Anti-inflammatory activity of berberine in non-alcoholic fatty liver disease via the Angptl2 pathway

Zengsheng Lu,Liyan Wu,Zhiyun Chen,Beihui He,Maoxiang Yan

doi:10.1186/s12865-020-00358-9

Abstract

BackgroundNonalcoholic fatty liver disease (NAFLD) has become the most common liver disease worldwide. Recent studies have shown that the Angptl2 pathway mediated hepatic inflammatory response plays an important role in the progression of nonalcoholic fatty liver disease. Our study investigated the possible molecular mechanisms of berberine (BBR) in the treatment of the liver inflammatory response in the livers of rats with high-fat diet-induced NAFLD via the Angptl2 pathway.ResultsAt the end of 12 weeks, compared with the control group rats, the high-fat- diet group rats showed obvious pathological and biochemical changes. The levels of pro-infalmmatory cytokines (CCL2, TNF-α) were increased, the infiltration of inflammatory cells (CCR2) was elevated, and the hepatic mRNA and protein levels of Angptl2, NF-κB and Foxo1 were increased to different degrees. Nevertheless, following treatment with BBR, liver tissue pathology, biochemical data, and Angptl2 pathway-related genes expression were significantly ameliorated.ConclusionsOur findings demonstrate that BBR might attenuate the liver inflammatory response in the livers of rats with high-fat diet-induced NAFLD through the regulation of the Angptl2 pathway.

Highlights

Nonalcoholic fatty liver disease (NAFLD) has become the most common liver disease worldwide
BBR ameliorates hepatic steatosis and inflammation in HFD-fed rats To confirm the therapeutic effect of BBR, we examined the effect of BBR on the liver of rats with HFD-fed induced NAFLD rats
The second hit is enhancement of liver lipid peroxidation and an increase of Free fatty acids (FFAs). This theory does not explain all of the problems, it can be surmised that chronic inflammation plays an important role in the progression of non-alcoholic steatohepatitis (NASH), and reducing the liver inflammatory response may be a potential target for treatment of NASH

Summary

Introduction

Nonalcoholic fatty liver disease (NAFLD) has become the most common liver disease worldwide. Angptl2-mediated signal transduction contributes to angiogenesis and tissue damage repair [17], whereas excessive Angptl signaling leads to chronic inflammation, which is accompanied by obesity and metabolic syndrome [17], type 2 diabetes [18], atherosclerosis [19], and even certain tumors [20].Angptl activates Racl through integrins, which activates nuclear factor-kappaB (NF-κB) and inhibits κB inhibitor (IκB), and promotes the release of inflammatory mediators, such as TNF-α and CCL2, and the aggregation of inflammatory cells; these processes, in turn, lead to the development of chronic inflammation of the liver Based on these data, our study used a highfat diet-induced rat model of NAFLD to study whether BBR has an anti-NAFLD effect by inhibiting the hepatic inflammatory response via the Angptl pathway

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