title: Kaempferol Attenuates Myocardial Ischemic Injury via Inhibition of MAPK Signaling Pathway in Experimental Model of Myocardial Ischemia-Reperfusion Injury.
abstract: Kaempferol (KMP), a dietary flavonoid, has antioxidant, anti-inflammatory, and antiapoptotic effects. Hence, we investigated the effect of KMP in ischemia-reperfusion (IR) model of myocardial injury in rats. We studied male albino Wistar rats that were divided into sham, IR-control, KMP-20 + IR, and KMP 20 per se groups. KMP (20 mg/kg; i.p.) was administered daily to rats for the period of 15 days, and, on the 15th day, ischemia was produced by one-stage ligation of left anterior descending coronary artery for 45 min followed by reperfusion for 60 min. After completion of surgery, rats were sacrificed; heart was removed and processed for biochemical, morphological, and molecular studies. KMP pretreatment significantly ameliorated IR injury by maintaining cardiac function, normalizing oxidative stress, and preserving morphological alterations. Furthermore, there was a decrease in the level of inflammatory markers (TNF-α, IL-6, and NFκB), inhibition of active JNK and p38 proteins, and activation of ERK1/ERK2, a prosurvival kinase. Additionally, it also attenuated apoptosis by reducing the expression of proapoptotic proteins (Bax and Caspase-3), TUNEL positive cells, and increased level of antiapoptotic proteins (Bcl-2). In conclusion, KMP protected against IR injury by attenuating inflammation and apoptosis through the modulation of MAPK pathway.
authors.affiliation: Department of Pharmacology, Cardiovascular Research Laboratory, All India Institute of Medical Sciences, New Delhi 110029, India.
authors.forename: Kapil
authors.initials: K
authors.lastname: Suchal
authors.affiliation: Department of Pharmacology, Cardiovascular Research Laboratory, All India Institute of Medical Sciences, New Delhi 110029, India.
authors.forename: Salma
authors.initials: S
authors.lastname: Malik
authors.affiliation: Department of Pharmacology, Cardiovascular Research Laboratory, All India Institute of Medical Sciences, New Delhi 110029, India.
authors.forename: Nanda
authors.initials: N
authors.lastname: Gamad
authors.affiliation: Department of Pharmacology, Cardiovascular Research Laboratory, All India Institute of Medical Sciences, New Delhi 110029, India.
authors.forename: Rajiv Kumar
authors.initials: RK
authors.lastname: Malhotra
authors.affiliation: Department of Pharmacology, R.C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Maharashtra 425405, India.
authors.forename: Sameer N
authors.initials: SN
authors.lastname: Goyal
authors.affiliation: Department of Biomedical Science, Bhaskaracharya College of Applied Science, University of Delhi, Delhi 110075, India.
authors.forename: Uma
authors.initials: U
authors.lastname: Chaudhary
authors.affiliation: Department of Pharmacology, Cardiovascular Research Laboratory, All India Institute of Medical Sciences, New Delhi 110029, India.
authors.forename: Jagriti
authors.initials: J
authors.lastname: Bhatia
authors.affiliation: Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box 17666, Al Ain, Abu Dhabi, UAE.
authors.forename: Shreesh
authors.initials: S
authors.lastname: Ojha
authors.affiliation: Department of Pharmacology, Cardiovascular Research Laboratory, All India Institute of Medical Sciences, New Delhi 110029, India.
authors.forename: Dharamvir Singh
authors.initials: DS
authors.lastname: Arya
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D006334:Heart Function Tests / Q000187:drug effects; D007249:Inflammation / Q000473:pathology; D015850:Interleukin-6 / Q000378:metabolism; D044949:Kaempferols / Q000494:pharmacology / Q000627:therapeutic use*; D015227:Lipid Peroxidation / Q000187:drug effects; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000473:pathology / Q000648:ultrastructure; D017208:Rats, Wistar; D016019:Survival Analysis; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D016276:Ventricular Function / Q000187:drug effects
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D015850:Interleukin-6; D044949:Kaempferols; D014409:Tumor Necrosis Factor-alpha; C006552:kaempferol