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Experimental and molecular docking studies of quercetin and vitamin E with diabetes-associated mitochondrial-ATPase as anti-apoptotic therapeutic strategies

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Abstract

Purpose

Researches have shown the relevance of antioxidants in the management of several diseases. In the present study, the effects of quercetin and vitamin E were investigated on the mitochondrial functions in vivo and in silico.

Methods

Structures of quercetin and vitamin E were docked against mitochondrial Adenosine triphosphatase (mATPase), and cytochrome c cavity. Activity of liver mATPase and mitochondrial permeability transition pore opening were determined by spectrophotometry and activation of cytochrome c was examined by immunohistochemistry.

Results

The binding energy of vitamin E (−9 Kcal/mol) in mATPase cavity compares well with glibenclamide (−9.4 Kcal/mol), while quercetin had a binding energy of −7.1 Kcal/mol. Similarly, vitamin E, quercetin were bound to cytochrome c by −6.4 and − 5.5 Kcal/mol energy, while glibenclamide had −7.0 Kcal/mol binding energy. The results showed that vitamin E was more accessible to the protoporphyrin prosthetic group in cytochrome c than quercetin. In the experimental studies, it was validated that vitamin E inhibited the uncontrolled activity of mATPase in diabetic rat liver. This was also proven and tested on the liver mitochondrial permeability transition pore opening observed in diabetic rats. Further experimental assessment of these on activation of cytochrome c showed that vitamin E reduced the extent of the activation more than quercetin and glibenclamide.

Conclusion

There is a favorable protein-ligand interaction between quercetin and vitamin E in certain apoptotic proteins implicated in diabetes complications.

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Data availability

The dataset generated during the study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors acknowledge the contributions of the Director, Biomembrane and Biotechnology Laboratory, Department of Biochemistry, College of Medicine, University of Ibadan, Nigeria.

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Authors and Affiliations

  1. Laboratories for Biomembrane Research and Biotechnology, Department of Biochemistry, College of Medicine, University of Ibadan, Ibadan, 200284, Nigeria

    Oluwatoyin O. Ojo, Titilayo Ogunleke & Olufunso O. Olorunsogo

  2. Department of Chemical Sciences, Faculty of Natural and Applied Sciences, Anchor University Lagos, Lagos, 100278, Nigeria

    Oluwatoyin O. Ojo & Joshua Ajeoge

Authors
  1. Oluwatoyin O. Ojo
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  2. Titilayo Ogunleke
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  4. Olufunso O. Olorunsogo
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Contributions

Material preparation, investigation, resources, funding, data collection [Oluwatoyin Ojo, Ogunleke Titlayo]; Computational Studies [Joshua Ajeoge]; Analysis, writing, editing [Oluwatoyin Ojo]; Conceptualization, supervision, project administration [Olufunso Olorunsogo].

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Correspondence to Oluwatoyin O. Ojo.

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All procedures performed using experimental animals were in accordance with the ethical standards of the procedures of the University of Ibadan Ethics Committee, Ibadan, Nigeria.

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The authors declare no conflict of interest.

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Ojo, O.O., Ogunleke, T., Ajeoge, J. et al. Experimental and molecular docking studies of quercetin and vitamin E with diabetes-associated mitochondrial-ATPase as anti-apoptotic therapeutic strategies. J Diabetes Metab Disord 21, 1717–1729 (2022). https://doi.org/10.1007/s40200-022-01132-x

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