Multi-targeting therapeutic mechanisms of the Chinese herbal medicine QHD in the treatment of non-alcoholic fatty liver disease.

Qin Feng,Qian Liu,Lingyu Guan,Cheng Chen,Hongshan Li,Ping Liu,Robert D Baker,Yiyang Hu,Lixin Zhu,Shijie Tang,Wensheng Liu,Maria Tsompana,Ruixin Zhu,Susan S Baker,Rafal Kozielski,Jinghua Peng

doi:10.18632/oncotarget.15482

Abstract

Beneficial effects of the Chinese herbal medicine Qushi Huayu Decoction (QHD) were observed with non-alcoholic fatty liver disease (NAFLD) patients and animal models. The impact of QHD or its active components (geniposide and chlorogenic acid, GC) on NAFLD liver transcriptome and gut microbiota was examined with NAFLD rats. Increased expression for genes required for glutathione production and decreased expression for genes required for lipid synthesis was observed in NAFLD livers treated with QHD and GC. GC treatment decreased serum LPS, which could be explained by reduced mucosal damage in the colon of GC-treated rats. Further, our data suggest an increased abundance of Treg-inducing bacteria that stimulated the Treg activity in GC treated colon, which in turn down-regulated inflammatory signals, improved gut barrier function and consequently reduced hepatic exposure to microbial products. Our study suggests that QHD simultaneously enhanced the hepatic anti-oxidative mechanism, decreased hepatic lipid synthesis, and promoted the regulatory T cell inducing microbiota in the gut.

Highlights

Non-alcoholic fatty liver disease (NAFLD) refers to a spectrum of conditions, including simple steatosis, nonalcoholic steatohepatitis (NASH), fibrosis and cirrhosis
Increased expression for genes required for glutathione production and decreased expression for genes required for lipid synthesis was observed in non-alcoholic fatty liver disease (NAFLD) livers treated with Qushi Huayu Decoction (QHD) and geniposide and chlorogenic acid (GC)
Global microarray gene expression analysis was performed with four groups of rats fed: (i) standard chow for 8 weeks, (ii) high fat diet (HFD) for 8 weeks (NAFLD group), (iii) HFD for 8 weeks with QHD therapy during the last 4 weeks (QHD group), and (iv) HFD for 8 weeks with GC therapy during the last 4 weeks (GC group)

Summary

Introduction

Non-alcoholic fatty liver disease (NAFLD) refers to a spectrum of conditions, including simple steatosis, nonalcoholic steatohepatitis (NASH), fibrosis and cirrhosis. As the hepatic component of the metabolic syndrome, NAFLD is characterized by hepatocellular lipid accumulation without excessive alcohol intake. According to the most current hypothesis, “multiple hits” contribute to the development of severe NAFLD or NASH [3], including, but not limited to oxidative stress as a consequence of excessive lipid oxidation, gut microbiome-related challenges, cytokines produced in the adipose tissue, innate immunity, endoplasmic reticulum (ER) stress and genetic predisposition. Therapies targeting one component of NAFLD pathology have achieved limited results so far [4,5,6]. Studies on the natural history of NAFLD have revealed that a sizable fraction of simple steatosis progresses to severe NAFLD stages including liver inflammation, fibrosis and cirrhosis [7]. Novel strategies integrating multiple parallel interventions are desirable for treating this serious disease

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