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Antifibrotic effects of Fraxetin on carbon tetrachloride-induced liver fibrosis by targeting NF-κB/IκBα, MAPKs and Bcl-2/Bax pathways

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Abstract

Background

Liver fibrosis is a chronic lesion which ultimately results in cirrhosis and possible death. Although the high incidence and lethality, few therapies are effective for liver fibrosis. Fraxetin (7,8-dihydroxy-6-methoxy coumarin), a natural product extracted from cortex fraxini, has exhibited a significant hepatoprotective and anti-fibrotic properties. However, the underlying mechanism of the anti-hepatic fibrotic property remains unknown.

Methods

48 Male Sprague Dawley rats were divided into four groups at random which were named as normal group, model group, fraxetin 25 mg/kg and 50 mg/kg group. The experimental model of liver fibrosis was founded by carbon tetrachloride (CCl4) rats which were simultaneously treated with fraxetin (25 mg/kg or 50 mg/kg). Normal groups received equal volumes of saline and peanut oil.

Results

Results showed that fraxetin ameliorated CCl4 induced liver damage and fibrosis. Furthermore, histopathology examinations revealed that fraxetin improved the morphology and alleviated collagen deposition in fibrotic liver. Fraxetin inhibited inflammation and hepatocytes apoptosis by modulating the NF-κB/IκBα, MAPKs and Bcl-2/Bax signaling pathways.

Conclusion

Our findings indicate that fraxetin is effective in preventing liver fibrosis through inhibiting inflammation and hepatocytes apoptosis which is associated with regulating NF-κB/IκBα, MAPKs and Bcl-2/Bax signaling pathways in rats.

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Author notes

  1. The first two authors equally contributed to this work.

Authors and Affiliations

  1. Department of Pharmacy, Shanghai 9th People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

    Bin Wu, Rong Wang, Shengnan Li, Yuanyuan Wang, Fuxing Song, Yanqiu Gu & Yongfang Yuan

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  1. Bin Wu
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  2. Rong Wang
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  3. Shengnan Li
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  4. Yuanyuan Wang
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  5. Fuxing Song
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  6. Yanqiu Gu
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  7. Yongfang Yuan
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Correspondence to Yongfang Yuan.

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Wu, B., Wang, R., Li, S. et al. Antifibrotic effects of Fraxetin on carbon tetrachloride-induced liver fibrosis by targeting NF-κB/IκBα, MAPKs and Bcl-2/Bax pathways. Pharmacol. Rep 71, 409–416 (2019). https://doi.org/10.1016/j.pharep.2019.01.008

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  • DOI: https://doi.org/10.1016/j.pharep.2019.01.008

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