Thymoquinone protects against cigarette smoke extract‐induced vascular dysfunction through inhibition of the RhoA/Rho‐kinase signaling pathway (849.1)
There is an ever-growing focus on the role of natural products in modulating reactive oxygen species (ROS) and RhoA/Rho kinase-mediated vascular disease. Thymoquinone (TQ), a constituent of the volatile oil derived from Nigella sativa seeds, possesses promising antioxidant and vasodilating properties via its effect on multiple signaling pathways; however, the effect of TQ on the RhoA/Rho-Kinase pathway remains to be investigated. Cigarette smoke extract (CSE)-exposed rat aortic rings were mounted in a wire myograph and subjected to contraction and relaxation. TQ protected against CSE-induced impairment of acetylcholine-induced endothelium-dependent relaxation, and decreased CSE-induced ROS generation and glutathione depletion. Preincubation of aortic rings for 20 min with TQ attenuated the CSE-enhanced phenylephrine-induced vascular tension in endothelium-denuded rings. TQ-pretreated rings showed a decrease in CSE-induced RhoA activation and phosphorylation of myosin light chain-20, myosin phosphatase-targeting subunit 1 and protein kinase CPI-17. These data indicate that TQ inhibited ROS generation-induced RhoA/Rho kinase pathway activation, protecting against CSE-induced vascular dysfunction. This study provides mechanistic insight for understanding the molecular basis and efficacy of TQ on vascular disease management. Grant Funding Source: Supported by NIH #00000784 to JLZ; Egyptian government