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Dig Dis Sci. 2018 Dec;63(12):3398-3408. doi: 10.1007/s10620-018-5268-0. Epub 2018 Sep 6.

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

Author information

1
The Eighth People's Hospital of Shanghai, No. 8 Caobao Road, Shanghai, 200235, China.
2
Department of Clinical Laboratory, Core Facility, Quzhou People's Hospital, Quzhou, Zhejiang, 324000, China.
3
Department of Clinical Laboratory, Core Facility, Quzhou People's Hospital, Quzhou, Zhejiang, 324000, China. felix.f.zhang@outlook.com.
4
The Eighth People's Hospital of Shanghai, No. 8 Caobao Road, Shanghai, 200235, China. shprozhou@163.com.
5
The Central Laboratory of the Eighth People's Hospital of Shanghai, No. 8 Caobao Road, Shanghai, 201508, China. shprozhou@163.com.
6
The Eighth People's Hospital of Shanghai, No. 8 Caobao Road, Shanghai, 200235, China. wuxiaolin999@hotmail.com.
7
The Central Laboratory of the Eighth People's Hospital of Shanghai, No. 8 Caobao Road, Shanghai, 201508, China. wuxiaolin999@hotmail.com.

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:

NF-κB signaling pathway; Nonalcoholic steatohepatitis; Oxidative stress; Silybin

PMID:
30191499
DOI:
10.1007/s10620-018-5268-0

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