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

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, NFкB p65, Iкβ, 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-b. These observations suggest that, through the modulation of proinflammatory and profibrotic markers in the lung and heart, allicin delays the progression of PAH.

Natural Products for the Treatment of Pulmonary Hypertension: Mechanism, Progress, and Future Opportunities

“…Furthermore, we also summarized the natural products involved in all mechanisms. Many of these natural products, such as TIIA, MLB, resveratrol, ligustrazine, astragaloside IV, baicalin, baicalein, betaine, and allicin, may act by reducing the inflammatory response [ 38 , 45 , 50 , 60 , 69 , 72 , 90 , 107 , 114 , 115 ]. MLB, SAA, ligustrazine, resveratrol, 18β-glycyrrhetinic, wogonin, and genistein ameliorate oxidative stress [ 42 , 43 , 129 , 131 , 132 , 134 , 162 ].…”

“…PVR is often accompanied by an increased expression of inflammatory factors such as TNF-α, IL-6, and IL-1β [ 113 ]. Resveratrol, puerarin, allicin, grape seed proanthocyanidin, and many other natural products can inhibit lung inflammation by reducing the expression of inflammatory factors such as TNF-α, IL-6, and IL-1β in the lung, thereby reducing pulmonary vasoconstriction and vascular remodeling [ 59 , 79 , 114 , 115 ]. Notably, some studies have indicated that IL-6 is one of the most important inflammatory cytokines in the development of PH [ 116 , 117 ].…”

Heart failure in systemic right ventricle: Mechanisms and therapeutic options

“…TGF-β pathways may therefore be beneficial as a therapeutic target. For example, treatment with allicin—derived from garlic—prevented RV fibrosis in rat models of pulmonary arterial hypertension ( 28 ). Neurohormones, such as aldosterone, angiotensin II, epinephrine, and norepinephrine, also activate cardiac myofibroblasts and stimulate collagen production ( 29 , 30 ).…”

Bioavailability, Health Benefits, and Delivery Systems of Allicin: A Review

“…40 Sanchez et al studied the anti-inflammatory effect of allicin on fibrosis in pulmonary hypertension. 41 They found that allicin inhibited the expression of interleukin-6 (IL-6), IL-1β, TNF-α, and macrophage marker (Cd68) and inhibited the activation of the NF-κB signaling pathway. Moreover, the circulating form of allicin (S-allylmercaptoglutathione, GSSA) in the in vivo system stimulated immunoglobulin secretion by binding to the scavenger receptor class B type 1 (SCARB 1) of CD 19 + B lymphocytes, which revealed an immunostimulatory effect of allicin.…”