Protective Effects of Allicin on Acute Myocardial Infarction in Rats via Hydrogen Sulfide-mediated Regulation of Coronary Arterial Vasomotor Function and Myocardial Calcium Transport

Abstract

Acute myocardial infarction (AMI) is a condition with high morbidity and mortality, for which effective treatments are lacking. Allicin has been reported to exert therapeutic effects on AMI, but the underlying mechanisms of its action have not been fully elucidated. To investigate this, a rat model of AMI was generated by ligating the left anterior descending branch of the coronary artery. DL-propargylglycine (PAG), a specific hydrogen sulfide (H2S) synthetase inhibitor, was used to examine the effects of allicin on H2S production. Isolated coronary arteries and cardiomyocytes were assessed for vascular reactivity and cellular Ca2+ transport using a multiwire myography system and a cell-contraction-ion detection system, respectively. Allicin administration improved cardiac function and myocardial pathology, reduced myocardial enzyme levels, and increased H2S and H2S synthetase levels. Allicin administration resulted in concentration-dependent effects on coronary artery dilation, which were mediated by receptor-dependent Ca2+ channels, ATP-sensitive K+ channels, and sarcoplasmic reticulum (SR) Ca2+ release induced by the ryanodine receptor. Allicin administration improved Ca2+ homeostasis in cardiomyocytes by increasing cardiomyocyte contraction, Ca2+ transient amplitude, myofilament sensitivity, and SR Ca2+ content. Allicin also enhanced Ca2+ uptake via SR Ca2+-ATPase and Ca2+ removal via the Na+/Ca2+ exchanger, and it reduced SR Ca2+ leakage. Notably, the protective effects of allicin were partially attenuated by blockade of H2S production with PAG. Our findings provide novel evidence that allicin-induced production of H2S mediates coronary artery dilation and regulation of Ca2+ homeostasis in AMI. Our study presents a novel mechanistic insight into the anti-AMI effects of allicin and highlights the therapeutic potential of this compound.

Allicin attenuated hepatic ischemia/reperfusion injury in mice by regulating PPARγ-IRAK-M-TLR4 signal pathway

“…13 It has been shown to protect against I/R injury in various organs, including the myocardium, kidney, and brain. [14][15][16] Additionally, it can help alleviate liver damage in various hepatic diseases. 17,18 Hence, we hypothesized that allicin might protect against hepatic I/R injury.…”

Cellular Mechanisms Underlying the Cardioprotective Role of Allicin on Cardiovascular Diseases

“…Other studies reported that allicin improved cardiac function, and reduced the myocardial infarct area, fibrosis, degeneration, necrosis and inflammatory cell infiltration in myocardial tissue as shown in experimental models of ischemia-reperfusion injury [ 77 , 79 , 80 , 81 ]. The cardioprotection induced by allicin was mediated by restoring the levels of SOD, CAT, GPx, and MDA in the myocardial tissue of rats [ 79 ].…”

“…Other studies in MI/R in mice showed that allicin, through modulation of the miR-19a-3p/PI3K/AKT pathway, can stimulate angiogenesis and thus revascularization of infarcted areas [ 81 ]. Moreover, it has been demonstrated that allicin improved coronary vascular reactivity in MI/R in rats through the production of hydrogen sulfide (H 2 S) and the regulation of Ca 2+ homeostasis [ 80 ]. The beneficial effects of allicin on ischemia-reperfusion have been well-known and demonstrated using cell cultures as well as in vivo in experimental models.…”

Editorial: Vascular smooth muscle cell fate and vascular remodeling: Mechanisms, therapeutic targets, and drugs, volume I

“…Benzoylaconitine enhanced endothelium-dependent vasorelaxation and reduced vascular inflammation, and therefore maybe a potential modulator of the renin-angiotensin system for the treatment of hypertension. Cui et al (2022) found that allicin, an active molecular derived from garlic, exaggerated coronary artery relaxation induced by 5-hydroxytryptamine (5-HT), 9,11-dideoxy-9α,11α-methanoepoxy-prosta-5Z,13E-dien-1-oic acid (U46619), or endothelin-1 (ET-1). Allicin relaxed VSMCs via activation of the ATP-sensitive potassium (K ATP ) channels.…”

“…VSMCs are the primary source of plaque cells and extracellular matrix in both early-and late-stage atherosclerosis Li et al (2022). have reviewed the effect of extracellular vesicles on VSMC in atherosclerosis.…”