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Molecules 2017, 22(1), 129;

Aspalathin Protects the Heart against Hyperglycemia-Induced Oxidative Damage by Up-Regulating Nrf2 Expression

Biomedical Research and Innovation Platform (BRIP), Medical Research Council (MRC), Tygerberg 7505, South Africa
Division of Medical Physiology, Faculty of Health Sciences, Stellenbosch University, Tygerberg 7505, South Africa
Department of Biochemistry and Microbiology, University of Zululand, Kwadlangezwa 3886, South Africa
Post-Harvest and Wine Technology Division, Agricultural Research Council (ARC) Infruitec-Nietvoorbij, Stellenbosch 7599, South Africa
Department of Food Science, Stellenbosch University, Stellenbosch 7599, South Africa
Cardio-Metabolic Research Group (CMRG), Department of Physiological Sciences, Stellenbosch University, Stellenbosch 7599, South Africa
Author to whom correspondence should be addressed.
Academic Editors: Dong-Kug Choi and Palanivel Ganesan
Received: 14 November 2016 / Revised: 26 December 2016 / Accepted: 5 January 2017 / Published: 14 January 2017
(This article belongs to the Special Issue Natural Products and Chronic Diseases)
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Aspalathin (ASP) can protect H9c2 cardiomyocytes against high glucose (HG)-induced shifts in myocardial substrate preference, oxidative stress, and apoptosis. The protective mechanism of ASP remains unknown. However, as one of possible, it is well known that phytochemical flavonoids reduce oxidative stress via nuclear factor (erythroid-derived 2)-like 2 (Nrf2) activation resulting in up-regulation of antioxidant genes and enzymes. Therefore, we hypothesized that ASP protects the myocardium against HG- and hyperglycemia-induced oxidative damage by up-regulating Nrf2 expression in H9c2 cardiomyocytes and diabetic (db/db) mice, respectively. Using an oxidative stress RT2 Profiler PCR array, ASP at a dose of 1 µM was demonstrated to protect H9c2 cardiomyocytes against HG-induced oxidative stress, but silencing of Nrf2 abolished this protective response of ASP and exacerbated cardiomyocyte apoptosis. Db/db mice and their non-diabetic (db/+) littermate controls were subsequently treated daily for six weeks with either a low (13 mg/kg) or high (130 mg/kg) ASP dose. Compared to nondiabetic mice the db/db mice presented increased cardiac remodeling and enlarged left ventricular wall that occurred concomitant to enhanced oxidative stress. Daily treatment of mice with ASP at a dose of 130 mg/kg for six weeks was more effective at reversing complications than both a low dose ASP or metformin, eliciting enhanced expression of Nrf2 and its downstream antioxidant genes. These results indicate that ASP maintains cellular homeostasis and protects the myocardium against hyperglycemia-induced oxidative stress through activation of Nrf2 and its downstream target genes. View Full-Text
Keywords: diabetes mellitus; cardiomyopathy; hyperglycemia; oxidative stress; aspalathin; Nrf2 diabetes mellitus; cardiomyopathy; hyperglycemia; oxidative stress; aspalathin; Nrf2

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Dludla, P.V.; Muller, C.J.F.; Joubert, E.; Louw, J.; Essop, M.F.; Gabuza, K.B.; Ghoor, S.; Huisamen, B.; Johnson, R. Aspalathin Protects the Heart against Hyperglycemia-Induced Oxidative Damage by Up-Regulating Nrf2 Expression. Molecules 2017, 22, 129.

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