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13-HODE and 13-HOTrE, Present in the Traditional Chinese Medicine Herbal Extract di gu pi, Selectively Inhibit
Dylan Simpson1, Eliana Botta2, Pooja Yalavarthi2
1Department of Chemistry and Biochemistry, University of California Santa Cruz, Santa Cruz, CA 95064, USA.
Insights
Traditional Chinese Medicine extracts, specifically di gu pi, contain oxylipins that inhibit platelet activation. These compounds show potential for developing new antiplatelet drugs to prevent cardiovascular events.
Area of Science:
- Pharmacology
- Cardiovascular Research
- Traditional Chinese Medicine
Background:
- Platelet hyperreactivity is a key factor in forming occlusive thrombi, leading to myocardial infarction and stroke.
- Traditional Chinese Medicine (TCM) has a long history of use, with many herbs exhibiting anti-inflammatory and anticoagulant properties.
Purpose of the Study:
- To identify specific compounds in TCM herbal extracts that can regulate platelet activity.
- To explore novel therapeutic targets for preventing thrombosis.
Main Methods:
- Screening of crude and fractioned TCM herbal extracts for inhibition of platelet activation.
- Utilizing platelet aggregation assays and flow cytometry to evaluate compound potency and selectivity.
- Chemical analysis to identify active constituents within effective extracts.
Main Results:
- Three TCM extracts (di gu pi, san qi, zi cao) showed significant inhibitory activity.
- Fractions from di gu pi (Lycium chinense root bark) inhibited collagen-mediated platelet aggregation and signaling.
- Oxidized lipids, including 13(S)-HODE and 13(S)-hydroxy-9Z,11E,15Z-octadecatrienoic acid (13-HOTrE), were identified as key active compounds.
- 13-HODE and 13-HOTrE selectively inhibited collagen-induced, but not thrombin-induced, platelet aggregation.
Conclusions:
- Oxylipins found in TCM are promising candidates for novel antiplatelet therapies.
- These compounds offer a potential new strategy for targeting platelet activity and thrombosis.
- The identified oxylipins have high therapeutic potential for next-generation antiplatelet drug development.
Abstract:
Background: 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. Objectives: We sought to identify key compounds within the TCM-derived herbal extracts that regulate platelet activity. Methods: 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. Results: 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 Lycium chinense, 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. Conclusions: 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.
