Effect of Flos carthami on stress-activated protein kinase activity in the isolated reperfused rat heart.
The apoptotic death of cardiomyocytes due to ischemia/reperfusion is one of the major complications of heart disease. Ischemia/reperfusion has been shown to lead to the activation of the stress-activated protein (SAP) kinases and the p38/reactivating kinase (p38/RK). In this study, the direct effect of an aqueous Flos carthami (FC) extract on SAP kinases was investigated. When isolated rat hearts were perfused by Langendorff mode with media containing FC extract prior to the induction of global ischemia and the subsequent reperfusion, SAP kinase activity was inhibited 95%. Untreated ischemic/reperfused hearts showed a 57% elevation in the activity of SAP kinase. The in vitro effect of these FC extracts on SAP kinase was also tested. At a concentration of 10 microg/ml, the aqueous FC extract resulted in 50% inhibition of SAP kinase activity in ischemic heart tissue. Our results showed that FC affected both the interaction of SAP kinase with c-jun as well as the phosphotransferase reaction. These results clearly demonstrate that extracts from Flos carthami exerted inhibitory effects on SAP kinase. The administration of the FC extract may lead to a modulation of the apoptotic effect of SAP kinase activation induced during ischemia/reperfusion.
Siow
Y L
YL
Department of Pharmacology, Faculty of Medicine, University of Hong Kong, Pokfulam, Hong Kong SAR, China.
Choy
P C
PC
Leung
W M
WM
O
K
K
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000517:prevention & control; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017202:Myocardial Ischemia / Q000150:complications; D015428:Myocardial Reperfusion Injury / Q000150:complications / Q000201:enzymology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D048051:p38 Mitogen-Activated Protein Kinases
D004365:Drugs, Chinese Herbal; D004791:Enzyme Inhibitors; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases