Pure total flavonoids from citrus improve nonalcoholic steatohepatitis liver inflammatory responses by regulating the CCL2/CCR2-PI3K-Akt signal transduction pathway.

Abstract

Nonalcoholic 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. A 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. Compared 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. PTFC 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.