Allicin, the principle active constituent in garlic, has been reported to have antihypertensive effects on drug-induced hypertension or renal hypertension in rats, but reports on spontaneously hypertensive rats (SHRs) are rare. Allicin is comprised of a variety of sulfur-containing compounds, and hydrogen sulfide (H2S) has been shown to have specific vasomotor effects. We therefore hypothesize that allicin may exert a vasorelaxant activity by inducing H2S production, and this eventually result in a reduction in blood pressure in SHRs. The in vivo antihypertensive effect of allicin was assessed using a tail-cuff method on SHRs. The in vitro vasorelaxant effect and in-depth mechanisms of allicin were explored on rat mesenteric arterial rings (RMARs) isolated from SD rats. In the in vivo study, administration of allicin (7 mg/kg and 14 mg/kg, 4 weeks, i.g) dramatically decreased the blood pressure in SHRs, which was also shown to be attenuated by H2S synthase inhibitor (PAG, 32 mg/kg, i.g). In in vitro studies, allicin (2.50-15.77 mM) produced a concentration-dependent vasorelaxation on RMARs, which was obviously reduced by preincubation with PAG. The removal of endothelium led to a decline in allicin's vasorelaxation, which was almost completely mitigated when treatment was followed with PAG. Inhibitors of nitric oxide (NO) and prostaglandin (PGI2) pathways separately suppressed the vasorelaxation induced by allicin to a certain degree. When the RMARs incubated with PAG were treated with or without the above inhibitors in separate groups, the relaxations caused by allicin were almost identical under both these conditions. Moreover, allicin treatment increased cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP) levels (downstream products of NO and PGI2 pathways), which was decreased by PAG. Additionally, allicin increased the acetylcholine-induced endothelium-derived hyperpolarizing factor (EDHF) -mediated relaxation, which was unaffected by PAG. Allicin exhibits a potent antihypertensive effect through vasodilatory properties and H2S mechanisms. Moreover, the vasodilation of allicin is partially dependent on endothelium. The endothelium-dependent vasodilation of allicin is mediated by the NO-sGC-cGMP, PGI2-AC-cAMP and EDHF pathways, of which H2S participates in the first two but not the third one. The endothelium independent vasodilation can be predominantly attributed to H2S production.

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 is the main active component of Traditional Chinese medicine, garlic. It is widely used to treat cardiovascular diseases. Our previous studies have confirmed that allicin significantly reduces blood pressure in Spontaneous Hypertension Rats (SHRs). However, the reports studying the effect of allicin on vascular and cardiac remodeling caused by hypertension are few, with their underlying mechanism not being studied in detail or fully elucidated. In this study, we treated 12-week-old SHRs with allicin for 4 weeks. After 4 weeks, allicin was shown to improve vascular and cardiac remodeling in SHRs, as evidenced by reduced cardiac left ventricular wall thickness, aortic vessel thickness, and reduced proliferating cell nuclear antigen (PCNA) and smooth muscle actin (α-SMA), and increased expression of and smooth muscle 22α (SM 22α). Additionally, allicin reduced serum IL-1β, IL-6, and TNF-α levels, improved calcium homeostasis in cardiomyocytes, downregulated calcium transportation-related CaMK II and inflammation-related NF-κB and NLRP3, which were observed in smooth muscle cells and cardiomyocytes. Thus, we inferred that allicin protected hypertensive vascular and cardiac remodeling in Spontaneous Hypertensive Rats by inhibiting the activation of the CaMK II/ NF-κB pathway. This study also provided new mechanistic insights into the anti-hypertensive vascular and cardiac remodeling effects of allicin, highlighting its therapeutic potential.

Cardiovascular disease (CVD) remains a leading cause of mortality and disability globally. Various cardiovascular diseases are often associated with ion dyshomeostasis within and outside cardiomyocytes, such as sodium ions, calcium ions and potassium ions. Calcium ions (Ca^2 +) not only participate in the contractile activity of cardiomyocytes and smooth muscle cells, but also participate in the tricarboxylic acid cycle as a cellular energy source, and act as a second messengers during many biological processes. Consequently, the concentration of calcium ions inside and outside the cell, as well as the distribution of calcium ions in various organelles and the cytoplasm are critical. Sarcoplasmic reticulum (SR)-mitochondrial calcium communication plays a crucial role in the distribution of Ca²⁺ in the cytoplasm and organelles. Disturbed calcium signaling caused by impaired calcium communication between the sarcoplasmic reticulum and mitochondria may play a significant role in the pathogenesis of cardiovascular diseases. Recent studies have increasingly demonstrated the significant role of SR-mitochondrial calcium communication in the progression of cardiovascular diseases, suggesting its potential as a therapeutic target. This review provides a summary of existing evidence supporting the contribution of SR-mitochondrial calcium communication disorders to the development of CVD, emphasizing its potential as a promising therapeutic target for CVD management.

Background: Acute myocardial infarction (AMI) is a common cardiovascular disease with high morbidity and mortality rates. Allicin, the primary active component of traditional Chinese herbs garlic, has multiple cardiovascular effects. However, the protective effect of allicin on AMI is rare. This study aimed to identify the pathways through which allicin stimulates hydrogen sulfide (H₂S) production to regulate calcium ion (Ca²⁺) homeostasis in cardiomyocytes, thereby contributing to AMI protection.Methods: In this study, we established an AMI rat model by ligating the left anterior descending branch of the coronary artery to assess the therapeutic effect of allicin. We also investigated its influence on cardiomyocyte Ca²⁺ homeostasis. To determine the role of H₂S production in the effects of allicin, we identified the H₂S synthase in healthy rat myocardial tissue and serum and then applied H₂S synthase inhibitors to block H₂S production.Results: The results indicate that allicin significantly enhanced cardiac function, raised H₂S levels in myocardial tissue and serum, reduced necrosis tissue size, decreased myocardial enzyme levels, and improved myocardial pathological changes. Surprisingly, allicin also notably increased H₂S synthase levels. These findings suggest that allicin shields AMI rats by stimulating H₂S production, acting both as a direct H₂S donor and indirectly boosting H₂S synthase expression. Furthermore, allicin enhanced Ca²⁺ homeostasis in cardiomyocytes by improving cardiomyocyte contraction kinetics and regulating the function and expression of key proteins related to Ca²⁺ transport in cardiomyocytes. The effect of allicin on Ca²⁺ homeostasis was partially decreased but not entirely abolished when H₂S production was inhibited using H₂S synthase inhibitors PAG and AOAA. This suggests that while the impact of allicin is strongly associated with H₂S, additional independent mechanisms are also involved.Conclusion: Our study presents novel evidence demonstrating that allicin modulates Ca²⁺ homeostasis in cardiomyocytes by stimulating H₂S production, thereby conferring protection against AMI. Furthermore, the protective effects of allicin are partly mediated by, but not solely reliant on, the generation of H₂S. These findings not only provide mechanistic insights into the anti-AMI effects of allicin but also underscore its therapeutic promise.