13-HODE and 13-HOTrE, Present in the Traditional Chinese Medicine Herbal Extract di gu pi, Selectively Inhibit Platelet Function

<b>Background</b>: Platelet hyperreactivity contributes to occlusive thrombus formation in vessels, precipitating acute cardiovascular events such as myocardial infarction and stroke. Traditional Chinese Medicine (TCM) has been used for centuries, and numerous TCM herbs have been reported to exert anti-inflammatory and anticoagulant effects. <b>Objectives</b>: We sought to identify key compounds within the TCM-derived herbal extracts that regulate platelet activity. <b>Methods</b>: Crude and fractioned herbal extracts were screened for their ability to inhibit platelet activation in response to multiple agonists. Platelet aggregation and flow cytometry were used to assess the potency and selectivity of the compounds within the extracts. <b>Results</b>: Three extracts, di gu pi (DGP), san qi (SQ), and zi cao (ZC), demonstrated inhibitory activity and were subsequently fractionated. Fractions derived from DGP, the root bark of <i>Lycium chinense</i>, inhibited platelet aggregation and suppressed integrin activation and granule secretion downstream of collagen receptor signaling. Further analysis identified the oxidized lipids 9(S)-hydroxy-9Z,11E-octadecadienoic acid (9-HODE), 13(S)-HODE, and 13(S)-hydroxy-9Z,11E,15Z-octadecatrienoic acid (13-HOTrE) as constituents of the bioactive fractions. Both 13-HODE and 13-HOTrE selectively inhibited collagen-mediated platelet aggregation without affecting thrombin-induced activation. <b>Conclusions</b>: Collectively, these findings identify oxylipins in TCM as promising candidates for the development of antiplatelet therapies targeting platelet activity and thrombosis. These oxylipins may represent novel approaches for thrombosis and have high therapeutic potential for development as next-generation antiplatelet drugs.