Yinchen Linggui Zhugan Decoction Ameliorates Nonalcoholic Fatty Liver Disease in Rats by Regulating the Nrf2/ARE Signaling Pathway.

Yi Guo,Ya-Fei Han,Tang-You Mao,Chen Chen,Yun-Liang Wang,Tian-Hong Xie,Jun-Xiang Li,Hai-Xiao Han,Xiang Tan

doi:10.1155/2017/6178358

Abstract

Yinchen Linggui Zhugan Decoction (YCLGZGD) is the combination of Linggui Zhugan (LGZGD) and Yinchenhao (YCHD) decoctions, two famous traditional Chinese medicine prescriptions. In previous studies, we found that Yinchen Linggui Zhugan Decoction (YCLGZGD) could regulate lipid metabolism disorder and attenuate inflammation in pathological process of nonalcoholic fatty liver disease (NAFLD). However, the exact underlying mechanism remains unknown. The aim of this study was to explore the effect of Yinchen Linggui Zhugan Decoction on experimental NAFLD and its mechanism in rats with high-fat diet (HFD) which was established by 8-week administration of HFD. YCLGZGD, LGZGD, and YCHD were administered daily for 4 weeks, after which the rats were euthanized. The level of blood lipid, liver enzymes, H&E, and Oil Red O staining were determined to evaluate NAFLD severity. Western blotting and real-time polymerase chain reaction were, respectively, used to determine hepatic protein and gene expression of Keap1, Nrf2, NQO1, and HO-1. Oral YCLGZGD ameliorated HFD-induced NAFLD. Furthermore, YCLGZGD increased the protein and gene expression of Nrf2, NQO1, and HO-1 without changing Keap1. Overall, these results suggest that YCLGZGD ameliorates HFD-induced NAFLD in rats by upregulating the Nrf2/ARE signaling pathway.

Highlights

Nonalcoholic fatty liver disease (NAFLD) is a type of liver disease that includes simple hepatic steatosis, nonalcoholic steatohepatitis (NASH), and irreversible cirrhosis [1]
These results suggest that Yinchen Linggui Zhugan Decoction (YCLGZGD) ameliorates high-fat diet (HFD)-induced NAFLD in rats by upregulating the Nrf2/antioxidant response element (ARE) signaling pathway
We found that Yinchen Linggui Zhugan Decoction (YCLGZGD) has an anti-inflammatory effect [16, 17], which could regulate lipid metabolism disorder and attenuate inflammation in pathological process of NAFLD

Summary

Introduction

Nonalcoholic fatty liver disease (NAFLD) is a type of liver disease that includes simple hepatic steatosis, nonalcoholic steatohepatitis (NASH), and irreversible cirrhosis [1]. NAFLD is regarded as the liver manifestation of metabolic syndrome. The pathogenesis of NAFLD is not fully understood far and the reported therapeutic trails are still under investigation [7, 8]. Some researchers agree with the “2-hit” hypothesis for the NAFLD pathogenesis. The “first hit” involves hepatic triglyceride accumulation or steatosis. The “second hit” represents the relationship between inflammatory cytokines and oxidative stress. The Nrf2/antioxidant response element (ARE) signaling pathway plays an important role in oxidative stress and can induce the expression of antioxidative genes to protect hepatocytes from apoptosis

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