Abstract: Objective: The aim of the current study was to investigate the effect of tetrahydrocurcumin (THC), the major intestinal metabolite of curcumin, on human platelet activation and aggregation, as well as the possible mechanisms. Methods: Human gel-filtered platelets were pre-incubated with various concentrations of THC (0, 0.5, 1 and 10 μmol/L) for 40 minutes in vitro, followed by activation with thrombin for two minutes. Platelet surface expression of CD62P and CD63 were determined by flow cytometry. Enzyme linked immunosorbent assay (ELISA) was used to measure the levels of secretion of platelet factor-4 (PF4) and chemokine ligand 5 (CCL5). The levels of ATP released from platelets and platelet aggregation were detected in an aggregometer. Moreover, the phosphorylation of phosphoinositide 3-kinase (PI3K) and Akt were measured by Western blot. Results: Compared with the control group (with 0.05% of dimethyl sulfoxide (DMSO)), THC inhibited thrombin-induced platelet surface expression of CD62P and CD63 and the release of PF4, CCL5 and ATP, reduced the maximum platelet aggregation rate, and down-regulated the phosphorylation levels of PI3K and Akt in a concentration-dependent manner, more obvious effect being observed at 10 μmol/L (P < 0.01, P < 0.001). A specific agonist of PI3K, 740 Y-P, could partially reverse the inhibitory effect of THC on the release of PF4 and CCL5 and platelet aggregation (P < 0.05, P < 0.01). Conclusion: THC attenuates platelet activation and aggregation possibly through inhibiting PI3K/Akt signaling pathway.

Key words: tetrahydrocurcumin; platelet activation; platelet aggregation