Combination of Colchicine and Ticagrelor Inhibits Carrageenan‐Induced Thrombi in Mice
Bu‐Chun Zhang, Rong Huang, Daigang Yang, GuiLan Chen, Yuanli Chen, Jihong Han, Shuang Zhang, Likun Ma, Xiaoxiao Yang
Abstract
The formation of a thrombus is closely related to oxidative stress and inflammation. Colchicine is one of the most commonly prescribed medication for gout treatment, with anti‐inflammation and antioxidative stress properties. Therefore, we speculated that it is possible for colchicine to treat thrombosis. In this study, we used carrageenan to induce thrombosis in BALB/c mice and fed mice with colchicine, ticagrelor, and their combination, respectively. We found colchicine inhibited carrageenan‐induced thrombi in mouse tail, and the inhibition was enhanced by ticagrelor. In vitro , colchicine inhibited thrombin‐induced retraction of human platelet clots. Mechanically, colchicine inhibited platelet activation by reducing the expression of platelet receptors, protease‐activated receptor 4 (PAR4) and CD36, and inactivating of AKT and ERK1/2 pathways. Furthermore, in human umbilical vein endothelial cells (HUVECs), colchicine showed antioxidative stress effects through increasing protein expression of glutathione peroxidase‐1 (GPx‐1), and mRNA levels of forkhead box O3 (FOXO3a) and superoxide dismutase 2 (SOD2). In RAW264.7 cells, colchicine reduced LPS‐enhanced inflammatory response through attenuating toll‐like receptor 4 (TLR4) activation. In addition, colchicine reduced LPS or ox‐LDL‐induced monocyte adhesion to HUVECs by inhibiting intercellular adhesion molecule‐1 (ICAM‐1) and vascular adhesion molecule‐1 (VCAM‐1) levels. Taken together, our study demonstrates that colchicine exerts antithrombotic function by attenuating platelet activation and inhibiting oxidative stress and inflammation. We also provide a potential new strategy for clinical treatment.