Original ArticleCrataegus oxycantha Extract Attenuates Apoptotic Incidence in Myocardial Ischemia-Reperfusion Injury by Regulating Akt and Hif-1 Signaling PathwaysJayachandran, Kesavan S PhD*†; Khan, Mahmood PhD*; Selvendiran, Karuppaiyah PhD*; Devaraj, S Niranjali PhD†; Kuppusamy, Periannan PhD*Author Information From the *Department of Internal Medicine, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH; and †Department of Biochemistry, University of Madras, Guindy Campus, Chennai, India. Received for publication June 21, 2010; accepted August 6, 2010. This work was supported by National Institutes of Health grants EB006135. The authors report no conflicts of interest. Reprints: Periannan Kuppusamy, PhD, Department of Internal Medicine, Davis Heart and Lung Research Institute, The Ohio State University, 420 West 12th Avenue, Room 114, Columbus, OH 43210 (e-mail: email@example.com). Journal of Cardiovascular Pharmacology: November 2010 - Volume 56 - Issue 5 - p 526-531 doi: 10.1097/FJC.0b013e3181f64c51 Buy Metrics Abstract The objective of the present study was to evaluate the efficacy and mechanism of Crataegus oxycantha (COC) extract in preventing ischemia-reperfusion (IR) injury in an in vivo rat model of acute myocardial infarction induced by a 30-minute regional ischemia followed by 72 hours of reperfusion. The COC extract [100 mg/(kg body weight)] was administered 12 hours after the surgical procedure and then at 24-hour intervals for 3 days. Animals treated with COC extract showed a significant decrease in creatine kinase activity and infarct size. At the molecular level, COC administration resulted in a significant attenuation of PTEN (phosphatase and tensin homolog deleted on chromosome 10) and upregulation of phospho-Akt and c-Raf levels in the heart. As a consequence, cleaved caspase-9 and cleaved caspase-7 levels were significantly downregulated, indicating negative regulation of apoptosis by COC extract. In part with the hypoxia-inducible factor (HIF) signaling pathway, COC extract administration significantly upregulated the prolyl hydroxylase-2 level. In contrast, other proapoptotic proteins such as nuclear factor-κB, cytochrome c, apoptosis-inducing factor, and cleaved poly(adenosine diphosphate-ribose) polymerase levels were significantly downregulated in the COC-treated group when compared with the untreated control group. The results suggested that COC extract attenuated apoptotic incidence in the experimental myocardial ischemia-reperfusion model by regulating Akt and HIF-1 signaling pathways. © 2010 Lippincott Williams & Wilkins, Inc.