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

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.

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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):1–6

    Google 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 45–50

    Google 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 58:899–907

    PubMed  Google Scholar 

  4. Bertman S (2003) Handbook to life in Ancient mesopotamia. Infobase Publishing History, New York, pp 258–305

    Google 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 52:3099–3105

    CAS  PubMed  Google 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 57:352–356

    CAS  PubMed  Google 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 6:94–98

    CAS  Google Scholar 

  8. Čolović MB, Krstić DZ, Lazarević-Pašti TD, Bondžić AM, Vasić VM (2013) Acetylcholinesterase inhibitors: pharmacology and toxicology. Curr Neuropharmacol 11:315–335

    PubMed  PubMed Central  Google Scholar 

  9. Dallakyan S, Olson AJ (2015) Small-molecule library screening by docking with PyRx. Methods Mol Biol 1263:243–450

    CAS  PubMed  Google 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 53:1583–1590

    Google Scholar 

  11. Dohi S, Terasaki M, Makino M (2009) Acetylcholinesterase inhibitory activity and chemical composition of commercial essential oils. J Agric Food Chem 57:4313–4318

    CAS  PubMed  Google Scholar 

  12. Ebada ME (2017) Cuminaldehyde: a potential drug candidate. J Pharmacol Clin Res 2:555–585

    Google Scholar 

  13. El Ashry ES, Rashed N, Salama OM, Saleh A (2003) Components, therapeutic value and uses of myrrh. Pharmazie 58:163–168

    PubMed  Google Scholar 

  14. Ellman GL, Courtney DK, Andreas V, Featherstone RM (1961) A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 7:88–95

    CAS  PubMed  PubMed Central  Google 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 Nairobi

  16. Hanuš LO, Řezanka T, Dembitsky VM, Moussaieff A (2005) Myrrh—commiphora chemistry. Biomed Papers 149:3–28

    Google Scholar 

  17. Haritakun W, Taworn W, Suebsakwong P (2016) Acetylcholinesterase inhibitory activity of a sesquiterpenoid from Curcuma aromatic rhizomes. SDU Res J 9:51–61

    Google Scholar 

  18. Haviv H, Wong DM, Silman I, Sussman JL (2007) Bivalent ligands derived from Huperzine A as acetylcholinesterase inhibitors. Curr Top Med Chem 7:375–387

    CAS  PubMed  Google Scholar 

  19. Him A, Özbek H, Turel I (2008) Antinociceptive activity of alpha-pinene and fenchone. PhOL 3:363–369

    Google Scholar 

  20. Hollingsworth RG (2005) Limonene, a citrus extract, for control of mealybugs and scale insects. J Econ Entomol 98:772–779

    CAS  PubMed  Google Scholar 

  21. Holzgrabe U, Kapková P, Alptüzün V, Scheiber J, Kugelmann E (2007) Targeting acetylcholinesterase to treat neurodegeneration. Expert Opin Ther Targets 11:161–179

    CAS  PubMed  Google Scholar 

  22. Houghton Peter J, Ren Yuhao, Howes Melanie-Jayne (2006) Acetylcholinesterase inhibitors from plants and fungi. Nat Prod Rep 2:181–199

    Google 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 1086:63–72

    CAS  PubMed  Google 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 12:217–225

    CAS  PubMed  Google 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 53:1677–1683

    CAS  PubMed  Google 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 3:1–7

    Google Scholar 

  27. Khaleel C, Tabanca N, Buchbauer G (2018) α-Terpineol, a natural monoterpene: a review of its biological properties. Open Chem 16:349–361

    CAS  Google 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):835–841

    CAS  PubMed  Google 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 7:297–307

    CAS  PubMed  Google Scholar 

  30. Laskowski RA, Swindells MB (2011) Ligplot+: multiple ligand-protein interaction diagrams for drug discovery. J Chem Inf Model 51:2778–2786

    CAS  PubMed  Google 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 4:217–229

    PubMed  PubMed Central  Google 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 18:10733–10746

    CAS  PubMed  PubMed Central  Google 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 16:3333–3352

    CAS  PubMed  Google 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 46:3431–3434

    CAS  Google Scholar 

  35. Mogey GA, Young PA (1949) The antagonism of curarizing activity by phenolic substances. Br J Pharmacol Chemother 4:359–365

    CAS  PubMed  PubMed Central  Google 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–H2345

    CAS  PubMed  Google 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 69:123–129

    CAS  PubMed  Google 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 5:247–258

    CAS  Google 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

    Article  Google 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 273:19509–19517

    CAS  PubMed  Google 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 2:850–857

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Parent MB, Baxter MG (2004) Septohippocampal acetylcholine: involved in but not necessary for learning and memory. Learn Memory 11:9–20

    Google Scholar 

  43. Picollo MI, Toloza AC, Cueto GM, Zygadlo J, Zerba E (2008) Anticholinesterase and pediculicidal activities of monoterpenoids. Fitoterapia 79(4):271–278

    CAS  PubMed  Google Scholar 

  44. Pramod K, Ansari SH, Ali J (2010) Eugenol: a natural compound with versatile pharmacological actions. Nat Prod Commun 5(12):1999–2006

    CAS  PubMed  Google 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 5:1–5

    CAS  Google 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):201–213

    CAS  Google 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):323–326

    CAS  PubMed  Google 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 249–260

  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):664–674

    CAS  PubMed  Google 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: 12483

  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 3:87–103

    Google Scholar 

  52. Thomsen R, Christensen MH (2006) Moldock: a new technique for high-accuracy molecular docking. J Med Chem 49(11):3315–3321

    CAS  PubMed  Google 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

    Article  PubMed  Google 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):3032–3040

    CAS  Google 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 Walden

    Google 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):1075–1084

    CAS  PubMed  Google 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):265–271

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Zahi MR, Liang H, Yuan Q (2015) Improving the antimicrobial activity of d-limonene using a novel organogel-based nanoemulsion. Food Control 50:554–559

    CAS  Google 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):643–652

    Google Scholar 

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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.

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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.

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Correspondence to Isaac Karimi.

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Hussein, B.A., Karimi, I. & Yousofvand, N. Computational insight to putative anti-acetylcholinesterase activity of Commiphora myrrha (Nees), Engler, Burseraceae: a lessen of archaeopharmacology from Mesopotamian Medicine I. In Silico Pharmacol. 7, 3 (2019). https://doi.org/10.1007/s40203-019-0052-1

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Keywords

  • Myrrh
  • Acetylcholinesterase
  • Nootropics
  • Insecticides
  • Terpenes
  • Sesquiterpenes
  • Cuscohygrine