Protective effect of mangiferin on myocardial ischemia-reperfusion injury in streptozotocin-induced diabetic rats: role of AGE-RAGE/MAPK pathways.
Hyperglycemia induced advanced glycation end products-receptor for advanced glycation end products (AGE-RAGE) activation is thought to involve in the development of cardiovascular disease in diabetics. Activation of AGE-RAGE axis results in the oxidative stress and inflammation. Mangiferin is found in the bark of mango tree and is known to treat diseases owing to its various biological activities. Thus, this study was designed to evaluate the effect of mangiferin in ischemia-reperfusion (IR) induced myocardial injury in diabetic rats. A single injection of STZ (70 mg/kg; i.p.) was injected to male albino Wistar rats to induce diabetes. After confirmation of diabetes, rats were administered vehicle (2 ml/kg; i.p.) and mangiferin (40 mg/kg; i.p.) for 28 days. On 28thday, left anterior descending coronary artery was ligated for 45 min and then reperfused for 60 min. Mangiferin treatment significantly improved cardiac function, restored antioxidant status, reduced inflammation, apoptosis and maintained myocardial architecture. Furthermore, mangiferin significantly inhibited the activation of AGE-RAGE axis, c-Jun N-terminal kinase (JNK) and p38 and increased the expression of extracellular regulated kinase 1/2 (ERK1/2) in the myocardium. Thus, mangiferin attenuated IR injury in diabetic rats by modulation of AGE-RAGE/MAPK pathways which further prevented oxidative stress, inflammation and apoptosis in the myocardium.
Department of Pharmacology, Cardiovascular Research Laboratory, All India Institute of Medical Sciences, New Delhi-110029, India.
Kapil
K
Suchal
Department of Pharmacology, Cardiovascular Research Laboratory, All India Institute of Medical Sciences, New Delhi-110029, India.
Salma
S
Malik
Department of Pharmacology, Cardiovascular Research Laboratory, All India Institute of Medical Sciences, New Delhi-110029, India.
Sana Irfan
SI
Khan
Department of Pharmacology, Cardiovascular Research Laboratory, All India Institute of Medical Sciences, New Delhi-110029, India.
Rajiv Kumar
RK
Malhotra
Department of Pharmacology, R.C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Maharashtra-425405, India.
Sameer N
SN
Goyal
Department of Pharmacology, Cardiovascular Research Laboratory, All India Institute of Medical Sciences, New Delhi-110029, India.
Jagriti
J
Bhatia
Indian Agricultural Research Institute, New Delhi 110012, India.
Santosh
S
Kumari
Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, Abu Dhabi 17666, United Arab Emirates.
Shreesh
S
Ojha
Department of Pharmacology, Cardiovascular Research Laboratory, All India Institute of Medical Sciences, New Delhi-110029, India.
Dharamvir Singh
DS
Arya
D000818:Animals; D002317:Cardiovascular Agents / Q000008:administration & dosage*; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D004195:Disease Models, Animal; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D008297:Male; D017202:Myocardial Ischemia / Q000150:complications*; D017208:Rats, Wistar; D000067759:Receptor for Advanced Glycation End Products / Q000378:metabolism*; D015427:Reperfusion Injury / Q000517:prevention & control*; D015398:Signal Transduction; D016896:Treatment Outcome; D044004:Xanthones / Q000008:administration & dosage*
C000593874:Ager protein, rat; D002317:Cardiovascular Agents; D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products; D044004:Xanthones; C013592:mangiferin