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Bioflavonoid (Hesperidin) Restrains Protein Oxidation and Advanced Glycation End Product Formation by Targeting AGEs and Glycolytic Enzymes

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Abstract

Alpha-amylase (α-amylase) not long ago has acquire recognition as a possible drug target for the management of diabetes. Here, we have investigated the binding and enzyme activity of α-amylase by hesperidin; a naturally occurring flavanone having wide therapeutic potential. Hesperidin exerted an inhibitory influence on α-amylase activity with an IC50 value of 16.6 µM. Hesperidin shows a significant binding toward α-amylase with a binding constant (Ka) of the order of 104 M−1. The evaluation of thermodynamic parameters (∆H and ∆S) suggested that van der Waals force and hydrogen bonding drive seemingly specific hesperidin-α-amylase complex formation. Glycation and oxidation studies were performed using human serum albumin (HSA) as ideal protein. Hesperidin inhibited fructosamine content ≈40% at 50 µM and inhibited advanced glycation end products (AGEs) formation by 71.2% at the same concentration. Moreover, significant recovery was evident in free –SH groups and carbonyl content of HSA. Additionally, molecular docking also entrenched in vitro observations and provided an insight into the important residues (Trp58, Gln63, His101, Glu233, Asp300, and His305) at the heart of hesperidin-α-amylase interaction. This study delineates mechanistic insight of hesperidin-α-amylase interaction and provides a platform for use of hesperidin to treat AGEs directed diseases.

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Acknowledgements

The authors extend their appreciation to the Deanship of Scientific Research at the KSU for funding this work through research group project number RGP-215.

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Authors and Affiliations

  1. Protein Research Chair, Department of Biochemistry, College of Science, King Saud University, Riyadh, Saudi Arabia

    Mohd Shahnawaz Khan, Mohamed A Ismael, Ghaida I. Alruwaished & Majed S. Alokail

  2. Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia

    Md Tabish Rehman & Mohamed F. AlAjmi

  3. Cosmetic Department, National Drug and Cosmetic Control Laboratory, Saudi Food and Drug Authority (SFDA), Riyadh, 11561, Saudi Arabia

    Ghaida I. Alruwaished

  4. Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia

    Mohammad Rashid Khan

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  1. Mohd Shahnawaz Khan
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Khan, M.S., Rehman, M.T., Ismael, M.A. et al. Bioflavonoid (Hesperidin) Restrains Protein Oxidation and Advanced Glycation End Product Formation by Targeting AGEs and Glycolytic Enzymes. Cell Biochem Biophys 79, 833–844 (2021). https://doi.org/10.1007/s12013-021-00997-8

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