2-methoxycinnamaldehyde and Myocardial-Infarction

Cinnamomum cassia Blume has been used as a traditional Chinese herbal medicine for alleviation of fever, inflammation, chronic bronchitis, and to improve blood circulation.. We addressed whether 2-methoxycinnamaldehyde (2-MCA), one of active ingredients of Cinnamomum cassia, reduces vascular cell adhesion molecule-1 (VCAM-1) expression in tumor necrosis factor-alpha (TNF-α)-activated endothelial cells and protects ischemia/reperfusion (I/R)-injury due to heme oxygenase (HO)-1 induction.. Adult male rats were subjected to 30 min of ischemia by occlusion of the left anterior descending coronary artery followed by 24h of reperfusion. Rats were randomized to receive vehicle or 2-MCA (i.v.) 10 min before reperfusion.. Administration of 2-MCA significantly improved I/R-induced myocardial dysfunction by increasing the values of the first derivative (±dp/dt) of left ventricular pressure and decreased infarct size. In addition, 2-MCA reduced the expression of high mobility group box 1 (HMGB1), an activator of the inflammatory cascade when released into the extracellular space, and VCAM-1 in I/R myocardium along with increase of HO-1 induction. The reduced injury was accompanied by significantly reduction of neutrophils infiltration and increased SOD activity in ischemic tissues and reduced serum level of cardiac troponin I (cTnI). Furthermore, 2-MCA significantly increased HO-1 induction by translocation of Nrf-2 from cytosol to nucleus in endothelial cells. Inhibition of VCAM-1 expression by 2-MCA was reversed both by SnPPIX, a HO-1 inhibitor and siHO-1 RNA trasfection in TNF-α-activated cells. In addition, 2-MCA significantly inhibited NF-κB luciferase activity in TNF-α-activated endothelial cells. As expected, 2-MCA significantly inhibited monocyte (U937) adhesion to endothelial cells.. We concluded that 2-MCA protects of myocardial I/R-injury due to antioxidant and anti-inflammatory action possibly by HO-1 induction which can be explained why Cinnamomum cassia has been used in inflammatory disorders.

Topics: Acrolein; Animals; Anti-Inflammatory Agents; Antioxidants; Cardiotonic Agents; Cinnamomum aromaticum; Coculture Techniques; Disease Models, Animal; Dose-Response Relationship, Drug; Enzyme Induction; Enzyme Inhibitors; Heme Oxygenase (Decyclizing); Heme Oxygenase-1; Hemodynamics; HMGB1 Protein; Human Umbilical Vein Endothelial Cells; Humans; Male; Myocardial Infarction; Myocardial Reperfusion Injury; Myocardium; Neutrophil Infiltration; NF-kappa B; Oxidative Stress; Plant Extracts; Plants, Medicinal; Rats; Rats, Sprague-Dawley; RNA Interference; Superoxide Dismutase; Time Factors; Transfection; Troponin I; Tumor Necrosis Factor-alpha; U937 Cells; Vascular Cell Adhesion Molecule-1; Ventricular Function, Left; Ventricular Pressure