Subscribe to RSS
DOI: 10.1055/s-2004-835841
© Georg Thieme Verlag KG Stuttgart · New York
Protective Effects of Evodiamine on Myocardial Ischemia-Reperfusion Injury in Rats
Publication History
Received: March 31, 2004
Accepted: June 27, 2004
Publication Date:
10 January 2005 (online)

Abstract
Previous investigations have indicated that the pharmacological activities of evodiamine, a major alkaloidal component of the dried, unripe fruit of Evodia rutaecarpa Bentham (Rutaceae), are associated with the stimulation of calcitonin gene-related peptide (CGRP) release and that CGRP protects the myocardium against ischemia-reperfusion injury. In the present study, we have examined whether evodiamine protects against myocardial ischemia-reperfusion injury in rats and whether the protective effects of evodiamine are related to the activation of capsaicin-sensitive sensory nerves. Rats were pretreated with evodiamine 10 min before the experiment, and then the left main coronary artery of rat hearts was subjected to 60 min occlusion followed by 180 min reperfusion. Infarct size, the activity of serum creatine kinase, serum concentrations of TNF-α and plasma concentrations of CGRP were measured. Pretreatment with evodiamine (30 or 60 μg/kg, i. v.) markedly increased the content of CGRP in plasma concomitantly with a significant reduction in infarct size, the activity of serum creatine kinase, and TNF-α level, and the effects of evodiamine were completely abolished by capsazepine (5.0 mg/kg, s. c.), a competitive vanilloid receptor antagonist. These results suggest that evodiamine exerts a protection against myocardial ischemia-reperfusion injury in rats and that the protective effects of evodiamine are related to stimulation of CGRP release via activation of vanilloid receptors.
Key words
Ischemia-reperfusion injury - CGRP (calcitonin gene-related peptide) - evodiamine - TNF-α (tumor necrosis factor-α) - CK (creatine kinase) - infarct size - hearts of rats
References
- 1 Kobayashi Y, Nakano Y, Hoshikuma K, Yokoo Y, Kamiya T. The bronchocionstrictive action of evodiamine, an indoloquinazoline alkaloid isolated from the Evodia rutaecarpa, on guinea pig isolated bronchus: possible involvement of vanilloid receptors. Planta Med. 2000; 66 526-30
- 2 Kobayashi Y, Nakano Y, Kizaki M, Hoshikuma K, Yokoo Y, Kamiya T. Capsaicin-like anti-obese activities of evodiamine from fruits of Evodia rutaecarpa, a vanilloid receptor agonist. Planta Med. 2001; 67 628-33
- 3 Kobayashi Y, Hoshikuma K, Nakano Y, Yokoo Y, Kamiya T. The positive inotropic and chronotropic effects of evodiamine and rutaecarpine, indoloquinazoline alkaloids isolated from the fruits of Evodia rutaecarpa, on the guinea-pig isolated right atria: possible involvement of vanilloid receptors. Planta Med. 2001; 67 244-8
- 4 Kobayashi Y. The nociceptive and anti-nociceptive effects of evodiamine from fruits of Evodia rutaecarpa in mice. Planta Med. 2003; 69 425-8
- 5 Rang W Q, Du Y H, Hu C P, Ye F, Tan G S, Deng H W, Li Y J. Protective effects of calcitonin gene-related peptide-mediated evodiamine on guinea-pig cardiac anaphylaxis. Naunyn Schmiedebergs Arch Pharmacol. 2003; 367 306-11
- 6 Li Y J, Peng J. The cardioprotection of calcitonin gene-related peptide-mediated preconditioning. Eur J Pharmacol. 2002; 442 173-7
- 7 Peng J, Xiao J, Ye F, Deng H W, Li Y J. Inhibition of cardiac tumor necrosis factor-alpha production by calcitonin gene-related peptide-mediated ischemic preconditioning in isolated rat hearts. Eur J Pharmacol. 2000; 407 303-8
- 8 He S Y, Li Y J, Deng H W. Monophosphoryl lipid A-induced delayed preconditioning is mediated by calcitonin gene-related peptide. Eur J Pharmacol. 2001; 420 143-9
- 9 Frangogiannis N G, Smith C W, Entman M L. The inflammatory response in myocardial infarction. Cardiovasc Res. 2002; 53 31-47
- 10 Neri B, Bartalucci S, Romano S, Ciapini A. Evaluation of creatine kinase isoenzyme BB as a marker of neoplastic growth in Yoshida ascites hepatoma of the rat. Anticancer Res. 1985; 5 533-6
- 11 Song Q J, Li Y J, Deng H W. Early and delayed cardioprotection by heat stress is mediated by calcitonin gene-related peptide. Naunyn Schmiedeberg Arch Pharmacol. 1999; 359 477-83
- 12 Chiou W F, Chou C J, Shum A Y, Chen C F. The vasorelaxant effect of evodiamine in rat isolated mesenteric arteries: mode of action. Eur J Pharmacol. 1992; 215 277-83
- 13 Harada N, Okajima K, Uchiba M, Katsuragi T. Ischemia/reperfusion-induced increase in the hepatic level of prostacyclin is mainly mediated by activation of capsaicin-sensitive sensory neurons in rats. J Lab Clin Med. 2002; 139 218-26
Yuan-Jian Li
Department of Pharmacology
School of Pharmaceutical Sciences
Central South University
Xiang-Ya Road 110
Changsha 410078
Hunan
P. R. China
Phone: +86-731-235-5078
Fax: +86-731-235-5078
Email: yuan_jianli@yahoo.com