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Article

The Combination Effect of Aspalathin and Phenylpyruvic Acid-2-O-β-d-glucoside from Rooibos against Hyperglycemia-Induced Cardiac Damage: An In Vitro Study

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Biomedical Research and Innovation Platform, South African Medical Research Council, Tygerberg 7505, South Africa
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Department of Life and Environmental Sciences, Polytechnic University of Marche, 60131 Ancona, Italy
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Division of Medical Physiology, Faculty of Health Sciences, Stellenbosch University, Private Bag X1, Tygerberg 7505, South Africa
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Department of Biochemistry and Microbiology, University of Zululand, KwaDlangezwa 3880, South Africa
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School of Pharmacy, University of Camerino, 62032 Camerino, Italy
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School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban 4000, South Africa
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Centre for Cardio-metabolic Research in Africa, Department of Physiological Sciences, Stellenbosch University, Stellenbosch 7600, South Africa
*
Author to whom correspondence should be addressed.
Nutrients 2020, 12(4), 1151; https://doi.org/10.3390/nu12041151
Received: 27 March 2020 / Revised: 14 April 2020 / Accepted: 16 April 2020 / Published: 20 April 2020
Recent evidence shows that rooibos compounds, aspalathin and phenylpyruvic acid-2-O-β-d-glucoside (PPAG), can independently protect cardiomyocytes from hyperglycemia-related reactive oxygen species (ROS). While aspalathin shows more potency by enhancing intracellular antioxidant defenses, PPAG acts more as an anti-apoptotic agent. Thus, to further understand the protective capabilities of these compounds against hyperglycemia-induced cardiac damage, their combinatory effect was investigated and compared to metformin. An in vitro model of H9c2 cardiomyocytes exposed to chronic glucose concentrations was employed to study the impact of such compounds on hyperglycemia-induced damage. Here, high glucose exposure impaired myocardial substrate utilization by abnormally enhancing free fatty acid oxidation while concomitantly suppressing glucose oxidation. This was paralleled by altered expression of genes involved in energy metabolism including acetyl-CoA carboxylase (ACC), 5′ AMP-activated protein kinase (AMPK), and peroxisome proliferator-activated receptor-alpha (PPARα). The combination treatment improved myocardial substrate metabolism, maintained mitochondrial membrane potential, and attenuated various markers for oxidative stress including nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity and glutathione content. It also showed a much-improved effect by ameliorating DNA damage when compared to metformin. The current study demonstrates that rooibos compounds offer unique cardioprotective properties against hyperglycemia-induced and potentially against diabetes-induced cardiac damage. These data also support further exploration of rooibos compounds to better assess the cardioprotective effects of different bioactive compound combinations. View Full-Text
Keywords: rooibos; aspalathin; phenylpropenoic acid glucoside; diabetes; hyperglycemia; oxidative stress; apoptosis rooibos; aspalathin; phenylpropenoic acid glucoside; diabetes; hyperglycemia; oxidative stress; apoptosis
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MDPI and ACS Style

Dludla, P.V.; Muller, C.J.F.; Louw, J.; Mazibuko-Mbeje, S.E.; Tiano, L.; Silvestri, S.; Orlando, P.; Marcheggiani, F.; Cirilli, I.; Chellan, N.; Ghoor, S.; Nkambule, B.B.; Essop, M.F.; Huisamen, B.; Johnson, R. The Combination Effect of Aspalathin and Phenylpyruvic Acid-2-O-β-d-glucoside from Rooibos against Hyperglycemia-Induced Cardiac Damage: An In Vitro Study. Nutrients 2020, 12, 1151. https://doi.org/10.3390/nu12041151

AMA Style

Dludla PV, Muller CJF, Louw J, Mazibuko-Mbeje SE, Tiano L, Silvestri S, Orlando P, Marcheggiani F, Cirilli I, Chellan N, Ghoor S, Nkambule BB, Essop MF, Huisamen B, Johnson R. The Combination Effect of Aspalathin and Phenylpyruvic Acid-2-O-β-d-glucoside from Rooibos against Hyperglycemia-Induced Cardiac Damage: An In Vitro Study. Nutrients. 2020; 12(4):1151. https://doi.org/10.3390/nu12041151

Chicago/Turabian Style

Dludla, Phiwayinkosi V., Christo J.F. Muller, Johan Louw, Sithandiwe E. Mazibuko-Mbeje, Luca Tiano, Sonia Silvestri, Patrick Orlando, Fabio Marcheggiani, Ilenia Cirilli, Nireshni Chellan, Samira Ghoor, Bongani B. Nkambule, M. F. Essop, Barbara Huisamen, and Rabia Johnson. 2020. "The Combination Effect of Aspalathin and Phenylpyruvic Acid-2-O-β-d-glucoside from Rooibos against Hyperglycemia-Induced Cardiac Damage: An In Vitro Study" Nutrients 12, no. 4: 1151. https://doi.org/10.3390/nu12041151

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