title: Crataegus oxycantha extract attenuates apoptotic incidence in myocardial ischemia-reperfusion injury by regulating Akt and HIF-1 signaling pathways.
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.
authors: Department of Internal Medicine, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210, USA.
authors: Kesavan S
authors: KS
authors: Jayachandran
authors: Mahmood
authors: M
authors: Khan
authors: Karuppaiyah
authors: K
authors: Selvendiran
authors: S Niranjali
authors: SN
authors: Devaraj
authors: Periannan
authors: P
authors: Kuppusamy
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D027825:Crataegus / Q000737:chemistry*; D003402:Creatine Kinase / Q000378:metabolism; D051793:Hypoxia-Inducible Factor 1 / Q000502:physiology*; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000473:pathology; D008517:Phytotherapy; D010936:Plant Extracts / Q000627:therapeutic use*; D011393:Procollagen-Proline Dioxygenase / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: D051017:Apoptosis Regulatory Proteins; D051793:Hypoxia-Inducible Factor 1; D010936:Plant Extracts; D011393:Procollagen-Proline Dioxygenase; C580731:Egln1 protein, rat; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases; D051057:Proto-Oncogene Proteins c-akt; D003402:Creatine Kinase