Allicin induced vasorelaxation via endothelium-dependent and endothelium-independent mechanisms

Abstract

Allicin is an active component of garlic that exerts protective effects against cardiovascular diseases. Vascular contraction and relaxation are the essential capacities of the vascular system to maintain its normal function. Endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) are the main types of cells that control vascular function. This study was aimed at assessing the effects of allicin on vascular function and exploring its potential regulatory mechanisms. Mass spectrometry analysis was used to identify potential downstream targets of allicin in the artery. A primary culture of mouse VSMCs and ECs was established via enzymatic digestion of the aorta. Small interfering RNA (siRNA) was used to knock down the expression of the target gene, and a vector was used to upregulate specific protein expressions. Protein levels were determined using western blotting. Our results showed that allicin treatment increased both endothelium-dependent and endothelium-independent relaxation in aortic rings. Based on mass spectrometry analysis, we proposed that ATP-binding cassette transporter G1 (ABCG1), ryanodine receptor 2 (RyR2), and peroxisome proliferator-activated receptor γ (PPAR γ) might be the downstream targets of allicin. In ECs, Allicin increased ABCG1 expression and nitric oxide (NO) production, ABCG1 siRNA decreased allicin-induced NO production. RyR2 expression and Ca²⁺ spark were inhibited by allicin in VSMCs; RyR2 overexpression partly reversed the allicin-induced Ca²⁺ spark decrease in VSMCs. PPAR γ siRNA significantly inhibited the effects of allicin in ECs and VSMCs. These results indicated that allicin treatment exerted vasorelaxation effects by increasing ABCG1 expression and NO production in ECs and reducing RyR2 expression and Ca²⁺ spark in VSMCs. The PPAR γ signaling pathway was confirmed to mediate these processes.