Catalpol decreases peroxynitrite formation and consequently exerts cardioprotective effects against ischemia/reperfusion insult. (April 2013)

• Record Type: Journal Article
• Authors: Huang, Chaolian; Cui, Yongliang; Ji, Lele; Zhang, Wei; Li, Rong; Ma, Lei; Xing, Wenjuan; Zhou, Heping; Chen, Baoying; Yu, Jun; Zhang, Haifeng
• Is Part Of: Pharmaceutical biology. Volume 51:Number 4(2013:Apr.)
• Page Start: 463
• Page End: 473
• Publication Date: 2013-04
• Subjects: Pharmacognosy -- Periodicals; Materia medica, Vegetable -- Periodicals; 615.321
• DOI: 10.3109/13880209.2012.740052
• Languages: English
• ISSNs: 1388-0209

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <p> <italic>Context</italic>: Peroxynitrite (ONOO<sup>−</sup>) formation triggers oxidative/nitrative stress and contributes to exacerbated myocardial ischemia/reperfusion (MI/R) injury. Catalpol, an iridoid glycoside, abundantly found in the roots of <italic>Rehmannia glutinosa</italic> L. that is included in the family Phrymaceae in the order Lamiales, endemic to China, was found to have neuroprotective effects. However, the effect of catalpol on MI/R injury has not been identified.</p> <p> <italic>Objective</italic>: This study investigated whether catalpol attenuates oxidative/nitrative stress in acute MI/R.</p> <p> <italic>Materials and methods</italic>: Adult male rats were subjected to 30 min of myocardial ischemia and 3 h of reperfusion and were treated with saline, catalpol (5 mg/kg, i.p., 5 min before reperfusion) or catalpol plus wortmannin (15 µg/kg intraperitoneally injected 15 min before reperfusion).</p> <p> <italic>Results</italic>: Pretreatment with catalpol significantly improved cardiac functions, reduced myocardial infarction, apoptosis and necrosis of cardiomyocytes after MI/R (all <italic>p</italic> < 0.05). Meanwhile, ONOO<sup>−</sup> formation was markedly reduced after catalpol treatment (3.01 ± 0.22 vs. 4.66 ± 0.53 pmol/mg protein in vehicle, <italic>p</italic> < 0.05). In addition, catalpol increased Akt and endothelial nitric oxide synthase phosphorylation, nitric oxide (NO) production, anti-oxidant capacity and reduced MI/R-induced inducible nitric oxide synthase expression and superoxide anion (·O<sub>2</sub><sup>−</sup>) production in I/R hearts. PI3K inhibitor wortmannin not only blocked catalpol-induced Akt activation, but also attenuated all the beneficial effects of catalpol. Suppression of ONOO<sup>−</sup> formation by either catalpol or an ONOO<sup>−</sup> scavenger uric acid (5 mg/kg) reduced myocardial infarct size in MI/R rats.</p> <p> <italic>Discussion and conclusion</italic>: In conclusion, catalpol affords cardioprotection against MI/R insult by attenuating ONOO<sup>−</sup> formation, which is attributable to increased physiological NO and decreased ·O<sub>2</sub><sup>−</sup> production.</p> </abstract>