Preprint Article Version 1 NOT YET PEER-REVIEWED

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

  1. Biomedical Research and Innovation Platform (BRIP), Medical Research Council (MRC), Tygerberg, South Africa
  2. Division of Medical Physiology, Faculty of Health Sciences, Stellenbosch University, Tygerberg, South Africa
  3. Post-Harvest and Wine Technology Division, Agricultural Research Council (ARC) Infruitec- Nietvoorbij, Stellenbosch, South Africa
  4. Department of Food Science, Stellenbosch University, Stellenbosch, South Africa
  5. Cardio-Metabolic Research Group (CMRG), Department of Physiological Sciences, Stellenbosch University, Stellenbosch, South Africa
Version 1 : Received: 17 November 2016 / Approved: 17 November 2016 / Online: 17 November 2016 (11:07:56 CET)

How to cite: Dludla, P.; Muller, C.; Joubert, E.; Louw, J.; Essop, M.; Gabuza, K.; Ghoor, S.; Huisamen, B.; Johnson, R. Aspalathin Protects the Heart against Hyperglycemia-Induced Oxidative Damage by Up-regulating Nrf2 Expression. Preprints 2016, 2016110093 (doi: 10.20944/preprints201611.0093.v1). Dludla, P.; Muller, C.; Joubert, E.; Louw, J.; Essop, M.; Gabuza, K.; Ghoor, S.; Huisamen, B.; Johnson, R. Aspalathin Protects the Heart against Hyperglycemia-Induced Oxidative Damage by Up-regulating Nrf2 Expression. Preprints 2016, 2016110093 (doi: 10.20944/preprints201611.0093.v1).

Abstract

Aspalathin (ASP) can protect H9c2 cardiomyocytes against high glucose (HG)-induced shifts in myocardial substrate preference, oxidative stress and apoptosis. While the protective mechanism of aspalathin remains unknown, nuclear factor (erythroid-derived 2)-like 2 (Nrf2) has emerged as a key factor for intracellular responses against oxidative stress. Therefore, we hypothesized that aspalathin protects the myocardium against hyperglycemia-induced oxidative damage by up-regulating Nrf2 expression in H9c2 cardiomyocytes and diabetic (db/db) mice. 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 6 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 6 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 stress through activation of Nrf2 and its downstream target genes.

Subject Areas

diabetes mellitus; cardiomyopathy; hyperglycemia; oxidative stress; aspalathin; Nrf2

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