Figure 3.

Predicted/established targets of selective flavonoids in platelets: Flavonoids modulate platelet activation through multiple mechanisms. For example, quercetin inhibits Fyn and Syk phosphorylation whilst also promoting nitric oxide (NO) generation in endothelial cells. Tamarexitin inhibits Syk phosphorylation. Chrysin inhibits glycoprotein (GP)VI-mediated signalling; however, the mechanism of action for this is unknown. Tangeretin and nobiletin inhibit phosphoinositide 3-kinase (PI3K) whilst nobiletin also promotes the generation of cyclic guanosine monophosphate (cGMP). Epigallocatechin-3-gallate inhibits calcium (Ca²⁺) mobilisation by promoting the inhibitory phosphorylation of inositol trisphosphate receptor (IP₃R). Apigenin inhibits thromboxane A₂ (TxA₂) signalling by antagonising the thromboxane A₂ (TxA₂) receptor (TP receptor) whilst ginkgetin inhibits the same pathway by reversibly inhibiting COX-1. Please note that these flavonoids may have additional targets beyond those shown in this figure, and these are only a selected examples. Flavonoids are highlighted in red. Naturally occuring signalling pathways are represented by black arrows. “T” arrows denote inhibition whether it occurs naturally (black) or due to the effects of flavonoids (red). Red, dashed line indicates uncertainty in the specific target of the flavonoid. Red arrows coupled with red pluses denote potentiation of activity evoked by the flavonoid.