Cryptotanshinone, a lipophilic compound of Salvia miltiorrriza root, inhibits TNF-α-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-kB-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-kB translocation, expression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6), neutrophil infiltration and MPO activity in ischemic myocardial tissues. CTS also significantly reduced plasma levels of TNF-α, IL-1β due to ischemia and reperfusion. Interestingly, H2O2-stimulated NF-kB-luciferase activity and TNF-α-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-kB-activation during ischemia and reperfusion.