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Investigation of the Effect of Pyrogallol on the Formation of Amylin Amyloid Fibrils as a Strategy for the Treatment of Type 2 Diabetic Patients: A Theoretical and Experimental Study

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Abstract

In more than 50 to 90% of type 2 diabetic patients, under the influence of various factors, the production of islet amyloid polypeptide or amylin in pancreatic beta cells increases. Spontaneous accumulation of amylin peptide in the form of insoluble amyloid fibrils and soluble oligomers is one of the main causes of beta cell death in diabetic patients. The objective of the present study was to evaluate the effect of pyrogallol, as a phenolic compound, on inhibiting the formation of amylin protein amyloid fibrils. In this study, different techniques such as the thioflavin T (ThT) and 1-Anilino-8-naphthalene sulfonate (ANS) fluorescence intensity and the circular dichroism (CD) spectrum, will be used to investigate the effects of this compound on inhibiting the formation of amyloid fibrils. To investigate the interaction sites of pyrogallol with amylin, docking studies were performed. Our results that pyrogallol in a dose-dependent manner (0.5:1, 1:1, and 5:1, Pyr to Amylin) inhibits the amylin amyloid fibrils formation. Docking analysis revealed that pyrogallol forms hydrogen bonds with valine 17 and asparagine 21. In addition, this compound forms 2 more hydrogen bonds with asparagine 22. This compound also forms hydrophobic bonds with histidine 18. Considering this data and the direct relationship between oxidative stress and the formation of amylin amyloid accumulations in diabetes, the use of compounds with both antioxidant and anti-amyloid properties can be considered an important therapeutic strategy for type 2 diabetes.

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This study’s data are included in the article, and the corresponding author can provide the primary data.

References

  • Bahramikia S, Yazdanparast R (2012) EUK-8 and EUK-134 reduce serum glucose and lipids and ameliorate streptozotocin-induced oxidative damage in the pancreas, liver, kidneys, and brain tissues of diabetic rats. Med Chem Res 21(10):3224–3232. https://doi.org/10.1007/s00044-011-9855-2

    Article  CAS  Google Scholar 

  • Bahramikia S, Yazdanparast R (2013) Inhibition of human islet amyloid polypeptide or amylin aggregation by two manganese-salen derivatives. Eur J Pharmacol 707(1–3):17–25. https://doi.org/10.1016/j.ejphar.2013.03.017

    Article  CAS  PubMed  Google Scholar 

  • Bardineshin F, Bahramikia S, Khodarahmi R, Hadi F (2023) Mesalazine inhibits amyloid formation and destabilizes pre-formed amyloid fibrils in the human insulin. J Fluoresc 1–8

  • Cheng B, Gong H, Li X, Sun Y, Zhang X, Chen H, Liu X, Zheng L, Huang K (2012) Silibinin inhibits the toxic aggregation of human islet amyloid polypeptide. Biochem Biophys Res Commun 419(3):495–499. https://doi.org/10.1016/j.bbrc.2012.02.042

    Article  CAS  PubMed  Google Scholar 

  • Cho N, Shaw J, Karuranga S, Huang Y, da Rocha Fernandes J, Ohlrogge A, Malanda B (2018) IDF Diabetes Atlas: global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res Clin Pract 138:271–281. https://doi.org/10.1016/j.diabres.2018.02.023

    Article  CAS  PubMed  Google Scholar 

  • Cynthia IF, Henry S, Akhmad D (2018) Antibacterial and antioxidant activities of pyrogallol and synthetic pyrogallol dimer. Res J Chem Environ 22(2):39–47

    Google Scholar 

  • Deng J, Liao Y, Liu J, Liu W, Yan D (2021) Research progress on epigenetics of diabetic cardiomyopathy in type 2 diabetes. Front Cell Dev Biol 9:3674

    Article  Google Scholar 

  • Di Giovanni S, Eleuteri S, Paleologou KE, Yin G, Zweckstetter M, Carrupt PA, Lashuel HA (2010) Entacapone and tolcapone, two catechol O- methyltransferase inhibitors, block the fibril formation of α-synuclein and β-amyloid and protect against amyloid-induced toxicity. J Biol Chem 285(20):14941–14954

    Article  PubMed  PubMed Central  Google Scholar 

  • Engel MF (2009) Membrane permeabilization by islet amyloid polypeptide. Chem Phys Lipids 160:1–10

    Article  CAS  PubMed  Google Scholar 

  • Esmaeili S, Ghobadi N, Akbari V, Moradi S, Shahlaie M, Ghobadi S, Jalalvand AR, Amani M, Khodarahmi R (2020) Pyridine-2,3-dicarboxylate, quinolinic acid, induces 1N4R tau amyloid aggregation in vitro: another evidence for the detrimental effect of the inescapable endogenous neurotoxin. Chemico-Biol Interact 315:108884. https://doi.org/10.1016/j.cbi.2019.108884

    Article  CAS  Google Scholar 

  • Faramarzian M, Bahramikia S, Nabi-Afjadi M (2022) Evaluation of the anti-amyloidogenic and fibril-destabilizing effects of Salvia officinalis flower extract against hen’s egg white lysozyme: an in vitro study. Iran J Sci Technol Trans A Sci 46(5):1349–1358

    Article  Google Scholar 

  • Furuno K, Akasako T, Sugihara N (2002) The contribution of the pyrogallol moiety to the superoxide radical scavenging activity of flavonoids. Biol Pharm Bull 25(1):19–23

    Article  CAS  PubMed  Google Scholar 

  • Gupta A, Jeyakumar E, Lawrence AR (2021) Pyrogallol: a competent therapeutic agent of the future. Biotech Env Sc 23(2):213–217

    Google Scholar 

  • Jaikaran ET, Clark A (2001) Islet amyloid and type 2 diabetes: from molecular misfolding to islet pathophysiology. Biochim Biophys Acta (BBA)-Mol Basis Dis 1537(3):179–203

    Article  CAS  Google Scholar 

  • Kim SW, Han YW, Lee ST, Jeong HJ, Kim SH, Kim IH, Park WH (2008) A superoxide anion generator, pyrogallol, inhibits the growth of HeLa cells via cell cycle arrest and apoptosis. Molecular carcinogenesis: published in cooperation with the University of Texas MD Anderson Cancer Center 47(2):114–125

    Article  CAS  Google Scholar 

  • Li X (2012) Improved pyrogallol autoxidation method: a reliable and cheap superoxide-scavenging assay suitable for all antioxidants. J Agric Food Chem 60(25):6418–6424

    Article  CAS  PubMed  Google Scholar 

  • Milardi D, Gazit E, Radford SE, Xu Y, Gallardo RU, Caflisch A, …, Ramamoorthy A (2021) Proteostasis of islet amyloid polypeptide: a molecular perspective of risk factors and protective strategies for type II diabetes. Chem Rev 121(3):1845–1893

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Phan HTT, Samarat K, Takamur Y, Azo-Oussou AF, Nakazono Y, Vestergaard MC (2019) Polyphenols modulate alzheimer’s amyloid beta aggregation in a structure-dependent manner. Nutrients 11(4):756. https://doi.org/10.3390/nu11040756

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ren B, Liu Y, Zhang Y, Zhang M, Sun Y, Liang G, …, Zheng J (2018) Tanshinones inhibit hIAPP aggregation, disaggregate preformed hIAPP fibrils, and protect cultured cells. J Mater Chem B 6(1):56–67

    Article  CAS  PubMed  Google Scholar 

  • Sasahara K (2018) Membrane-mediated am33yloid deposition of human islet amyloid polypeptide. Biophys Rev 10:453–462

    Article  CAS  PubMed  Google Scholar 

  • Shouhani P, Bahramikia S, Hejazi SH (2022) Experimental and theoretical studies on the anti-amyloidogenic and destabilizing effects of pyrogallol against human insulin protein. J Food Biochem 46(10):e14293

    Article  CAS  PubMed  Google Scholar 

  • Sulatsky MI, Sulatskaya AI, Povarova OI, Antifeeva IA, Kuznetsova IM, Turoverov KK (2020) Effect of the fluorescent probes ThT and ANS on the mature amyloid fibrils. Prion 14(1):67–75. https://doi.org/10.1080/19336896.2020.1720487

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Westermark P, Andersson A, Westermark GT (2011) Islet amyloid polypeptide, islet amyloid, and diabetes mellitus. Physiol Rev 91(3):795–826

    Article  CAS  PubMed  Google Scholar 

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Funding

This study was supported by Lorestan University (Lorestan, Iran).

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Authors and Affiliations

  1. Department of Biology, Faculty of Basic Sciences, Lorestan University, Khorramabad, Iran

    Seifollah Bahramikia & Nasrin Shirzadi

  2. Department of Biology, Urmia University, West Azerbaijan, Iran

    Nasim Pirmohammadi

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  1. Seifollah Bahramikia
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  2. Nasrin Shirzadi
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  3. Nasim Pirmohammadi
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Contributions

S.B., the project designer, writes the paper, editing, and supervision, N.S., Performs experiments and draws diagrams. N.P., Performs experiments and molecular Docking analysis. The authors declare that all data were generated in-house and that no paper mill was used.

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Correspondence to Seifollah Bahramikia.

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Bahramikia, S., Shirzadi, N. & Pirmohammadi, N. Investigation of the Effect of Pyrogallol on the Formation of Amylin Amyloid Fibrils as a Strategy for the Treatment of Type 2 Diabetic Patients: A Theoretical and Experimental Study. J Fluoresc 34, 245–251 (2024). https://doi.org/10.1007/s10895-023-03259-3

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