In vivo analgesic effect of different extracts of Hopea odorata leaves in mice and in silico molecular docking and ADME/T property analysis of some isolated compounds from this plant
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Md. Sajjad Ul Hoque
Abstract
Background
The current study evaluates the analgesic effect of different extracts of Hopea odorata leaves in mice followed by molecular docking and absorption, distribution, metabolism, excretion, and toxicity (ADME/T) analysis of isolated compounds derived from the plant with the COX-1 enzyme.
Methods
In the present study, the dried leaves of H. odorata were subjected to extraction using methanol, ethanol, and water. In vivo analgesic activity was evaluated by using the acetic acid-induced writhing test and formalin-induced paw licking test, and in silico molecular docking and ADME/T study were performed using Schrödinger Maestro (version 11.1) and online-based tools, respectively, on eight isolated compounds.
Results
The results showed that the methanolic extract of leaves has highest significant dose-dependent analgesic activity at both 200 and 400 mg/kg followed by ethanolic extract of leaves. Among all the compounds, ampelopsin showed the best docking score of −7.055, ensuring strong binding affinity between the ligand and the receptor, and ADME/T analysis using Web-based tools ensures the compound has not violated Lipinski’s rule of five indicating its safety consumption.
Conclusions
The result confirms the analgesic activity of H. odorata leaves in both in vivo and in silico assays. The data support ampelopsin to be a potent analgesic compound worthy of future clinical trials and its “drug-likeliness”
Acknowledgments
Authors are grateful to the management of the Department of Pharmacy, International Islamic University Chittagong, Bangladesh, for providing all the laboratory facilities and support with a research grant to accomplish the study (grant no. Pharm-P&D 71/10-15/38), and also thanks to all the members of GUSTO for their kind help in the experiment.
Author contributions: M.S.H.K. collected and prepared the extracts. M.S.U.H. and M.S.H.K. conceived and designed the in vivo experiments. M.S.H.K., A.P., M.S.C., and S. S. Z. conceived and designed the in silico studies. A.P., M.S.C., and S.S.Z. performed molecular docking study and analyzed the primary in silico data. M.S.U.H., J.B., and M.S.H.K. performed ADME/T properties analysis. M.S.H.K., M.S.C., S.S.Z., M.M.H., J.B., S.D.G., S.B., and S.A. analyzed the data, wrote different parts of the manuscript, and checked the whole manuscript. All authors read and approved the final manuscript.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
References
1. Hopea odorata. The IUCN Red List of Threatened Species. Available at: http://www.iucnredlist.org/details/32305/0. Accessed: 21 Dec 2017.Search in Google Scholar
2. Yusuf M, Wahab M, Yousuf M, Chowdhury JU, Begum J. Some tribal medicinal plants of Chittagong hill tracts, Bangladesh. Bangladesh J Plant Taxon 2007;14:117–28.10.3329/bjpt.v14i2.531Search in Google Scholar
3. Kennedy T. Managing the drug discovery/development interface. Drug Discov Today 1997;2:436–44.10.1016/S1359-6446(97)01099-4Search in Google Scholar
4. Mohamed I, Shuid A, Borhanuddin B, Fozi N. The application of phytomedicine in modern drug development. IJHPM 2012;1:16–22.10.1155/2012/250584Search in Google Scholar
5. Robinson MM, Zhang X. The world medicines situation 2011, traditional medicines: global situation, issues and challenges. Geneva: World Health Organization, 2011.Search in Google Scholar
6. Rates SMK. Plants as source of drugs. Toxicon 2001; 39:603–13.10.1016/S0041-0101(00)00154-9Search in Google Scholar PubMed
7. Bonica JJ. The need of a taxonomy. Pain 1979;6:247–8.10.1016/0304-3959(79)90046-0Search in Google Scholar PubMed
8. Holden AV. The neurobiology of pain: symposium of the Northern Neurobiology Group, held at Leeds on 18 April 1983. Manchester: Manchester University Press.Search in Google Scholar
9. Bakhle YS. Structure of COX-1 and COX-2 enzymes and their interaction with inhibitors. Drugs Today (Barcelona, Spain:1998) 1999;35:237–50.10.1358/dot.1999.35.4-5.552200Search in Google Scholar
10. Chen YF, Jobanputra P, Barton P, Bryan S, Fry-Smith A, Harris G, et al. Cyclooxygenase-2 selective non-steroidal anti-inflammatory drugs (etodolac, meloxicam, celecoxib, rofecoxib, etoricoxib, valdecoxib and lumiracoxib) for osteoarthritis and rheumatoid arthritis: a systematic review and economic evaluation. Health Technol Assess 2008;12:1–278.10.3310/hta12110Search in Google Scholar PubMed
11. Kurumbail RG, Kiefer JR, Marnett LJ. Cyclooxygenase enzymes: catalysis and inhibition. Curr Opin Struct Biol 2001;11:752–60.10.1016/S0959-440X(01)00277-9Search in Google Scholar PubMed
12. McGettigan P, Henry D. Cardiovascular risk and inhibition of cyclooxygenase: a systematic review of the observational studies of selective and nonselective inhibitors of cyclooxygenase 2. J Am Med Assoc 2006;296:1633–44.10.1001/jama.296.13.jrv60011Search in Google Scholar PubMed
13. Morris GM, Lim-Wilby M. Molecular docking. In: Kukol A, editor. Molecular modeling of proteins. Totowa, NJ: Humana Press, 2008:365–82.10.1007/978-1-59745-177-2_19Search in Google Scholar PubMed
14. Meng X-Y, Zhang H-X, Mezei M, Cui M. Molecular docking: a powerful approach for structure-based drug discovery. Curr Comput Aided Drug Des 2011;7:146–57.10.2174/157340911795677602Search in Google Scholar PubMed PubMed Central
15. Van De Waterbeemd H, Gifford E. ADMET in silico modelling: towards prediction paradise? Nat Rev Drug Discov 2003;2:192–204.10.1038/nrd1032Search in Google Scholar PubMed
16. Satiraphan M, Thai QD, Sotanaphun U, Sittisombut C, Michel S, Cachet X. A new 3,4-seco-cycloartane from the leaves of Hopea odorata Roxb. Nat Prod Res 2015;29:1820–7.10.1080/14786419.2015.1007975Search in Google Scholar PubMed
17. Atun S, Aznam N, Arianingrum R. Oligoresveratrol isolated from stem bark of Hopea odorata as antioxidant and cytotoxicity againt human cancer cell line. Int Proceed Chem Biol Env 2012;38:6.Search in Google Scholar
18. Satiraphan M, Pamonsinlapatham P, Sotanaphun U, Sittisombut C, Raynaud F, Garbay C, et al. Lupane triterpenes from the leaves of the tropical rain forest tree Hopea odorata Roxb. and their cytotoxic activities. Biochem Syst Ecol 2012;44:407–12.10.1016/j.bse.2012.05.014Search in Google Scholar
19. Koster R. Acetic acid for analgesic screening. Fed Proc 1959;18:412–17.Search in Google Scholar
20. Yaro A, Magaji M, Danjuma N, Malami S, Isah A. Studies on analgesic and anti-inflammatory activities of Cissampelos mucronata Linn. in laboratory animals. Int J Pure Appl Sci 2008;2:111–7.Search in Google Scholar
21. Dubuisson D, Dennis SG. The formalin test: a quantitative study of the analgesic effects of morphine, meperidine, and brain stem stimulation in rats and cats. Pain 1977;4:161–74.10.1016/0304-3959(77)90130-0Search in Google Scholar PubMed
22. Hunskaar S, Fasmer OB, Hole K. Formalin test in mice, a useful technique for evaluating mild analgesics. J Neurosci Methods 1985;14:69–76.10.1016/0165-0270(85)90116-5Search in Google Scholar PubMed
23. Sabitha K. Nilotinib based pharmacophore models for BCRABL. Bioinformation 2012;8:658.10.6026/97320630008658Search in Google Scholar PubMed
24. Harman CA, Turman MV, Kozak KR, Marnett LJ, Smith WL, Garavito RM. Structural basis of enantioselective inhibition of cyclooxygenase-1 by S-α-substituted indomethacin ethanolamides. J Biol Chem 2007;282:28096–105.10.1074/jbc.M701335200Search in Google Scholar PubMed
25. Friesner RA, Murphy RB, Repasky MP, Frye LL, Greenwood JR, Halgren TA, et al. Extra precision glide: docking and scoring incorporating a model of hydrophobic enclosure for protein-ligand complexes. J Med Chem 2006;49:6177–96.10.1021/jm051256oSearch in Google Scholar PubMed
26. Singh P, Bast F. In silico molecular docking study of natural compounds on wild and mutated epidermal growth factor receptor. Med Chem Res 2014;23:5074–85.10.1007/s00044-014-1090-1Search in Google Scholar
27. Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev 1997;23:3–25.10.1016/S0169-409X(96)00423-1Search in Google Scholar
28. SwissADME. Available at: http://www.swissadme.ch/. Accessed: 15 Oct 2017.Search in Google Scholar
29. Calculation of molecular properties and bioactivity score. Available at: http://www.molinspiration.com/cgi-bin/properties. Accessed: 15 Oct 2017.Search in Google Scholar
30. ACD/I-Lab. Available at: https://ilab.acdlabs.com/iLab2/index.php. Accessed: 15 Oct 2017.Search in Google Scholar
31. Park JH, Son KH, Kim SW, Chang HW, Bae K, Kang SS, et al. Antiinflammatory activity of Synurus deltoides. Phytother Res 2004;18:930–3.10.1002/ptr.1595Search in Google Scholar PubMed
32. Li RW, Myers SP, Leach DN, Lin GD, Leach G. A cross-cultural study: anti-inflammatory activity of Australian and Chinese plants. J Ethnopharmacol 2003;85:25–32.10.1016/S0378-8741(02)00336-7Search in Google Scholar PubMed
33. Ahmed F, Hossain MH, Rahman AA, Shahid IZ. Antinociceptive and sedative effects of the bark of Cerbera odollam Gaertn. Orient Pharm Exp Med 2006;6:344–8.10.3742/OPEM.2006.6.4.344Search in Google Scholar
34. Tjølsen A, Berge O-G, Hunskaar S, Rosland JH, Hole K. The formalin test: an evaluation of the method. Pain 1992;51:5–17.10.1016/0304-3959(92)90003-TSearch in Google Scholar PubMed
35. Hunskaar S, Hole K. The formalin test in mice: dissociation between inflammatory and non-inflammatory pain. Pain 1987;30:103–14.10.1016/0304-3959(87)90088-1Search in Google Scholar PubMed
36. Shibata M, Ohkubo T, Takahashi H, Inoki R. Modified formalin test: characteristic biphasic pain response. Pain 1989;38:347–52.10.1016/0304-3959(89)90222-4Search in Google Scholar PubMed
37. Annegowda H, Gooi T, Awang S, Alias N, Mordi M, Ramanathan S, et al. Evaluation of analgesic and antioxidant potency of various extracts of Cinamomum iners bark. Int J Pharmacol 2012;8:198–203.10.3923/ijp.2012.198.203Search in Google Scholar
38. Kumbhare M, Sivakumar T. Anti-inflammatory and analgesic activity of stem bark of Moringa oleifera. Pharmacologyonline 2011;3:641–50.Search in Google Scholar
39. Öztürk N, Can Başer KH, Aydin S, Öztürk Y, Çaliş I. Effects of Gentiana lutea ssp. symphyandra on the central nervous system in mice. Phytother Res 2002;16:627–31.10.1002/ptr.998Search in Google Scholar PubMed
40. Chen Y, Zhi D. Ligand-protein inverse docking and its potential use in the computer search of protein targets of a small molecule. Proteins Struct Funct Bioinf 2001;43:217–26.10.1002/1097-0134(20010501)43:2<217::AID-PROT1032>3.0.CO;2-GSearch in Google Scholar
41. Singh J, Chuaqui CE, Boriack-Sjodin PA, Lee W-C, Pontz T, Corbley MJ, et al. Successful shape-based virtual screening: the discovery of a potent inhibitor of the type I TGFβ receptor kinase (TβRI). Bioorg Med Chem Lett 2003;13:4355–9.10.1016/j.bmcl.2003.09.028Search in Google Scholar PubMed
42. Rester U. From virtuality to reality – virtual screening in lead discovery and lead optimization: a medicinal chemistry perspective. Curr Opin Drug Discov Dev 2008;11:559–68.Search in Google Scholar
43. Hay M, Thomas DW, Craighead JL, Economides C, Rosenthal J. Clinical development success rates for investigational drugs. Nat Biotechnol 2014;32:40–51.10.1038/nbt.2786Search in Google Scholar PubMed
44. Dahlin JL, Inglese J, Walters MA. Mitigating risk in academic preclinical drug discovery. Nat Rev Drug Discov 2015; 14:279–94.10.1038/nrd4578Search in Google Scholar PubMed PubMed Central
45. Duffy FJ, Devocelle M, Shields DC. Computational approaches to developing short cyclic peptide modulators of protein-protein interactions. Methods Mol Biol 2015;1268:241–71.10.1007/978-1-4939-2285-7_11Search in Google Scholar PubMed
46. Daina A, Michielin O, Zoete V. iLOGP: a simple, robust, and efficient description of n-octanol/water partition coefficient for drug design using the GB/SA approach. J Chem Inf Model 2014;54:3284–301.10.1021/ci500467kSearch in Google Scholar PubMed
©2019 Walter de Gruyter GmbH, Berlin/Boston
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- Re-establishing normal diet following high fat-diet-induced obesity reverses the altered salivary composition in Wistar rats
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- Hepatoprotective activity of Tamarindus indica Linn stem bark ethanolic extract against hepatic damage induced by co-administration of antitubercular drugs isoniazid and rifampicin in Sprague Dawley rats
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Articles in the same Issue
- Frontmatter
- Reviews
- Immune response and inflammatory pathway of ulcerative colitis
- Current insights and future perspectives of hypoxia-inducible factor-targeted therapy in cancer
- Behavior and Neuroprotection
- Effect of caffeine on alcohol consumption and alcohol-induced conditioned place preference in rodents
- Reproduction
- Pubertal anabolic androgenic steroid exposure in male rats affects levels of gonadal steroids, mating frequency, and pregnancy outcome
- Dynamics of inflammatory reaction and oxidative stress across maternal serum, placenta and amniotic fluid in laboratory rats and the role played by genistein aglycone
- Cardiovascular-Pulmonary Interactions
- Local inhibition of carbonic anhydrase does not decrease sweat rate
- The standardized extract of Nigella sativa and its major ingredient, thymoquinone, ameliorates angiotensin II-induced hypertension in rats
- Correlation between the blood level of irisin and the severity of acute myocardial infarction in exercise-trained rats
- Oxidative Stress
- Zataria multiflora extract and carvacrol affect cardiotoxicity induced by Adriamycin in rat
- Attenuation of oxidative stress and hepatic damage by white butterfly (Clerodendrum volubile) leaves in streptozotocin-induced diabetes in rats
- Proline supplementation mitigates the early stage of liver injury in bile duct ligated rats
- Pravastatin attenuates testicular damage induced by doxorubicin – a stereological and histopatological study
- Metabolism
- Re-establishing normal diet following high fat-diet-induced obesity reverses the altered salivary composition in Wistar rats
- Phytotherapy
- In vivo analgesic effect of different extracts of Hopea odorata leaves in mice and in silico molecular docking and ADME/T property analysis of some isolated compounds from this plant
- Hepatoprotective activity of Tamarindus indica Linn stem bark ethanolic extract against hepatic damage induced by co-administration of antitubercular drugs isoniazid and rifampicin in Sprague Dawley rats
- Case Report
- Drug-induced optic neuropathy in a case of extensively drug-resistant pulmonary tuberculosis