Elucidation of protective efficacy of Pentahydroxy flavone isolated from Madhuca indica against arsenite-induced cardiomyopathy: Role of Nrf-2, PPAR-γ, c-fos and c-jun |
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| Institution: | 1. College of Animal Science and Veterinary Medicine, Henan Agricultural University, Zhengzhou 450002, Henan, China;2. College of Veterinary Medicine, Hunan Agricultural University, Changsha 410128, Hunan, China;3. Kansas State University, Manhattan 66506, the United States of America;1. School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, PR China;2. Center of Laboratory Animals, Sun Yat-sen University, Guangzhou 510006, PR China;3. Department of Pharmacology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, PR China;1. Department of Physiology, UCSTA, University of Calcutta, 92, A.P.C. Road, Kolkata 700009, India;2. Department of Zoology, University of Calcutta, 35, Ballygunge Circular Road, Kolkata 700019, India;1. Department of Normal Physiology, Kazan State Medical University, Butlerova st., 49, Kazan 420012, Russia;2. Kazan Institute of Biochemistry and Biophysics, Kazan Scientific Center of Russian Academy of Sciences, Laboratory of Biophysics of Synaptic Processes, Lobatchevsky str. 2/31, P.O. 30, Kazan 420111, Russia |
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| Abstract: | BackgroundMadhuca indica J. F. Gmel. (Sapotaceae) is widely used ethnobotanically as anti-diabetic, antipyretic, hepatoprotective, anti-inflammatory and analgesic. It was shown to possess potent anti-apoptotic property.The aim of the studyTo evaluate the possible mechanism of action of isolated phytoconstituent from Madhuca indica Leaves methanolic extract (MI-ALC) on arsenic-induced cardiotoxicity in rats.Materials and methodsThe 3,5,7,3′,4′-Pentahydroxy flavone (QTN) was isolated and characterized by using HPTLC, 1H NMR, and LC–MS from MI-ALC. QTN (5, 10 and 20 mg/kg, p.o.) was administered in arsenic intoxicated rats (5 mL/kg, p.o.) for 28 days and evaluated for various behavioral, biochemical, molecular and ultra-histological changes.ResultsTreatment with QTN (10 and 20 mg/kg, p.o.) significantly inhibited (p < 0.05) arsenic-induced electrocardiographic, hemodynamic and left ventricular function alterations. Elevated levels of cardiac markers (LDH, CK-MB, AST, ALT, and ALP), altered lipid metabolism (total cholesterol, triglyceride, LDL, HDL, and VLDL) was significantly restored (p < 0.05) by QTN. It also significantly inhibited (p < 0.05) altered cardiac oxido-nitrosative stress, Na-K-ATPase level and mitochondrial enzymes (I–IV) activity after arsenite administration. QTN significantly increased (p < 0.05) myocardial Nrf-2, PPAR-γ and significantly decreased (p < 0.05) myocardial c-fos and c-jun mRNA expressions. Flow cytometric analysis showed that treatment with QTN (10 and 20 mg/kg) significantly inhibited (p < 0.05) arsenite-induce ROS and apoptosis. It also reduced ultra-histological aberrations induced by sodium arsenite.ConclusionAdministration of 3,5,7,3′,4′- Pentahydroxy flavone (i.e. Quercetin (QTN)) isolated from MI-ALC showed significant protection against arsenic-induced oxido-nitrosative stress and myocardial injury via modulation of Nrf2, PPAR-γ, and apoptosis. |
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| Keywords: | 3 5 7 3′ 4′- Pentahydroxy flavone Apoptosis Cardiotoxicity c-fos c-jun Nrf-2 PPAR-γ Sodium arsenite |
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