The Compound of Mangiferin-Berberine Salt Has Potent Activities in Modulating Lipid and Glucose Metabolisms in HepG2 Cells.

Can Wang,Wei-Jia Kong,Wei Wu,Jian-Dong Jiang

doi:10.1155/2016/8753436

Abstract

The mangiferin-berberine (MB) salt was synthesized by ionic bonding of mangiferin (M) and berberine (B) at an equal molecular ratio. This study aimed to investigate the activities of MB salt in modulating lipid and glucose metabolisms in HepG2 cells. After 24 h treatment of the studying compounds, cellular AMP-activated protein kinase α (AMPKα)/acetyl-CoA carboxylase (ACC) protein levels and carnitine palmitoyltransferase (CPT) 1 activities, intracellular lipid contents, mRNA expression levels of target genes, glucose consumption, and glucose production amounts were determined. Compound C (CC) was used in the blocking experiments. Our results showed that MB salt increased p-AMPKα (Thr172)/p-ACC (Ser79) levels and CPT1 activity and suppressed oleic acid- (OA-) induced lipid accumulation and upregulation of lipogenic genes potently in HepG2 cells. The above activities of MB salt were AMPK dependent and were superior to those of M or B when administered at an equal molar concentration. MB salt enhanced basal and insulin-stimulated glucose consumption and suppressed gluconeogenesis more potently than M or B alone. The inhibiting activity of MB salt on cellular gluconeogenesis was AMPK dependent. Our results may support MB salt as a new kind of agent for the development of novel lipid or glucose-lowering drugs in the future.

Highlights

The metabolism syndrome (MS) is characterized by dyslipidemia, glucose intolerance and/or insulin resistance, hypertension, and obesity [1]
We report for the first time that MB salt, a novel compound synthesized by conjugation of natural products M and B, is a potent AMPactivated protein kinase (AMPK) activator and has strong activities in modulating lipid and glucose metabolisms in HepG2 cells
The advantages of M and B are able to be combined in MB salt, which has greater effectiveness in modulating lipid and glucose metabolisms as compared to either agent alone

Summary

Introduction

The metabolism syndrome (MS) is characterized by dyslipidemia, glucose intolerance and/or insulin resistance, hypertension, and obesity [1]. If there are no proper interventions, MS may lead to diabetes and complications, coronary heart disease, or even cancer eventually. Chemical drugs such as biguanide and thiazolidinedione are commonly used in clinic for treatment of MS in order to improve metabolic disorders [1]. In addition to the abovementioned chemical drugs, numerous studies indicated that natural products isolated from plants might have beneficial effects in modulating lipid and glucose metabolisms, both in vitro and in animal models [2]. Some natural products are subjected to clinical studies for the treatment of metabolic diseases; among them, a few compounds may have promising application prospects [3]. The beneficial effects of M on lipid and glucose metabolisms might be related to the activation of AMPactivated protein kinase (AMPK) [5, 17, 18], a key molecule that controls energy balance and metabolism in organisms [19]

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