title: Suppression of methylglyoxal hyperactivity by mangiferin can prevent diabetes-associated cognitive decline in rats.
abstract: BACKGROUND
  Evidences indicate that methylglyoxal, a highly reactive metabolite of hyperglycemia, can enhance protein glycation, oxidative stress, or inflammation. Mangiferin, a polyphenol compound of C-glucoside, has many beneficial biological activities, including anti-inflammation, anti-oxidation, neuroprotection, cognitive enhancement, etc. Whether mangiferin alleviates diabetes-associated cognitive impairment is still unclear.
  
  
  OBJECTIVE
  The present study was designed to investigate the effects of mangiferin on the behavioral deficits of diabetic rats induced by streptozotocin; the mechanisms associated with methylglyoxal toxicity are especially investigated.
  
  
  METHODS
  Diabetic rats were treated with mangiferin (15, 30, and 60 mg/kg, p.o.) for 9 weeks. Cognitive performances were evaluated with the Morris water maze. Hippocampus and blood were obtained for evaluation of the effects of mangiferin on protein glycation, oxidative stress, and inflammation in diabetic state.
  
  
  RESULTS
  Mangiferin significantly improved the behavioral performances of diabetic rats, evidenced by a decrease in escape latency as well as increases in numbers of crossing the platform and percentage of time spent in the target quadrant, which were accompanied by decreases in the levels of advanced glycation end-products and their receptor (RAGE), interleukin-1β, TNF-α, and malondialdehyde and increases in the activity and expression of glyoxalase 1 as well as glutathione level in the hippocampus of diabetic rats. Furthermore, mangiferin produced a significant decrease in malondialdehyde level and increased glutathione level and superoxide dismutase activity in the serum of diabetic rats.
  
  
  CONCLUSIONS
  This study demonstrates that mangiferin can markedly ameliorate diabetes-associated cognitive decline in rats, which is done likely through suppressing methylglyoxal hyperactivity (promoting protein glycation, oxidative stress, and inflammation) mediated noxious effects.
authors.affiliation: Key Laboratory of New Drugs and Clinical Application, Xuzhou Medical College, No. 209, Tongshan Road, Xuzhou, 221004, Jiangsu, China.
authors.forename: Yao-Wu
authors.initials: YW
authors.lastname: Liu
authors.forename: Xia
authors.initials: X
authors.lastname: Zhu
authors.forename: Qian-Qian
authors.initials: QQ
authors.lastname: Yang
authors.forename: Qian
authors.initials: Q
authors.lastname: Lu
authors.forename: Jian-Yun
authors.initials: JY
authors.lastname: Wang
authors.forename: Hui-Pu
authors.initials: HP
authors.lastname: Li
authors.forename: Ya-Qin
authors.initials: YQ
authors.lastname: Wei
authors.forename: Jia-Le
authors.initials: JL
authors.lastname: Yin
authors.forename: Xiao-Xing
authors.initials: XX
authors.lastname: Yin
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000187:drug effects / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000187:drug effects; D006624:Hippocampus / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy / Q000209:etiology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018782:Maze Learning / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D011765:Pyruvaldehyde / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin; D013482:Superoxide Dismutase / Q000187:drug effects / Q000378:metabolism; D044004:Xanthones / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D017127:Glycation End Products, Advanced; D044004:Xanthones; C013592:mangiferin; D008315:Malondialdehyde; D013311:Streptozocin; D011765:Pyruvaldehyde; D013482:Superoxide Dismutase; D005978:Glutathione