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Grape seed proanthocyanidins improves mitochondrial function and reduces oxidative stress through an increase in sirtuin 3 expression in EA.hy926 cells in high glucose condition

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Abstract

Proanthocyanidins are phenolic compounds abundant in the diet, commonly found in grapes and derivatives, foods known for their health-promoting benefits. There is previous evidence showing the antidiabetic activity of proanthocyanidins, however, their mechanisms of action have not been fully elucidated. This study evaluated the capacity of grape seed proanthocyanidins extract (GSPE) to modulate oxidative stress, nitric oxide levels, mitochondrial dysfunction, apoptosis, and sirtuin expression in endothelial cells EA.hy926 under high glucose condition. In addition, the possible toxic effects of GSPE was evaluated in a zebrafish embryos model. The results showed that GSPE was able to enhance cell viability and avoid the disturbance in redox metabolism induced by high glucose. Moreover, GSPE was able to avoid mitochondria dysfunction and the increased in p53 and poly-(ADP-ribose) polymerase expression induced by high glucose exposition. These effects were attributed to the increase in expression of sirtuin 3, a protein able to regulate mitochondrial function. GSPE in an effective concentration did not show toxic effects in zebrafish embryos model. Taken together, these data elucidate the key molecular target of GSPE for future pharmacological interventions in diabetic patients.

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Acknowledgements

This work was supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS), and the Coordenação de Apoio de Pessoal de Nível Superior (CAPES). A.F.C. is the recipient of a CAPES Research Fellowship and M.S. is the recipient of a CNPq Research Fellowship (3033383/2015-1). Special thanks to L.A.B for technical contribution and M.A.O.S. for all the support.

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  1. Laboratory of Oxidative Stress and Antioxidants, Biotechnology Institute, University of Caxias Do Sul, Caxias do Sul, RS, 95070560, Brazil

    Aline Fagundes Cerbaro, Victoria Soldatelli Borges Rodrigues, Marina Rigotti, Catia Santos Branco & Mirian Salvador

  2. Cellular Neurochemistry Laboratory, Department of Biochemistry, Institute Health Basic Sciences, Federal University of Rio Grande Do Sul, Porto Alegre, RS, 90035003, Brazil

    Giovana Rech & Diogo Losch de Oliveira

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  1. Aline Fagundes Cerbaro
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  2. Victoria Soldatelli Borges Rodrigues
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Cerbaro, A.F., Rodrigues, V.S.B., Rigotti, M. et al. Grape seed proanthocyanidins improves mitochondrial function and reduces oxidative stress through an increase in sirtuin 3 expression in EA.hy926 cells in high glucose condition. Mol Biol Rep 47, 3319–3330 (2020). https://doi.org/10.1007/s11033-020-05401-x

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