title: Aspalathin, a dihydrochalcone C-glucoside, protects H9c2 cardiomyocytes against high glucose induced shifts in substrate preference and apoptosis.
abstract: METHODS
  Energy deprivation in the myocardium is associated with impaired heart function. This study aims to investigate if aspalathin (ASP) can ameliorate hyperglycemic-induced shift in substrate preference and protect the myocardium against cell apoptosis.
  
  
  RESULTS
  H9c2 cells were exposed to, either normal (5.5 mM) or high (33 mM) glucose concentrations for 48 h. Thereafter, cells exposed to 33 mM glucose were treated with metformin (1 μM) or ASP (1 μM), as well as a combination of metformin and ASP for 6 h. In vitro studies revealed that ASP improved glucose metabolism by decreasing fatty acid uptake and subsequent β-oxidation through the decreased expression of adenosine monophosphate-activated protein kinase threonine 172 (pAMPK (Thr172)) and carnitine palmitoyltransferase 1 (CPT1), while increasing acetyl-CoA carboxylase (ACC) and glucose transporter 4 (GLUT4) expression. ASP inhibited high glucose induced loss of membrane potential in H9c2 cells as observed by an increase in 5' ,6,6'-tetrachloro-1,1',3,3' -tetraethylbenzimidazolyl-carbocyanine iodide (JC-1) ratio (orange\red fluorescence) and decreased apoptosis by reducing intracellular reactive oxygen species and DNA nick formation, while increasing glutathione, superoxide dismutase, uncoupling protein 2 (UCP2), and Bcl-2\Bax ratio.
  
  
  CONCLUSIONS
  Our study provides evidence that ASP increases glucose oxidation and modulates fatty acid utilization producing a favorable substrate shift in H9c2 cardiomyocytes exposed to high glucose. Such a favorable shift will be of importance in the protection of cardiomyocytes in the diabetic heart.
authors.affiliation: Biomedical Research and Innovation Platform, Cape Town, South Africa.
authors.forename: Rabia
authors.initials: R
authors.lastname: Johnson
authors.affiliation: Biomedical Research and Innovation Platform, Cape Town, South Africa.|Division of Medical Physiology, Faculty of Health Sciences, Stellenbosch University, Tygerberg, South Africa.
authors.forename: Phiwayinkosi
authors.initials: P
authors.lastname: Dludla
authors.affiliation: Division of Post-Harvest and Wine Technology, Agricultural Research Council (ARC) Infruitec-Nietvoorbij, Stellenbosch, South Africa.|Department of Food Science, Stellenbosch University, Stellenbosch, South Africa.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Joubert
authors.affiliation: Department of Biotechnology, University of Western Cape, Bellville, South Africa.
authors.forename: Faghri
authors.initials: F
authors.lastname: February
authors.affiliation: Biomedical Research and Innovation Platform, Cape Town, South Africa.
authors.forename: Sithandiwe
authors.initials: S
authors.lastname: Mazibuko
authors.affiliation: Biomedical Research and Innovation Platform, Cape Town, South Africa.
authors.forename: Samira
authors.initials: S
authors.lastname: Ghoor
authors.affiliation: Biomedical Research and Innovation Platform, Cape Town, South Africa.
authors.forename: Christo
authors.initials: C
authors.lastname: Muller
authors.affiliation: Biomedical Research and Innovation Platform, Cape Town, South Africa.
authors.forename: Johan
authors.initials: J
authors.lastname: Louw
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D047188:Chalcones / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D005947:Glucose / Q000009:adverse effects*; D005978:Glutathione / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008687:Metformin / Q000494:pharmacology; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D020011:Protective Agents / Q000494:pharmacology; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494828:Bax protein, rat; D047188:Chalcones; D020011:Protective Agents; D017382:Reactive Oxygen Species; C517016:aspalathin; D051028:bcl-2-Associated X Protein; D008687:Metformin; D013482:Superoxide Dismutase; D005978:Glutathione; D005947:Glucose
keywords: Apoptosis; Aspalathin; Cardiomyopathy; Diabetes; Fatty acid oxidation