Exploring the anti-diabetic potential of Antidesma alexiteria L.: In vitro GLUT-4 expression and molecular docking studies
Abstract
GLUT-4, an insulin-regulated glucose transporter primarily located in skeletal muscle and adipose tissue, plays a crucial role in the insulin-stimulated uptake of glucose uptake. Impaired GLUT-4 transcription and translocation lead to insulin resistance and hyperglycemia. Hence, this study investigates the role of bioactive compounds from plant sources using gene-level and in-silico interaction studies. In the present investigation, in-silico and in-vitro gene expression analysis of the GLUT-4 gene with acetone bark extract of A. alexiteria were conducted. GLUT-4 gene expression was analysed using 3T3-L1 adipose cells and insulin as standard. The results demonstrated a dose-dependent increase in GLUT-4 expression, with the highest expression observed at a 100μg/ml concentration. According to molecular docking research, the compound juziphine interacted with the catalytic residues Glu177 and Gly400 of the GLUT-4 protein, satisfying ADMET properties. The stability of protein-ligand complex was further validated by molecular dynamics simulations. The study suggested that the extract has insulin-mimetic properties, enhancing GLUT-4 expression, and that juziphine could serve as a promising anti-diabetic agent.
Keywords:
Antidesma alexiteria, GLUT-4, In-silico analysis, anti-diabetic effectDOI
https://doi.org/10.25004/IJPSDR.2025.170308References
Krongyut O, Sutthanut K. Phenolic profile, antioxidant activity, and anti-obesogenic bioactivity of Mao Luang fruits (Antidesma bunius L.). Molecules. 2019;24(22):4109. Available from: doi.org/10.3390/molecules24224109
Dechayont B, Itharat A, Phuaklee P, Chunthorng-Orn J, Juckmeta T, Prommee N, Nuengchamnong N, Hansakul P. Antioxidant activities and phytochemical constituents of Antidesma thwaitesianum Müll. Arg. leaf extracts. Journal of integrative medicine. 2017;15(4):310-9. Available from: doi.org/10.1016/S2095-4964(17)60334-0
Sithara AP, Ravi M, Mallya S, Bairy S, Srikanth P. Experimental evaluation of analgesic and anti-inflammatory potential of leaves of Antidesma menasu on wistar albino rats. International Journal of Pharmacology and Clinical Sciences. 2013;2(4). Available from: doi.org/10.7897/2321-6328.02101
Seebaluck-Sandoram R, Lall N, Fibrich B, Van Staden AB, Mahomoodally F. Antibiotic-potentiation, antioxidant, cytotoxic, anti-inflammatory and anti-acetylcholinesterase potential of Antidesma madagascariense Lam. (Euphorbiaceae). South African Journal of Botany. 2017; 111:194-201. Available from: doi.org/10.1016/j.sajb.2017.03.034
Pratiwi RY, Elya B, Setiawan H, Forestrania RC, Dewi RT. Antidiabetic Properties and Toxicological Assessment of Antidesma celebicum Miq: Ethanolic Leaves Extract in Sprague–Dawley Rats. Advances in Pharmacological and Pharmaceutical Sciences. 2022;2022(1):2584698. Available from: doi.org/10.1155/2022/2584698
Mauldina MG, Sauriasari R, Elya B. α-Glucosidase inhibitory activity from ethyl acetate extract of Antidesma bunius (L.) Spreng stem bark containing triterpenoids. Pharmacognosy magazine. 2017;13(52):590. Available from: doi.org/10.4103/pm.pm_25_17
Rangel ÉB, Rodrigues CO, De Sa JR. Micro-and macrovascular complications in diabetes mellitus: preclinical and clinical studies. Journal of diabetes research. 2019; 2019:2161085. Available from: doi.org/10.1155/2019/2161085
Salsali A, Nathan M. A review of types 1 and 2 diabetes mellitus and their treatment with insulin. American journal of therapeutics. 2006;13(4):349-61. Available from: doi.org/10.1097/00045391-200607000-00012
Corrales P, Vidal-Puig A, Medina-Gómez G. PPARs and metabolic disorders associated with challenged adipose tissue plasticity. International Journal of Molecular Sciences. 2018;19(7):2124. Available from: doi.org/10.3390/ijms19072124
Huang S, Czech MP. The GLUT4 glucose transporter. Cell metabolism. 2007;5(4):237-52. Available from: doi.org/10.1016/j.cmet.2007.03.006
Joost HG, Thorens B. The extended GLUT-family of sugar/polyol transport facilitators: nomenclature, sequence characteristics, and potential function of its novel members. Molecular membrane biology. 2001;18(4):247-56. Available from: doi.org/10.1080/09687680110090456
Garvey WT, Maianu L, Zhu JH, Hancock JA, Golichowski AM. Multiple defects in the adipocyte glucose transport system cause cellular insulin resistance in gestational diabetes: heterogeneity in the number and a novel abnormality in subcellular localization of GLUT4 glucose transporters. Diabetes. 1993;42(12):1773-85. Available from: doi.org/10.2337/diab.42.12.1773
Govers R. Molecular mechanisms of GLUT4 regulation in adipocytes. Diabetes & metabolism. 2014 Dec 1;40(6):400-10. Available from: doi.org/10.1016/j.diabet.2014.01.005
George NG, Suja SR, Meera TS, BijuKumar BS, Kumar RP. Preliminary phytochemical screening and Invitro antioxidant activities of “Antidesma alexitera L.” leaf extract. International Journal of Advance Research, Ideas and Innovations in Technology 2021;7(3): 1009-1017.
Abeysuriya HI, Bulugahapitiya VP, Jayatissa LP. Comparative account of vitamin C contents, antioxidant properties and iron contents of minor fruits in Sri Lanka. Available from: doi.org/10.14719/pst.2021.8.4.1266
Somasiri IV, Herath H, Ratnayake RM, Senanayake SP. Propagation of Antidesma alexiteria and Syzygium caryophyllatum, two underexploited fruit plants in Sri Lanka: Effect of cutting types, potting media and auxin application. Dendrobiology. 2023; 89:65-76. Available from: doi.org/10.12657/denbio.089.007
Aerni-Flessner L, Abi-Jaoude M, Koenig A, Payne M, Hruz PW. GLUT4, GLUT1, and GLUT8 are the dominant GLUT transcripts expressed in the murine left ventricle. Cardiovascular diabetology. 2012 Dec;11:1-0.
Margarida Martins A, Sha W, Evans C, Martino‐Catt S, Mendes P, Shulaev V. Comparison of sampling techniques for parallel analysis of transcript and metabolite levels in Saccharomyces cerevisiae. Yeast. 2007 Mar;24(3):181-8. Available from: doi.org/10.1002/yea.1442
Voet D, Gratzer WB, Cox RA, Doty P. Absorption spectra of nucleotides, polynucleotides, and nucleic acids in the far ultraviolet. Biopolymers: Original Research on Biomolecules. 1963 Jun;1(3):193-208. Available from: doi.org/10.1002/bip.360010302
Zhao FQ, Keating AF. Functional properties and genomics of glucose transporters. Current genomics. 2007 Apr 1;8(2):113-28. Available from: doi.org/10.2174/138920207780368187
Leto D, Saltiel AR. Regulation of glucose transport by insulin: traffic control of GLUT4. Nature reviews Molecular cell biology. 2012 Jun;13(6):383-96. Available from: doi:10.1038/nrm3351
Sayem AS, Arya A, Karimian H, Krishnasamy N, Ashok Hasamnis A, Hossain CF. Action of phytochemicals on insulin signaling pathways accelerating glucose transporter (GLUT4) protein translocation. Molecules. 2018 Jan 28;23(2):258. Available from: doi.org/10.3390/molecules23020258
Al-Shaqha WM, Khan M, Salam N, Azzi A, Chaudhary AA. Anti-diabetic potential of Catharanthus roseus Linn. and its effect on the glucose transport gene (GLUT-2 and GLUT-4) in streptozotocin induced diabetic wistar rats. BMC complementary and alternative medicine. 2015 Dec;15:1-8. Available from: DOI 10.1186/s12906-015-0899-6
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