Protective Effects of Kaempferol against Myocardial Ischemia/Reperfusion Injury in Isolated Rat Heart via Antioxidant Activity and Inhibition of Glycogen Synthase Kinase-3β.
OBJECTIVE
This study aimed to evaluate the protective effect of kaempferol against myocardial ischemia/reperfusion (I/R) injury in rats.


METHODS
Left ventricular developed pressure (LVDP) and its maximum up/down rate (±dp/dt max) were recorded as myocardial function. Infarct size was detected with 2,3,5-triphenyltetrazolium chloride staining. Cardiomyocyte apoptosis was determined using terminal deoxynucleotidyl nick-end labeling (TUNEL). The levels of creatine kinase (CK), lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione/glutathione disulfide (GSH/GSSG) ratio, and tumor necrosis factor-alpha (TNF-α) were determined using enzyme linked immunosorbent assay (ELISA). Moreover, total glycogen synthase kinase-3β (GSK-3β), phospho-GSK-3β (P-GSK-3β), precaspase-3, cleaved caspase-3, and cytoplasm cytochrome C were assayed using Western blot analysis.


RESULTS
Pretreatment with kaempferol significantly improved the recovery of LVDP and ±dp/dt max, as well as increased the levels of SOD and P-GSK-3β and GSH/GSSG ratio. However, the pretreatment reduced myocardial infarct size and TUNEL-positive cell rate, as well as decreased the levels of cleaved caspase-3, cytoplasm cytochrome C, CK, LDH, MDA, and TNF-α.


CONCLUSIONS
These results suggested that kaempferol provides cardioprotection via antioxidant activity and inhibition of GSK-3β activity in rats with I/R.
Shandong Provincial Qianfoshan Hospital, Jinan 250014, China ; Weifang Medical University, Weifang 261031, China.
Mingjie
M
Zhou
Binzhou Medical University, Yantai 264003, China.
Huanhuan
H
Ren
Binzhou Medical University, Yantai 264003, China.
Jichun
J
Han
Binzhou Medical University, Yantai 264003, China.
Wenjuan
W
Wang
Binzhou Medical University, Yantai 264003, China ; Pharmacy School, Shihezi University, Shihezi 832002, China.
Qiusheng
Q
Zheng
Shandong Provincial Qianfoshan Hospital, Jinan 250014, China.
Dong
D
Wang
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D044949:Kaempferols / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D020011:Protective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism; D013830:Thiadiazoles / Q000494:pharmacology
C494356:4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione; D044949:Kaempferols; D020011:Protective Agents; D013830:Thiadiazoles; C006552:kaempferol; D045304:Cytochromes c; D013482:Superoxide Dismutase; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D038362:Glycogen Synthase Kinase 3; D053148:Caspase 3; D005978:Glutathione