Shexiang Baoxin Pills Inhibited Proliferation and Migration of Human Coronary Artery Smooth Muscle Cells via PI3K/AKT/mTOR Pathway.

Lei Hua,Hanxiao Zhou,Shu He,Enzhi Jia,Jiaxin Chen,Yaqing Zhou,Yanjun Wang,Can Hou,Sheng Zhang

doi:10.3389/fcvm.2021.700630

Abstract

Background: Proliferation and migration of smooth muscle cells in the coronary artery contribute to the deterioration of coronary artery disease (CAD).Aim: This research was designed to study the function of Shexiang Baoxin pills (SBPs) on the proliferation and migration of human coronary artery smooth muscle cells (HCASMCs) and their mechanism.Methods: Oxidized low-density lipoprotein (ox-LDL) was applied to stimulate the proliferation and migration of HCASMCs. The function of ox-LDL and SBP on HCASMCs was evidenced by the cell counting kit-8 assay, cell cycle, and Transwell assay. Network pharmacology was employed to predict the potential targets and pathways of SBP on CAD. Western blot assay and molecular docking were conducted to validate the potential targets and pathways.Results: The current research revealed that 2.5 mg/L SBP significantly inhibited the proliferation and migration of HCASMCs. Besides, network pharmacology revealed 11 candidate targets. Molecular docking and Western blot assay validated that the activation of the top 2 targets STAT3 and MAPK14 was associated with the inhibition of HCASMCs. Moreover, the Western blot assay also detected that HCASMCs treated with ox-LDL promoted the phosphorylation of the PI3K/AKT/mTOR pathway, and SBP inhibited the activation of the PI3K/AKT/mTOR pathway in HCASMCs stimulated by ox-LDL.Conclusion: This study demonstrated that the treatment of CAD using SBP may result from the suppression of the proliferation and migration of HCASMCs. The mechanism of this function partly resulted from relieving the phosphorylation of targets STAT3 and MAPK14 and the PI3K/AKT/mTOR pathway. This study enhanced our comprehension of SBP and provides new targets for the treatment of CAD.

Highlights

Coronary artery disease (CAD) remains the leading cause of mortality worldwide
The addition of Shexiang Baoxin pills (SBPs) suppressed the activation of the PI3K/AKT/mTOR pathway in ox-LDL-stimulated human coronary artery smooth muscle cells (HCASMCs). These results suggested that ox-LDL increased the proliferation of HCASMCs through activating the PI3K/AKT/mTOR pathway, and SBP inhibited the phosphorylation of the pathway to suppress the multiplication of the cells
The phosphorylated protein expression of PI3K/AKT/mTOR in ox-LDL was significantly higher than the control group and the SBP group, suggesting that the mechanism of ox-LDL contributing to the proliferation of HCASMCs was through activating the phosphorylation of the PI3K/AKT/mTOR pathway, and the inhibition of the PI3K/AKT/mTOR pathway may be the reason SBP suppresses the proliferation of HCASMCs induced by ox-LDL

Summary

Introduction

Coronary artery disease (CAD) remains the leading cause of mortality worldwide. A major characteristic of atherosclerotic plaque development is the migration of vascular smooth muscle cells (VSMCs) into the intima where they proliferate. Shexiang Baoxin pills (SBPs) is a Moschus-based traditional Chinese medicine (TCM) commonly used in the clinical treatment for the relief of cardiovascular diseases [6, 7]. A previous study showed that SBP enhanced the expression of α-SMA and SM-MHC in VSMCs and decrease cell proliferation. The previous study has illustrated that SBP inhibited the proliferation and migration of VMSCs, the exact effect and the potential pathways of SBP acting on human coronary artery smooth muscle cells (HCASMCs) remain unanswered. Proliferation and migration of smooth muscle cells in the coronary artery contribute to the deterioration of coronary artery disease (CAD)

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