Investigating The Effects of Trans-chalcone on Insulin Amyloid Fibrillation

Subject Areas : Journal of Animal Biology

Maria  Omidi Shahsavandi ¹ (Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran)
Parichehr  Yaghmaee ² (Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran)
Shahin  Ahmadian ³ (Tehran Biochemistry and Biophysics Research Center, University of Tehran, Tehran, Iran)
Azadeh  Ebrahim-Habibi ⁴ (Endocrine and Metabolism Research Center, Tehran University of Medical Sciences, Tehran, Iran)

Received: 2023-06-17 Accepted : 2023-07-31 Published : 2024-02-20

Keywords: insulin, Aromatic compounds, docking, Congo Red, Trans-chalcone, Amyloid aggregates, Thioflavin S,

Abstract :

Amyloid fibrils are string-like aggregates that form due to the disruption of natural structure and misfolding of various types of peptides and proteins. These amyloid aggregates are associated with some neurodegenerative and systemic diseases such as Alzheimer's, Parkinson's, and type 2 diabetes. The aim of this study was to investigate the inhibitory effects of Trans-chalcone on insulin fibrillation (as a model protein). In this study, insulin was incubated for 24 hours in the presence and absence of Trans-chalcone under amyloid formation conditions. The formed fibrils were analyzed using various techniques including Congo red absorption spectral changes by spectroscopy, electron microscopy images by TEM, and fluorescent staining of amyloid aggregates by fluorescent microscopy. Then, possible interactions between Trans-chalcone and insulin were analyzed using molecular docking method by AutoDock software. The results showed a significant reduction in amyloid fibril formation in the additive-containing sample compared to the control sample. This study provides evidence that Trans-chalcone has an inhibitory effect on insulin fibrillation and could be a potential therapeutic agent for amyloid-related diseases.

References:

1. Albert S.G., Obadiah J., Parseghian S.A.,Yadira Hurley M., Mooradian A.D. 2007. Severe insulin resistance associated with subcutaneous amyloid deposition. Diabetes Research and Clinical Practice, 75(3):374-376.


2. Arora A., Ha C., Park C.B. 2004. Insulin amyloid fibrillation at above 100°C: New insights into protein folding under extreme temperatures. Protein Science, .13(9):2429-236.


3. Bahramikia S., Yazdanparast R., Gheysarzadeh A. 2012. Syntheses and Structure-Activity Relationships of Seven Manganese-Salen Derivatives as Anti-amyloidogenic and Fibril-destabilizing Agents Against Hen Egg-white Lysozyme Aggregation. Chemical Biology and Drug Design, 80(2):227-236.


4. Butler A., Janson J., Bonner-Weir S., Ritzel R., Rizza R., Butler P. 2003. Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes. Diabetes, 52:102-110.


5. Chinisaz M., Ebrahim-Habibi A., Yaghmaei P., Parivar K., Dehpour A.R., Generating local amyloidosis in mice by the subcutaneous injection of human insulin amyloid fibrils. Experimental and Therapeutic Medicine, 8(2):405-408.


6. Chiti F., Dobson C.M. Protein misfolding, amyloid formation, and human disease: A summary of progress over the last decade. Annual Review of Biochemistry, 86:27-68.


7. D’Souza A., Theis J., Vrana J.A., Dogan A. 2014. Pharmaceutical amyloidosis associated with subcutaneous insulin and enfuvirtide administration. The Journal of Protein Folding Disorders, 21(2):71-75.


8. Dubrey S.W., Hawkins P.N., Falk R.H. 2010. Amyloid diseases of the heart: assessment, diagnosis, and referral. Heart, 97(1):75-84.


9. Ecroyd H., Carver J.A. 2008. Unraveling the mysteries of protein folding and misfolding. IUBMB Life, 60(12):769-774.


10. Ehrlich J.C., Ratner M. 1961. Amyloidosis of the islets of Langerhans. A restudy of islet hyalin in diabetic and non-diabetic individuals. The American Journal of Pathology, 38(1):49-59.


11. Feng S., Song X.H., Zeng C.M. 2012. Inhibition of amyloid fibrillation of lysozyme by phenolic compounds involves quinoprotein formation. FEBS Letters, 586(22):3951–5.


12. Gancar M., Kurin E., Bednarikova Z., Marek J., Mucaji P., Nagy M., Gazova 2020. Amyloid Aggregation of Insulin: An Interaction Study of Green Tea Constituents. Scientific Reports, 10(1):9115.


13. Hecht M.H., Das A., Go A., Bradley L.H., Wei Y. 2004. De novo proteins from designed combinatorial libraries. Protein Science, 13(7):1711–23.


14. Hughes E., Burke R.M., Doig A.J. 2000. Inhibition of toxicity in the β-amyloid peptide fragment β-(25-35) using N-methylated derivatives. A general strategy to prevent amyloid formation. Journal of Biological Chemistry, 275(33):25109–25115.


15. Jardim G.A.M., Guimarães T.T., Pinto M., Cavalcanti B., De Farias K.M., Pessoa C., Gatto  , Nair D.K., Namboothiri I., Júnior S., Eufrânio N. 2015. Naphthoquinone-based chalcone hybrids and derivatives: Synthesis and potent activity against cancer cell lines. MedChemComm, 6(1):120-150.


16. Karuppagounder S.S., Pinto J.T., Xu H., Chen H.L., Beal M.F., Gibson G.E. 2009. Dietary supplementation with resveratrol reduces plaque pathology in a transgenic model of Alzheimer’s disease. Neurochemistry International, 54(2):111-118.


17. Krebs M.R., Wilkins D.K., Chung E.W.. Pitkeathly M.C., Chamberlain A.K., Zurdo J., Robinson V., Dobson C.M. 2000. Formation and seeding of amyloid fibrils from wild-type hen lysozyme and a peptide fragment from the β-domain. Journal of Molecular Biology, 300(3):541–549.


18. Langmuir I., Waugh D.F. 2023. Pressure-soluble and pressure-displaceable components of monolayers of native and denatured proteins. Journal of the American Chemical Society, 62(10):2771-2793.


19. Lutter L., Serpell C.J., Tuite M.F., Xue W.F. 2019. The molecular lifecycle of amyloid– Mechanism of assembly, mesoscopic organisation, polymorphism, suprastructures, and biological consequences. Biochimica et Biophysica Acta. Proteins and Proteomics, 1867(11):140257.


20. Mauro M., Craparo E.F., Podestà A., Bulone D., Carrotta R., Martorana V., Tiana G., San Biagio P.L. 2007. Kinetics of different processes in human insulin amyloid formation. Journal of Molecular Biology, 366(1):258-274.


21. Morshedi D., Rezaei-Ghaleh N., Ebrahim-Habibi A., Ahmadian S., Nemat-Gorgani M. 2007. Inhibition of amyloid fibrillation of lysozyme by indole derivatives - Possible mechanism of action. FEBS Journal, 274(24):6415-6425.


22. Nguyen H.D., Hall C.K. 2004. Molecular dynamics simulations of spontaneous fibril formation by random-coil peptides. Proceedings of the National Academy of Sciences of the United States of America, 101(46):16180-16185.


23. Nielsen L., Khurana R., Coats A., Frokjaer S., Brange J., Vyas S., Uversky V.N., Fink A.L. Effect of environmental factors on the kinetics of insulin fibril formation: Elucidation of the molecular mechanism. Biochemistry, 40(20):6036-6046.


24. Pérez-Garrido A., Helguera A.M., Morillas Ruiz J., Zafrilla Rentero P. 2012 .Topological sub-structural molecular design approach: Radical scavenging activity. European Journal of Medicinal Chemistry, 49:86-94.


25. Porat Y., Abramowitz A., Gazit E., 2006. Inhibition of amyloid fibril formation by polyphenols: Structural similarity and aromatic interactions as a common inhibition mechanism. Chemical Biology and Drug Design, 67(1):27-37.


26. Qiu T., Liu Q., Chen Y.X., Zhao Y.F., Li Y.M. 2015. Aβ42 and Aβ40: similarities and differences. Journal of Peptide Sciences, 21(7):522-529.


27. Rabiee A., Ebrahim-Habibi A., Ghasemi A., Nemat-Gorgani M. 2013. How curcumin affords effective protection against amyloid fibrillation in insulin. Food Function, 4(10):1474-1480.


28. Rhoades E., Agarwal J., Gafni A. 2000. Aggregation of an amyloidogenic fragment of human islet amyloid polypeptide. Biochim Biophys Acta - Protein Structure and Molecular Enzymology, 1476(2):230-238.


29. Rudrapal M., Khan J., Bin Dukhyil A.A., Alarousy R.M.I.I., Attah E.I., Sharma T., KhairnarJ. 2021. Chalcone scaffolds, bioprecursors of flavonoids: chemistry, bioactivities, and pharmacokinetics. Molecules, 26(23):1-23.


30. Selivanova O.M., Galzitskaya O.V. 2012. Structural polymorphism and possible pathways of amyloid fibril formation on the example of insulin protein. Biochemistry, 77(11):1237-1247.


31. Syam S., Abdelwahab S., Al-Mamary M.A., Mohan S. 2012. Synthesis of chalcones with anticancer activities. Molecules, 17(6):6179-6195.


32. Tomita S., Yoshikawa H., Shiraki K. 2011. Arginine Controls Heat-Induced Cluster-Cluster Aggregation of Lysozyme at Around the Isoelectric Point. Biopolymers, 95(10):695-701.


33. Walsh D.M., Teplow D.B. 2012 . Alzheimer’s disease and the amyloid β-protein. Progress in Molecular Biology and Translational Science, 107:101-124.


34. Waterhouse S.H., Gerrard J.A. 2004. Amyloid fibrils in bionanotechnology. Australian Journal of Chemistry, 57(6):519-523.


35. Waugh D.F. 1946. Fibrous Modification of Insulin. I. The Heat Precipitate of Insulin. Journal of the American Chemical Society, 68(2):247-250.


36. Weyer C., Bogardus C., Mott D.M., Pratley R.E. 1999. The natural history of insulin secretory dysfunction and insulin resistance in the pathogenesis of type 2 diabetes mellitus. Journal of Clinical Investigation, 104(6):787-794.


37. Yakupova E.I., Bobyleva L.G., Vikhlyantsev I.M., Bobylev A.G. 2019. Congo Red and amyloids: History and relationship. Bioscience Reports, 39(1): 20181415.


38. Yoshihara H., Saito J., Tanabe A,. Amada T., Asakura T., Kitagawa K., Asada 2016. Characterization of Novel Insulin Fibrils That Show Strong Cytotoxicity under Physiological pH. Journal of Pharmaceutical Sciences, 105(4):1419-1426.