Thymoquinone Reverses Homocysteine-Induced Endothelial Dysfunction Via Inhibition of Endoplasmic Reticulum-Stress Induced Oxidative Stress Pathway

• DOI: 10.17576/jsm-2024-5303-09
• Publication Date: 2024-03-20T03:55:45Z
• Authors: Siti Sarah M. Sof...; Dharmani Devi Mur...; Suhaila Abd Muid; Yuan Seng Wu; Nor Hisam Zamaksh...; Quan Fu Gan; Melonney Patrick; Norasikin Ab Azis; Srinivasa Rao Sir...; Ker Woon Choy
• Keywords: Apocynin; Endothelial Dysfunction; Tauroursodeoxycholic acid; NOX4; Thymoquinone

Hyperhomocysteinemia causes endoplasmic reticulum (ER) stress, which elevates reactive oxygen species (ROS) and induces endothelial dysfunction, the hallmark of cardiovascular diseases. Nigella sativa seeds contain thymoquinone (TQ), a cardioprotective bioactive component. Nevertheless, research on investigating effectiveness TQ in preventing dysfunction caused by homocysteine (Hcy) is scarce. Therefore, purpose this work was to examine role restoring Hcy-induced as well mechanisms behind role. Male Sprague-Dawley (SD) rat aortas were isolated then co-treated an organ bath with Hcy TQ, tauroursodeoxycholic acid (TUDCA), apocynin, or Tempol vascular function. Furthermore, human umbilical vein cells (HUVECs) treated Tempol, TUDCA H2O2 determine cell viability via phase contrast microscope dye exclusion test. ER stress pathway involvement, ROS NO bioavailability investigated using immunoassays fluorescence staining, respectively. The binding affinity GRP78 has been identified molecular docking. According our findings, hindered endothelium-dependent relaxation aorta apoptosis HUVECs. TUDCA, apocynin able counteract these negative effects. In HUVECs, treatment decreased levels, increased bioavailability, NOX4 protein. docking study outcomes, could attach effectively hydrogen bond hydrophobic connection amino at ATP pocket. Taken together, findings show that protected function inhibiting stress-mediated eNOS uncoupling.