dc.contributor.author	Nadri, Muhammad Helmi
dc.date.accessioned	2023-04-29T03:34:48Z
dc.date.available	2023-04-29T03:34:48Z
dc.date.issued	2016
dc.description	Thesis (Ph.D (Bioscience))
dc.description.abstract	Previous cell culture-based studies have shown potential health benefits of polyphenolic compounds conveyed by fruit and vegetables. However, most of these studies have rather tested higher concentrations of polyphenols than those maximum plasma concentrations, which is rarely exceed 10 µM, attained after a consumption of polyphenol-rich diet. Therefore, the present in vitro study investigates the antiinflammatory and cytoprotective effects of 5,7-dimethoxyflavone (DMF) and 4’,5,7- trimethoxyflavone (TMF) at both physiological and supraphysiological concentrations. DMF and TMF were tested for inhibitory activities on cyclooxygenase-2 (COX-2) and 15-lipoxygenase (15-LOX), both play important role in inflammation, using direct enzyme inhibition assay. DMF at concentrations of 0.01-10 µM were also used to treat oxidative stress-induced human umbilical vein endothelial cells (HUVEC), to assess effects on the expression of markers related to increased vasodilation and inflammation. Particularly, markers for vasodilation including endothelial nitric oxide synthase (eNOS) and endothelin-1 (ET-1), and markers for inflammation such as intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), were assayed using qRT-PCR. DMF and TMF strongly inhibit prostaglandins production through direct suppression of COX-2 activity, nearly equivalent to indomethacin with the mechanism mimicked current used drug, diclofenac based on molecular docking. Physiological and supraphysiological concentrations of DMF and TMF have been found to effectively abolish the effect of hydrogen peroxide (H2O2)-induced cell death in HUVEC independent of antioxidant activities. Furthermore, DMF at supraphysiological concentration was found to regulate eNOS expression at transcription rather than translational level in H2O2-induced HUVEC. In addition, H2O2 was found to increase ET-1, ICAM-1 and VCAM-1 mRNA expression in HUVEC culture and these negative effects was reversed by DMF at supraphysiological concentration. Since tested markers are the key molecules involved in the early atherogenic process, the present study emphasize a novel mechanism by which DMF may exert antiatherogenic activities under oxidative stress condition.
dc.description.sponsorship	Faculty of Biosciences and Medical Engineering
dc.identifier.uri	http://openscience.utm.my/handle/123456789/358
dc.language.iso	en
dc.publisher	Universiti Teknologi Malaysia
dc.subject	Biosciences and medical engineering
dc.title	Anti-inflammatory and cytoprotective effects of 5, 7-dimethoxyflavone and 4', 5-7 - trimethoxyflavone on human umbilical vein endothelial cells
dc.type	Thesis
dc.type	Dataset

Anti-inflammatory and cytoprotective effects of 5, 7-dimethoxyflavone and 4', 5-7 - trimethoxyflavone on human umbilical vein endothelial cells

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