title: 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.
abstract: 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.
authors.affiliation: Department of Pharmacology, School of Medicine, Gyeongsang National University, Jinju, South Korea.
authors.forename: Yong Chun
authors.initials: YC
authors.lastname: Jin
authors.forename: Chun Wook
authors.initials: CW
authors.lastname: Kim
authors.forename: Young Min
authors.initials: YM
authors.lastname: Kim
authors.forename: Irina Tsoy
authors.initials: IT
authors.lastname: Nizamutdinova
authors.forename: Yu Mi
authors.initials: YM
authors.lastname: Ha
authors.forename: Hye Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Han Geuk
authors.initials: HG
authors.lastname: Seo
authors.forename: Kun Ho
authors.initials: KH
authors.lastname: Son
authors.forename: Su Jin
authors.initials: SJ
authors.lastname: Jeon
authors.forename: Sam Sik
authors.initials: SS
authors.lastname: Kang
authors.forename: Yeong Shik
authors.initials: YS
authors.lastname: Kim
authors.forename: Sung-Chul
authors.initials: SC
authors.lastname: Kam
authors.forename: Jea Heun
authors.initials: JH
authors.lastname: Lee
authors.forename: Ki Churl
authors.initials: KC
authors.lastname: Chang
mesh_terms: 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
chemical_list: 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