TY - JOUR
T1 - Kaempferide Protects against Myocardial Ischemia/Reperfusion Injury through Activation of the PI3K/Akt/GSK-3 β Pathway
AU - Wang, Dong
AU - Zhang, Xinjie
AU - Li, Defang
AU - Hao, Wenjin
AU - Meng, Fanqing
AU - Wang, Bo
AU - Han, Jichun
AU - Zheng, Qiusheng
N1 - Funding Information:
This study was supported by a funding from the Binzhou Medical University (BY2014KYQD30) to Wenjin Hao.
PY - 2017
Y1 - 2017
N2 - The aim of this study is to investigate both the efficacy and mechanism of action of kaempferide (Kae) as a therapy for the treatment of cardiovascular disease. A rat model of myocardial ischemia/reperfusion (I/R) injury was established by ligation of the left anterior descending coronary artery for 30 min followed by a 2 h perfusion. In our study, we show that Kae remarkably improved cardiac function, alleviated myocardial injury via a decrease in myocardial enzyme levels, and attenuated myocardial infarct size in a dose-dependent manner. In addition, preconditioning treatment with Kae was found to significantly decrease serum TNF-α, IL-6, C-reactive protein (CRP), MDA, and ROS levels, while it was found to increase serum levels of SOD. Nuclear factor erythroid 2-related factor 2 (Nrf2) and cleaved caspase-3 expression levels were observed to be downregulated, while phospho-Akt (p-Akt) and phospho-glycogen synthase kinase-3β (p-GSK-3β) expression levels were upregulated. However, cotreatment with LY294002 (a PI3K inhibitor) or TDZD-8 (a GSK-3β inhibitor) was found to abolish the above cardioprotective effects observed with the Kae treatment. The data presented in this study provides evidence that Kae attenuates I/R-induced myocardial injury through inhibition of the Nrf2 and cleaved caspase-3 signaling pathways via a PI3K/Akt/GSK 3β-dependent mechanism.
AB - The aim of this study is to investigate both the efficacy and mechanism of action of kaempferide (Kae) as a therapy for the treatment of cardiovascular disease. A rat model of myocardial ischemia/reperfusion (I/R) injury was established by ligation of the left anterior descending coronary artery for 30 min followed by a 2 h perfusion. In our study, we show that Kae remarkably improved cardiac function, alleviated myocardial injury via a decrease in myocardial enzyme levels, and attenuated myocardial infarct size in a dose-dependent manner. In addition, preconditioning treatment with Kae was found to significantly decrease serum TNF-α, IL-6, C-reactive protein (CRP), MDA, and ROS levels, while it was found to increase serum levels of SOD. Nuclear factor erythroid 2-related factor 2 (Nrf2) and cleaved caspase-3 expression levels were observed to be downregulated, while phospho-Akt (p-Akt) and phospho-glycogen synthase kinase-3β (p-GSK-3β) expression levels were upregulated. However, cotreatment with LY294002 (a PI3K inhibitor) or TDZD-8 (a GSK-3β inhibitor) was found to abolish the above cardioprotective effects observed with the Kae treatment. The data presented in this study provides evidence that Kae attenuates I/R-induced myocardial injury through inhibition of the Nrf2 and cleaved caspase-3 signaling pathways via a PI3K/Akt/GSK 3β-dependent mechanism.
UR - http://www.scopus.com/inward/record.url?scp=85029790608&partnerID=8YFLogxK
U2 - 10.1155/2017/5278218
DO - 10.1155/2017/5278218
M3 - Journal article
C2 - 28928604
AN - SCOPUS:85029790608
SN - 0962-9351
VL - 2017
JO - Mediators of Inflammation
JF - Mediators of Inflammation
M1 - 5278218
ER -