ReferenceID 6499
Effect of Withanolide A on 7-Ketocholesterol Induced Cytotoxicity in hCMEC/D3 Brain Endothelial Cells
Cells
Withanolide A is a naturally occurring phytochemical that is found in Ashwagandha ( Withania somnifera , fam. Solanaceae) or Indian Ginseng. In the current study, we elucidated the effect of withanolide A on 7-ketocholes
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Record Fields
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- Reference Id
- 6499
- Evidence Id
- 23089
- Core Evidence Id
- 23089
- Source Reference Id
- 6297
- Herb2 Reference Id
- HBREF007094
- Subject Paper Key
- HBIN048308_35159267
- Pubmed Id
- 35159267
- Doi
- 10.3390/cells11030457
- Paper Title
- Effect of Withanolide A on 7-Ketocholesterol Induced Cytotoxicity in hCMEC/D3 Brain Endothelial Cells
- Paper Abstract
- Withanolide A is a naturally occurring phytochemical that is found in Ashwagandha ( Withania somnifera , fam. Solanaceae) or Indian Ginseng. In the current study, we elucidated the effect of withanolide A on 7-ketocholesterol (7KC) induced injury in hCMEC/D3 human brain endothelial cells. 7KC is a cholesterol oxidation product or oxysterol that is present in atherosclerotic plaques and is elevated in the plasma of patients with hypercholesterolemia and/or diabetes mellitus. Results showed that withanolide A significantly reduced the effects of 7KC, which include loss of endothelial cell viability, increase in expression of pro-inflammatory genes-IL-1β, IL-6, IL-8, TNF-α, cyclooxygenase-2 (COX-2), increased COX-2 enzyme activity, increased ROS formation, increased expression of inducible nitric oxide synthase and genes associated with blood clotting, including Factor 2/thrombin, Factor 8, von Willebrand factor, and thromboxane A synthase, and increased human thrombin enzyme activity. Some of the above effects of withanolide A on 7KC were reduced in the presence of the glucocorticoid receptor antagonist, mifepristone (RU486). These findings suggest that the glucocorticoid receptor could play a role in the cytoprotective, antioxidant, and anti-clotting effects of withanolide A against 7KC. Further studies are necessary to elucidate the detailed mechanisms of action of withanolide A against oxysterol-induced injury.
- Journal
- Cells
- Publish Year
- 2022
- Experiment Subject
- human; patient; hcmec/d3 human brain endothelial cells
- Experiment Type
- Cell Experiment
- Phenotype Related
- Von Willebrand; Hypercholesterolemia; Diabetes Mellitus
- Paper Title Cn
- Paper Title En
- Effect of Withanolide A on 7-Ketocholesterol Induced Cytotoxicity in hCMEC/D3 Brain Endothelial Cells
- Bilingual Status
- semi_complete