Dendrobium nobile lindl extract modulates integrin αIIbβ3-mediated signaling pathways to inhibit platelet activation and thrombosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Dendrobium nobile Lindl. (DNL) is a promising medicinal plant. It has the traditional medicinal effects of promoting blood circulation and resolving stasis, as well as regulating the meridians and collaterals.

AIM OF THE STUDY: We studyed how DNL extract was involved in platelet activation and thrombosis and used network pharmacology and molecular docking analysis to help clarify the underlying mechanisms.

MATERIALS AND

METHODS

The effect of DNL extract on platelet aggregation and ATP release function was examined by aggregometer; The effect of DNL extract on the binding of PAC-1 and fibrinogen to integrin was determined by flow cytometry; The effect of DNL extract on "outside-in" platelet signals was detected by platelet adhesion, spreading and clot retraction; Key compounds and major targets of platelet interactions with DNL extract were analyzed by network pharmacology and molecular docking and verified against related pathway proteins by western blotting; The effect of DNL extract on thrombosis was tested by mesenteric artery embolism model.

RESULTS

DNL extract exhibited inhibition of platelet function and PAC-1 and fibrinogen binding to integrin αIIbβ3. In addition, it delayed FeCl3-induced mesenteric artery thrombosis without affecting the clotting time and the hemostatic time of tail in mice. The detection of platelet "inside-out" and "outside-in" signaling by Western blot further confirmed the inhibitory effect of DNL extract on platelet activation.

CONCLUSIONS

DNL extract may affect the thrombosis process by inhibiting platelet activation via inhibiting integrin αⅡbβ3-mediated bidirectional signaling pathway proteins.