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The methanolic fraction of Centratherum anthelminticum seed downregulates pro-inflammatory cytokines,oxidative stress,and hyperglycemia in STZ-nicotinamide-induced type 2 diabetic rats
Authors:Aditya Arya  Shiau Chuen Cheah  Chung Yeng Looi  Hairin Taha  Mohd. Rais Mustafa  Mustafa Ali Mohd
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
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.
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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