Quercetin targeted NF-κB to regulate platelet activation and prevent arterial thrombosis

While the inactivation effect of quercetin on platelets has been widely studied, the underlying mechanisms remained insufficiently explored. This research examined how quercetin inactivated platelets and helps to prevent thrombosis. We validated quercetin's inhibitory effects on platelet activation by CRP and collagen. We also investigated how quercetin regulated the NF-κB pathway during platelet activation and its potential impact on this process. To validate in vitro results, we created an in vivo arterial thrombus model using FeCl₃ and observed thrombus formation after quercetin administration. Quercetin inhibited platelet activation by CRP and collagen, reduced aggregation rate, and suppressed adhesion to collagen surface. This effect was linked to the NF-κB pathway. The in vitro results were validated in a FeCl₃-induced carotid artery thrombosis model. The effects of quercetin, as previously mentioned, were observed to be dose-dependent. Furthermore, the essential function of the NF-κB signaling pathway in this process has been substantiated. NF-κB was the drug target of quercetin. However, the inhibitory effect of quercetin was attenuated when the NF-κB pathway was pre-activated. Our study confirmed the antiplatelet and antithrombotic effects of quercetin. This study not only confirmed that quercetin exerted its antithrombotic effects by inhibiting the NF-κB pathway but also, more importantly, clearly identified NF-κB p65 as a direct target of quercetin through molecular docking and DARTS assays.