Skip to content
2000
  1. Home
  2. A-Z Publications
  3. Current Pharmaceutical Biotechnology
  4. Volume 26, Issue 2
  5. Article
Volume 26, Issue 2
  • ISSN: 1389-2010
  • E-ISSN: 1873-4316

Abstract

Background

is historically used for inducing vivid and prophetic lucid dreams, but limited information exists on its phytochemical composition and potential pharmacological properties.

Objective

This study aimed to investigate the phytochemical composition of through LC-MS/MS analysis and explore its potential serotonergic activity, which could support and confirm the traditional use of as a dream-inducing plant.

Methods

LC-MS/MS analysis was conducted on extract, identifying 51 phytochemicals, including norharman, harmalol, harmaline, harmine, and ibogaine alkaloids. ADMET and Molecular docking investigations were employed to assess the serotonergic potential of these compounds.

Results

The analysis revealed the presence of -carboline alkaloids, such as norharman, harmalol, harmaline, harmine, and ibogaine, within extract. ADMET analysis showed that these compounds have a favourable pharmacokinetic properties. In addition, molecular docking investigations showed that harmaline (-8.90 kcal/mol), harmalol (-8.56 kcal/mol), and ibogaine (-8.75 kcal/mol) exhibited binding affinities comparable to the control molecule, LSD (-9.14 kcal/mol), indicating potential agonistic activity at serotonin 5-HT2A receptor.

Conclusion

These findings provide insights into the potential therapeutic benefits of , supporting its traditional use as a psychoactive plant. This study investigated the chemical constituents and potential serotonergic agonist activity of for the first time. While promising, further research is necessary to uncover additional medicinal properties associated with the identified phytochemical components.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cpb/10.2174/0113892010299804240324140017
2024-03-29
2024-12-26

  • From This Site

    /content/journals/cpb/10.2174/0113892010299804240324140017
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. AitonW.T. Hortus Kewensis; or, a catalogue of the plants cultivated in the Royal Botanic Garden at Kew; Cambridge University Press:London18146
     [Google Scholar]
  2. BrownD.J. Dreaming wide awake: Lucid dreaming, shamanic healing, and psychedelics.New York, United StatesSimon and Schuster2016
     [Google Scholar]
  3. SobieckiJ.F. Psychoactive ubulawu spiritual medicines and healing dynamics in the initiation process of Southern Bantu diviners.J. Psychoactive Drugs201244321622310.1080/02791072.2012.70310123061321
     [Google Scholar]
  4. ToroG. ThomasB. Drugs of the dreaming: Oneirogens: Salvia divinorum and other dream-enhancing plants.New York, United StatesSimon and Schuster2007
     [Google Scholar]
  5. KraehenmannR. PokornyD. VollenweiderL. PrellerK.H. PokornyT. SeifritzE. VollenweiderF.X. Dreamlike effects of LSD on waking imagery in humans depend on serotonin 2A receptor activation.Psychopharmacology (Berl.)2017234132031204610.1007/s00213‑017‑4610‑028386699
     [Google Scholar]
  6. Császár-NagyN. BobP. BóَkkonI. A Multidisciplinary Hypothesis about Serotonergic Psychedelics. Is it Possible that a Portion of Brain Serotonin Comes From the Gut?J. Integr. Neurosci.202221514810.31083/j.jin210514836137971
     [Google Scholar]
  7. PsiukD. NowakE. CholewaK. ŁopuszańskaU. SamardakiewiczM. The potential role of serotonergic hallucinogens in depression treatment.Life (Basel)202111876510.3390/life1108076534440508
     [Google Scholar]
  8. ReicheS. HermleL. GutwinskiS. JungaberleH. GasserP. MajićT. Serotonergic hallucinogens in the treatment of anxiety and depression in patients suffering from a life-threatening disease: A systematic review.Prog. Neuropsychopharmacol. Biol. Psychiatry20188111010.1016/j.pnpbp.2017.09.01228947181
     [Google Scholar]
  9. CorreiaV.T.V. SilvaV.D.M. MendonçaH.O.P. RamosA.L.C.C. SilvaM.R. AugustiR. de PaulaA.C.C.F.F. FerreiraR.M.S.B. MeloJ.O.F. FanteC.A. Efficiency of different solvents in the extraction of bioactive compounds from Plinia cauliflora and Syzygium cumini fruits as evaluated by paper spray mass spectrometry.Molecules2023285235910.3390/molecules2805235936903602
     [Google Scholar]
  10. DhawanD. GuptaJ. Research article comparison of different solvents for phytochemical extraction potential from datura metel plant leaves.International Journal of Biological Chemistry2016111172210.3923/ijbc.2017.17.22
     [Google Scholar]
  11. AlhawarriM.B. DianitaR. RawaM.S.A. NogawaT. WahabH.A. Potential anti-cholinesterase activity of bioactive compounds extracted from Cassia grandis L.f. and Cassia timoriensis DC.Plants202312234410.3390/plants1202034436679057
     [Google Scholar]
  12. MabikiF.P. Optimization of extraction conditions and phytochemical screening of root extract of Synadenium glaucescens Pax.Int. J. Chem.20135410310.5539/ijc.v5n4p103
     [Google Scholar]
  13. XiongG. WuZ. YiJ. FuL. YangZ. HsiehC. YinM. ZengX. WuC. LuA. ChenX. HouT. CaoD. ADMETlab 2.0: An integrated online platform for accurate and comprehensive predictions of ADMET properties.Nucleic Acids Res.202149W1W5W1410.1093/nar/gkab25533893803
     [Google Scholar]
  14. LarueL. KenzhebayevaB. Al-ThiabatM.G. Jouan-HureauxV. Mohd-GazzaliA. WahabH.A. BouraC. YeligbayevaG. NakanU. FrochotC. AcherarS. tLyp–1: A peptide suitable to target NRP–1 receptor.Bioorg. Chem.202313010620010.1016/j.bioorg.2022.10620036332316
     [Google Scholar]
  15. Amir RawaM.S. Al-ThiabatM.G. NogawaT. FutamuraY. OkanoA. WahabH.A. Naturally occurring 8ß 13ß kaur-15-en-17-al and anti-malarial activity from Podocarpus polystachyus Leaves.Pharmaceuticals (Basel)202215790210.3390/ph1507090235890200
     [Google Scholar]
  16. YunosN.M. WahabH.A. Al-ThiabatM.G. SallehudinN.J. JauriM.H. In vitro and in silico analysis of the anticancer effects of eurycomanone and eurycomalactone from Eurycoma longifolia.Plants20231215282710.3390/plants1215282737570981
     [Google Scholar]
  17. KimK. Structure of a hallucinogen-activated Gq-coupled 5-HT2A serotonin receptor.Cell2020182615741588
     [Google Scholar]
  18. WestbrookJ. FengZ. ChenL. YangH. BermanH.M. The protein data bank and structural genomics.Nucleic Acids Res.200331148949110.1093/nar/gkg06812520059
     [Google Scholar]
  19. SarkarB. HossainS. Thrombolytic activity, drug likeness property and ADME/T analysis of isolated phytochemicals from ginger (zingiber officinale) using in silico approaches.Mod. Res. Inflamm.201983936
     [Google Scholar]
  20. DolinskyT.J. CzodrowskiP. LiH. NielsenJ.E. JensenJ.H. KlebeG. BakerN.A. PDB2PQR: Expanding and upgrading automated preparation of biomolecular structures for molecular simulations.Nucleic Acids Res.200735(Web Server)(Suppl. 2)W522W52510.1093/nar/gkm276174888412
     [Google Scholar]
  21. Al-ThiabatM.G. GazzaliA.M. MohtarN. MurugaiyahV. KamarulzamanE.E. YapB.K. RahmanN.A. OthmanR. WahabH.A. Conjugated β-cyclodextrin enhances the affinity of folic acid towards FRα: Molecular dynamics study.Molecules20212617530410.3390/molecules2617530434500740
     [Google Scholar]
  22. OlssonM.H.M. Søndergaard,, C.R.; Rostkowski, M.; Jensen, J.H. PROPKA3: Consistent treatment of internal and surface residues in empirical p K a predictions.J. Chem. Theory Comput.20117252553710.1021/ct100578z26596171
     [Google Scholar]
  23. WilliamsC.J. HeaddJ.J. MoriartyN.W. PrisantM.G. VideauL.L. DeisL.N. VermaV. KeedyD.A. HintzeB.J. ChenV.B. JainS. LewisS.M. ArendallW.B.III SnoeyinkJ. AdamsP.D. LovellS.C. RichardsonJ.S. RichardsonD.C. MolProbity: More and better reference data for improved all‐atom structure validation.Protein Sci.201827129331510.1002/pro.333029067766
     [Google Scholar]
  24. WangY. XiaoJ. SuzekT.O. ZhangJ. WangJ. BryantS.H. PubChem: A public information system for analyzing bioactivities of small molecules.Nucleic Acids Res.200937(Web Server)(Suppl. 2)W623W63310.1093/nar/gkp45619498078
     [Google Scholar]
  25. Al-ThiabatM.G. SaqallahF.G. GazzaliA.M. MohtarN. YapB.K. ChoongY.S. WahabH.A. Heterocyclic substitutions greatly improve affinity and stability of folic acid towards FRα. An in silico insight.Molecules2021264107910.3390/molecules2604107933670773
     [Google Scholar]
  26. AlidmatM.M. Synthesis, characterization, molecular docking and cytotoxicity evaluation of new thienyl chalcone derivatives against breast cancer cells.Syst. Rev. Pharm.20221311
     [Google Scholar]
  27. MorrisG.M. HueyR. LindstromW. SannerM.F. BelewR.K. GoodsellD.S. OlsonA.J. AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility.J. Comput. Chem.200930162785279110.1002/jcc.2125619399780
     [Google Scholar]
  28. NorganA.P. CoffmanP.K. KocherJ.P.A. KatzmannD.J. SosaC.P. Multilevel parallelization of AutoDock 4.2.J. Cheminform.2011311210.1186/1758‑2946‑3‑1221527034
     [Google Scholar]
  29. HoraiH. AritaM. KanayaS. NiheiY. IkedaT. SuwaK. OjimaY. TanakaK. TanakaS. AoshimaK. OdaY. KakazuY. KusanoM. TohgeT. MatsudaF. SawadaY. HiraiM.Y. NakanishiH. IkedaK. AkimotoN. MaokaT. TakahashiH. AraT. SakuraiN. SuzukiH. ShibataD. NeumannS. IidaT. TanakaK. FunatsuK. MatsuuraF. SogaT. TaguchiR. SaitoK. NishiokaT. MassBank: A public repository for sharing mass spectral data for life sciences.J. Mass Spectrom.201045770371410.1002/jms.177720623627
     [Google Scholar]
  30. RuttkiesC. SchymanskiE.L. WolfS. HollenderJ. NeumannS. MetFrag relaunched: Incorporating strategies beyond in silico fragmentation.J. Cheminform.201681310.1186/s13321‑016‑0115‑926834843
     [Google Scholar]
  31. VaniyaA. MassBank of North America: Using untargeted metabolomics and multistage fragmentation mass spectral libraries to annotate natural products in plants.Int. Plant Spectroscopy Conf. (IPSC - 2019),20192043
     [Google Scholar]
  32. WangF. LiigandJ. TianS. ArndtD. GreinerR. WishartD.S. CFM-ID 4.0: More accurate ESI-MS/MS spectral prediction and compound identification.Anal. Chem.20219334116921170010.1021/acs.analchem.1c0146534403256
     [Google Scholar]
  33. FrisonG. FavrettoD. ZancanaroF. FazzinG. FerraraS.D. A case of β-carboline alkaloid intoxication following ingestion of Peganum harmalaseed extract.Forensic Sci. Int.20081792-3e37e4310.1016/j.forsciint.2008.05.00318603389
     [Google Scholar]
  34. PassosC.D.S. Simoes-PiresC. HenriquesA. CuendetM. CarruptP-A. ChristenP. Alkaloids as inhibitors of monoamine oxidases and their role in the central nervous system.Studi. Nat. Prod.Chem.20144312314410.1016/B978‑0‑444‑63430‑6.00004‑7
     [Google Scholar]
  35. HerraizT. González, D.; Ancín-Azpilicueta, C.; Arán, V.J.; Guillén, H. β-Carboline alkaloids in Peganum harmalaand inhibition of human monoamine oxidase (MAO).Food Chem. Toxicol.201048383984510.1016/j.fct.2009.12.01920036304
     [Google Scholar]
  36. FaroukL. LaroubiA. AboufatimaR. BenharrefA. ChaitA. Evaluation of the analgesic effect of alkaloid extract of Peganum harmalaL.: Possible mechanisms involved.J. Ethnopharmacol.2008115344945410.1016/j.jep.2007.10.01418054186
     [Google Scholar]
  37. MonsefH.R. GhobadiA. IranshahiM. AbdollahiM. Antinociceptive effects of Peganum harmalaL. alkaloid extract on mouse formalin test.J. Pharm. Pharm. Sci.200471656915144736
     [Google Scholar]
  38. NasibovaT. GaraevE. Potential anti‐Alzheimer alkaloids of Peganum harmala.Alzheimers Dement.202117S9e05672210.1002/alz.056722
     [Google Scholar]
  39. ThamerM.J. Antibacterial, muscle relaxant, and hypnotic effects of seeds of Peganum harmalaon mice.Afr. J. Microbiol. Res.2019132135335610.5897/AJMR2014.7297
     [Google Scholar]
  40. KontrimaviciūteV. MathieuO. Mathieu-DaudéJ.C. VainauskasP. CasperT. BaccinoE. BressolleF.M.M. Distribution of ibogaine and noribogaine in a man following a poisoning involving root bark of the Tabernanthe iboga shrub.J. Anal. Toxicol.200630743444010.1093/jat/30.7.43416959135
     [Google Scholar]
  41. LuzM. MashD.C. Evaluating the toxicity and therapeutic potential of ibogaine in the treatment of chronic opioid abuse.Expert Opin. Drug Metab. Toxicol.20211791019102210.1080/17425255.2021.194409934139922
     [Google Scholar]
  42. PapadodimaS.A. DonaA. EvaggelakosC.I. GoutasN. AthanaselisS.A. Ibogaine related sudden death: A case report.J. Forensic Leg. Med.201320780981110.1016/j.jflm.2013.06.03224112325
     [Google Scholar]
  43. LitjensR.P.W. BruntT.M. How toxic is ibogaine?Clin. Toxicol. (Phila.)201654429730210.3109/15563650.2016.113822626807959
     [Google Scholar]
  44. SchepL.J. SlaughterR.J. GaleaS. NewcombeD. Ibogaine for treating drug dependence. What is a safe dose?Drug Alcohol Depend.20161661510.1016/j.drugalcdep.2016.07.00527426011
     [Google Scholar]
  45. ZenginG. MahomoodallyM.F. AktumsekA. CeylanR. UysalS. MocanA. YilmazM.A. Picot-AllainC.M.N. ĆirićA. GlamočlijaJ. SokovićM. Functional constituents of six wild edible Silene species: A focus on their phytochemical profiles and bioactive properties.Food Biosci.201823758210.1016/j.fbio.2018.03.010
     [Google Scholar]
  46. GoleaL. BenkhaledM. LavaudC. LongC. HabaH. Phytochemical components and biological activities of Silene arenarioides Desf.Nat. Prod. Res.201731232801280510.1080/14786419.2017.129417428278644
     [Google Scholar]
  47. MunkhzhargalN. ZibarevaL.N. LafontR. PribytkovaL.N. PisarevaS.I. Investigation of ecdysteroid content and composition of Silene repens indigenous in Mongolia and introduced into western Siberia.Russ. J. Bioorganic Chem.201036792392810.1134/S1068162010070216
     [Google Scholar]
  48. MouffoukC. Antioxidant and antibacterial activities of the species Silene inflata SM.: Biological activities of S. inflata.PSM Biological Research2019427486
     [Google Scholar]
  49. MahmoudS. HassanA. Abu El WafaS. MohamedA.E-S. UPLCMS/ MS profiling and antitumor activity of Silene succulenta Forssk. Growing in Egypt.Azhar Int. J. Pharmaceut. Med. Sci.202100010.21608/aijpms.2021.57206.1039
     [Google Scholar]
  50. SeoC. Isolation and structure of new β-carboline alkaloids from Silene seoulensis.Korean Soc. Anal. Sci.20212021156
     [Google Scholar]
  51. ChaurasiyaN.D. MuhammadI. TekwaniB.L. Inhibition of human monoamine oxidase A and B by beta-Carboline Alkaloids: Structure activity relationship analysis.Planta Med.20107659310.1055/s‑0030‑1251855
     [Google Scholar]
  52. TasconM. BenaventeF. Sanz-NebotV.M. GagliardiL.G. Fast determination of harmala alkaloids in edible algae by capillary electrophoresis mass spectrometry.Anal. Bioanal. Chem.2015407133637364510.1007/s00216‑015‑8579‑425749794
     [Google Scholar]
  53. SeoC. ShinH.S. LeeJ.E. JungY.W. KimJ.K. KwonJ.G. JeongW. ChoiC.W. OhJ.S. HongS.S. Isolation and structure elucidation of siliendines A‒D, new β-carboline alkaloids from Silene seoulensis.Phytochem. Lett.202036586210.1016/j.phytol.2020.01.010
     [Google Scholar]
  54. ShaoH. HuangX. ZhangY. ZhangC. Main alkaloids of Peganum harmalaL. and their different effects on dicot and monocot crops.Molecules20131832623263410.3390/molecules1803262323446919
     [Google Scholar]
  55. NenaahG. Antibacterial and antifungal activities of (beta)-carboline alkaloids of Peganum harmala(L) seeds and their combination effects.Fitoterapia201081777978210.1016/j.fitote.2010.04.00420398742
     [Google Scholar]
  56. SassouiD. SeridiR. AzinK. UsaiM. Evaluation of phytochemical constituents by GC-MS and antidepressant activity of Peganum harmalaL. seeds extract.Asian Pac. J. Trop. Dis.201551297197410.1016/S2222‑1808(15)60967‑7
     [Google Scholar]
  57. ZhangQ. ZanY.H. YangH.G. YangM.Y. LiuF.S. LiS.G. PengX.H. LinB. LiZ.L. LiD.H. HuaH.M. Anti-tumor alkaloids from Peganum harmala.Phytochemistry202219711310710.1016/j.phytochem.2022.11310735121215
     [Google Scholar]
  58. DoskaliyevA. Alkaloids of Peganum harmalaL. and their pharmacological activity.Open Access Maced. J. Med. Sci.20219766775
     [Google Scholar]
  59. GuanL. YangH. CaiY. SunL. DiP. LiW. LiuG. TangY. ADMET-score – a comprehensive scoring function for evaluation of chemical drug-likeness.MedChemComm201910114815710.1039/C8MD00472B30774861
     [Google Scholar]
  60. KarS. LeszczynskiJ. Open access in silico tools to predict the ADMET profiling of drug candidates.Expert Opin. Drug Discov.202015121473148710.1080/17460441.2020.179892632735147
     [Google Scholar]
  61. KarS. RoyK. LeszczynskiJ. In silico tools and software to predict ADMET of new drug candidates.Methods Mol. Biol.202224258511510.1007/978‑1‑0716‑1960‑5_4
     [Google Scholar]
  62. TranT.T.V. TayaraH. ChongK.T. Recent studies of artificial intelligence on in silico drug absorption.J. Chem. Inf. Model.202363206198621110.1021/acs.jcim.3c0096037819031
     [Google Scholar]
  63. GleesonM.P. Plasma protein binding affinity and its relationship to molecular structure: An in-silico analysis.J. Med. Chem.200750110111210.1021/jm060981b17201414
     [Google Scholar]
  64. ZhaoT. HeY. WangJ. DingK. WangC. WangZ. Inhibition of human cytochrome P450 enzymes 3A4 and 2D6 by β-carboline alkaloids, harmine derivatives.Phytother. Res.201125111671167710.1002/ptr.345821433154
     [Google Scholar]
  65. van de WaterbeemdH. GiffordE. ADMET in silico modelling: Towards prediction paradise?Nat. Rev. Drug Discov.20032319220410.1038/nrd103212612645
     [Google Scholar]
  66. MorrisG.M. Lim-WilbyM. Molecular docking.Methods Mol. Biol.200844336538210.1007/978‑1‑59745‑177‑2_19
     [Google Scholar]
  67. TripathiA. MisraK. Molecular docking: A structure-based drug designing approach.JSM Chem.20175210421047
     [Google Scholar]
  68. MengX.Y. ZhangH.X. MezeiM. CuiM. Molecular docking: A powerful approach for structure-based drug discovery.Curr. Computeraided Drug Des.20117214615710.2174/15734091179567760221534921
     [Google Scholar]
  69. ŚledźP. CaflischA. Protein structure-based drug design: From docking to molecular dynamics.Curr. Opin. Struct. Biol.2018489310210.1016/j.sbi.2017.10.01029149726
     [Google Scholar]
  70. TomaševićN. VujovićM. KostićE. RagavendranV. ArsićB. MatićS.L. BožovićM. FioravantiR. ProiaE. RagnoR. MladenovićM. Molecular docking assessment of cathinones as 5-HT2AR ligands: Developing of predictive structure-based bioactive conformations and three-dimensional structure-activity relationships models for future recognition of abuse drugs.Molecules20232817623610.3390/molecules2817623637687065
     [Google Scholar]
  71. KhastarH. Molecular docking and binding interaction between psychedelic drugs and human serum albumin. BioTechnologia.J. Biotechnol. Comput. Bio. Bionanotechnol.20201012109116
     [Google Scholar]
  72. KarabulutS. KaurH. GauldJ.W. Applications and potential of in silico approaches for psychedelic chemistry.Molecules20232816596610.3390/molecules2816596637630218
     [Google Scholar]
  73. De AbreuI.R. BarkdullA. MunozJ.R. SmithR.P. CraddockT.J.A. A molecular analysis of substituted phenylethylamines as potential microtubule targeting agents through in silico methods and in vitro microtubule-polymerization activity.Sci. Rep.20231311440610.1038/s41598‑023‑41600‑937658096
     [Google Scholar]
  74. HelsleyS. FiorellaD. RabinR.A. WinterJ.C. Behavioral and biochemical evidence for a nonessential 5-HT2A component of the ibogaine-induced discriminative stimulus.Pharmacol. Biochem. Behav.199859241942510.1016/S0091‑3057(97)00451‑69476990
     [Google Scholar]
/content/journals/cpb/10.2174/0113892010299804240324140017
Loading
Potential Serotonin 5-HT2A Receptor Agonist of Psychoactive Components of Silene undulata Aiton: LC-MS/MS, ADMET, and Molecular Docking Studies
Current Pharmaceutical Biotechnology 26, 260 (2025); https://doi.org/10.2174/0113892010299804240324140017
/content/journals/cpb/10.2174/0113892010299804240324140017
/content/journals/cpb/10.2174/0113892010299804240324140017
Loading

Data & Media loading...

Supplements

Supplementary material and the published article are available on the publisher's website.

file format download Download

  • Article Type:     Research Article
Keyword(s): ADMET; chemical profiling; LC-MS/MS; molecular docking; Silene undulata; β-carboline

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test