Anti-Inflammatory Effect of Allicin Associated with Fibrosis in Pulmonary Arterial Hypertension.

José L Sánchez-Gloria,Karla M Rada,Ivan Rubio-Gayosso,Rogelio Hernández-Pando,Fausto Sánchez-Muñoz,Abraham S Arellano-Buendía,Horacio Osorio-Alonso,Constanza Estefanía Martínez-Olivares,Pedro Rojas-Morales,Roxana Carbó

doi:10.3390/ijms22168600

Abstract

Pulmonary arterial hypertension (PAH) is characterized by pulmonary vascular remodeling. Recent evidence supports that inflammation plays a key role in triggering and maintaining pulmonary vascular remodeling. Recent studies have shown that garlic extract has protective effects in PAH, but the precise role of allicin, a compound derived from garlic, is unknown. Thus, we used allicin to evaluate its effects on inflammation and fibrosis in PAH. Male Wistar rats were divided into three groups: control (CON), monocrotaline (60 mg/kg) (MCT), and MCT plus allicin (16 mg/kg/oral gavage) (MCT + A). Right ventricle (RV) hypertrophy and pulmonary arterial medial wall thickness were determined. IL-1β, IL-6, TNF-α, NFκB p65, Iκβ, TGF-β, and α-SMA were determined by Western blot analysis. In addition, TNF-α and TGF-β were determined by immunohistochemistry, and miR-21-5p and mRNA expressions of Cd68, Bmpr2, and Smad5 were determined by RT-qPCR. Results: Allicin prevented increases in vessel wall thickness due to TNF-α, IL-6, IL-1β, and Cd68 in the lung. In addition, TGF-β, α-SMA, and fibrosis were lower in the MCT + A group compared with the MCT group. In the RV, allicin prevented increases in TNF-α, IL-6, and TGF-β. These observations suggest that, through the modulation of proinflammatory and profibrotic markers in the lung and heart, allicin delays the progression of PAH.

Highlights

Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by the progressive loss and obstructive remodeling of the pulmonary vascular bed
We found that Right ventricle (RV) hypertrophy in the allicin-treated group was lower compared with the monocrotaline group (MCT) group (Figure 1A)
We showed that the pulmonary vessel wall was thickened and that the lumen was narrower in the MCT group compared with the control group (Figure 1B,C) (p < 0.05)

Summary

Introduction

Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by the progressive loss and obstructive remodeling of the pulmonary vascular bed. PAH leads to a progressive elevation in pulmonary arterial pressure (PAP) and pulmonary vascular resistance (PVR), resulting in functional decline and right heart failure [1]. The poor clinical outcome in patients with PAH is determined by the adaptation of right ventricle (RV). The pathogenesis of PAH remains unclear and involves numerous factors, including endothelial dysfunction, oxidative stress, and the exaggerated infiltration of inflammatory cells, as well as alterations in signaling pathways 4.0/). PAH treatments are limited to the production of vasoactive substances such as nitric oxide (NO) and prostacyclin [5]. Numerous studies have demonstrated that inflammation is associated with the development of experimental and human PAH [6]

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Discussion

Conclusion