龙胆苦苷对ANIT所致小鼠胆汁淤积性肝损伤的保肝作用评估中胆汁酸目标谱分析

Target profiling analyses of bile acids in the evaluation of hepatoprotective effect of gentiopicroside on ANIT-induced cholestatic liver injury in mice
2017-03-03 08:50发表评论
作者:Tang, X , Yang, Q , Yang, F , Gong, J , Han, H , Yang, L , Wang, Z
机构: 中药标准化教育部重点实验室,国家中医药管理局中药新资源与品质评价重点实验室,上海中医药大学中药研究所
期刊: J Ethnopharmacol2016年12月期194卷

Ethnopharmacological relevance Gentiopicroside (GPS), one of iridoid glucoside representatives, is the most potential active component in Gentiana rigescens Franch. ex Hemsl and Gentiana macrophylla Pall. These two herbs have been used to treat jaundice and other hepatic and billiary diseases in traditional Chinese medicine for thousands of years. Aim of the study This study aimed to investigate the protective effects and mechanisms of GPS on α-naphthylisothiocyanate (ANIT) induced cholestatic liver injury in mice. Materials and methods Mice were treated with GPS (130 mg/kg, ig) for 5 consecutive days. On the third day, mice were given a single dose of Alpha-naphthylisothiocyanate (75 mg/kg, ig). Serum biochemical markers and individual bile acids in serum, liver, urine and feces were measured at different time points after ANIT administration. The expression of hepatic bile acid synthesis, uptake and transporter genes as well as ileum bile acid transporter genes were assayed. Results In this study, ANIT exposure resulted in serious cholestasis with liver injury, which was demonstrated by dramatically increased serum levels of ALT, ALP, TBA and TBIL along with TCA CA, MCAs and TMCAs accumulation in both liver and serum. Furthermore, ANIT significantly decreased bile acid synthesis related gene expressions, and increased expression of bile acid transporters in liver. Continuous treatment with GPS attenuated ANIT-induced acute cholestasis as well as liver injury and correct the dyshomeostasis of bile acids induced by ANIT. Our data showed that GPS significantly upregulated the hepatic mRNA levels of synthesis enzymes (Cyp8b1 and Cyp27a1) and transporters (Mrp4 Mdr1 and Ost-β) as well as ileal bile acid circulation mediators (Asbt and Fgf15), accompanied by serum and hepatic bile acid levels decrease and further urinary and fecal bile acid levels increase. Conclusion GPS can change bile acids metabolism which highlights its importance in mitigating cholestasis, resulting in the marked decrease of intracellular bile acid pool back toward basal levels. And the protective mechanism was associated with regulation of bile acids-related transporters, but the potential mechanism warrants further investigation. © 2016 The Authors

通讯机构:The MOE Key Laboratory for Standardization of Chinese Medicines and the SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China
学科代码:内科学 补充和替代医学 药学   关键词:龙胆苦苷 小鼠胆汁淤积性肝损伤 保肝 ,中国作者重要发表 爱思唯尔医学网, Elseviermed
来源: Scopus
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