Medicinal Chemistry Research

, Volume 22, Issue 6, pp 2902–2911 | Cite as

Neurological activities of lapachol and its furano derivatives from Kigelia africana

  • Kenneth O. Eyong
  • Harquin S. Foyet
  • Charles A. Eyong
  • Lazare S. Sidjui
  • Marie C. Yimdjo
  • Sidoine N. Nwembe
  • Marc Lamshöft
  • Gabriel N. Folefoc
  • Michael Spiteller
  • Veronica Nastasa
Original Research

Abstract

This study was carried out to investigate some neurological activities of lapachol and other chemical constituents isolated from Kigeliaafricana in male albino mice using elevated plus-maze (EPM) test, open-field test (OFT), and forced swimming test (FST). The anxiolytic-like and antidepressant effects of these constituents were compared to known active anxiolytic (diazepam, 2 mg/kg) and antidepressant (imipramine, 15 mg/kg) reference drugs. The compounds 1 [50 mg/kg, intraperitoneally (i.p.)] and 3 (100 mg/kg, i.p.) significantly increased the number of lines crossed in the OFT and the duration of immobility in the FST, indicating a possible antidepressant activity, but no significant effect was observed in the EPM test. The compound 4 (100 mg/kg, i.p.) significantly increased the time spent on the open arms, but the increase in number of open arms entries was not significant in the EPM test. Meanwhile, the duration of the immobility time was significant and quite close to that of the standard drug, imipramine used in the FST. The compound 5 (100 mg/kg, i.p.) substantially increased the time spent and entries into open arms of the EPM, and reduced the time spent and entries into closed arms, when compared with saline controls (P < 0.05). This compound also increased the exploratory activity of the mice as well as the swimming duration in the OFT and FST, respectively. These results indicate that among the compounds tested, quinones displayed significant anxiolytic and/or antidepressant effects at all doses tested. Kojic acid, a fungal metabolite whose structure was unambiguously confirmed by single-crystal X-ray studies, is also isolated for the first time from K.africana, suggesting that it is a possible taxonomic marker in the biogenesis of the quinone skeleton.

Keywords

Anxiolytic Antidepressant Kigeliaafricana Lapachol Quinones 

References

  1. Akunyili DN, Houghton PJ (1993) Monoterpenoids and naphthoquinones from Kigelia pinnata. Phytochemistry 32(4):1015–1018CrossRefGoogle Scholar
  2. Barua CC, Roy JD, Buragohain B, Barua AG, Borah P, Lahkar M (2009) Anxiolytic effects of hydroethanolic extract of Drymaria cordata L. Willd. Ind J Exp Biol 47:969–973Google Scholar
  3. Bourin M, Fiocco AJ, Clenet F (2001) How valuable are animal models in defining antidepressant activity. Hum Psychopharmacol 16:9–21PubMedCrossRefGoogle Scholar
  4. Carrey N, McFadyen MP, Brown RE (2000) Effects of chronic methylphenidate administration on the locomotor and exploratory behaviour of prepubertal mice. J Child Adolesc Psychopharmacol 10(4):277–286PubMedCrossRefGoogle Scholar
  5. da Silva AJM, Buarque CD, Brito FV, Aurelian L (2002) Synthesis and preliminary pharmacological evaluation of new (±) 1,4-naphthoquinones structurally related to lapachol. Bioorg Med Chem 10:2731–2738PubMedCrossRefGoogle Scholar
  6. Dang H, Sun L, Liu X, Peng B, Wang Q, Jia W, Chen Y, Pan A, Xiao P (2009) Preventive action of Kai Xin San aqueous extract on depressive-like symptoms and cognition deficit induced by chronic mild stress. Exp Biol Med 234:785–793CrossRefGoogle Scholar
  7. Eyong KO, Krohn K, Hussain H, Folefoc GN, Nkengfack AE, Schulz B, Hu Q (2005) Newbouldiaquinone and newbouldiamide: a new naphthoquinone-anthraquinone coupled pigment and a new ceramide from Newbouldia laevis. Chem Pharm Bull 53(6):616–619PubMedCrossRefGoogle Scholar
  8. Eyong KO, Folefoc GN, Kuete V, Beng VP, Hussain H, Krohn K, Nkengfack AE, Saeftel M, Sarite SR, Hoerauf A (2006) Newbouldiaquinone A: a naphthoquinone–anthraquinone ether coupled pigment, as a potential antimicrobial and antimalarial agent from Newbouldia laevis. Phytochemistry 67:605–609PubMedCrossRefGoogle Scholar
  9. Eyong KO, Kumar PS, Kuete V, Folefoc GN, Nkengfack EA, Baskaran S (2008) Semisynthesis and antitumoral activity of 2-acetylfuranonaphthoquinone and other naphthoquinone derivatives from lapachol. Bioorg Med Chem Lett 8:5387–5390CrossRefGoogle Scholar
  10. Eyong KO, Kumar SP, Kuete V, Folefoc GN, Langmi H, Meyer MJJ, Lall N, Baskaran S (2011) Cobalt mediated ring contraction reaction of lapachol and initial antibacterial evaluation of naphthoquinones derived from lapachol. Med Chem Res 21(8):2117–2122CrossRefGoogle Scholar
  11. Fernández SP, Wasowski C, Paladini A, Marder M (2005) Synergistic interaction between hesperidin, a natural flavonoid, and diazepam. Eur J Pharmacol 512:189–198PubMedCrossRefGoogle Scholar
  12. Foyet HS, Hritcu L, Ciobica A, Stefan M, Kamtchouing P, Cojocaru D (2011) Methanolic extract of Hibiscus asper leaves improves spatial memory deficits in the 6-hydroxydopamine-lesion rodent model of Parkinson’s disease. J Ethnopharmacol 133:773–779PubMedCrossRefGoogle Scholar
  13. Galdino PM, Nascimento MVM, Sampaio BL, Ferreira RN, Paula JR, Costa EA (2009) Antidepressant-like effect of Lafoensia pacari A. St-Hill ethanol extract and fractions in mice. J Ethnopharmacol 124:581–585PubMedCrossRefGoogle Scholar
  14. Han H, Ma Y, Eun JS, Li R, Hong JT, Lee MK, Oh KW (2009) Anxiolytic-like effects of sanjoinine A isolated from Zizyphi Spinosi Semen: possible involvement of GABAergic transmission. Pharmacol Biochem Behav 92:206–213PubMedCrossRefGoogle Scholar
  15. Herbert LH, Diakow PRP, Cregg JT (1978) 13C-Nuclear magnetic resonance spectra of some C-19-hydroxy, C-5,6 epoxy, C-24 ethyl, and C-19-norsteroids. Can J Chem 56:3125–3127Google Scholar
  16. Hurd CD, Sims RJ, Trofimenko S (1959) Anomalous reactions of kojic acid and related compounds with acrylonitrile and acrylic ester. J Am Chem Soc 81:1684–1687CrossRefGoogle Scholar
  17. Inoue K, Inouye H, Chen C (1981) A Naphthoquinone and a lignan from the wood of Kigelia pinnata. Phytochemistry 20:2271–2276CrossRefGoogle Scholar
  18. Jesse CR, Bortolatto CF, Savegnago L, Rocha JBT, Nogueira CW (2008) Involvement of l-arginine–nitric oxide–cyclic guanosine monophosphate pathway in the antidepressant-like effect of tramadol in the rat forced swimming test. Prog Neuro-Psychopharmacol Biol Psychiatry 32:1838–1843CrossRefGoogle Scholar
  19. Jung JW, Cho J, Ahn NY, Kim SY, Jang CG (2005) Effect of Chronic Albizzia Julibrissin. Treatment on 5-hydroxytryptamine1. A receptor in rat brain. Pharmacol Biochem Behav 81:205–210PubMedCrossRefGoogle Scholar
  20. Kuete V, Eyong KO, Folefoc GN, Beng VP, Hussain H, Krohn K, Nkengfack AE (2007) Antimicrobial screening of methanolic extract and chemical constituents isolated from Newbouldia laevis seem. Pharmazie 62:552–556PubMedGoogle Scholar
  21. Mahmoudi M, Ebrahimzadeh MA, Ansaroudi F, Nabavi SF, Nabavi SM (2009) Antidepressant and antioxidant activities of Artemisia absinthium L. at flowering stage. Afr J Biotechnol 8(24):7170–7175Google Scholar
  22. Matthews K, Christmas D, Swan J, Sorrell E (2005) Animal model of depression navigating through the clinical fog. Neurosci Behav Rev 29:503–513CrossRefGoogle Scholar
  23. Mora S, Diaz-Veliz G, Lungenstrass H, Garcıa-Gonzalez M, Coto-Morales M, Polettic C, De Limac TCM, Herrera-Ruizd M, Tortoriello J (2005) Central nervous system activity of the hydroalcoholic extract of Casimiroa edulis in rats and mice. J Ethnopharmacol 97(2):191–197PubMedCrossRefGoogle Scholar
  24. Olatunji AG, Atolani O (2009) Comprehensive scientific demystification of Kigelia africana: a review. Afr J Pure Appl Chem 3(9):158–164Google Scholar
  25. Owolabi OJ, Amaechina FC, Eledan AB (2008) Central nervous system stimulant effect of the ethanolic extract of kigelia. Afr J Med Plant Res 2(2):20–23Google Scholar
  26. Palucha A, Pile A (2002) On the role of metabotropic glutamate receptors in the mechanisms of action of antidepressants. Polish J Pharmacol 54:581–586Google Scholar
  27. Sánchez-Mateo CC, Bonkanka CX, Prado B, Rabanal RM (2009) Hypericum grandifolium Choisy: a species native to Macaronesian Region with antidepressant effect. J Ethnopharmacol 121(2):297–303PubMedCrossRefGoogle Scholar
  28. Sethi A, Das BP, Bajaj BK (2005) The anxiolytic activity of gabapentin in mice. J Appl Res 5:415–422Google Scholar
  29. Wang XL, Zheng XF, Liu RH, Reiner J, Chang JB (2007) Synthesis of novel substituted naphthoquino[b]-benzo[e][1,4]diazepines via Pictet–Spengler cyclization. Tetrahedron 63:3389–3394CrossRefGoogle Scholar
  30. Whiting PJ (2006) GABA-A receptors: a viable target for novel anxiolytics. Curr Opin Pharmacol 6:24–29PubMedCrossRefGoogle Scholar
  31. Wilkinson JA (2009) Anti inflammatory and other Effects of Kigelia africana extracts. PhytoTrade Africa. http://www.phytochemistry.freeserve.co.uk
  32. Zohar J, Westenberg HG (2000) Anxiety disorders: a review of tricyclic antidepressants and selective serotonin reuptake inhibitors. Acta Psychiatr Scand 403:39–49CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  • Kenneth O. Eyong
    • 1
    • 2
  • Harquin S. Foyet
    • 3
  • Charles A. Eyong
    • 4
  • Lazare S. Sidjui
    • 1
  • Marie C. Yimdjo
    • 1
  • Sidoine N. Nwembe
    • 1
  • Marc Lamshöft
    • 2
  • Gabriel N. Folefoc
    • 1
  • Michael Spiteller
    • 2
  • Veronica Nastasa
    • 5
  1. 1.Department of Organic ChemistryUniversity of Yaoundé 1YaoundéCameroon
  2. 2.Institute of Environmental Research of the Faculty of ChemistryDortmund University of TechnologyDortmundGermany
  3. 3.Department of Agriculture, Livestock and By-ProductsThe Higher Institute of the Sahel, University of MarouaMarouaCameroon
  4. 4.Department of Biological SciencesUniversity of BueaBueaCameroon
  5. 5.Departments of Pharmacodynamics and Clinical PharmacyUniversity of Medicine and PharmacyIasiRomania

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