Yu Jin Pulvis inhibits carbon tetrachloride-induced liver fibrosis by blocking the MAPK and PI3K/Akt signaling pathways

Am J Transl Res. 2019 Sep 15;11(9):5998-6006. eCollection 2019.

Abstract

Traditional Chinese medicine theory indicates that Yu Jin Pulvis (YJP) could prevent liver fibrosis progression and this has been verified in liver fibrosis patients. However, the mechanism underlying the protective effects of YJP against liver fibrosis remains unclear. While different signaling pathways are involved in liver fibrosis progression, mitogen-activated protein kinase (MAPK) and phosphoinositide-3-kinase-protein kinase B/Akt (PI3K/Akt) are the most crucial. To determine whether YJP regulates these signaling pathways to prevent liver fibrosis, we used a mouse model of liver fibrosis induced by intraperitoneal injection of carbon tetrachloride (CCl4). Mice were randomly divided into normal, CCl4, YJP (300 mg/kg), CCl4+YJP (100, 200, and 300 mg/kg), and two positive control silybin (100 mg/kg) and Fuzheng Huayu (FZHY) capsule (2 g/kg) groups. The mice were gavaged daily for 6 weeks. Then liver fibrosis markers; tissue morphology; serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and proinflammatory cytokine levels; and expression of α-smooth muscle actin (α-SMA) and collagen type I (Col1) were examined to determine liver fibrosis progression. Liver injury and collagen deposition were significantly reduced in the YJP treatment group compared with the CCl4 group. Furthermore, the expression of phosphorylated-extracellular-signal-regulated kinase (p-ERK), p-jun N-terminal kinase (p-JNK), p-P38MAPK, p-PI3K and p-Akt was decreased by YJP treatment compared with CCl4 treatment. Collectively, these results demonstrate the antifibrosis effect of YJP on CCl4-induced liver fibrosis in mice, mediated through blockade of the MAPK and PI3K/Akt signaling pathways. Therefore, YJP has therapeutic potential against liver fibrosis.

Keywords: Carbon tetrachloride; Fuzheng Huayu capsule; Yu Jin Pulvis; liver fibrosis; signaling pathway; silybin.