title: Cardioprotective effect of embelin on isoproterenol-induced myocardial injury in rats: possible involvement of mitochondrial dysfunction and apoptosis.
abstract: OBJECTIVE
  Preventive and/or therapeutic interventions using natural products for ischemic heart disease have gained considerable attention worldwide. This study investigated the cardioprotective effect and possible mechanism of embelin, a major constituent of Embelia ribes Burm, using isoproterenol (ISO)-induced myocardial infarction model in rats.
  
  
  METHODS
  Rats were pretreated for three days with embelin (50mg/kg, p.o) before inducing myocardial injury by administration of ISO (85 mg/kg) subcutaneously at an interval of 24h for 2 consecutive days. Serum was analyzed for cardiac specific injury biomarkers, lipids and lipoprotein content. Heart tissues were isolated and were used for histopathology, antioxidant and mitochondrial respiratory enzyme activity assays and western blot analysis.
  
  
  RESULTS
  Results showed that pretreatment with embelin significantly decreased the elevated levels of serum specific cardiac injury biomarkers (CK-MB, LDH and AST), serum levels of lipids and lipoproteins and histopathological changes when compared to ISO-induced controls. Exploration of the underlying mechanisms of embelin action revealed that embelin pretreatment restored the myocardial mitochondrial respiratory enzyme activities (NADH dehydrogenase, succinate dehydrogenase, cytochrome c oxidase and mitochondrial redox activity), strengthened antioxidant status and attenuated ISO-induced myocardial lipid peroxidation. Immunoblot analysis revealed that embelin interrupted mitochondria dependent apoptotic damage by increasing the myocardial expression of Bcl-2 and downregulating the expression of Bax, cytochrome c, cleaved-caspase-3 & 9 and PARP. Histopathology findings further strengthened the cardioprotective findings of embelin.
  
  
  CONCLUSIONS
  Result suggested that embelin may have a potential benefit in preventing ischemic heart disease like myocardial infarction.
authors.affiliation: Medicinal Chemistry and Pharmacology Division, CSIR-Indian Institute of Chemical Technology (IICT), Hyderabad 500 007, India.
authors.forename: Bidya Dhar
authors.initials: BD
authors.lastname: Sahu
authors.affiliation: Medicinal Chemistry and Pharmacology Division, CSIR-Indian Institute of Chemical Technology (IICT), Hyderabad 500 007, India.
authors.forename: Harika
authors.initials: H
authors.lastname: Anubolu
authors.affiliation: Medicinal Chemistry and Pharmacology Division, CSIR-Indian Institute of Chemical Technology (IICT), Hyderabad 500 007, India.
authors.forename: Meghana
authors.initials: M
authors.lastname: Koneru
authors.affiliation: CSIR-Centre for Cellular and Molecular Biology (CCMB), Hyderabad 500 007, India.
authors.forename: Jerald Mahesh
authors.initials: JM
authors.lastname: Kumar
authors.affiliation: Medicinal Chemistry and Pharmacology Division, CSIR-Indian Institute of Chemical Technology (IICT), Hyderabad 500 007, India.
authors.forename: Madhusudana
authors.initials: M
authors.lastname: Kuncha
authors.affiliation: Faculty of Pharmacy, Osmania University, Hyderabad 500 007, India.
authors.forename: Shyam Sunder
authors.initials: SS
authors.lastname: Rachamalla
authors.affiliation: Medicinal Chemistry and Pharmacology Division, CSIR-Indian Institute of Chemical Technology (IICT), Hyderabad 500 007, India. Electronic address: sistla@iict.res.in.
authors.forename: Ramakrishna
authors.initials: R
authors.lastname: Sistla
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects*; D016227:Benzoquinones / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D002316:Cardiotonic Agents / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D007545:Isoproterenol / Q000633:toxicity*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D009203:Myocardial Infarction / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D029623:Primulaceae / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000975:Antioxidants; D016227:Benzoquinones; D015415:Biomarkers; D002316:Cardiotonic Agents; D005978:Glutathione; D007545:Isoproterenol; C010945:embelin
keywords: Apoptosis; Embelin; Isoproterenol; Mitochondrial dysfunction; Oxidative stress