Geum japonicum Thunb. exhibits anti-platelet activity via the regulation of cyclic guanosine monophosphate

초록

Introduction Traditionally, Geum japonicum 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.Methods 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 alpha IIb beta 3 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.Results 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 alpha IIb beta 3. 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 in vivo.Discussion 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.

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