{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T09:19:27Z","timestamp":1764494367404,"version":"3.41.2"},"reference-count":62,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,3,26]],"date-time":"2025-03-26T00:00:00Z","timestamp":1742947200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>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 (H<jats:sub>2<\/jats:sub>S) production to regulate calcium ion (Ca<jats:sup>2+<\/jats:sup>) homeostasis in cardiomyocytes, thereby contributing to AMI protection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>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 Ca<jats:sup>2+<\/jats:sup> homeostasis. To determine the role of H<jats:sub>2<\/jats:sub>S production in the effects of allicin, we identified the H<jats:sub>2<\/jats:sub>S synthase in healthy rat myocardial tissue and serum and then applied H<jats:sub>2<\/jats:sub>S synthase inhibitors to block H<jats:sub>2<\/jats:sub>S production.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The results indicate that allicin significantly enhanced cardiac function, raised H<jats:sub>2<\/jats:sub>S levels in myocardial tissue and serum, reduced necrosis tissue size, decreased myocardial enzyme levels, and improved myocardial pathological changes. Surprisingly, allicin also notably increased H<jats:sub>2<\/jats:sub>S synthase levels. These findings suggest that allicin shields AMI rats by stimulating H<jats:sub>2<\/jats:sub>S production, acting both as a direct H<jats:sub>2<\/jats:sub>S donor and indirectly boosting H<jats:sub>2<\/jats:sub>S synthase expression. Furthermore, allicin enhanced Ca<jats:sup>2+<\/jats:sup> homeostasis in cardiomyocytes by improving cardiomyocyte contraction kinetics and regulating the function and expression of key proteins related to Ca<jats:sup>2+<\/jats:sup> transport in cardiomyocytes. The effect of allicin on Ca<jats:sup>2+<\/jats:sup> homeostasis was partially decreased but not entirely abolished when H<jats:sub>2<\/jats:sub>S production was inhibited using H<jats:sub>2<\/jats:sub>S synthase inhibitors PAG and AOAA. This suggests that while the impact of allicin is strongly associated with H<jats:sub>2<\/jats:sub>S, additional independent mechanisms are also involved.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our study presents novel evidence demonstrating that allicin modulates Ca<jats:sup>2+<\/jats:sup> homeostasis in cardiomyocytes by stimulating H<jats:sub>2<\/jats:sub>S production, thereby conferring protection against AMI. Furthermore, the protective effects of allicin are partly mediated by, but not solely reliant on, the generation of H<jats:sub>2<\/jats:sub>S. These findings not only provide mechanistic insights into the anti-AMI effects of allicin but also underscore its therapeutic promise.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fphar.2025.1557685","type":"journal-article","created":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T17:40:02Z","timestamp":1743183602000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Allicin ameliorates acute myocardial infarction in rats by modulating calcium homeostasis in cardiomyocytes through the induction of hydrogen sulfide production"],"prefix":"10.3389","volume":"16","author":[{"given":"Weiyu","family":"Liu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shaojun","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinxia","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruiting","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Le","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yikui","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rongmei","family":"Shi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinyan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,3,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"S1","DOI":"10.1111\/bph.13882","article-title":"The concise guide to pharmacology 2017\/18: Overview","volume":"174","author":"Alexander","year":"2017","journal-title":"Br. 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