title: Phenylpyruvic Acid-2-O-β-D-Glucoside Attenuates High Glucose-Induced Apoptosis in H9c2 Cardiomyocytes.
abstract: Chronic hyperglycemia is closely associated with impaired substrate metabolism, dysregulated mitochondrial membrane potential, and apoptosis in the diabetic heart. As adult cardiomyocytes display a limited capacity to regenerate following an insult, it is essential to protect the myocardium against the detrimental effects of chronic hyperglycemia. This study therefore investigated whether phenylpyruvic acid-2-O-β-D-glucoside, present inAspalathus linearis(rooibos), is able to attenuate hyperglycemia-induced damage in H9c2 cardiomyocytes. H9c2 cardiomyocytes were exposed to a high glucose concentration (33 mM) prior to treatment with phenylpyruvic acid-2-O-β-D-glucoside (1 µM), metformin (1 µM), or a combination of phenylpyruvic acid-2-O-β-D-glucoside and metformin (both at 1 µM). Our data revealed that high glucose exposure increased cardiac free fatty acid uptake and oxidation, mitochondrial membrane potential, and apoptosis (caspase 3/7 activity and TUNEL), and decreased the Bcl2/Bax protein expression ratio. Phenylpyruvic acid-2-O-β-D-glucoside treatment, alone or in combination with metformin, attenuated these glucose-induced perturbations, confirming its protective effect in H9c2 cardiomyocytes exposed to chronic hyperglycemia.
authors.affiliation: Biomedical Research and Innovation Platform (BRIP), Medical Research Council (MRC), Tygerberg, South Africa.
authors.forename: Phiwayinkosi Vusi
authors.initials: PV
authors.lastname: Dludla
authors.affiliation: Biomedical Research and Innovation Platform (BRIP), Medical Research Council (MRC), Tygerberg, South Africa.
authors.forename: Christo John Frederick
authors.initials: CJ
authors.lastname: Muller
authors.affiliation: Post-Harvest and Wine Technology Division, Agricultural Research Council (ARC) Infruitec-Nietvoorbij, Stellenbosch, South Africa.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Joubert
authors.affiliation: Biomedical Research and Innovation Platform (BRIP), Medical Research Council (MRC), Tygerberg, South Africa.
authors.forename: Johan
authors.initials: J
authors.lastname: Louw
authors.affiliation: Biomedical Research and Innovation Platform (BRIP), Medical Research Council (MRC), Tygerberg, South Africa.
authors.forename: Kwazi Bethuel
authors.initials: KB
authors.lastname: Gabuza
authors.affiliation: Biomedical Research and Innovation Platform (BRIP), Medical Research Council (MRC), Tygerberg, South Africa.
authors.forename: Barbara
authors.initials: B
authors.lastname: Huisamen
authors.affiliation: Cardio-Metabolic Research Group (CMRG), Department of Physiological Sciences, Stellenbosch University, Stellenbosch, South Africa.
authors.forename: M Faadiel
authors.initials: MF
authors.lastname: Essop
authors.affiliation: Biomedical Research and Innovation Platform (BRIP), Medical Research Council (MRC), Tygerberg, South Africa.
authors.forename: Rabia
authors.initials: R
authors.lastname: Johnson
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000009:adverse effects*; D005960:Glucosides / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008687:Metformin / Q000494:pharmacology; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000473:pathology; D010666:Phenylpropionates / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C000591224:2-(glucopyranosyloxy)-3-phenylpropenoic acid; C494828:Bax protein, rat; D005960:Glucosides; D010666:Phenylpropionates; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; D000255:Adenosine Triphosphate; D008687:Metformin; D005947:Glucose