Protective Effects of Evodiamine on Myocardial Ischemia-Reperfusion Injury in Rats

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

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