Cryptotanshinone, a lipophilic compound of Salvia miltiorrriza root, inhibits TNF-alpha-induced expression of adhesion molecules in HUVEC and attenuates rat myocardial ischemia/reperfusion injury in vivo.
The aim of the present study was to evaluate the protective effect of cryptotanshinone (CTS), one of active ingredients of Salvia miltiorrhiza root, on myocardial ischemia-reperfusion injury in rat due to inhibition of some inflammatory events that occur by NF-kappaB-activation during ischemia and reperfusion. Myocardial ischemia and reperfusion injury was induced by occluding the left anterior descending coronary artery for 30 min followed by either 2 h (biochemical analysis) or 24 h (myocardial function and infarct size measurement) reperfusion. CTS injected (i.v.) 10 min before ischemia and reperfusion insult. CTS significantly reduced the infarct size and improved ischemia and reperfusion-induced myocardial contractile dysfunction. Furthermore, CTS inhibited NF-kappaB translocation, expression of pro-inflammatory cytokines (TNF-alpha, IL-1beta, IL-6), neutrophil infiltration and MPO activity in ischemic myocardial tissues. CTS also significantly reduced plasma levels of TNF-alpha, IL-1beta due to ischemia and reperfusion. Interestingly, H(2)O(2)-stimulated NF-kappaB-luciferase activity and TNF-alpha-induced expression of vascular cell adhesion molecule-1 (VCAM-1) and intracellular adhesion molecule-1 (ICAM-1) expressions in human umbilical vein endothelial cells (HUVEC) were significantly inhibited by CTS. Taken together, it is concluded that CTS may attenuate ischemia and reperfusion-induced microcirculatory disturbances by inhibition of proinflammatory cytokine production, reduction of neutrophil infiltration and possibly inhibition of adhesion molecules through inhibition of NF-kappaB-activation during ischemia and reperfusion.
Jin
Yong Chun
YC
Department of Pharmacology, School of Medicine, Gyeongsang National University, Jinju, South Korea.
Kim
Chun Wook
CW
Kim
Young Min
YM
Nizamutdinova
Irina Tsoy
IT
Ha
Yu Mi
YM
Kim
Hye Jung
HJ
Seo
Han Geuk
HG
Son
Kun Ho
KH
Jeon
Su Jin
SJ
Kang
Sam Sik
SS
Kim
Yeong Shik
YS
Kam
Sung-Chul
SC
Lee
Jea Heun
JH
Chang
Ki Churl
KC
D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002460:Cell Line; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D057927:Hydrophobic and Hydrophilic Interactions; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy / Q000209:etiology; D017202:Myocardial Ischemia / Q000150:complications; D015428:Myocardial Reperfusion Injury / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D016328:NF-kappa B / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D010616:Phenanthrenes / Q000494:pharmacology* / Q000627:therapeutic use; D018517:Plant Roots / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D027561:Salvia miltiorrhiza / Q000737:chemistry*; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000235:genetics*; D014470:Umbilical Cord / Q000166:cytology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D015815:Cell Adhesion Molecules; D016328:NF-kappa B; D010616:Phenanthrenes; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; C037886:cryptotanshinone; D006861:Hydrogen Peroxide