Hyperoside inhibits the effects induced by oxidized low-density lipoprotein in vascular smooth muscle cells via oxLDL-LOX-1-ERK pathway

Zhengyu Zhang,Baoling Du,Dongdong Zhang,Zhiqiang Chen

doi:10.1007/s11010-017-3025-x

Abstract

Hyperoside is a major active constituent in many medicinal plants traditionally used in Chinese medicines for their anti-inflammatory, antioxidative, and vascular protective effects. Recent studies have focused on the protective effects of hyperoside on hyperlipidemia. However, the molecular mechanisms underlying these effects are unknown. In this study, vascular smooth muscle cells (VSMCs) were treated in vitro with oxidized low-density lipoprotein (oxLDL) in the presence or absence of hyperoside. Western blotting, quantitative PCR, and tetrazolium assay were used to detect lectin-like oxLDL receptor-1 (LOX-1) expression and extracellular signal-regulated kinases (ERK) activation, and to determine VSMCs viability. The results demonstrated that oxLDL promoted LOX-1 expression, ERK activation, and proliferation in VSMCs. Hyperoside significantly inhibited the oxLDL-stimulated effects after long time exposure. However, it promoted ERK activation directly following a short incubation duration (25 min). In conclusion, hyperoside inhibits oxLDL-induced LOX-1 expression, ERK activation, and cell proliferation through the oxLDL-LOX-1-ERK pathway in VSMCs. Our findings suggest a novel role of hyperoside in treating and preventing atherosclerosis.

Highlights

Hyperoside is a flavonoid compound mainly found in herbal plants traditionally used in Chinese medicines and has many biological effects
The results demonstrated that oxidized low-density lipoprotein (oxLDL) promoted like oxLDL receptor-1 (LOX-1) expression, extracellular signal-regulated kinases (ERK) activation, and proliferation in vascular smooth muscle cells (VSMCs)
To determine whether hyperoside could affect LOX-1 expression induced by oxLDL, quiescent VSMCs were treated with oxLDL with or without hyperoside

Summary

Introduction

Hyperoside is a flavonoid compound mainly found in herbal plants traditionally used in Chinese medicines and has many biological effects. Accumulating evidence suggests that hyperoside has neuroprotective, anti-cancer, anti-inflammatory, antioxidative, and vascular protective effects [1,2,3,4,5,6]. The molecular mechanism underlying these effects is unknown. Oxidation and inflammation both play important roles in the development of atherosclerosis and vascular remodeling. These effects are all involved in oxidized low-density lipoprotein (oxLDL)-induced vascular damage. OxLDL-LOX-1-ERK pathway inhibition is important in the development of atherosclerosis and cardiovascular remodeling

Methods

Results

Conclusion