Nuciferine Prevents Hepatic Steatosis and Injury Induced by a High-Fat Diet in Hamsters

Fuchuan Guo,Rennan Feng,Xue Yang,Ying Li,Xiaoxia Li,Changhao Sun,Chunmei Guan,Yanwen Wang,Matias A Avila

doi:10.1371/journal.pone.0063770

Abstract

BackgroundNuciferine is a major active aporphine alkaloid from the leaves of N. nucifera Gaertn that possesses anti-hyperlipidemia, anti-hypotensive, anti-arrhythmic, and insulin secretagogue activities. However, it is currently unknown whether nuciferine can benefit hepatic lipid metabolism.Methodology/Principal FindingsIn the current study, male golden hamsters were randomly divided into four groups fed a normal diet, a high-fat diet (HFD), or a HFD supplemented with nuciferine (10 and 15 mg/kg·BW/day). After 8 weeks of intervention, HFD-induced increases in liver and visceral adipose tissue weight, dyslipidemia, liver steatosis, and mild necroinflammation in hamsters were analyzed. Nuciferine supplementation protected against HFD-induced changes, alleviated necroinflammation, and reversed serum markers of metabolic syndrome in hamsters fed a HFD. RT-PCR and western blot analyses revealed that hamsters fed a HFD had up-regulated levels of genes related to lipogenesis, increased free fatty acid infiltration, and down-regulated genes involved in lipolysis and very low density lipoprotein secretion. In addition, gene expression of cytochrome P4502E1 and tumor necrosis factor-α were also increased in the HFD group. Nuciferine supplementation clearly suppressed HFD-induced alterations in the expression of genes involved in lipid metabolism.Conclusions/SignificanceNuciferine supplementation ameliorated HFD-induced dyslipidemia as well as liver steatosis and injury. The beneficial effects of nuciferine were associated with altered expression of hepatic genes involved in lipid metabolism.

Highlights

Non-alcoholic fatty liver disease (NAFLD) is increasingly diagnosed worldwide and considered to be the most prevalent liver disorder in Western countries and China [1]
Effects of Nuciferine on Serum and Hepatic Lipids Hamsters fed a high-fat diet (HFD) showed significantly higher serum levels of total cholesterol (TC), TG, low-density lipoprotein cholesterol (LDL-C), and free fatty acid (FFA) compared to those fed a normal diet (ND), but nuciferine supplementation significantly reversed the HFDinduced elevation in serum lipid concentrations (Figure 1)
The hepatic accumulation of HFD-induced TG, TC, and FFA was significantly alleviated by nuciferine supplementation (Figure 2)

Summary

Introduction

Non-alcoholic fatty liver disease (NAFLD) is increasingly diagnosed worldwide and considered to be the most prevalent liver disorder in Western countries and China [1]. NAFLD comprises a disease spectrum which includes variable degrees of simple steatosis (fatty liver), non-alcoholic steatohepatitis (NASH), and cirrhosis. Lotus leaf extracts have been shown to possess several pharmacological properties, including antioxidant [5], antiobesity [6], hypolipidemic [7], and insulin secretagogue activities [8], which have been mainly attributed the alkaloid nuciferine ((R)-1,2dimethoxyaporphine), an aromatic ether-containing compound and a major active aporphine that was recorded as the major constituent of lotus leaf in the 2005 Chinese Pharmacopoeia [3,9]. Nuciferine is a major active aporphine alkaloid from the leaves of N. nucifera Gaertn that possesses antihyperlipidemia, anti-hypotensive, anti-arrhythmic, and insulin secretagogue activities. It is currently unknown whether nuciferine can benefit hepatic lipid metabolism

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