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.
In: Environmental Toxicology & Pharmacology, Jg. 56 (2017-12-01), S. 172-185
academicJournal
Zugriff:
Background Madhuca 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 study To 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 methods The 3,5,7,3′,4′-Pentahydroxy flavone (QTN) was isolated and characterized by using HPTLC, 1 H 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. Results Treatment 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. Conclusion Administration 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. [ABSTRACT FROM AUTHOR]
Titel: |
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.
|
---|---|
Autor/in / Beteiligte Person: | Mukherjee, Anwesha A. ; Kandhare, Amit D. ; Bodhankar, Subhash L. |
Link: | |
Zeitschrift: | Environmental Toxicology & Pharmacology, Jg. 56 (2017-12-01), S. 172-185 |
Veröffentlichung: | 2017 |
Medientyp: | academicJournal |
ISSN: | 1382-6689 (print) |
DOI: | 10.1016/j.etap.2017.08.027 |
Schlagwort: |
|
Sonstiges: |
|