Advertisement

In Silico Pharmacology

, 7:3 | Cite as

Computational insight to putative anti-acetylcholinesterase activity of Commiphora myrrha (Nees), Engler, Burseraceae: a lessen of archaeopharmacology from Mesopotamian Medicine I

  • Baydaa Abed Hussein
  • Isaac KarimiEmail author
  • Namdar Yousofvand
Original Research
  • 80 Downloads

Abstract

Commiphora spp., Burseraceae family and their resinous matter, myrrh, are used in Mesopotamian medicine as fragrance or antiinsectant. Based on in vitro, leaves, bark, and resin methyl alcohol extract of C. myrrha showed similar inhibitory effects of 17.00, 26.00, and 29.33% for acetylcholinesterase (AChE) as compared to eserine, respectively. The ADMET properties and putative anticholinesterase activity of phytochemicals of myrrh were computationally predicted using in silico tools. Phytochemicals of C. myrrha had acceptable binding affinity (BA) towards principal sites of AChE ranging from − 5.8 (m-cresol) to − 10.5 (abietic acid) kcal/mol. In this regard, all terpenoid compounds (25 out of 28) of myrrh were dual inhibitors since they hydrophobically interacted with both catalytic triad and peripheral anionic site (PAS) of AChE while alpha-terpineol, elemol, and eugenol employed hydrogen bonds with AChE. Cuscohygrine as a pyrrolidine alkaloid has been docked with AChE through hydrogen bonds with PAS and through hydrophobic interactions with catalytic triad thereby we initially proposed it as dual inhibitor of AChE. M-cresol as a methylphenol has been loosely docked with AChE via hydrogen bond and would be a hit molecule for further drug synthesis. This study not only confirmed archaeopharmacological applications of myrrh as antiinsectant or nootropics but also offered an array of terpenoid compounds, cuscohygrine, and m-cresol as a good starting point for hit-to-lead-to-drug optimization phase in synthesis of phyto-nootropics and ecofriendly insecticides.

Keywords

Myrrh Acetylcholinesterase Nootropics Insecticides Terpenes Sesquiterpenes Cuscohygrine 

Notes

Acknowledgements

This paper emanates from MSc thesis of first author submitted to Department of Biology, Faculty of Science, Razi University 67149-67346, Kermanshah, Iran. This study was supported by intramural fund and first and second authors paid the fee of in silico investigation.

Author contributions

BAH and NY gathered data of Mesopotamian Medicine, authenticated plants, and carried out the experiments. BAH and IK analyzed data and carried out the molecular docking work. BAH and IK prepared the manuscript while all authors have read and approved the final manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

References

  1. Ali SE, Chehri K, Karimi N, Karimi I (2017) In vitro antibacterial activity of Citrus limon (L.) Burm against gentamicin-resistant Escherichia coli complemented with in silico molecular docking of its major phytochemicals with ribosome recycling factor. Basic Appl Pharm Pharmacol 1(1):1–6Google Scholar
  2. Ben-Yehoshua S, Borowitz C, Hanuš LO (2012) Spices: frankincense, myrrh, and balm of Gilead: ancient spices of Southern Arabia and Judea. In: Janick J (ed) Horticultural reviews. Wiley, New York, USA, pp 45–50Google Scholar
  3. Berman HM, Battistuz T, Bhat TN, Bluhm WF, Bourne PE, Burkhardt K, Fagan P (2002) The protein data bank. Acta Crystallogr D Biol Crystallogr 58:899–907PubMedGoogle Scholar
  4. Bertman S (2003) Handbook to life in Ancient mesopotamia. Infobase Publishing History, New York, pp 258–305Google Scholar
  5. Cheng F, Li W, Zhou Y, Shen J, Wu Z, Liu G, Lee PW, Tang Y (2012) Admetsar: a comprehensive source and free tool for assessment of chemical admet properties. J Chem Inf Model 52:3099–3105PubMedGoogle Scholar
  6. Claeson P, Andersson R, Samuelsson G (1991) T-cadinol: a pharmacologically active constituent of scented myrrh: introductory pharmacological characterization and high field 1H- and 13C-NMR data. Planta Med 57:352–356PubMedGoogle Scholar
  7. Claeson P, Rådström P, Sköld O, Nilsson Å, Höglund S (1992) Bactericidal effect of the sesquiterpene T-cadinol on Staphylococcus aureus. Phytother Res 6:94–98Google Scholar
  8. Čolović MB, Krstić DZ, Lazarević-Pašti TD, Bondžić AM, Vasić VM (2013) Acetylcholinesterase inhibitors: pharmacology and toxicology. Curr Neuropharmacol 11:315–335PubMedPubMedCentralGoogle Scholar
  9. Dallakyan S, Olson AJ (2015) Small-molecule library screening by docking with PyRx. Methods Mol Biol 1263:243–450PubMedGoogle Scholar
  10. de Santana MF, Guimarães AG, Chaves DO, Silva JC, Bonjardim LR, de Lucca Júnior W, Ferro JN, Barreto Ede O, dos Santos FE, Soares MB, Villarreal CF, Quintans Jde S, Quintans-Júnior LJ (2015) The anti-hyperalgesic and anti-inflammatory profiles of p-cymene: evidence for the involvement of opioid system and cytokines. Pharma Biol 53:1583–1590Google Scholar
  11. Dohi S, Terasaki M, Makino M (2009) Acetylcholinesterase inhibitory activity and chemical composition of commercial essential oils. J Agric Food Chem 57:4313–4318PubMedGoogle Scholar
  12. Ebada ME (2017) Cuminaldehyde: a potential drug candidate. J Pharmacol Clin Res 2:555–585Google Scholar
  13. El Ashry ES, Rashed N, Salama OM, Saleh A (2003) Components, therapeutic value and uses of myrrh. Pharmazie 58:163–168PubMedGoogle Scholar
  14. Ellman GL, Courtney DK, Andreas V, Featherstone RM (1961) A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 7:88–95PubMedPubMedCentralGoogle Scholar
  15. Gitau WJ (2015) Evaluation of the composition, physico-chemical characteristics, surfactant and anti-microbial potential of Commiphora abyssinica gum resin. Doctoral dissertation, University of NairobiGoogle Scholar
  16. Hanuš LO, Řezanka T, Dembitsky VM, Moussaieff A (2005) Myrrh—commiphora chemistry. Biomed Papers 149:3–28Google Scholar
  17. Haritakun W, Taworn W, Suebsakwong P (2016) Acetylcholinesterase inhibitory activity of a sesquiterpenoid from Curcuma aromatic rhizomes. SDU Res J 9:51–61Google Scholar
  18. Haviv H, Wong DM, Silman I, Sussman JL (2007) Bivalent ligands derived from Huperzine A as acetylcholinesterase inhibitors. Curr Top Med Chem 7:375–387PubMedGoogle Scholar
  19. Him A, Özbek H, Turel I (2008) Antinociceptive activity of alpha-pinene and fenchone. PhOL 3:363–369Google Scholar
  20. Hollingsworth RG (2005) Limonene, a citrus extract, for control of mealybugs and scale insects. J Econ Entomol 98:772–779PubMedGoogle Scholar
  21. Holzgrabe U, Kapková P, Alptüzün V, Scheiber J, Kugelmann E (2007) Targeting acetylcholinesterase to treat neurodegeneration. Expert Opin Ther Targets 11:161–179PubMedGoogle Scholar
  22. Houghton Peter J, Ren Yuhao, Howes Melanie-Jayne (2006) Acetylcholinesterase inhibitors from plants and fungi. Nat Prod Rep 2:181–199Google Scholar
  23. Jesionek A, Poblocka-Olech L, Zabiegala B, Bucinski A, Krauze-Baranowska M, Luczkiewicz M (2018) Validated HPTLC method for determination of ledol and alloaromadendrene in the essential oil fractions of Rhododendron tomentosum plants and in vitro cultures and bioautography for their activity screening. J Chromatogr B Analyt Technol Biomed Life Sci 1086:63–72PubMedGoogle Scholar
  24. Johnson G, Moore SW (2006) The peripheral anionic site of acetylcholinesterase: structure, functions and potential role in rational drug design. Curr Pharm Des 12:217–225PubMedGoogle Scholar
  25. Jyotshna Srivastava N, Singh B, Chanda D, Shanker K (2015) Chemical composition and acetylcholinesterase inhibitory activity of Artemisia maderaspatana essential oil. Pharm Biol 53:1677–1683PubMedGoogle Scholar
  26. Karimi I, Zahraminoosh SH, Najafi A, Becker LA (2017) Nootropic effects of quince leaf (Cydonia oblonga miller.) decoct in mice: a neurobehavioral approach complemented with kinetics and molecular docking studies of encephalic acetyl cholinesterase inhibition. J Bioinfo Proteomics Rev 3:1–7Google Scholar
  27. Khaleel C, Tabanca N, Buchbauer G (2018) α-Terpineol, a natural monoterpene: a review of its biological properties. Open Chem 16:349–361Google Scholar
  28. Kimura M, Nojima H, Muroi M, Kimura I (1991) Mechanism of the blocking action of beta-eudesmol on the nicotinic acetylcholine receptor channel in mouse skeletal muscles. Neuropharmacology 30(8):835–841PubMedGoogle Scholar
  29. Kryger G, Silman I, Sussman JL (1999) Structure of acetylcholinesterase complexed with E2020 (Aricept): implications for the design of new anti-Alzheimer drugs. Structure 7:297–307PubMedGoogle Scholar
  30. Laskowski RA, Swindells MB (2011) Ligplot+: multiple ligand-protein interaction diagrams for drug discovery. J Chem Inf Model 51:2778–2786PubMedGoogle Scholar
  31. Lee DC, Ahn YJ (2013) Laboratory and simulated field bioassays to evaluate larvicidal activity of Pinus densiflora hydrodistillate, its constituents and structurally related compounds against Aedes albopictus, Aedes aegypti and Culex pipiens pallens in relation to their inhibitory effects on acetylcholinesterase activity. Insects 4:217–229PubMedPubMedCentralGoogle Scholar
  32. Liu XC, Li YP, Li HQ, Deng ZW, Zhou L, Liu ZL, Du SS (2013) Identification of repellent and insecticidal constituents of the essential oil of Artemisia rupestris L. aerial parts against Liposcelis bostrychophila Badonnel. Molecules 18:10733–10746PubMedPubMedCentralGoogle Scholar
  33. Messer A, McCormick K, Sunjaya, Hagedorn HH, Tumbel F, Meinwald J (1990) Defensive role of tropical tree resins: antitermitic sesquiterpenes from Southeast Asian Dipterocarpaceae. J Chem Ecol 16:3333–3352PubMedGoogle Scholar
  34. Miyazawa M, Watanabe H, Umemoto K, Kameoka H (1998) Inhibition of acetylcholinesterase activity by essential oils of Mentha species. J Agri Food Chem 46:3431–3434Google Scholar
  35. Mogey GA, Young PA (1949) The antagonism of curarizing activity by phenolic substances. Br J Pharmacol Chemother 4:359–365PubMedPubMedCentralGoogle Scholar
  36. Morshedi D, Aliakbari F, Tayaranian-Marvian A, Fassihi A, Pan-Montojo F, Pérez-Sánchez H (2015) Cuminaldehyde as the major component of Cuminum cyminum, a natural aldehyde with inhibitory effect on alpha-synuclein fibrillation and cytotoxicity. J Food Sci 80(10):H2336–H2345PubMedGoogle Scholar
  37. Murata K, Matsumura S, Yoshioka Y, Ueno Y, Matsuda H (2015) Screening of β-secretase and acetylcholinesterase inhibitors from plant resources. J Nat Med 69:123–129PubMedGoogle Scholar
  38. Murthy KSR, Reddy MC, Rani SS, Pullaiah T (2016) Bioactive principles and biological properties of essential oils of Burseraceae: a review. J Pharmacogn Phytochem 5:247–258Google Scholar
  39. Odimegwu JI, Odukoya O, Yadav RK, Chanotiya CS, Ogbonnia S, Sangwan NS (2013) A new source of elemol rich essential oil and existence of multicellular oil glands in leaves of the Dioscorea species. Sci World J.  https://doi.org/10.1155/2013/943598 CrossRefGoogle Scholar
  40. Ordentlich A, Barak D, Kronman C, Ariel N, Segall Y, Velan B, Shafferman A (1998) Functional characteristics of the oxyanion hole in human acetylcholinesterase. J Biol Chem 273:19509–19517PubMedGoogle Scholar
  41. Owokotomo IA, Ekundayo O, Abayomi TG, Chukwuka AV (2015) In-vitro anti-cholinesterase activity of essential oil from four tropical medicinal plants. Toxicol Rep 2:850–857PubMedPubMedCentralGoogle Scholar
  42. Parent MB, Baxter MG (2004) Septohippocampal acetylcholine: involved in but not necessary for learning and memory. Learn Memory 11:9–20Google Scholar
  43. Picollo MI, Toloza AC, Cueto GM, Zygadlo J, Zerba E (2008) Anticholinesterase and pediculicidal activities of monoterpenoids. Fitoterapia 79(4):271–278PubMedGoogle Scholar
  44. Pramod K, Ansari SH, Ali J (2010) Eugenol: a natural compound with versatile pharmacological actions. Nat Prod Commun 5(12):1999–2006PubMedGoogle Scholar
  45. Ramnath MG, Thirugnanasampandan R, Sadasivam M, Mohan PS (2015) Antioxidant, antibacterial and antiacetylcholinesterase activities of abietic acid from Isodon wightii (Bentham) H. Hara. Free Rad Antiox 5:1–5Google Scholar
  46. Remya C, Dileep KV, Variayr EJ, Sadasivan C (2016) An in silico guided identification of nAChR agonists from Withania somnifera. Front Life Sci 9(3):201–213Google Scholar
  47. Rubio NC, Thurmann D, Krumbiegel F, Pragst F (2017) Behaviour of hygrine and cuscohygrine in illicit cocaine production establishes their use as markers for chewing coca leaves in contrast with cocaine abuse. Drug Test Anal 9(2):323–326PubMedGoogle Scholar
  48. Shamsizadeh A, Roohbakhsh A, Ayoobi F, Moghaddamahmadi A (2017) The Role of natural products in the prevention and treatment of multiple sclerosis. In: Nutrition and Lifestyle in Neurological Autoimmune Diseases Multiple Sclerosis. Academic Press, pp 249–260Google Scholar
  49. Sharon-Asa L, Shalit M, Frydman A, Bar E, Holland D, Or E, Lavi U, Lewinsohn E, Eyal Y (2003) Citrus fruit flavor and aroma biosynthesis: isolation, functional characterization, and developmental regulation of Cstps1, a key gene in the production of the sesquiterpene aroma compound Valencene. Plant J 36(5):664–674PubMedGoogle Scholar
  50. Singh KD, Labala RK, Devi TB, Singh NI, Chanu HD, Sougrakpam S, Nameirakpam BS, Sahoo D, Rajashekar Y (2017) Biochemical efficacy, molecular docking and inhibitory effect of 2, 3-dimethylmaleic anhydride on insect acetylcholinesterase. Sci Rep 7, Article number: 12483Google Scholar
  51. Suganthy N, Pandian SK, Devi KP (2009) Cholinesterase inhibitors from plants: possible treatment strategy for neurological disorders-a review. Int J Biomed Pharmaceut Sci 3:87–103Google Scholar
  52. Thomsen R, Christensen MH (2006) Moldock: a new technique for high-accuracy molecular docking. J Med Chem 49(11):3315–3321PubMedGoogle Scholar
  53. Tung BT, Thu DK, Thu NTK, Hai NT (2017) Antioxidant and acetyl-cholinesterase inhibitory activities of ginger root (Zingiber officinale Roscoe) extract. J Complement Integr Med.  https://doi.org/10.1515/jcim-2016-0116 CrossRefPubMedGoogle Scholar
  54. Wang S, Zhao Z, Yun-ting S, Zeng Z, Zhan X, Li C, Xie T (2012) A review of medicinal plant species with elemene in China. Af J Pharm Pharmacol 6(44):3032–3040Google Scholar
  55. Watt M, Sellar W (1996) Frankincense and myrrh: through the ages, and a complete guide to their use in herbalism and aromatherapy today. C. W. Daniel Co., Saffron WaldenGoogle Scholar
  56. Xie Y, Isman MB, Feng Y, Wong A (1993) Diterpene resin acids: major active principles in tall oil against Variegated cutworm, Peridroma saucia (Lepidoptera: Noctuidae). J Chem Ecol 19(6):1075–1084PubMedGoogle Scholar
  57. Yu Z, Wang B, Yang F, Sun Q, Yang Z, Zhu L (2011) Chemical composition and anti-acetyl cholinesterase ctivity of flower essential oils of Artemisia annua at different flowering stage. Iran J Pharm Res. 10(2):265–271PubMedPubMedCentralGoogle Scholar
  58. Zahi MR, Liang H, Yuan Q (2015) Improving the antimicrobial activity of d-limonene using a novel organogel-based nanoemulsion. Food Control 50:554–559Google Scholar
  59. Zarred K, Laarif A, Ben Hamouda A, Chaieb I, Mediouni-Ben Jemaa J (2017) Anticholinesterase Potential of monoterpenoids on the whitefly Bemisia tabaci and their kinetic studies. JAST 19(3):643–652Google Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Biology, Faculty of ScienceRazi UniversityKermanshahIran

Personalised recommendations