ALT, AST and TG but down regulated serum TC and TP. The expression of bile acid-associated transporters and enzymes was detected by western blot, and the results showed that psoralen significantly down-regulates the expressions of CYP7A1, CYP27A1, BSEP and OSTα protein while up-regulates the expressions of HMGCR and FASN, resulting in the obstacles of bile acid efflux in the liver. The contents of 24 kinds of bile acids in the liver were measured by LC-MS/MS, and the results showed that psoralen led to the accumulation of unconjugated bile acids in the liver, such as ALCA and CA, which were more severe in male mice than female mice. It was indicated that psoralen may disrupt the balance of bile acid metabolism by inhibiting the expression of the efflux transporter, which then leads to liver damage.
补骨脂素是补骨脂的主要成分，可导致肝损伤。在这项研究中，C57BL/6J 小鼠分别给予 80mg/kg 的补骨脂素 3、7 和 14 天。采集血液和肝脏样本，分别用于血清生化和组织病理学检查。补骨脂素导致肝损伤，表现为肝重和肝系数显著增加，血清 ALT、AST 和 TG 升高，血清 TC 和 TP 降低。通过 Western blot 检测胆汁酸相关转运体和酶的表达，结果表明补骨脂素显著下调 CYP7A1、CYP27A1、BSEP 和 OSTα 蛋白的表达，而上调 HMGCR 和 FASN 的表达，导致胆汁酸在肝脏中流出受阻。通过 LC-MS/MS 测定肝脏中 24 种胆汁酸的含量，结果表明补骨脂素导致未结合胆汁酸在肝脏中蓄积，如 ALCA 和 CA，雄性小鼠比雌性小鼠更严重。表明补骨脂素可能通过抑制外排转运体的表达破坏胆汁酸代谢平衡，进而导致肝损伤。
