Sweroside ameliorates α-naphthylisothiocyanate induced cholestatic liver injury through bile acid regulation and further pro-inflammatory responses mediation
Aim: Sweroside, an iridoid glycoside, exerts diverse biological activities.The study aimed to investigate how sweroside attenuates the α-naphthylisothiocyanate (ANIT)-induced cholestatic liver injury in mice.Methods: C57BL mice were treated with sweroside (120 mg/kg, ig) or INT-747 (12 mg/kg, ig) for five consecutive days (once daily), respectively.On the 3rd day, 4h after sweroside or INT-747 treatment, mice were orally administered a single dose of ANIT in olive oil (75 mg/kg, ig).Serum biochemical markers, histological change, and hepatic bile acids were analyzed.Hepatic pro-inflammatory mediators and bile acid metabolism-related genes were also analyzed.In addition, to explore the role of bile acids in the progress of ANIT-induced liver injury, primary hepatoeytes were treated with bile acid milieu, which were composed of the most elevated hepatic individual bile acids afterANIT exposure in vivo study.Results: Sweroside effectively ameliorated ANIT-induced cholestatic liver injury in mice, as evidenced by reduction of serum biochemical markers and attenuation of pathological changes.Furthermore, sweroside dramatically decreased the elevation of hepatic individual bile acids caused by ANIT treatment, such as the β-MCA, CA, and TCA levels.The underlying insights were possibly related to the regulation of mRNA expression of bile acid synthesis, bile acid transports, and pro-inflammatory responses.In addition, overload hepatic bile acids after ANIT exposure may act as an inducer of pro-inflammatory responses.Conclusions: Sweroside effectively attenuated the ANIT-induced cholestatic liver injury in mice by regulating bile acids and restoring their normal levels, as well as repressing pro-inflammatory responses.
sweroside ANIT cholestasis inflammation bile acids
Qiaoling Yang Fan Yang Junting Gong Xiaowen Tang Guangyun Wang Zhengtao Wang Li Yang
The Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicines and the Stat The Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicines and the Stat
国内会议
南昌
英文
667-685
2016-09-27（万方平台首次上网日期，不代表论文的发表时间）