The methanolic fraction of Centratherum anthelminticum seed downregulates pro-inflammatory cytokines,oxidative stress,and hyperglycemia in STZ-nicotinamide-induced type 2 diabetic rats |
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Authors: | Aditya Arya Shiau Chuen Cheah Chung Yeng Looi Hairin Taha Mohd. Rais Mustafa Mustafa Ali Mohd |
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Affiliation: | 1. Department of Pharmacology, Faculty of medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia;2. Department of Pharmacy, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia |
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Abstract: | This study aimed to ascertain the potential of Centratherum anthelminticum seeds methanolic fraction (CAMFs) for the management of type 2 diabetes and its associated complications. CAMFs was initially tested on β-TC6 cells for H2O2-induced nuclear factor-κB (NF-κB) translocation effects. The result displayed that CAMFs significantly inhibited NF-κB translocation from cytoplasm into the nucleus, dose-dependently. Furthermore, a 12-week sub-chronic CAMFs study was carried out on streptozotocin (STZ)-nicotinamide–induced type 2 diabetic rat model to evaluate glycemia, essential biochemical parameters, lipid levels, oxidative stress markers, and pro-inflammatory cytokines level. Our study result showed that CAMFs reduced hyperglycemia by increasing serum insulin, C-peptide, total protein, and albumin levels, significantly. Whereas, elevated blood glucose, glycated hemoglobin, lipids and enzyme activities were restored to near normal. CAMFs confirmed antioxidant potential by elevating glutathione (GSH) and reducing malondialdehyde (MDA) levels in diabetic rats. Interestingly, CAMFs down-regulated elevated tumor necrosis factor α (TNF-α), interleukin (IL)-1β and IL-6 in the tissues and serum of the diabetic rats. We conclude that CAMFs exerted apparent antidiabetic effects and demonstrated as a valuable candidate nutraceutical for insulin-resistant type 2 diabetes and its associated complications such as dyslipidemia, oxidative stress, and inflammation. |
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Keywords: | γ-GT, γ-glutamyl transpeptidase ALP, alkaline phosphatase ALT, alanine transaminase ANOVA, analysis of variance AST, aspartate transaminase ATCC, American Type Culture Collection bw, body weight CA, Centratherum anthelminticum CAMFs, crude methanolic fraction of C. anthelminticum seeds CRP, C-reactive protein DM2, type 2 diabetes DMEM, Dulbecco&rsquo s modified Eagle medium DTNB, 5,5&prime -dithiobis-2-nitrobenzoic acid FBS, fetal bovine serum FFA, free fatty acid GSSG, oxidized glutathione HbAlc, glycated hemoglobin HCS, high content screening HDL-C, high-density lipoprotein cholesterol IKK-β, NF-κB regulatory protein kinase IL, interleukin IRS, insulin receptor substrate LCMS&ndash MS, liquid chromatography&ndash tandem mass spectrometry LDL-C, low-density lipoprotein cholesterol NMR, nuclear magnetic resonance NF-κB, nuclear factor-κB PBS, phosphate-buffered saline PKC, protein kinase C ROS, reactive oxygen species SD, standard deviation SH, sulfhydryl SMc, smooth muscle cell STZ, streptozotocin TC, total cholesterol TG, triglycerides TNB, 5-thio-2-nitrobenzoic acid |
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