Abstract
Aim:
Sweroside is an iridoid glycoside with diverse biological activities. In the present study we investigated the effects of sweroside on α-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.
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Acknowledgements
This work was financially supported by the Natural Science Foundations of China (81222053 and 81573581), the Program for New Century Excellent Talents in University (NCET-12-1056) and the National S&T Major Special Projects (2014ZX09301306-007).
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Supplementary Figure S1 (download DOCX )
Hepatoprotection of sweroside against ANIT-induced hepatotoxicity and cholestasis. (DOCX 119 kb)
Supplementary Figure S2 (download DOCX )
Serum TC, TG, LDL-C and HDL-C levels were affected by sweroside treatment. (DOCX 95 kb)
Supplementary Figure S3 (download DOCX )
Sweroside demonstrated no obvious liver toxicity by histological study and biochemical analysis. (DOCX 1968 kb)
Supplementary Figure S4 (download DOCX )
Cells viability and cells apoptosis were not affected by sweroside exposure. (DOCX 193 kb)
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Yang, Ql., Yang, F., Gong, Jt. et al. Sweroside ameliorates α-naphthylisothiocyanate-induced cholestatic liver injury in mice by regulating bile acids and suppressing pro-inflammatory responses. Acta Pharmacol Sin 37, 1218–1228 (2016). https://doi.org/10.1038/aps.2016.86
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DOI: https://doi.org/10.1038/aps.2016.86
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