Arctigenin prevents monocrotaline-induced pulmonary arterial hypertension in rats.

Wei-Long Jiang,Yu-Feng Zhang,Jia-Ming Zhang,Qing-Qing Xia,Feng Wang,Xiao Han

doi:10.1039/c8ra07892k

Abstract

The hallmark features of the development of pulmonary arterial hypertension (PAH) include the proliferation of pulmonary vascular smooth muscle cells, oxidative stress, inflammation, and pulmonary artery remodeling. Arctigenin is a bioactive component of Arctium lappa that exerts anti-inflammatory and antiproliferative effects in several diseases; however, its effects on pulmonary arteries are still unclear. This study aimed to investigate the efficacy of arctigenin to prevent PAH. Rats injected with monocrotaline (MCT) progressively developed PAH. Arctigenin treatment (50 mg per kg per day, intra-peritoneally) ameliorated right ventricular systolic pressure and pulmonary arterial remodeling, decreased the expression of inflammatory cytokines, and limited the proliferation of pulmonary vascular smooth muscle cells in lungs. Mechanistically, arctigenin effectively inhibited the MCT-induced elevation of NLRP3, caspase-1, and interleukin 1-beta expression in the lungs. These results indicate that arctigenin ameliorates MCT-induced PAH, at least in part, through exerting its anti-inflammatory, antioxidant, and antiproliferative effects, which inhibit the NLRP3 inflammasome signal pathway in rats.

Highlights

Pulmonary arterial hypertension (PAH) is a progressive and fatal disease featuring structural changes in the pulmonary vasculature, which may induce a severe increase in pulmonary arterial pressure, right ventricular (RV) failure, and death.[1]
ARC prevents the MCT-induced increase in Right ventricle systolic pressure (RVSP), RV hypertrophy, and pulmonary artery remodeling MCT-exposed rats developed signi cant pulmonary hypertension 28 days a er MCT injection
In the MCT groups, signi cant RV hypertrophy and increased medial thickness of pulmonary arteries developed as a consequence of PAH

Summary

Introduction

Pulmonary arterial hypertension (PAH) is a progressive and fatal disease featuring structural changes in the pulmonary vasculature, which may induce a severe increase in pulmonary arterial pressure, right ventricular (RV) failure, and death.[1] the pathogenesis of PAH is still unclear, evidence suggests that PAH development is associated with in ammatory activation, endothelial dysfunction, and vascular remodeling, including cellular proliferation in both the intima and media.[2] Current therapies for chronic PAH, such as endothelin receptor antagonists and phosphodiesterase inhibitors, are mainly designed to reduce pulmonary arterial resistance by inducing vasodilation. We investigated whether ARC exerts bene cial effects on PASMC proliferation and in ammation

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