Polygonum cuspidatum Extract Exerts Antihyperlipidemic Effects by Regulation of PI3K/AKT/FOXO3 Signaling Pathway

Ting Tao,Jiayue Feng,Zibo Liu,Ting Zhang,Qing Zhang,Yunhui Chen,Yang Chen,Jia Liu,Lingyu Wang,Tao He,Ana Cipak Gasparovic

doi:10.1155/2021/3830671

Abstract

Polygonum cuspidatum (PC) has been reported to exert a potent antihyperlipidemic effect. However, its mechanisms of action and active ingredients remain elusive and require further research. In this study, we first conducted in vivo experiments to validate that Polygonum cuspidatum extract (PCE) could ameliorate the blood lipid level in hyperlipidemia model rats. Then, ultrahigh performance liquid chromatography coupled with Q-Exactive MS/MS (UPLC-QE-MS/MS) was applied to verify its 12 main active ingredients. The pharmacophore matching model was employed to predict the target point of the active ingredient, and 27 overlapping genes were identified via database and literature mining. String online database and Cytoscape software were utilized to construct a Protein-Protein Interaction (PPI) network, followed by function annotation analysis and pathway enrichment analysis. The results showed that the PI3K/AKT signaling pathway and its downstream FOXO3/ERα factors were significantly enriched. Furthermore, in vitro experiments were performed to determine the lipid content and oxidative stress (OS) indicators in OA-induced HepG2 cells, and immunofluorescence and western blotting analysis were carried out to analyze the effects of PCE on related proteins. Our experimental results show that the mechanism of antihyperlipidemic action of PCE is related to the activation of the PI3K/AKT signaling pathway and its downstream FOXO3/ERα factors, and polydatin and resveratrol are the main active ingredients in PCE that exert antihyperlipidemic effects.

Highlights

Hyperlipidemia is a disease of lipid metabolism featured by elevated total cholesterol (TC), total triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) and reduced high-density lipoprotein cholesterol (HDL-C) in the peripheral blood
PI3K, and no significant difference was noted in PI3K expression. These results suggested that Polygonum cuspidatum extract (PCE) might activate the PI3K/AKT pathway to exert a protective effect on OAstimulated HepG2 cells, showing an antihyperlipidemic effect
Modern studies have shown that PCE can ameliorate blood glucose and lipid metabolism and exert significant effects on the treatment of metabolic syndrome

Summary

Introduction

Hyperlipidemia is a disease of lipid metabolism featured by elevated total cholesterol (TC), total triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) and reduced high-density lipoprotein cholesterol (HDL-C) in the peripheral blood. The incidence of hyperlipidemia continues to rise due to decreased physical activities and increased consumption of fast foods high in calorie and low in fiber [1]. Proper treatment of hyperlipidemia is of great significance. Its mainstay treatments include fibrates, statins, niacin, resins, and other lipid-lowering medications [3]. They may associate with treatment resistance and intolerance and cause numerous adverse effects, such as gastrointestinal symptoms, myalgia, and respiratory infections [4]. It is necessary to research and develop more therapeutic options for hyperlipidemia

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