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Digestive Diseases and Sciences

, Volume 63, Issue 12, pp 3398–3408 | Cite as

Silybin Alleviates Hepatic Steatosis and Fibrosis in NASH Mice by Inhibiting Oxidative Stress and Involvement with the Nf-κB Pathway

  • Qiang Ou
  • Yuanyuan Weng
  • Siwei Wang
  • Yajuan Zhao
  • Feng ZhangEmail author
  • Jianhua ZhouEmail author
  • Xiaolin WuEmail author
Original Article

Abstract

Background and Aim

Silybin is the major biologically active compound of silymarin, the standardized extract of the milk thistle (Silybum marianum). Increasing numbers of studies have shown that silybin can improve nonalcoholic steatohepatitis (NASH) in animal models and patients; however, the mechanisms underlying silybin’s actions remain unclear.

Methods

Male C57BL/6 mice were fed a methionine-choline deficient (MCD) diet for 8 weeks to induce the NASH model, and silybin was orally administered to the NASH mice. The effects of silybin on lipid accumulation, hepatic fibrosis, oxidative stress, inflammation-related gene expression and nuclear factor kappa B (NF-κB) activities were evaluated by biochemical analysis, immunohistochemistry, immunofluorescence, quantitative real-time PCR and western blot.

Results

Silybin treatment significantly alleviated hepatic steatosis, fibrosis and inflammation in MCD-induced NASH mice. Moreover, silybin inhibited HSC activation and hepatic apoptosis and prevented the formation of MDBs in the NASH liver. Additionally, silybin partly reversed the abnormal expression of lipid metabolism-related genes in NASH. Further study showed that the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway played important roles in the silybin-derived antioxidant effect, as evidenced by the upregulation of Nrf2 target genes in the silybin treatment group. In addition, silybin significantly downregulated the expression of inflammation-related genes and suppressed the activity of NF-κB signaling.

Conclusions

Silybin was effective in preventing the MCD-induced increases in hepatic steatosis, fibrosis and inflammation. The effect was related to alteration of lipid metabolism-related gene expression, activation of the Nrf2 pathway and inhibition of the NF-κB signaling pathway in the NASH liver.

Keywords

Silybin Nonalcoholic steatohepatitis Oxidative stress NF-κB signaling pathway 

Notes

Acknowledgments

This work was supported by the National Natural Science Foundation of China (81670129 to Xiaolin Wu).

Compliance with ethical standards

Conflict of interest

There is no conflict of interest to disclose.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.The Eighth People’s Hospital of ShanghaiShanghaiChina
  2. 2.Department of Clinical Laboratory, Core FacilityQuzhou People’s HospitalQuzhouChina
  3. 3.The Central Laboratory of the Eighth People’s Hospital of ShanghaiShanghaiChina

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