2-methoxycinnamaldehyde from Cinnamomum cassia reduces rat myocardial ischemia and reperfusion injury in vivo due to HO-1 induction.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE:

Cinnamomum cassia Blume has been used as a traditional Chinese herbal medicine for alleviation of fever, inflammation, chronic bronchitis, and to improve blood circulation.

AIM OF THE STUDY:

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.

MATERIALS AND METHODS:

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.

RESULTS:

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.

CONCLUSION:

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.

• Authors: Jeong Seok Hwa, Yong Chun Jin, Young Soo Lee, Young Shin Ko, Young Min Kim, Lian Yu Shi, Hye Jung Kim, Jae Heun Lee, Tran Minh Ngoc, Ki Hwan Bae, Yeong Shik Kim, Ki Churl Chang
• Journal: Journal of ethnopharmacology (J Ethnopharmacol) Vol. 139 Issue 2 Pg. 605-15 (Jan 31 2012) ISSN: 1872-7573 [Electronic] Ireland
• PMID: 22179023 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Antioxidants
• Cardiotonic Agents
• Enzyme Inhibitors
• HMGB1 Protein
• Hbp1 protein, rat
• NF-kappa B
• Plant Extracts
• Troponin I
• Tumor Necrosis Factor-alpha
• Vascular Cell Adhesion Molecule-1
• 2-methoxycinnamaldehyde
• Acrolein
• HMOX1 protein, human
• Heme Oxygenase (Decyclizing)
• Heme Oxygenase-1
• Hmox1 protein, rat
• Superoxide Dismutase

Topics

• Acrolein (analogs & derivatives, isolation & purification, pharmacology)
• Animals
• Anti-Inflammatory Agents (pharmacology)
• Antioxidants (pharmacology)
• Cardiotonic Agents (isolation & purification, pharmacology)
• Cinnamomum aromaticum (chemistry)
• Coculture Techniques
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Enzyme Induction
• Enzyme Inhibitors (pharmacology)
• HMGB1 Protein (metabolism)
• Heme Oxygenase (Decyclizing) (antagonists & inhibitors, biosynthesis, genetics)
• Heme Oxygenase-1 (biosynthesis)
• Hemodynamics (drug effects)
• Human Umbilical Vein Endothelial Cells (drug effects, enzymology, immunology)
• Humans
• Male
• Myocardial Infarction (enzymology, pathology, physiopathology, prevention & control)
• Myocardial Reperfusion Injury (enzymology, pathology, physiopathology, prevention & control)
• Myocardium (enzymology, pathology)
• NF-kappa B (genetics, metabolism)
• Neutrophil Infiltration (drug effects)
• Oxidative Stress (drug effects)
• Plant Extracts (isolation & purification, pharmacology)
• Plants, Medicinal
• RNA Interference
• Rats
• Rats, Sprague-Dawley
• Superoxide Dismutase (metabolism)
• Time Factors
• Transfection
• Troponin I (metabolism)
• Tumor Necrosis Factor-alpha (metabolism)
• U937 Cells
• Vascular Cell Adhesion Molecule-1 (metabolism)
• Ventricular Function, Left (drug effects)
• Ventricular Pressure (drug effects)