title: Mangiferin suppressed advanced glycation end products (AGEs) through NF-κB deactivation and displayed anti-inflammatory effects in streptozotocin and high fat diet-diabetic cardiomyopathy rats.
abstract: Given the importance of the aggregation of advanced glycation end products (AGEs) and cardiac inflammation in the onset and progression of diabetic cardiomyopathy (DCM), our objective in this study was to demonstrate the cardioprotective effect of mangiferin, an antidiabetic and anti-inflammatory agent, on diabetic rat model. The DCM model was established by a high-fat diet and a low dose of streptozotocin. DCM rats were treated orally with mangiferin (20 mg/kg) for 16 weeks. Serum and left ventricular myocardium were collected for determination of inflammatory cytokines. AGEs mRNA and protein expression of nuclear factor kappa B (NF-κB) and receptor for AGEs (RAGE) in myocardium were assayed by real-time PCR and Western blot. ROS levels were measured by dihydroethidium fluorescence staining. NF-κB binding activity was assayed by TransAM NF-κB p65 ELISA kit. Chronic treatment with mangiferin decreased the levels of myocardial enzymes (CK-MB, LDH) and inflammatory mediators (TNF-α, IL-1β). Meanwhile, NF-κB is inhibited by the reduction of nuclear translocation of p65 subunit, and mangiferin reduced AGE production and decreased the mRNA and protein expression of RAGE in DCM rats. Our data indicated that mangiferin could significantly ameliorate DCM by preventing the release of inflammatory cytokines, and inhibiting ROS accumulation, AGE/RAGE production, and NF-κB nuclear translocation, suggesting that mangiferin treatment might be beneficial in DCM.
authors.affiliation: a Department of Pharmacy, Chengdu Military General Hospital, Chengdu, China.|b Centre for Heart Lung Innovation, St. Paul's Hospital, Department of Pathology and Laboratory Medicine, The University of British Columbia, Vancouver, BC, Canada.
authors.forename: Jun
authors.initials: J
authors.lastname: Hou
authors.affiliation: e Department of Cardiovascular Surgery, Jinan Military General Hospital, Jinan, China.
authors.forename: Dezhi
authors.initials: D
authors.lastname: Zheng
authors.affiliation: b Centre for Heart Lung Innovation, St. Paul's Hospital, Department of Pathology and Laboratory Medicine, The University of British Columbia, Vancouver, BC, Canada.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Fung
authors.affiliation: b Centre for Heart Lung Innovation, St. Paul's Hospital, Department of Pathology and Laboratory Medicine, The University of British Columbia, Vancouver, BC, Canada.
authors.forename: Haoyu
authors.initials: H
authors.lastname: Deng
authors.affiliation: c Department of Cardiovascular Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.affiliation: e Department of Cardiovascular Surgery, Jinan Military General Hospital, Jinan, China.
authors.forename: Jiali
authors.initials: J
authors.lastname: Liang
authors.affiliation: a Department of Pharmacy, Chengdu Military General Hospital, Chengdu, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: d Department of Traditional Chinese Medicine, Chengdu Military General Hospital, Chengdu, China.
authors.forename: Yonghe
authors.initials: Y
authors.lastname: Hu
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D058065:Diabetic Cardiomyopathies / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects*; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000067759:Receptor for Advanced Glycation End Products / Q000378:metabolism; D013311:Streptozocin / Q000494:pharmacology*; D044004:Xanthones / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; D017127:Glycation End Products, Advanced; D053583:Interleukin-1beta; D016328:NF-kappa B; D012333:RNA, Messenger; D000067759:Receptor for Advanced Glycation End Products; D044004:Xanthones; C013592:mangiferin; D013311:Streptozocin
keywords: NF-κB; advanced glycation end products; cardiomyopathie diabétique; cytokines inflammatoires; diabetic cardiomyopathy; inflammatory cytokines; mangiferin; mangiférine; produits finaux de glycation avancée