Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

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

Phiwayinkosi V. Dludla
ORCID logo ,
Christo J. F. Muller
ORCID logo ,
Elizabeth Joubert
ORCID logo ,
Johan Louw
,
M. Faadiel Essop
,
Kwazi B. Gabuza
,
Samira Ghoor
,
Barbara Huisamen
,
Rabia Johnson
* ORCID logo
Version 1 : Received: 17 November 2016 / Approved: 17 November 2016 / Online: 17 November 2016 (11:07:56 CET)

A peer-reviewed article of this Preprint also exists.

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. 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.

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.

Keywords

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

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

Copyright: 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.

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