Sweroside ameliorates a-naphthylisothiocyanate- induced cholestatic liver injury in mice by regulating bile acids and suppressing pro-inflammatory responses

Aim： Sweroside is an iridoid glycoside with diverse biological activities. In the present study we investigated the effects of sweroside on a-naphthylisothiocyanate （ANIT）-induced cholestatic liver injury in mice. Methods： Mice received sweroside （120 mg·kg^-1·d^-1, ig） or a positive control INT-747 （12 mg·kg^-1·d^-1, ig） for 5 d, and ANIT （75 mg/kg, ig） was administered on d 3. The mice were euthanized on d 5, and serum biochemical markers, hepatic bile acids and histological changes were analyzed. Hepatic expression of genes related to pro-inflammatory mediators and bile acid metabolism was also assessed. Primary mouse hepatocytes were exposed to a reconstituted mixture of hepatic bile acids, which were markedly elevated in the ANIT-treated mice, and the cell viability and expression of genes related to pro-inflammatory mediators were examined. Results： Administration of sweroside or INT-747 effectively ameliorated ANIT-induced cholestatic liver injury in mice, as evidenced by significantly reduced serum biochemical markers and attenuated pathological changes in liver tissues. Furthermore, administration of sweroside or INT-747 significantly decreased ANIT-induced elevation of individual hepatic bile acids, such as β-MCA, CA, and TCA, which were related to its effects on the expression of genes responsible for bile acid synthesis and transport as well as pro-inflammatory responses. Treatment of mouse hepatocytes with the reconstituted bile acid mixture induced significant pro-inflammatory responses without affecting the cell viability. Conclusion： Sweroside attenuates ANIT-induced cholestatic liver injury in mice by restoring bile acid synthesis and transport to their normal levels, as well as suppressing pro-inflammatory responses.