The Protective Effects of Levo-Tetrahydropalmatine on ConA-Induced Liver Injury Are via TRAF6/JNK Signaling.

Qiang Yu,Fan Wang,Liwei Wu,Yingqun Zhou,Peiqin Niu,Ling Xu,Sainan Li,Tong Liu,Weiqi Dai,Wenwen Wang,Kan Chen,Chuanyong Guo,Yujing Xia,Jiao Feng

doi:10.1155/2018/4032484

Abstract

Aims Levo-tetrahydropalmatine (L-THP) is an active ingredient of Corydalis yanhusuo W. T. Wang, which has many bioactive properties. Herein, we investigated the protective effects of L-THP on concanavalin A- (ConA-) induced hepatitis in mice and explored its possible mechanisms of these effects. Main Methods Balb/c mice were intravenously injected with 25 mg/kg ConA to generate a model of acute autoimmune hepatitis, and L-THP (20 or 40 mg/kg) was administered orally once daily for 5 d before the ConA injection. The liver enzyme levels, proinflammatory cytokine levels, and other marker protein levels were determined 2, 8, and 24 h after ConA injection. Results L-THP could decrease serum liver enzymes and pathological damage by reducing the release of inflammatory factors like IL-6 and TNF-α. The results of Western Blot and PCR indicated that L-THP could ameliorate liver cell apoptosis and autophagy. L-THP could suppress T lymphocyte proliferation and the production of TNF-α and IL-6 induced by ConA in a dose-dependent manner in vitro. Additionally, the protective functions of L-THP depended on downregulating TRAF6/JNK signaling. Conclusion. The present study indicated that L-THP attenuated acute liver injury in ConA-induced autoimmune hepatitis by inhibiting apoptosis and autophagy via the TRAF6/JNK pathway.

Highlights

The liver is the largest digestive organ and plays an important role in detoxification, metabolism, and immunity
We showed that L-THP ameliorated concanavalin A- (ConA-)induced Autoimmune hepatitis (AIH) by modulating inflammation, apoptosis, and autophagy and that these activities were linked to the TRAF6/Jun N-terminal kinase (JNK) pathway
To determine whether L-THP or 1% Dimethyl sulfoxide (DMSO) have effects on liver function, we examined the levels of liver enzymes and the release of cytokines in the L-THP and DMSO groups

Summary

Introduction

The liver is the largest digestive organ and plays an important role in detoxification, metabolism, and immunity. Hepatitis is a disease characterized by the presence of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the serum and hepatocyte apoptosis and necrosis in histology. Autoimmune hepatitis (AIH) is regarded as a chronic liver disease which has many causes [1]. While AIH is still considered a rare disease, its incidence rate has risen worldwide in recent years [2], becoming a global health burden. The administration of glucocorticoid combined with azathioprine has been used for many years in the clinic to control AIH, but the severe side effects of this treatment can be harmful. Animal models of AIH should be generated to facilitate research into the pathogenesis of AIH and to develop new targeted therapies [3,4,5]

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Results

Discussion

Conclusion