Effects of dahuangzhechong pills on cytokines and mitogen activated protein kinase activation in rats with hepatic fibrosis

Relevance to ethnopharmacologyDahuangzhechong pill (DHZCP), a well-known and canonical Chinese medicine formula from “The Synopsis of Prescriptions of the Golden Chamber”, is officially approved and recommended by Chinese association of integrative medicine for the prevention and treatment of hepatic fibrosis in China.Aim of the studyTo test the hypothesis that therapeutic effects of DHZCP on hepatic fibrosis are conferred by regulating cytokine profile through a mitogen activated protein kinase (MAPK) pathway.Materials and methodsHepatic fibrosis is inducted by carbon tetrachloride (CCl4) in rats which then were randomly divided into six groups: hepatic fibrosis model group, high dose DHZCP group, low dose DHZCP group, Fufang Biejia Ruangan Pian (FBRP) group, Colchicine group and control group. Pathological, immunohistochemical, multiplex immunoassay and protein expression studies (Western blotting) are performed.ResultsDHZCP significantly decreases the levels of alanine aminotransferase, aspartate aminotransferase, hyaluronic acid, laminin, type IV collagen and procollagen III, and reverses hepatic fibrosis in rat model. DHZCP also could reduce the expression of α-smooth muscle actin, and lower the serum level of tumor necrosis factor alpha (TNF-α) and interleukin 13 (IL-13). The expressions of phosphorylated p38 MAPK and extracellular signal-regulated kinase (ERK) are down-regulated, while no significant changes are found in phosphorylation of c-Jun N-terminal kinase (JNK).ConclusionsDHZCP can alleviate hepatic fibrosis induced by CCl4. The anti-fibrotic effects of DHZCP are conferred by decreasing the secretion of TNF-α and IL-13 through down-regulating p38 and ERK phosphorylation.

Graphical abstractThe anti-fibrotic effects of dahuangzhechong pills were supported by histological examinations, immunohistochemistry staining and serum fibrogenesis markers analysis. Dahuangzhechong pills might lowered the expression of TNF-α and IL-13 through down-regulation of phosphorylation of p38 and ERK.Figure optionsDownload full-size imageDownload as PowerPoint slide