Background: Nonalcoholic 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. Results: At 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. Conclusions: Our 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.

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Background and AimNonalcoholic steatohepatitis (NASH) is a critical stage in the prognosis of nonalcoholic fatty liver disease (NAFLD). Pure total flavonoids from circus (PTFC) play essential roles in the improvement of NASH symptoms, but the underlying regulatory mechanism remains elusive. Our previous high‐throughput omics screening results indicate that the CCL2/CCR2‐PI3K‐Akt signaling pathway is a key pathway that regulates the liver inflammatory response. PTFC may regulate the CCL2/CCR2‐PI3K‐Akt signaling pathway to improve the liver inflammatory response.MethodsA mice model of NASH was established by a high‐fat diet, and PTFC was used as treatment. Hematoxylin‐eosin and oil red O staining were used to observe the pathological changes in the liver tissue. Western blotting and real‐time PCR were used to measure the mRNA and protein levels in the liver. The expression of proinflammatory cytokines in the peripheral blood and liver tissues was measured by liquid suspension array. An automatic biochemical method was used to examine serum transaminases and lipids levels, as well as liver lipids.ResultsCompared with the mice in the high‐fat diet group, mice in the HFD + PTFC group showed significantly improved liver histopathology, and levels of serum transaminase and lipids, liver lipids and serum proinflammatory cytokines. Moreover, the mRNA and protein expression and phosphorylation levels of key signaling molecules in the CCL2/CCR2‐PI3K‐Akt signal transduction pathway were obviously reduced by PTFC treatment.Conclusive RemarksPTFC can ameliorate NASH symptoms, and the mechanism may be related to regulating the CCL2/CCR2‐PI3K‐Akt signal transduction pathway to reduce the liver inflammatory response.