Psoralea corylifolia L. Attenuates Nonalcoholic Steatohepatitis in Juvenile Mouse.

Lishan Zhou,Lingling Zhang,Suqi Yan,Huan Qin,Hui Dong,Shunchang Zhou,Juan Huang,Xiaoli Xiong,Jianqiao Tang

doi:10.3389/fphar.2017.00876

Abstract

Psoralea corylifolia L. (PC) is a traditional Chinese herb used to treat yang deficiency of the spleen and kidney in pediatric disease. Recent studies have shown its liver protection and anti-oxidative effects. The aim of this study was to explore the effect and mechanism of PC on nonalcoholic steatohepatitis in juvenile mice. The juvenile mouse model of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH) was established by being fed a high-fat diet in maternal-offspring manner. PC granules were prepared and the quality was assessed. The main components were identified by high performance liquid chromatography. Then, different dosages of PC were administered for 6 weeks. Homeostatic model assessment of insulin resistance, plasma liver enzymes, hepatic morphology, hepatic superoxide anion, and triglyceride/total cholesterol levels were examined. The changes of nuclear factor-κB (NF-κB) activity phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt) and protein kinase C-α (PKC-α)/nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase signaling pathways in hepatic tissues were also determined. Our data demonstrated that PC significantly improved liver dysfunction, liver triglyceride/total cholesterol accumulation and insulin resistance in juvenile NAFLD/NASH mice. PC also alleviated hepatic steatosis, inflammatory cell infiltration, and fibroplasia in the portal area. Additionally, PC inhibited the activation of NF-κB and the mRNA expression of inflammatory factors while enhancing PI3K/Akt signaling in hepatic tissues. PC could also reduce hepatic superoxide anion levels, and NADPH oxidase activity as well as p47phox protein expression and PKCα activation in hepatic tissues. The results suggest that PC is effective in the treatment of NASH in juvenile mice. The mechanism may be related to the attenuation of hepatic oxidative stress through the PKC-α/NADPH oxidase signaling pathway.

Highlights

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide
NAFLD includes a broad spectrum of liver disease, ranging from simple steatosis to nonalcoholic steatohepatitis (NASH) and NASH can progress to liver cirrhosis and hepatocellular carcinoma
The result verified that Psoralea corylifolia L. (PC) concentrated granules prepared from Chinese traditional medicinal PC and demonstrated that the three batch granules of testing data adhere to the Chinese Pharmacopoeia standard, as qualified samples can be used in the experiment

Summary

Introduction

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. The epidemic of NAFLD is rapidly becoming a severe public health problem (Watanabe et al, 2015; Younossi et al, 2016). In China, the prevalence of childhood obesity is a major public concern (Ji, 2008; Guo et al, 2013). This may be attributed to the rise of middle-class families and the comprehensive opening of the “two-child” policy with the process of urbanization in China.

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