In Silico Pharmacology

, 5:3 | Cite as

Revealing the potency of Annona muricata leaves extract as FOXO1 inhibitor for diabetes mellitus treatment through computational study

  • Dini Sri Damayanti
  • Didik Huswo Utomo
  • Chandra Kusuma
Original Research


FOXO1 protein inactivation in the nucleus is one of targets for the treatment of diabetes mellitus. Annona muricata leaves contain flavonoid and phenolic compound alkaloids that were known to be able to increase pancreatic β cell proliferation in animal experiment. This research aimed to predict the active compound ability of the Annona muricata leaves to bind and inhibit FOXO1 protein through in silico study. Analysis of molecular docking was performed by using Autodock Vina PyRx. this research proved that anonaine, rutin, muricatocin a, isolaureline, xylopine, and kaempferol 3-O-rutinoside had an equal or smaller free binding energy compared to the control compound. Rutin and Muricatocin A had the same binding ability toward 66% amino acid residues, compared to control compound with hydrogen bond type, while xylopine, anonaine, isolaureline, kaempferol 3-O-rutinoside had a similar binding ability towards 33% amino acid residues compared to control compound with hydrogen bond type.


Anonaine Active compound Annona muricata leaves FOXO1 In silico Isolaureline Kaempferol 3-O-rutinoside Muricatocin A Rutin Xylopine 


  1. Adeyemi DO, Komolafe OA, Adewole OS, Obuotor EM, Abiodun AA, Adenowo TK (2010) Histomorphological and morpholometric studies of the pancreatic islet cell of diabetic rats treated with extracts of Annona muricata. Folia Morphol 69:92–100Google Scholar
  2. Chang R (2006) Kimia dasar: konsep-konsep inti, 1st edn. Erlangga, JakartaGoogle Scholar
  3. Dallakyan S, Olson AJ (2015) Small-molecule library screening by docking with PyRx. Methods Mol Biol 1263:243–250. doi:10.1007/978-1-4939-2269-7_19 CrossRefPubMedGoogle Scholar
  4. DeLano WL (2002) The PyMOL molecular graphics system. DeLano Scientific, Palo Alto. Accessed 28 July 2016
  5. Gajalakshmi S, Vijayalakshmi D, Rajeswari V (2012) Phytochemical and pharchological of properties of Annona muricata: a review. Int J Pharm Pharm Sci 4:3–6Google Scholar
  6. Gilson MK, Zhou HX (2007) Calculation of protein-ligand binding affinities. Annu Rev Biophys Biomol Struct 36:21–42CrossRefPubMedGoogle Scholar
  7. Gross DN, van den Heuvel AP, Birnbaum MJ (2008) The role of FoxO in the regulation of metabolism. Oncogene 27:2320–2336. doi:10.1038/onc.2008.25 CrossRefPubMedGoogle Scholar
  8. Hileman B (2006) Accounting for R&D, many doubt the $800 million pharmaceutical price tag. Chem Eng News 84:50Google Scholar
  9. Jeffrey GA (1997) An introduction to hydrogen bonding. Oxford University Press, OxfordGoogle Scholar
  10. Malviya N, Jain S, Malviya S (2010) Antidiabetic potential of medicinal plants. Acta Pol Pharm 67:113–118PubMedGoogle Scholar
  11. Martinez SC, Cras-Méneur C, Bernal-Mizrachi E, Permutt MA (2006) Glucose regulates Foxo1 through insulin receptor signaling in the pancreatic islet beta-cell. Diabetes 55:1581–1591. doi:10.2337/db05-0678 CrossRefPubMedGoogle Scholar
  12. Martinez SC, Tanabe K, Cras-Méneur C, Abumrad NA, Bernal-Mizrachi E, Permutt MA (2008) Inhibition of Foxo1 protects pancreatic islet beta-cells against fatty acid and endoplasmic reticulum stress-induced apoptosis. Diabetes 57:846–859. doi:10.2337/db07-0595 CrossRefPubMedGoogle Scholar
  13. Moghamtousi SZ, Fadaeinasab M, Nikyad S, Mohan G, Ali HM, Kadir HA (2015) Annona muricata (Annonaceae): a review of traditional uses, isolated acetogenins and biological activities. Int J Mol Sci 16:15625–15658. doi:10.3390/ijms160715625 CrossRefGoogle Scholar
  14. Nagashima T, Shigematsu N, Maruki R, Urano Y, Tanaka H, Shimaya A, Shimokawa T, Shibasaki M (2010) Discovery of novel forkhead box O1 inhibitors for treating type 2 diabetes: improvement of fasting glycemia in diabetic db/db mice. Mol Pharmacol 78:961–970. doi:10.1124/mol.110.065714 CrossRefPubMedGoogle Scholar
  15. Pedro F, Lei H (2010) A systematic review on computer-aided drug design: docking and scoring. J Macao Politech Inst 4:47–51Google Scholar
  16. Talchai C, Xuan S, Lin HV, Sussel L, Domenico A (2012) Pancreatic β-cell dedifferentiation as mechanism of diabetic β-cell failure. Cell 150:1223–1234. doi:10.1016/j.cell.2012.07.029 CrossRefPubMedPubMedCentralGoogle Scholar
  17. Wadood A, Ahmed N, Shah L, Ahmad A, Hassan H, Shams S (2013) In-silico drug design: an approach which revolutionarised the drug discovery process. OA Drug Des Deliv 1:1–3Google Scholar
  18. Wallace AC, Laskowski RA, Thornton JM (1995) LIGPLOT: a program to generate schematic diagrams of protein-ligand interactions. Protein Eng 8:127–134CrossRefPubMedGoogle Scholar
  19. Zukhurullah M, Aswad M, Subehan S (2012) Kajian beberapa senyawa antiinflamsi: docking terhadap siklooksigenase-2 secara in silico. Majalah Farmasi dan Famakologi 16:37–44Google Scholar

Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • Dini Sri Damayanti
    • 1
  • Didik Huswo Utomo
    • 2
  • Chandra Kusuma
    • 1
  1. 1.Faculty of MedicineBrawijaya UniversityMalangIndonesia
  2. 2.Department of Biology, Faculty of Mathematics and Natural SciencesBrawijaya UniversityMalangIndonesia

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