Chronic hyperglycemia is closely associated with impaired substrate metabolism, dysregulated mitochondrial membrane potential, and apopto-sis 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 hyper-glycemia. This study therefore investigated whether phenylpyruvic acid-2-O-β-D-glucoside, present in Aspalathus 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-glu-coside and metformin (both at 1 µM). Our data re-vealed that high glucose exposure increased car-diac free fatty acid uptake and oxidation, mito-chondrial membrane potential, and apoptosis (caspase 3/7 activity and TUNEL), and decreased the Bcl2/Bax protein expression ratio. Phenylpy-ruvic 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.