Literature-Based Drug Repurposing in Traditional Chinese Medicine: Reduced Inflammatory M1 Macrophage Polarization by Jisil Haebaek Gyeji-Tang Alleviates Cardiovascular Disease In Vitro and Ex Vivo.

Ga-Ram Yu,Dong-Woo Lim,Jai-Eun Kim,Won-Hwan Park,Hyuck Kim,Da-Hoon Kim,Seung-Jun Lee

doi:10.1155/2020/8881683

Abstract

Relatively high proportions of proinflammatory M1-like macrophages in tissues may lead to vascular impairment and trigger numerous diseases including atherosclerosis-related cardiovascular disease (CVD). Jisil Haebaek Gyeji-tang (JHGT), a polyherbal decoction, is traditionally used to treat various human ailments including chest pain, angina, and myocardial infarction. In the present study, we investigated the anti-inflammatory effects of JHGT on lipopolysaccharide- (LPS-) stimulated M1 macrophage polarization generated via the mitogen-activated protein kinases (MAPKs) pathway in RAW 264.7 mouse macrophages. The reducing power of JHGT was also investigated using DAF-FA DA in a zebrafish model. JHGT significantly reduced inflammatory mediator levels, including iNOS, COX2, TNF-α, IL-6, and IL-1β, as compared with LPS-stimulated controls in vitro and ex vivo. Furthermore, JHGT suppressed the ERK1/2, JNK, and p38 MAPK pathways and reduced p-IκBα levels and the nuclear translocation of NF-κB in RAW 264.7 cells. In addition, treatment with JHGT significantly reduced the NO levels in LPS-treated zebrafish larva ex vivo. Our findings show the potent anti-inflammatory properties of JHGT are due to its suppression of MAPK signaling, NF-κB translocation, and M1 macrophage polarization.

Highlights

Inflammation is complex physiological response to noxious stimuli, such as physical or chemical injuries, or infections including exogenous pathogens such as bacterial lipopolysaccharide (LPS) [1, 2]
When inflammatory responses occur in blood vessels, macrophages are polarized into proinflammatory M1 and anti-inflammatory M2 types, and the proinflammatory M1 form predominates in atherosclerotic plaque [11]
Primary antibodies for lamin B, inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX2), and β-actin and horseradish peroxidase- (HRP-) conjugated secondary antibodies were purchased from Santa Cruz (Dallas, TX, USA)

Summary

Introduction

Inflammation is complex physiological response to noxious stimuli, such as physical or chemical injuries, or infections including exogenous pathogens such as bacterial lipopolysaccharide (LPS) [1, 2]. Excessive, uncontrolled proinflammatory responses can cause severe vascular damage and result in atherosclerosis-related cardiovascular diseases (CVD) [3]. Atherosclerosis is the result of a proinflammatory response of arterial walls and can give rise to macrophage polarization via plaque rupture or tissue erosion [4, 5]. E incidence of atherosclerosis-related CVD are steadily increasing in developing and developed countries, and they remain the leading cause of mortality worldwide [6]. Macrophages are the major antigen-presenting cells (APCs) and are well-known to provide crucial molecular alarm signals, which include proinflammatory cytokines, after pathogen invasion [7, 8].

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Conclusion