Exploring Glucagon-like peptide-1 as a Target Protein for Diabetes Mellitus Treatment: Molecular Docking and Pharmacokinetic Analysis of Phytocompounds from Momordica charantia

[{“box”:0,”content”:”[if 992 equals=”Open Access”]n

n

n

n

Open Access

nn

n

n[/if 992]n

n

Year : May 28, 2024 at 12:44 pm | [if 1553 equals=””] Volume : [else] Volume :[/if 1553] | [if 424 equals=”Regular Issue”]Issue[/if 424][if 424 equals=”Special Issue”]Special Issue[/if 424] [if 424 equals=”Conference”][/if 424] : | Page : –

n

n

n

n

n

n

By

n

[foreach 286]n

n

n

Dishant Chandgude

n

    n t

  • n

n

n[/foreach]

n

n[if 2099 not_equal=”Yes”]n

    [foreach 286] [if 1175 not_equal=””]n t

  1. Resarch Intern BioNome | For Genomics and Bioinformatics Solution Bengaluru, Karnataka India
  2. n[/if 1175][/foreach]

n[/if 2099][if 2099 equals=”Yes”][/if 2099]n

n

Abstract

nObjective: The aim of this study was to use molecular docking techniques to explore the potential of GLP-1 (glucagon-like peptide-1) as a target protein for the treatment of diabetes mellitus, a chronic metabolic disease marked by elevated blood glucose levels. Given its crucial role in maintaining insulin secretion and glucose homeostasis, GLP-1 may serve as a future target for diabetes therapy.

Method: The study employed a multi-phase method. Initially, protein extraction was carried out using the Protein Data Bank ID 3C59 for GLP-1. The extracted structure was then verified through secondary structure prediction and Ramachandran Plot analysis to ensure its reliability. Phytocompounds from “Momordica charantia” were obtained using the IMPPAT Database. An ADME study was conducted to evaluate the pharmacokinetic characteristics of these compounds, including their absorption, distribution, metabolism, and excretion profiles. Molecular docking was then performed using PyRx to assess the binding affinity and interaction patterns between GLP-1 and the identified phytocompounds. The 3D and 2D interaction structures were subsequently examined using Biovia Discovery Studio to visualize the binding interactions and to identify key amino acid residues involved.

Result: The molecular docking study identified Diosgenin, alpha-Spinasterol, and Momordicoside I as potential drug candidates capable of modulating the activity of GLP-1. These compounds exhibited strong binding affinities and favourable interaction patterns with the GLP-1 protein.

Conclusion: The study suggests that GLP-1 is a promising target for diabetes treatment, demonstrating favourable molecular interactions with phytocompounds derived from Momordica charantia. Structural validation and ADME analysis further support the potential efficacy of these compounds. These findings could lead to the development of new therapeutic approaches for managing diabetes, highlighting the significance of GLP-1 in diabetes therapy.

n

n

n

Keywords: GLP-1, diabetes treatment, molecular docking, Momordica charantia, phytocompounds, ADME analysis, structural validation.

n[if 424 equals=”Regular Issue”][This article belongs to International Journal of Biochemistry and Biomolecule Research(ijbbr)]

n

[/if 424][if 424 equals=”Special Issue”][This article belongs to Special Issue under section in International Journal of Biochemistry and Biomolecule Research(ijbbr)][/if 424][if 424 equals=”Conference”]This article belongs to Conference [/if 424]

n

n

n

How to cite this article: Dishant Chandgude. Exploring Glucagon-like peptide-1 as a Target Protein for Diabetes Mellitus Treatment: Molecular Docking and Pharmacokinetic Analysis of Phytocompounds from Momordica charantia. International Journal of Biochemistry and Biomolecule Research. May 28, 2024; ():-.

n

How to cite this URL: Dishant Chandgude. Exploring Glucagon-like peptide-1 as a Target Protein for Diabetes Mellitus Treatment: Molecular Docking and Pharmacokinetic Analysis of Phytocompounds from Momordica charantia. International Journal of Biochemistry and Biomolecule Research. May 28, 2024; ():-. Available from: https://journals.stmjournals.com/ijbbr/article=May 28, 2024/view=0

nn[if 992 equals=”Open Access”] Full Text PDF Download[/if 992] n[if 992 not_equal=”Open Access”]

[/if 992]n[if 992 not_equal=”Open Access”]


n


n

n[/if 992]nn[if 379 not_equal=””]n

Browse Figures

n

n

[foreach 379]n

n[/foreach]n

n

n

n[/if 379]n

n

References

n[if 1104 equals=””]n

  1. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care [Internet]. 2009;32(Supplement_1):S62–7. Available from: http://dx.doi.org/10.2337/dc09-s062
  2. Cole JB, Florez JC. Genetics of diabetes mellitus and diabetes complications. Nat Rev Nephrol [Internet]. 2020;16(7):377–90. Available from: http://dx.doi.org/10.1038/s41581-020-0278-5
  3. Schellenberg ES, Dryden DM, Vandermeer B, Ha C, Korownyk C. Lifestyle interventions for patients with and at risk for type 2 diabetes: A systematic review and meta-analysis. Ann Intern Med [Internet]. 2013;159(8):543. Available from: http://dx.doi.org/10.7326/0003-4819-159-8-201310150-00007
  4. Cho NH, Shaw JE, Karuranga S, Huang Y, da Rocha Fernandes JD, Ohlrogge AW, et al. IDF Diabetes Atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res Clin Pract [Internet]. 2018;138:271–81. Available from: http://dx.doi.org/10.1016/j.diabres.2018.02.023
  5. Grover JK, Yadav S, Vats V. Medicinal plants of India with anti-diabetic potential. J Ethnopharmacol [Internet]. 2002;81(1):81–100. Available from: http://dx.doi.org/10.1016/s0378-8741(02)00059-4
  6. Richter E, Geetha T, Burnett D, Broderick TL, Babu JR. The effects of Momordica charantia on type 2 diabetes mellitus and Alzheimer’s disease. Int J Mol Sci [Internet]. 2023;24(5):4643. Available from: http://dx.doi.org/10.3390/ijms24054643
  7. Cortez-Navarrete M, Pérez-Rubio KG, Escobedo-Gutiérrez M de J. Role of Fenugreek, Cinnamon, Curcuma longa, Berberine and Momordica charantia in Type 2 Diabetes Mellitus Treatment: A Review. Pharmaceuticals (Basel) [Internet]. 2023;16(4):515. Available from: http://dx.doi.org/10.3390/ph16040515
  8. Dans AML, Villarruz MVC, Jimeno CA, Javelosa MAU, Chua J, Bautista R, et al. The effect of Momordica charantia capsule preparation on glycemic control in Type 2 Diabetes Mellitus needs further studies. J Clin Epidemiol [Internet]. 2007;60(6):554–9. Available from: http://dx.doi.org/10.1016/j.jclinepi.2006.07.009
  9. Drucker DJ. Mechanisms of action and therapeutic application of glucagon-like peptide-1. Cell Metab [Internet]. 2018;27(4):740–56. Available from: http://dx.doi.org/10.1016/j.cmet.2018.03.001
  10. Nauck MA, Quast DR, Wefers J, Meier JJ. GLP-1 receptor agonists in the treatment of type 2 diabetes – state-of-the-art. Mol Metab [Internet]. 2021;46(101102):101102. Available from: http://dx.doi.org/10.1016/j.molmet.2020.101102
  11. Bailey CJ, Flatt PR, Conlon JM. An update on peptide-based therapies for type 2 diabetes and obesity. Peptides [Internet]. 2023;161(170939):170939. Available from: http://dx.doi.org/10.1016/j.peptides.2023.170939
  12. Muzurović EM, Volčanšek Š, Tomšić KZ, Janež A, Mikhailidis DP, Rizzo M, et al. Glucagon-like peptide-1 receptor agonists and dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 receptor agonists in the treatment of obesity/metabolic syndrome, prediabetes/diabetes and non-alcoholic fatty liver disease—current evidence. J Cardiovasc Pharmacol Ther [Internet]. 2022;27:107424842211463. Available from: http://dx.doi.org/10.1177/10742484221146371
  13. Klen J, Dolžan V. Glucagon-like peptide-1 receptor agonists in the management of type 2 diabetes mellitus and obesity: The impact of pharmacological properties and genetic factors. Int J Mol Sci [Internet]. 2022;23(7):3451. Available from: http://dx.doi.org/10.3390/ijms23073451
  14. RCSB Protein Data Bank. RCSB PDB: Homepage [Internet]. Rcsb.org. [cited 2024 Jan 21]. Available from: https://www.rcsb.org/
  15. Systèmes D. Free download: BIOVIA Discovery Studio Visualizer [Internet]. Dassault Systèmes. 2020 [cited 2024 Jan 21]. Available from: https://discover.3ds.com/discovery-studio-visualizer-download
  16. PROCHECK home page [Internet]. Ebi.ac.uk. [cited 2024 Jan 21]. Available from: https://www.ebi.ac.uk/thornton-srv/software/PROCHECK/
  17. PDBsum home page [Internet]. Ebi.ac.uk. [cited 2024 Jan 21]. Available from: https://www.ebi.ac.uk/thornton-srv/databases/pdbsum/
  18. AS. IMPPAT [Internet]. Res.in. [cited 2024 Jan 21]. Available from: https://cb.imsc.res.in/imppat/
  19. PubChem. PubChem [Internet]. Nih.gov. [cited 2024 Jan 21]. Available from: https://pubchem.ncbi.nlm.nih.gov/
  20. SwissADME [Internet]. Swissadme.ch. [cited 2024 Jan 22]. Available from: http://www.swissadme.ch/
  21. Welcome to the PyRx website [Internet]. Sourceforge.io. [cited 2024 Jan 24]. Available from: https://pyrx.sourceforge.io/

nn[/if 1104][if 1104 not_equal=””]n

    [foreach 1102]n t

  1. [if 1106 equals=””], [/if 1106][if 1106 not_equal=””],[/if 1106]
  2. n[/foreach]

n[/if 1104]

nn


nn[if 1114 equals=”Yes”]n

n[/if 1114]

n

n

[if 424 not_equal=””][else]Ahead of Print[/if 424] Subscription Original Research

n

n

[if 2146 equals=”Yes”][/if 2146][if 2146 not_equal=”Yes”][/if 2146]n

n

n

n

n

n

n

n

n

n

n

n

n

n

n

n

n

n

n

n

n[if 1748 not_equal=””]

[else]

[/if 1748]n

n

n

Volume
[if 424 equals=”Regular Issue”]Issue[/if 424][if 424 equals=”Special Issue”]Special Issue[/if 424] [if 424 equals=”Conference”][/if 424]
Received May 15, 2024
Accepted May 27, 2024
Published May 28, 2024

n

n

n

n

n

n function myFunction2() {n var x = document.getElementById(“browsefigure”);n if (x.style.display === “block”) {n x.style.display = “none”;n }n else { x.style.display = “Block”; }n }n document.querySelector(“.prevBtn”).addEventListener(“click”, () => {n changeSlides(-1);n });n document.querySelector(“.nextBtn”).addEventListener(“click”, () => {n changeSlides(1);n });n var slideIndex = 1;n showSlides(slideIndex);n function changeSlides(n) {n showSlides((slideIndex += n));n }n function currentSlide(n) {n showSlides((slideIndex = n));n }n function showSlides(n) {n var i;n var slides = document.getElementsByClassName(“Slide”);n var dots = document.getElementsByClassName(“Navdot”);n if (n > slides.length) { slideIndex = 1; }n if (n (item.style.display = “none”));n Array.from(dots).forEach(n item => (item.className = item.className.replace(” selected”, “”))n );n slides[slideIndex – 1].style.display = “block”;n dots[slideIndex – 1].className += ” selected”;n }n”}]