{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T01:49:09Z","timestamp":1774489749639,"version":"3.50.1"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T00:00:00Z","timestamp":1750896000000},"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>Introduction<\/jats:title><jats:p>Traditionally, <jats:italic>Geum japonicum<\/jats:italic> Thunb. (GJ) extract has been used to treat headaches and dizziness. We hypothesize that GJ exhibits anti-platelet activity that may prevent ischemic events to alleviate these symptoms. In this study, we investigated the anti-platelet activity of GJ as a potential mechanism for enhancing blood flow and preventing vessel occlusion.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Platelets were stimulated with collagen, adenosine diphosphate (ADP) or thrombin. Platelet aggregation was carried out using a platelet aggregometer with washed platelets from Sprague-Dawley rats. We observed the mobilization of calcium ions using Fura-2AM and adenosine triphosphate (ATP) release via a luminometer. The activation of integrin \u03b1IIb\u03b23 and population of platelet-neutrophil aggregates (PNAs) were investigated using flow cytometry. Platelet shape change was observed using scanning electron microscopy and transmission electron microscopy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>GJ extract inhibited collagen, ADP and thrombin-induced platelet aggregation. It effectively prevented the mobilization of calcium ions, ATP secretion, and serotonin release while thromboxane B2 levels did not change. Moreover, GJ inhibited the inside-out and outside-in signaling of integrin \u03b1IIb\u03b23. Notably, GJ treatment led to elevated expression of cyclic guanine monophosphate (GMP) (but not cyclic adenosine monophosphate). The protein expressions in the PI3K\/Akt pathway were inhibited and platelet shape change was prevented. Finally, GJ treatment resulted in a decreased population of PNAs <jats:italic>in vivo<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>GJ exhibits potent anti-platelet activity acting by upregulating cGMP. It holds promise as a potential candidate for supplementation in patients with cardiovascular disease and thrombosis.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fphar.2025.1538417","type":"journal-article","created":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T05:29:47Z","timestamp":1750915787000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Geum japonicum Thunb. exhibits anti-platelet activity via the regulation of cyclic guanosine monophosphate"],"prefix":"10.3389","volume":"16","author":[{"given":"Yuan Yee","family":"Lee","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abdul Wahab","family":"Akram","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Young-Hee","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muhammad","family":"Irfan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sung Dae","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evelyn","family":"Saba","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tae Wan","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bong-Sik","family":"Yun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Man Hee","family":"Rhee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,6,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1038\/513481a","article-title":"Chemistry: Chemical con artists foil drug discovery","volume":"513","author":"Baell","year":"2014","journal-title":"Nature"},{"key":"B2","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1016\/j.micron.2005.10.007","article-title":"Monocyte recruitment and foam cell formation in atherosclerosis","volume":"3","author":"Bobryshev","year":"2006","journal-title":"Micron"},{"key":"B3","doi-asserted-by":"publisher","first-page":"18S","DOI":"10.1378\/chest.124.3_suppl.18s","article-title":"Thrombin and platelet activation","volume":"3","author":"Brass","year":"2003","journal-title":"Chest"},{"key":"B4","doi-asserted-by":"publisher","first-page":"23","DOI":"10.14712\/fb2018064010023","article-title":"Pyrogallol induces apoptosis in human platelets","volume":"1","author":"Bruges","year":"2018","journal-title":"Folia Biol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"271","DOI":"10.3389\/fimmu.2016.00271","article-title":"Platelets: new bricks in the building of neutrophil extracellular traps","volume":"7","author":"Carestia","year":"2016","journal-title":"Front. 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