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 (eFirst)

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.

Supporting Information