Kaempferide Protects against Myocardial Ischemia/Reperfusion Injury through Activation of the PI3K/Akt/GSK-3β Pathway.
Dong WangXinjie ZhangDefang LiWen-Jin HaoFanqing MengBo WangJichun HanQiusheng ZhengPublished in: Mediators of inflammation (2017)
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.
Keyphrases
- signaling pathway
- pi k akt
- cardiovascular disease
- cell proliferation
- coronary artery
- left ventricular
- ischemia reperfusion injury
- induced apoptosis
- nuclear factor
- oxidative stress
- poor prognosis
- cell death
- rheumatoid arthritis
- epithelial mesenchymal transition
- immune response
- magnetic resonance imaging
- computed tomography
- pulmonary artery
- tyrosine kinase
- artificial intelligence
- protein kinase
- deep learning
- pulmonary hypertension
- breast cancer cells
- blood brain barrier
- stress induced
- machine learning
- cerebral ischemia