Bidya Dhar Sahu1, Harika Anubolu1, Meghana Koneru1, Jerald Mahesh Kumar2, Madhusudana Kuncha1, Shyam Sunder Rachamalla3, Ramakrishna Sistla4. 1. Medicinal Chemistry and Pharmacology Division, CSIR-Indian Institute of Chemical Technology (IICT), Hyderabad 500 007, India. 2. CSIR-Centre for Cellular and Molecular Biology (CCMB), Hyderabad 500 007, India. 3. Faculty of Pharmacy, Osmania University, Hyderabad 500 007, India. 4. Medicinal Chemistry and Pharmacology Division, CSIR-Indian Institute of Chemical Technology (IICT), Hyderabad 500 007, India. Electronic address: sistla@iict.res.in.
Abstract
AIMS: 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 (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. 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.
AIMS: 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 (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. 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.
Authors: Najam Ali Khan; M Abid; Aftab Ahmad; Mohammed F Abuzinadah; Mohammed Basheikh; Kamal Kishore Journal: J Pharmacol Pharmacother Date: 2017 Jul-Sep
Authors: Taseer Ahmad; Taous Khan; Tahira Tabassum; Yahya S Alqahtani; Mater H Mahnashi; Bandar A Alyami; Ali O Alqarni; Mohammed Y Alasmary; Sultan A Almedhesh; Abdul Jabbar Shah Journal: Curr Issues Mol Biol Date: 2022-07-16 Impact factor: 2.976