Berberine ameliorates non‑alcoholic steatohepatitis in ApoE-/- mice

Yang,Jin; Ma,Xiao‑Jie; Li,Ling; Wang,Lei; Chen,Ying‑Gi; Liu,Jing; Luo,Yan; Zhuang,Zhen‑Jie; Yang,Wen‑Jun; Zang,Shu‑Fei; Shi,Jun‑Ping

doi:10.3892/etm.2017.5051

Berberine ameliorates non‑alcoholic steatohepatitis in ApoE-/- mice

Authors:
- Jin Yang
- Xiao‑Jie Ma
- Ling Li
- Lei Wang
- Ying‑Gi Chen
- Jing Liu
- Yan Luo
- Zhen‑Jie Zhuang
- Wen‑Jun Yang
- Shu‑Fei Zang
- Jun‑Ping Shi
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Affiliations: Center for Translational Medicine, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang 310015, P.R. China, College of Medical Science, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang, P.R. China
Published online on: August 28, 2017 https://doi.org/10.3892/etm.2017.5051
Pages: 4134-4140
Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The aim of the present study was to explore the protective effects of Berberine (BBR) against non‑alcoholic steatohepatitis (NASH). Male 4‑week‑old C57BL/6J Apolipoprotein E‑deficient (ApoE-/-) mice were divided into the following three groups, which were given different diets: Normal chow diet (SC group); high‑fat high‑cholesterol diet (HFHC group); and HFHC diet supplemented with BBR (BBR group). Serum biochemical indicators of hepatic function and histological liver tissue changes were evaluated. The expression of neutrophil elastase (NE) and genes involved in the inflammatory response was measured. ApoE-/- mice fed a HFHC diet for 12 weeks developed NASH, characterized by steatosis and liver inflammation. Body weight, and serum triglyceride and cholesterol levels were markedly reduced by BBR. BBR supplementation significantly lowered serum alanine aminotransferase and aspartate aminotransferase levels in mice with HFHC diet‑induced NASH, and significantly downregulated hepatic expression and activity of NE, whereas α1‑antitrypsin (α1‑AT) expression was significantly recovered by BBR (all P<0.05 vs. the HFHC group). Furthermore, treatment with BBR induced a significant reduction in the expression of key genes, including phospoinositide 3‑kinase, nuclear factor‑κB and interleukin‑8, in the C‑X‑C chemokine receptor type 4 (CXCR4) signaling pathway (all P<0.05 vs. the HFHC group). These results suggest that BBR alleviates NASH in ApoE-/- mice fed a HFHC diet. Restoration of the balance of NE and α1‑AT levels, which in turn facilitate the inhibition of the CXCR4 signaling pathways, may be involved in the hepatoprotective effect of BBR. These results indicate that BBR may be a candidate therapeutic agent for the treatment of NASH.

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