Hylocereus polyrhizus Peel Extract Retards Alcoholic Liver Disease Progression by Modulating Oxidative Stress and Inflammatory Responses in C57BL/6 Mice.

Wan-Ju Yeh,Hsin-Yi Yang,Chia-Chun Tsai,Jung Ko

doi:10.3390/nu12123884

Abstract

Alcoholic liver disease (ALD) has become a health problem as alcohol consumption has increased annually. Hepatic lipid accumulation, oxidative stress, and inflammation are important factors in the progression of ALD. Red pitaya (Hylocereus polyrhizus (Weber) Britt. & Rose) peel is rich in polyphenols and betanins, which possess antioxidative and anti-inflammatory properties. Therefore, the aim of this study was to investigate the effects of red pitaya peel extract (PPE) on ALD and explore the associated mechanisms. C57BL/6 J mice were administered an ethanol liquid diet for 11 weeks with or without two different doses of PPE (500 and 1000 mg/kg BW). PPE treatment significantly ameliorated liver injury and hepatic fat accumulation, and it improved hepatic lipid metabolism via increases in AMPK and PPAR-α protein expression and a decrease in SREBP-1 expression. In addition, PPE inhibited CYP2E1 and Nrf2 protein expression, reduced endotoxin levels in the serum, and decreased TLR4 and MyD88 expression and inflammatory cytokine TNF-α and IL-1β levels in the liver. In conclusion, these findings suggest that PPE may prevent the progression of ALD by modulating lipid metabolism and reducing oxidative stress and inflammatory responses.

Highlights

According to a report by the World Health Organization, alcohol consumption is related to the risks of many diseases and public health problems [1]
Long-term alcohol exposure may lead to ectopic fat accumulation in the liver because of an imbalance in lipid metabolism regulated through AMP-activated protein kinase (AMPK) [4]
We found no difference in body weight (BW) or food intake among all groups during the 11-week experimental period, and there was no difference in daily ethanol intake among the E, E + LP, and E + HP groups (15.6 ± 1.0, 14.9 ± 0.6, and 15.3 ± 0.5 g/kg/d; p > 0.05)

Summary

Introduction

According to a report by the World Health Organization, alcohol consumption is related to the risks of many diseases and public health problems [1]. Alcohol consumption may lead to alcoholic liver disease (ALD), which is the most prevalent chronic liver disease in the world and can progress from fatty liver to steatohepatitis and even fibrosis and cirrhosis [2]. Alcohol-induced lipid metabolism impairment, increased oxidative stress, and proinflammatory responses play important roles in the pathogenesis of ALD. Long-term alcohol exposure may lead to ectopic fat accumulation in the liver because of an imbalance in lipid metabolism regulated through AMP-activated protein kinase (AMPK) [4]. The inhibitory effect of ethanol on AMPK phosphorylation may upregulate hepatic sterol regulatory element-binding protein 1c (SREBP-1c) expression to increase fatty acid synthesis [5] and downregulate peroxisome proliferator-activated receptor (PPAR)-α to decrease fatty acid oxidation [6]

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