Sweroside ameliorated carbon tetrachloride (CCl4)-induced liver fibrosis through FXR-miR-29a signaling pathway

Abstract

To date, there are very few effective drugs for liver fibrosis treatment; therefore, it is urgent to develop novel therapeutic targets and approaches. In the present research, we sought to study the protective effect of sweroside contained in Lonicera japonica or blue honeysuckle berries in a mouse model of liver fibrosis and investigate the underlying mechanism. The mouse model of liver fibrosis in was induced by intraperitoneal injections of 10% CCl4 for 6 weeks (three times/week). At the beginning of the fourth week, sweroside was intragastrically administered once a day and at the end of the treatment, biochemical and histological studies were investigated. The expression of FXR, miR-29a and the downstream targets were analyzed as well. Moreover, the effect of sweroside on cell proliferation was observed in human hepatic stellate cells (HSCs) (LX-2), along with using the siRNA for FXR and miR-29a inhibitor to investigate the underpinning of the anti-fibrotic effect of sweroside. Sweroside successfully protected the liver fibrosis in CCl4-induced mouse model, accompanied by miR-29a induction. Furthermore, sweroside also induced miR-29a in HSCs, resulting in the inhibition of COL1 and TIMP1. Our data also showed that either silencing miR-29a or knockdown of FXR in LX-2 cell abolished the inhibition of COL1 and TIMP1 as well as the inhibition of cell proliferation by sweroside treatment. In conclusion, sweroside exerted its anti-fibrotic effect in vivo and in vitro by up-regulation of miR-29a and repression of COL1 and TIMP1, which was at least in part through FXR.

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Acknowledgements

This work is financially supported by the Natural Science Foundations of China (81573581), the Program of Shanghai Academic/Technology Research Leader (17XD1403500) and the National S&T Major Special Projects (2017ZX09309006 and 2014ZX09301306-007).

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Correspondence to Li Yang.

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Gong, J., Yang, F., Yang, Q. et al. Sweroside ameliorated carbon tetrachloride (CCl4)-induced liver fibrosis through FXR-miR-29a signaling pathway. J Nat Med 74, 17–25 (2020). https://doi.org/10.1007/s11418-019-01334-3

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Keywords

  • Liver fibrosis
  • Sweroside
  • miR-29a
  • FXR
  • ECM