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Planta Med 2014; 80(04): 306-314
DOI: 10.1055/s-0033-1360390
Natural Product Chemistry
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Libiguins A and B: Novel Phragmalin Limonoids Isolated from Neobeguea mahafalensis Causing Profound Enhancement of Sexual Activity

Solofoniaina Razafimahefa
1   Institut Malgache de Recherches Appliquées, Fondation Rakoto-Ratsimamanga, Antananarivo, Madagascar
,
Felikss Mutulis
2   Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden
,
Ilze Mutule
2   Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden
,
Edvards Liepinsh
3   Latvian Institute of Organic Synthesis, Riga, Latvia
,
Maija Dambrova
3   Latvian Institute of Organic Synthesis, Riga, Latvia
,
Helena Cirule
3   Latvian Institute of Organic Synthesis, Riga, Latvia
,
Baiba Svalbe
3   Latvian Institute of Organic Synthesis, Riga, Latvia
,
Sviatlana Yahorava
2   Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden
,
Aleh Yahorau
2   Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden
,
Benoit Rasolondratovo
4   Department of Chemistry, University of Toliara, Toliara, Madagascar
,
Philippe Rasoanaivo
1   Institut Malgache de Recherches Appliquées, Fondation Rakoto-Ratsimamanga, Antananarivo, Madagascar
,
Jarl E.S. Wikberg
2   Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden
› Author Affiliations
Further Information

Publication History

received 13 October 2013
revised 01 January 2014

accepted 20 January 2014

Publication Date:
18 February 2014 (online)

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Abstract

In a screening programme directed towards the discovery of drugs that could enhance sexual activity, we found that a decoction of the root bark of Neobeguea mahafalensis displayed an extraordinarily high potency and remarkably long duration in augmenting sexual activity in male rodents. Bioassay-guided fractionation led to the isolation of two pharmacoactive constituents, which turned out to be novel 1,8,9-orthoacetate phragmalin limonoids that we named libiguins A and B, each with a C-16/30 δ-lactone ring. Chemical structures were established by the interpretation of their 1D and 2D NMR data. In vivo pharmacological tests showed that starting with a treatment from 0.004–0.4 mg/kg/day for three consecutive days, over a 3-h sampling period, these limonoids induced a long-lasting augmentation of frequency and sustainment of mounting behaviour in male rodents, with an effect lasting for up to 11 days post-treatment. Libiguin A proved to be markedly more potent than libiguin B. This report is the first of limonoids having such an effect, and the findings could lead to novel therapies for the treatment of sexual dysfunction. Moreover, the results can serve as an opening to elucidate the central physiological control of mating behaviour, which is still not well mapped out.

Key words

Neobeguea mahafalensis - Meliaceae - limonoids - libiguin - sexual enhancing activity

Supporting Information

 

  • References

  • 1 Grant P, Jackson G, Baig I, Quin J. Erectile dysfunction in general medicine. Clin Med 2013; 13: 136-140
    CrossrefPubMedSearch in Google Scholar
  • 2 Debray MM. Contribution à lʼinventaire des plantes médicinales du Sud-Ouest de Madagascar. In: Debray M, Jacqemin H, Razafindrambao R, editors Contribution à lʼinventaire des plantes médicinales de Madagascar. Paris: ORSTOM; 1971: 21
    Search in Google Scholar
  • 3 Boiteau P, Boiteau M, Allorge-Boiteau L. Dictionnaire des noms malgaches des végétaux, Vol. 1. Grenoble: Editions Alzieu; 1999: 436
    Search in Google Scholar
  • 4 Mulholland DA, Taylor DAH. Limonoid extractives from the genera Capuronianthus, Neobeguea and Quivisianthe . Phytochemistry 1988; 27: 1741-1743
    CrossrefPubMedSearch in Google Scholar
  • 5 Randrianarivelojosia M, Kotso MP, Mulholland DA. A limonoid from Neobeguea mahafalensis . Phytochemistry 1999; 52: 1141-1143
    CrossrefPubMedSearch in Google Scholar
  • 6 Naidoo D, Mulholland DA, Randrianarivelojosia M, Coombes PH. Limonoids and triterpenoids from the seed of Neobeguea mahafalensis . Biochem Syst Ecol 2003; 31: 1047-1050
    CrossrefPubMedSearch in Google Scholar
  • 7 Wikberg JS, Rasoanaivo P, Rasolondratovo B, Razafimahefa AS. Novel compounds and pharmaceutical preparations. PCT Patent WO 2008/145996 A2; 2008.
    PubMed
  • 8 Scott AI. Interpretation of the ultraviolet spectra of natural products. O- and S-heteroaromatic compounds. Oxford: Pergamon Press; 1964: 136-138
    CrossrefSearch in Google Scholar
  • 9 Scott AI. Interpretation of the ultraviolet spectra of natural products. Conjugated chromophores. Oxford: Pergamon Press; 1964: 69-71
    Search in Google Scholar
  • 10 Saad MMG, Iwagawa T, Doe M, Nakatani M. Swietenialides, novel ring D opened phragmalin limonoid orthoesters from Swietenia mahogani JACQ. Tetrahedron 2003; 59: 8027-8033
    CrossrefPubMedSearch in Google Scholar
  • 11 Luo J, Wang JS, Wang XB, Huang XF, Luo JG, Kong LY. Chukvelutilides A–F, phragmalin limonoids from the stem barks of Chukrasia tabularis var. velutina . Tetrahedron 2009; 65: 3425-3431
    CrossrefPubMedSearch in Google Scholar
  • 12 Li Y, Luo J, Wang Q, Kong LY. Two new limonoids from the stem barks of Chukrasia tabularis var. velutina . J Asian Nat Prod Res 2011; 13: 781-786
    CrossrefPubMedSearch in Google Scholar
  • 13 Luo J, Li Y, Wang JS, Kong LY. Two new C-15 enolic acyl phragmalin-type limonoids from Chukrasia tabularis var. velutina . Nat Prod Res 2012; 27: 1-6
    PubMedSearch in Google Scholar
  • 14 Chen XL, Liu HL, Guo YW. Phragmalin limonoids from Chukrasia tabularis var. velutina . Planta Med 2012; 78: 286-290
    Thieme ConnectPubMedSearch in Google Scholar
  • 15 Sumalatha K, Saravana Kumar A, Mohana Lakshmi S. Review on natural aphrodisiac potentials to treat sexual dysfunction. Int J Pharm Ther 2010; 1: 6-14
    PubMedSearch in Google Scholar
  • 16 Kotta S, Ansari SH, Ali J. Exploring scientifically proven herbal aphrodisiacs. Pharmacogn Rev 2013; 7: 1-10
    CrossrefPubMedSearch in Google Scholar
  • 17 Riley AJ. Yohimbine in the treatment of erectile disorder. Br J Clin Pract 1994; 48: 133-136
    PubMedSearch in Google Scholar
  • 18 Drewes SE, Horn MM, Munro OQ, Dhlamini JTB, Meyer JJM, Rakuambo NC. Pyrano-isoflavonoles with erectile-dysfunction activity from Eriosema kraussianum . Phytochemistry 2002; 59: 739-747
    CrossrefPubMedSearch in Google Scholar
  • 19 Gauthaman K, Ganesan AP. The hormonal effects of Tribulus terrestris and its role in the management of male erectile dysfunction – an evaluation using primates, rabbit and rat. Phytomedicine 2008; 15: 44-54
    CrossrefPubMedSearch in Google Scholar
  • 20 Dambrova M, Cirule H, Svalbe B, Zvejniece L, Pugovichs O, Zorenko T, Kalvinsh I, Liepinsh E, Belozertseva I. Effect of inhibiting carnitine biosynthesis on male rat sexual performance. Physiol Behav 2008; 95: 341-347
    CrossrefPubMedSearch in Google Scholar