Cardioprotective effect of embelin on isoproterenol-induced myocardial injury in rats: Possible involvement of mitochondrial dysfunction and apoptosis

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• 作者：Bidya Dhar Sahu^a ; Harika Anubolu^a ; Meghana Koneru^a ; Jerald Mahesh Kumar^b ; Madhusudana Kuncha^a ; Shyam Sunder Rachamalla^c ; Ramakrishna Sistla^a ; ^{sistla@iict.res.in" class="auth_mail}
• 关键词：AST ; aspartate transaminase ; CAT ; catalase ; CDNB ; 1-chloro-2 ; 4-dinitrobenzene ; CK-MB ; creatine kinase-MB isoenzyme ; DCIP ; 2 ; 6-dichlorophenolindophenol ; DTNB ; 5 ; 5-dithio-bis (2-nitrobenzoic acid) ; GPx ; glutathione peroxidase ; GR ; glutathione reductase ; GSH ; reduced glutathione ; GSSH ; oxidized glutathione ; GST ; glutathione S-transferase ; HDL ; high density lipoprotein ; ISO ; isoproterenol ; LDH ; lactate dehydrogenase ; LDL ; low density lipoprotein ; MTT ; 3-(4 ; 5-dimethylthiazol-2-yl)-2 ; 5-diphenylte
• 刊名：Life Sciences
• 出版年：27 June 2014
• 年：2014
• 卷：107
• 期：1-2
• 页码：59-67
• 全文大小：1224 K

文摘

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.

Materials and methods

Rats were pretreated for three days with embelin (50 mg/kg, p.o) before inducing myocardial injury by administration of ISO (85 mg/kg) subcutaneously at an interval of 24 h 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.

Key findings

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.

Significance

Result suggested that embelin may have a potential benefit in preventing ischemic heart disease like myocardial infarction.