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

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...

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Main Authors: SITI SARAH, M. SOFIULLAH, DHARMANI DEVI, MURUGAN, SUHAILA, ABD MUID, Wu, Yuan Seng, Nor Hisam, Zamakshshari, QUAN, FU GAN, MELONNEY, PATRICK, NORASIKIN, AB AZIS, SRINIVASA RAO, SIRASANAGANDLA, Choy, Ker Woon
Format: Article
Language:English
Published: Penerbit UKM 2024
Subjects:
QD Chemistry
RM Therapeutics. Pharmacology
Online Access:http://ir.unimas.my/id/eprint/44483/3/Thymoquino.pdf
http://ir.unimas.my/id/eprint/44483/
https://www.ukm.my/jsm/english_journals/vol53num3_2024/contentsVol53num3_2024.html
http://doi.org/10.17576/jsm-2024-5303-09
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spelling my.unimas.ir.444832024-03-20T06:51:19Z http://ir.unimas.my/id/eprint/44483/ Thymoquinone Reverses Homocysteine-Induced Endothelial Dysfunction via Inhibition of Endoplasmic Reticulum-Stress Induced Oxidative Stress Pathway SITI SARAH, M. SOFIULLAH DHARMANI DEVI, MURUGAN SUHAILA, ABD MUID Wu, Yuan Seng Nor Hisam, Zamakshshari QUAN, FU GAN MELONNEY, PATRICK NORASIKIN, AB AZIS SRINIVASA RAO, SIRASANAGANDLA Choy, Ker Woon QD Chemistry RM Therapeutics. Pharmacology 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 the effectiveness of TQ in preventing endothelial dysfunction caused by homocysteine (Hcy) is scarce. Therefore, the purpose of this work was to examine the role of TQ in restoring Hcy-induced endothelial dysfunction as well as the mechanisms behind this role. Male Sprague-Dawley (SD) rat aortas were isolated and then co-treated in an organ bath with Hcy and TQ, tauroursodeoxycholic acid (TUDCA), apocynin, or Tempol to examine vascular function. Furthermore, human umbilical vein endothelial cells (HUVECs) were treated with Hcy and TQ, Tempol, apocynin, TUDCA or H2 O2 to determine the cell viability via a phase contrast microscope and dye exclusion test. ER stress pathway involvement, ROS and NO bioavailability were investigated using immunoassays and fluorescence staining, respectively. The binding affinity of TQ to GRP78 has been identified using molecular docking. According to our findings, Hcy hindered endotheliumdependent relaxation in an isolated aorta and caused apoptosis in HUVECs. TQ, TUDCA, Tempol, and apocynin were able to counteract these negative effects. In HUVECs, treatment with TQ decreased ROS levels, increased NO bioavailability, and decreased GRP78 and NOX4 protein. According to the molecular docking study outcomes, TQ could attach to GRP78 effectively via a hydrogen bond and a hydrophobic connection to the amino acid at GRP78 ATP binding pocket. Taken together, the findings show that TQ protected endothelial function caused by Hcy via inhibiting ER stress-mediated ROS and eNOS uncoupling. Penerbit UKM 2024 Article PeerReviewed text en http://ir.unimas.my/id/eprint/44483/3/Thymoquino.pdf SITI SARAH, M. SOFIULLAH and DHARMANI DEVI, MURUGAN and SUHAILA, ABD MUID and Wu, Yuan Seng and Nor Hisam, Zamakshshari and QUAN, FU GAN and MELONNEY, PATRICK and NORASIKIN, AB AZIS and SRINIVASA RAO, SIRASANAGANDLA and Choy, Ker Woon (2024) Thymoquinone Reverses Homocysteine-Induced Endothelial Dysfunction via Inhibition of Endoplasmic Reticulum-Stress Induced Oxidative Stress Pathway. Sains Malaysiana, 53 (3). pp. 591-604. ISSN 2735-0118 https://www.ukm.my/jsm/english_journals/vol53num3_2024/contentsVol53num3_2024.html http://doi.org/10.17576/jsm-2024-5303-09
institution Universiti Malaysia Sarawak
building Centre for Academic Information Services (CAIS)
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Malaysia Sarawak
content_source UNIMAS Institutional Repository
url_provider http://ir.unimas.my/
language English
topic QD Chemistry
RM Therapeutics. Pharmacology
spellingShingle QD Chemistry
RM Therapeutics. Pharmacology
SITI SARAH, M. SOFIULLAH
DHARMANI DEVI, MURUGAN
SUHAILA, ABD MUID
Wu, Yuan Seng
Nor Hisam, Zamakshshari
QUAN, FU GAN
MELONNEY, PATRICK
NORASIKIN, AB AZIS
SRINIVASA RAO, SIRASANAGANDLA
Choy, Ker Woon
Thymoquinone Reverses Homocysteine-Induced Endothelial Dysfunction via Inhibition of Endoplasmic Reticulum-Stress Induced Oxidative Stress Pathway
description 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 the effectiveness of TQ in preventing endothelial dysfunction caused by homocysteine (Hcy) is scarce. Therefore, the purpose of this work was to examine the role of TQ in restoring Hcy-induced endothelial dysfunction as well as the mechanisms behind this role. Male Sprague-Dawley (SD) rat aortas were isolated and then co-treated in an organ bath with Hcy and TQ, tauroursodeoxycholic acid (TUDCA), apocynin, or Tempol to examine vascular function. Furthermore, human umbilical vein endothelial cells (HUVECs) were treated with Hcy and TQ, Tempol, apocynin, TUDCA or H2 O2 to determine the cell viability via a phase contrast microscope and dye exclusion test. ER stress pathway involvement, ROS and NO bioavailability were investigated using immunoassays and fluorescence staining, respectively. The binding affinity of TQ to GRP78 has been identified using molecular docking. According to our findings, Hcy hindered endotheliumdependent relaxation in an isolated aorta and caused apoptosis in HUVECs. TQ, TUDCA, Tempol, and apocynin were able to counteract these negative effects. In HUVECs, treatment with TQ decreased ROS levels, increased NO bioavailability, and decreased GRP78 and NOX4 protein. According to the molecular docking study outcomes, TQ could attach to GRP78 effectively via a hydrogen bond and a hydrophobic connection to the amino acid at GRP78 ATP binding pocket. Taken together, the findings show that TQ protected endothelial function caused by Hcy via inhibiting ER stress-mediated ROS and eNOS uncoupling.
format Article
author SITI SARAH, M. SOFIULLAH
DHARMANI DEVI, MURUGAN
SUHAILA, ABD MUID
Wu, Yuan Seng
Nor Hisam, Zamakshshari
QUAN, FU GAN
MELONNEY, PATRICK
NORASIKIN, AB AZIS
SRINIVASA RAO, SIRASANAGANDLA
Choy, Ker Woon
author_facet SITI SARAH, M. SOFIULLAH
DHARMANI DEVI, MURUGAN
SUHAILA, ABD MUID
Wu, Yuan Seng
Nor Hisam, Zamakshshari
QUAN, FU GAN
MELONNEY, PATRICK
NORASIKIN, AB AZIS
SRINIVASA RAO, SIRASANAGANDLA
Choy, Ker Woon
author_sort SITI SARAH, M. SOFIULLAH
title Thymoquinone Reverses Homocysteine-Induced Endothelial Dysfunction via Inhibition of Endoplasmic Reticulum-Stress Induced Oxidative Stress Pathway
title_short Thymoquinone Reverses Homocysteine-Induced Endothelial Dysfunction via Inhibition of Endoplasmic Reticulum-Stress Induced Oxidative Stress Pathway
title_full Thymoquinone Reverses Homocysteine-Induced Endothelial Dysfunction via Inhibition of Endoplasmic Reticulum-Stress Induced Oxidative Stress Pathway
title_fullStr Thymoquinone Reverses Homocysteine-Induced Endothelial Dysfunction via Inhibition of Endoplasmic Reticulum-Stress Induced Oxidative Stress Pathway
title_full_unstemmed Thymoquinone Reverses Homocysteine-Induced Endothelial Dysfunction via Inhibition of Endoplasmic Reticulum-Stress Induced Oxidative Stress Pathway
title_sort thymoquinone reverses homocysteine-induced endothelial dysfunction via inhibition of endoplasmic reticulum-stress induced oxidative stress pathway
publisher Penerbit UKM
publishDate 2024
url http://ir.unimas.my/id/eprint/44483/3/Thymoquino.pdf
http://ir.unimas.my/id/eprint/44483/
https://www.ukm.my/jsm/english_journals/vol53num3_2024/contentsVol53num3_2024.html
http://doi.org/10.17576/jsm-2024-5303-09
_version_ 1794644185846906880
score 13.211869

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