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BINA LOHITA SARI

Judul : Screening of Alpha Glucosidase inhibitors from Terminalia Catappa fruits using molecular docking method and in vitro test
Abstrak :

Objective: Terminalia catappa L. (T. catappa L.) fruit has inhibitory activity on α-glucosidase, therefore, can be a potential natural source for the treatment of type II diabetes mellitus. Inhibitory activity of ethanol fruit extract with IC50 3.02 µg/ml was the strongest inhibition when compared with 54 medicinal plants used as an antidiabetic agent in Indonesia. This project was aimed to find the active compound from T. catappa L. fruit using molecular docking, identification ethyl acetate subfraction using TLC and GC-MC, determine in vitro test on α-glucosidase inhibitory activity from ethyl acetate extract and subfraction.

Methods: Molecular docking using AutoDock 4.2 was performed to predict the binding modes of α-glucosidase enzyme from Saccharomyces cereviciae with 13 chemical constituents of T. catappa. α-Glucosidase enzyme was obtained from Protein Data Bank (PDB code: 3A4A). Acarbose, voglibose and miglitol were used as standards. Docking result determines the highest binding energy (ΔG) and inhibition constants (Ki) as an active compound. Visualization of amino acid residues around the active compound was identified with PyMOL and LigPlot. Screening of active compound was carried out by T. catappa L. fruit remaceration extraction use hexane and ethyl acetate. Ethyl acetate extract was separated on silica gel column chromatography using n-hexane, ethyl acetate and methanol sequentially based on polarity of each solvent. Identification of an active compound from ethyl acetate sub fractions using TLC and GC-MS method. The inhibitory activity of the active compound of α-glucosidase was determined with in vitro test using α-glucosidase enzyme.

Results: The highest binding energy and inhibition constant is β–sitosterol with ΔG-10.61 kcal/mol and Ki 0.02 µM. The ligand was situated around of 18 amino acid residues. Ethyl acetate subfractions A, B and C showed that subfraction B contains similar spot characteristic and Rf value (0.42) with β-Sitosterol standard. Identification with GC-MS gave β–sitosterol acetate and sitostenone. Redocking process of β–sitosterol acetate and sitostenone showed ΔG-11.14 kcal/mol and-9.79 kcal/mol with Ki 0.01 μM and 0.07 μM respectively. In vitro test of acarbose, ethyl acetate extract and subfraction B gave IC50 17.52; 192.51 and 296.28 µg/ml.

Conclusion: Three steroids that are β-sitosterol, β-sitosterol acetate and sitostenone were the active compounds responsible for α-glucosidase inhibitory activity of T. catappa L. fruit. According to the in vitro test, ethyl acetate extract has stronger α-glucosidase inhibitory activity than ethyl acetate subfraction B.

Tahun : 2019 Media Publikasi : jurnal internasional
Kategori : Jurnal No/Vol/Tahun : 8 / 12 / 2016
ISSN/ISBN : 0975-1491
PTN/S : UNPAK Program Studi : FARMASI
Bibliography :

  1. Sicree R, Shaw J, Zimmet P. The Global Burden. Diabetes and impaired glucose tolerance. Prevalence and Projections. In: Gan

D. editor. Diabetes atlas. 3rd ed. Brussels: International Diabetes Federation; 2006. p. 16-103.

  1. Olokoba AB, Olusegun AO, Lateefat BO. Type 2 diabetes mellitus: a review of current trends. Oman Med J 2012;27:269-73.
  2. Sireesha K, Raghunandan N. Evaluation of in vivo antidiabetic and antioxidant activity of Artocarpus hirsutus seeds in streptozotocin-induced diabetic rats. Asian J Pharm Clin Res 2016;9 Suppl 1:170-2.
  3. Mun’im A, Katrin, Azizahwati, Ari A, Kun FM, Maya M. Screening of α-glucosidase inhibitory activity of some Indonesian medicinal plants. Int J Med Arom Plants 2013;3:144-50.

 

  1. Nagappa AN, Thakurdesai PA, Venkat NR, Jiwan S. Antidiabetic activity of Terminalia catappa Linn fruits. J Ethnopharmacol 2003;88:45-50.
  2. Meng XY, Hong-Xing, Mihaly M, Meng C. Molecular docking: a powerful approach for structure-baseddrug discovery. Curr Comput Aided Drug Des 2011;7:146–57.
  3. Tiwary BK, Pathak RK, Pradhan K, Nanda AK, Bothra AK, Chakraborty R. Evaluation of drug candidature of some quinazoline-4-(3h)-ones as inhibitor of human dihydrofolate reductase enzyme: molecular docking and in silico studies. Int J Pharm Pharm Sci 2014;6 Suppl 2:393-9.
  4. Bourne PE, Weissig H. editors. Structural Bioinformatics. New Jersey: Wiley-Liss. Inc; 2003. p. 507-19.
  5. Arnold K, Lorenza B, Jurgen K, Torsten S. The SWISS-MODEL Workspace: A web based environment for protein structure homology modelling. Bioinformatics 2003;22:195.
  6. Laskowski RA, Mac Arthur MW, Moss DS, Thornton JM. Prochek: aprogram to check the stereochemical quality of protein structures. J Appl Crystallogr 1993;26:283-91.
  7. Morris GM, Huey R, Lindstrom W, Sanner MF, Belew RK, Goodsell DS, et al. Autodock4 and AutoDockTools4: automated docking with selective receptor flexiblity. J Computational Chem 2009;16:2785-91.
  8. Yamamoto K, HideoM, Masami K, Shigeyoshi O. Crystal structures of isomaltase from Sacharomyces cerevisiae and in complex with its competitive inhibitor maltose. FEBS J 2010;277:4205-14.
  9. Sneha JA, Chaudhari S. Alpha-amylase inhibitory and hypoglycemic activity of Clerodendrone multiflorum Linn. Stems. Asian J Pharm Clin Res 2011;4 Issue 2:99-100.
  10. Jirawattanapong W, Yenchit T, Thaweephol. Chemical investigation of three kinds of Terminalia Fruits. Bull Dept Med Sci 1997;39:222.
  11. Dr Duke’s. Phytochemical and Ethnobotanical Databases; 2008. p. 11.
  12. Mohale DS, Dewani AP, Chandewar AV, Khadse CD, Tripathi AS, Agrawal SS. Brief review on medicinal potential of Terminalia Catappa. J Herbal Med Toxicol 2009;3:8.
  13. Huey R, Garrett MM. Using AutoDock with AutoDock tools: a tutorial. The scripps research Institute Molecular Graphics Laboratory; 2006. p. 7-50.
  14. Sundararajan S, Balajee R, Rajan MSD. Comparative docking analysis of neuraminidase with various inhibitors. Int J Pharm Pharm Sci 2010;2 Issue 3:83-5.
  15. Elya B, Basah K, Novi FU, Marista GM, Anindita RA. Alfa glucosidase inhibitory activity of Kayu Tuah (Antidesma celebicum MIQ). Int Res J Pharm 2013;4:30.
  16. Morris AL, Mac Arthur MW, Hutchinson EG, Thornton JM. Stereochemical quality of protein structure coordinates. Protein 1992;12:345-64.
  17. Ramachandran GN, Ramakrishnan C, Sasisekharan V. Stereochemistry of polypeptide chain configurations. J Mol Biol 1963;7:95–9.
  18. Yin Z, Wei Z, Fajin F, Yong Z, Wenyi K. α-Glucosidase inhibitors isolated from medicinal plants. Food Sci Human Wellness 2014;3:136.
  19. PyMOL. Available from: http://www.pymol.org. [Last accessed on 03 Aug 2014].
  20. LigPlot.    Available    from:    http://www.ebi.ac.uk/thornton- srv/software/lIGPLOT. [Last accessed on 03 Aug 2014].
  21. Morris GM, Goodsell DS, Halliday RS, Huey R, Hart WE. Automated docking using a Lamarckian genetic algorithm and an empirical free energy function. J Comput Chem 1998;19:1639–62.
  22. Karan SK, Sagar KM, Dilipkumar P, Arijit M. Isolation of β- sitosterol and evaluation of antidiabetic activity of Aristolochia indica in alloxan-induced diabetic mice with a reference to in vitro antioxidant activity. J Med Plants Res 2012;6:1219-23.
  23. Hossain MA, Wafa AS Al-Toubi, Afaf MW, Qasim A Al-Riyami, Jamal N Al-Sabahi. Identification and characterization of chemical compounds indifferent crude extracts from leaves of Omani neem. J Taibah Univ Sci 2013;7:181–8.
  24. Hakamata W, Masaaki K, Harunhiro O, Toshiyuki N, Tadatake O. Design and screening strategies for α-glucosidase inhibitors based on enzymological information. Curr Topics Med Chem 2009;9:5-7.

 

 

 

  1. Okuda T, Ito H. Tannins of constant structure in medicinal and food plants hydrolyzable tannins and polyphenols related to tannins. Molecules 2011;16:2191-217.
  2. Rupeshkumar M, Kavitha K, Haldar PK. Role of herbal plants in the diabetes mellitus therapy: an overview. Int J Appl Pharm 2014;6:1-3.

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