Publication: EVALUATION OF ANTIATHEROSCLEROTIC ACTIVITY OF 6-SHOGAOL AND ITS UNDERLYING MECHANISMS IN HIGH-FAT DIET INDUCED ATHEROSCLEROSIS IN MICE AND HAMSTERS
| dc.contributor.author | ZHANG SHIMING | |
| dc.date.accessioned | 2024-07-14T05:56:02Z | |
| dc.date.available | 2024-07-14T05:56:02Z | |
| dc.date.issued | 2023 | |
| dc.description.abstract | 6-Shogaol is a naturally occurring compound mainly present in Zingiber officinale rhizomes and belongs to the category of a class of compounds known as gingerols. It is synthesised in plants via dehydration of 6-gingerol, a principal bioactive constituent in Z. officinale rhizomes. 6-Shogaol is the most potent active compound among all the gingerols present in Z. officinale. Many bioactivities (in vitro and in vivo), such as anti-inflammatory, antioxidant, anticancer, antiobesity, antihyperlipidaemic, etc., have been reported for 6-shogaol in the literature. Few in vitro studies have suggested the possible protective role of 6-shogaol in atherosclerosis. However, there were no in vivo studies to ascertain the antiatherosclerotic activity of 6-shogaol in physiologically relevant animal models. Many animal models to study atherosclerosis are reported in the literature, including apolipoprotein E-deficient (ApoE-/-) mice, low-density lipoprotein receptor-deficient (LDL R-/-) mice, golden hamsters, rats, etc. This study evaluated the activity and molecular mechanism of 6-shogaol in HFD-induced atherosclerosis in ApoE-/- mice and golden hamsters. 6-Shogaol was purchased from commercial suppliers, and its purity is confirmed using LC-MS. The 6-shogaol was dissolved in 10% aqueous dimethylsulfoxide (DMSO) and administered intraperitoneally. In mice, the 6-shogaol was tested at three doses: 0, 20, and 40 mg/kg, whereas in hamsters, the activity was tested at only one dose: 40 mg/kg. Atorvastatin at 10 mg/kg was used as a reference standard. The ApoE-/- mice and hamsters were fed an HFD for 3 months, followed by intraperitoneal administration of 6-shogaol and Atorvastatin on alternative days for 3 months while maintaining the animals on an HFD. The antiatherosclerotic activity of 6-shogaol in APOE -/- mice and hamsters was preliminarily assessed by observing the changes in serum biochemical parameters (glucose, cholesterol, triglycerides, liver function markers, oxidative stress markers and kidney function markers). In the case of mice, the histological changes in the aorta and liver tissues were quantified using , followed by the quantification of genes and proteins of interest associated with atherosclerosis. In the hamsters' case, the liver's histological changes were quantified using H&E and Oil Red O staining, followed by lipidomics analysis of the liver and aorta tissues. The genes were quantified using RT-qPCR (Reverse transcription-quantitative polymerase chain reaction) following the 2- Ct method. The proteins were quantified using immunohistochemical studies. The lipidomics analysis was conducted using Waters Acquity HPLC, equipped with a Q-Extractive Orbitrap mass spectrometer. 6-Shogaol has shown a dose-dependent effect in ApoE (-/-) mice and reversed the dysregulated atherosclerosis-associated biochemical parameters, histological features, gene expression, and protein expression. The activity was further confirmed in golden hamsters through biochemical, histological and lipidomics studies. The mechanism of action of 6- shogaol is multi-folded and is mediated via the regulation of lipogenesis, inflammation and oxidative stress. | |
| dc.identifier.uri | https://hdl.handle.net/20.500.14377/36546 | |
| dc.language.iso | en | |
| dc.publisher | International Medical University | |
| dc.subject | Oxidative Stress | |
| dc.subject | Diet, High-Fat | |
| dc.subject | In Vitro Techniques | |
| dc.subject | Atherosclerosis | |
| dc.subject | Inflammation | |
| dc.subject | Lipogenesis | |
| dc.title | EVALUATION OF ANTIATHEROSCLEROTIC ACTIVITY OF 6-SHOGAOL AND ITS UNDERLYING MECHANISMS IN HIGH-FAT DIET INDUCED ATHEROSCLEROSIS IN MICE AND HAMSTERS | |
| dc.type | Thesis | |
| dspace.entity.type | Publication | |
| oairecerif.author.affiliation | #PLACEHOLDER_PARENT_METADATA_VALUE# |