Liensinine Prevents Vascular Inflammation by Attenuating Inflammatory Mediators and Modulating VSMC Function

Moon Young Jun,Dong-Wook Kim,Keshav Raj Paudel,Hari Prasad Devkota,Nisha Panth,Rajendra Karki

doi:10.3390/app11010386

Moon Young Jun, Dong-Wook Kim + Show 4 more

Open Access

https://doi.org/10.3390/app11010386

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Journal: Applied sciences	Publication Date: Jan 3, 2021
Citations: 8	License type: CC BY 4.0

Affiliation: Mokpo National University, Kumamoto University

Abstract

Liensinine is a bisbenzylisoquinoline alkaloid found in various parts of the lotus (Nelumbo nucifera Gaertn.) including seeds. In this study, we explored the preventive activity of liensinine on vascular inflammation via attenuation of inflammatory mediators in macrophage and targeting the proliferation and migration of human vascular smooth muscle cells (VSMC). Anti-oxidative activity was evaluated by using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging assay method and measuring the peroxidation of serum lipid. Inflammatory markers were studied by evaluating the release of nitric oxide (NO) and the protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-2) in macrophage cells (RAW264.7) and interleukin (IL)-6 production in VSMC. Similarly, anti-proliferative activity in VSMC was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The enzymatic activity of matrix metalloproteinase (MMP)-9 in VSMC was evaluated by gelatin zymography. Liensinine possesses significant anti-oxidative activity as revealed by the DPPH assay and inhibition of serum lipid peroxidation. Likewise, liensinine decreased NO generation in RAW 264.7 cells. In VSMC, liensinine suppressed platelet-derived growth factor stimulated proliferation and tumor necrosis factor-α (TNF-α) induced MMP-9 enzymatic activity as well as IL-6 expression. Our results revealed the potential preventive effect of liensinine on vascular inflammation, suggesting it as a promising compound for the prevention of vascular inflammation.

Highlights

Atherosclerosis is defined as a chronic vascular inflammatory disorder that progresses with the lipid oxidation due to hypercholesteremia, diabetes mellitus, hypertension and various other disorders [1]
We have shown that liensinine inhibits the key features of vascular inflammation mediated by altered vascular smooth muscle cells (VSMC) function due to PDGF and tumor necrosis factor-α (TNF-α), and macrophage function by LPS (Figure 7)
Toxic insults to the blood vessel vessel wall are mediated by oxidative peroxidation, and inflammation mediwall are mediated by oxidative stress,stress, lipid lipid peroxidation, and inflammation mediators ators released by VSMC

Summary

Introduction

Atherosclerosis is defined as a chronic vascular inflammatory disorder that progresses with the lipid oxidation due to hypercholesteremia, diabetes mellitus, hypertension and various other disorders [1]. Oxidized lipids induce the secretion of various cytokines and recruit macrophages and T-lymphocytes at the site of a lesion [2]. Accelerated vascular smooth muscle cell (VSMC) migration and proliferation contribute to atherosclerotic plaque development [3,4]. It is stimulated by oxidative stress, which produces different inflammatory cytokines; tumor necrosis factor-A(TNF-A), interleukin-6 (IL-6) and growth factor such as platelet-derived growth factor-BB (PDGF-BB).

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