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

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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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Authors and Affiliations

  1. The MOE Key Laboratory for Standardization of Chinese Medicines and the SHTCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China

    Junting Gong, Fan Yang, Qiaoling Yang, Xiaowen Tang, Fangfang Shu, Zhengtao Wang & Li Yang

  2. Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China

    Fangfang Shu & Li Yang

  3. Institute of Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China

    Lieming Xu

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  1. Junting Gong
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  2. Fan Yang
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  3. Qiaoling Yang
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  4. Xiaowen Tang
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  5. Fangfang Shu
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  6. Lieming Xu
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  8. Li Yang
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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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