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Investigating molecular interactions between human transferrin and resveratrol through a unified experimental and computational approach: Role of natural compounds in Alzheimer’s disease therapeutics

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Abstract

Disruptions to iron metabolism and iron homeostasis have emerged as significant contributors to the development and progression of Alzheimer's disease (AD). Human transferrin plays a key part in maintaining iron equilibrium throughout the body, highlighting its importance in AD. Many plant-derived compounds and dietary constituents show promise for preventing AD. Polyphenols that are abundant in fruits, vegetables, teas, coffee, and herbs possess neuroprotective attributes. Resveratrol is a natural polyphenol present in various plant sources like grapes, berries, peanuts, and red wine that has garnered research interest due to its wide range of biological activities. Notably, resveratrol exhibits neuroprotective effects that may help prevent or treat AD through multiple mechanisms. In the present study, we employed a combination of molecular docking and all-atom molecular dynamic simulations (MD) along with experimental approaches to unravel the intricate interactions between transferrin and resveratrol deciphering the binding mechanism. Through molecular docking analysis, it was determined that resveratrol occupies the iron binding pocket of transferrin. Furthermore, MD simulations provided a more profound insight into the stability and conformational dynamics of the complex suggesting that the binding of resveratrol introduced localized flexibility, while maintaining overall stability. The spectroscopic observations yielded clear evidence of substantial binding between resveratrol and transferrin, confirming the computational findings. The identified binding mechanism and conformational stability hold potential for advancing the development of innovative therapeutic approaches targeting AD through resveratrol, particularly concerning iron homeostasis. These insights serve as a platform for considering the natural compounds in the realm of AD therapeutics.

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Acknowledgements

M.S.K. acknowledges the generous support from the Research Supporting project (RSP2023R352) by the King Saud University, Riyadh, Kingdom of Saudi Arabia. A.S. is grateful to Ajman University for supporting this publication.

Funding

M.S.K. acknowledges the generous support from the Research Supporting project (RSP2023R352) by the King Saud University, Riyadh, Kingdom of Saudi Arabia. A.S. is grateful to Ajman University for supporting this publication.

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Authors and Affiliations

  1. Department of Biochemistry, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia

    Mohd Shahnawaz Khan

  2. Department of Biochemistry, Aligarh Muslim University, Aligarh, India

    Mohammad Furkan

  3. Department of Clinical Sciences, College of Pharmacy and Health Sciences, Ajman University, Ajman, United Arab Emirates

    Moyad Shahwan

  4. Center for Medical and Bio-Allied Health Sciences Research, Ajman University, Ajman, United Arab Emirates

    Moyad Shahwan & Anas Shamsi

  5. Gachon Institute of Pharmaceutical Science and Department of Pharmacy, College of Pharmacy, Gachon University, Incheon, Republic of Korea

    Dharmendra Kumar Yadav

  6. Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi, 110025, India

    Saleha Anwar

  7. Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, India

    Rizwan Hasan Khan

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  1. Mohd Shahnawaz Khan
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  2. Mohammad Furkan
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Contributions

AS, MSK, and RHK designed the original studies; AS and MSK carried out in silico studies; MF and SA performed spectroscopic analysis, DKY and RHK analyzed the data, AS and MSK secured funding, AS, MSK, MS, and DKY drafted the paper; all authors revised the draft and approved the final version of the manuscript.

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Correspondence to Anas Shamsi.

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Khan, M.S., Furkan, M., Shahwan, M. et al. Investigating molecular interactions between human transferrin and resveratrol through a unified experimental and computational approach: Role of natural compounds in Alzheimer’s disease therapeutics. Amino Acids 55, 1923–1935 (2023). https://doi.org/10.1007/s00726-023-03355-5

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