title: Akt/GSK-3β/eNOS phosphorylation arbitrates safranal-induced myocardial protection against ischemia-reperfusion injury in rats.
abstract: OBJECTIVE
  Traditional medicine has been appropriately identified as the most productive soil for the cultivation and harvesting of modern medicines. Herein, we postulate that safranal, an active constituent of Crocus sativus, owing to its strong antioxidant and anti-apoptotic potential, could be a valuable molecule in alleviating myocardial ischemia-reperfusion (IR) injury.
  
  
  METHODS
  To evaluate this hypothesis, safranal (0.1-0.5 mL/kg/day, i.p.) or saline were administered to rats for 14 days, and on 15th day, one-stage ligation of left anterior descending coronary artery for 45 min was performed, followed by 60 min reperfusion.
  
  
  RESULTS
  We concluded that safranal not only significantly decreased infarct size, but also improved left ventricular functions and the overall hemodynamic status of the myocardium. Interestingly, safranal enhanced phosphorylation of Akt/GSK-3β/eNOS and suppressed IKK-β/NF-κB protein expressions in IR-challenged myocardium. Our findings also imply that safranal exhibits strong anti-apoptotic potential, as evidenced by upregulated Bcl-2 expression and downregulated Bax and caspase3 expression with decreased TUNEL positivity. Moreover, safranal dose-dependently normalized myocardial antioxidant and nitrotyrosine levels, cardiac injury markers (LDH and CK-MB), and decreased TNF-α level in IR-insulted myocardium. Histopathological and ultrastructural findings correlated with the functional and biochemical outcomes showing preserved myocardial architecture and decreased inflammatory cells and edema.
  
  
  CONCLUSIONS
  Taken together, these results provide convincing evidence of safranal as an invaluable molecule in myocardial IR setting probably due to its fortified antioxidant and anti-apoptotic potential.
authors: Department of Pharmacology, All India Institute of Medical Sciences, New Delhi, India.
authors: Saurabh
authors: S
authors: Bharti
authors: Mahaveer
authors: M
authors: Golechha
authors: Santosh
authors: S
authors: Kumari
authors: Khalid Mehmood
authors: KM
authors: Siddiqui
authors: Dharamvir Singh
authors: DS
authors: Arya
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D053138:Cyclohexenes / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D020834:Ethnopharmacology; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006321:Heart / Q000187:drug effects; D007194:India; D007274:Injections, Intraperitoneal; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000276:immunology / Q000378:metabolism* / Q000648:ultrastructure; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D013729:Terpenes / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D000975:Antioxidants; D053138:Cyclohexenes; D013729:Terpenes; C087963:safranal; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3