Psoraleae induces hepatotoxicity by affecting bile acid balance

• 作者: An-Hong Wang Bin Yu Hong Shi Kun Zhou Wei-Ling Pu Ya-Nan Bi
• 来源期刊: 亚洲毒理学研究
• 学科: 医学
• 关键词: PSORALEN HEPATOTOXICITY Bile acid Hepatic transporter
• 年，卷（期）: 2021,（1）
• 页码范围: 15-22
• 页数: 8页
• 分类号: R57

摘要

Buguzhi(Psoraleae fructus),the seed of Psoralea corylifolia Linn,is used to treat osteoporosis,nephritis,vitiligo and other diseases.However,long-term routine or overdose of Psoraleae fructus may lead to hepatotoxicity and become a major obstacle of its clinical usage.Psoralen was a key active component of Psoraleae fructus,and a main cause of Psoraleae fructus toxicity.This research was to investigate the hepatotoxicity of psoralen and whether it’s related with bile acid imbalance.Methods:C57BL/6 mice were randomly divided into 4 groups(n=10).Psoralen(20 mg/kg,40 mg/kg and 80 mg/kg)was administrated intragastrically once every day and control group with equivalent water until 4 weeks.Results:The results showed that psoralen caused an increase in liver coefficient and the injury of hepatocytes microstructure of mice.It also inhibited cell viability of HepG2 cells.Mice treated with psoralen exerted liver total bile acid increased while serum total bile acid decreased,which indicated that psoralen-induced liver injury may partly associate with cholestasis.For further study of liver transporters,high dose of psoralen inhibited the expression of some important hepatic efflux transporters(including BSEP,p-gp and ABCG5)in vivo and in vitro.Conclusion:We provide evidence for the first time that psoralen may induce cholestatic hepatotoxicity for the bile acid retention by inhibition on bile acid export pumps.