title: Libiguins A and B: novel phragmalin limonoids isolated from Neobeguea mahafalensis causing profound enhancement of sexual activity.
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.
authors.affiliation: Institut Malgache de Recherches Appliquées, Fondation Rakoto-Ratsimamanga, Antananarivo, Madagascar.
authors.forename: Solofoniaina
authors.initials: S
authors.lastname: Razafimahefa
authors.affiliation: Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
authors.forename: Felikss
authors.initials: F
authors.lastname: Mutulis
authors.affiliation: Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
authors.forename: Ilze
authors.initials: I
authors.lastname: Mutule
authors.affiliation: Latvian Institute of Organic Synthesis, Riga, Latvia.
authors.forename: Edvards
authors.initials: E
authors.lastname: Liepinsh
authors.affiliation: Latvian Institute of Organic Synthesis, Riga, Latvia.
authors.forename: Maija
authors.initials: M
authors.lastname: Dambrova
authors.affiliation: Latvian Institute of Organic Synthesis, Riga, Latvia.
authors.forename: Helena
authors.initials: H
authors.lastname: Cirule
authors.affiliation: Latvian Institute of Organic Synthesis, Riga, Latvia.
authors.forename: Baiba
authors.initials: B
authors.lastname: Svalbe
authors.affiliation: Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
authors.forename: Sviatlana
authors.initials: S
authors.lastname: Yahorava
authors.affiliation: Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
authors.forename: Aleh
authors.initials: A
authors.lastname: Yahorau
authors.affiliation: Department of Chemistry, University of Toliara, Toliara, Madagascar.
authors.forename: Benoit
authors.initials: B
authors.lastname: Rasolondratovo
authors.affiliation: Institut Malgache de Recherches Appliquées, Fondation Rakoto-Ratsimamanga, Antananarivo, Madagascar.
authors.forename: Philippe
authors.initials: P
authors.lastname: Rasoanaivo
authors.affiliation: Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
authors.forename: Jarl E S
authors.initials: JE
authors.lastname: Wikberg
mesh_terms: D000818:Animals; D001046:Aphrodisiacs / Q000302:isolation & purification / Q000494:pharmacology*; D036701:Limonins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D008297:Male; D029582:Meliaceae / Q000737:chemistry*; D051379:Mice; D015394:Molecular Structure; D024301:Plant Bark; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D018517:Plant Roots; D051381:Rats; D012725:Sexual Behavior / Q000187:drug effects*
chemical_list: D001046:Aphrodisiacs; D036701:Limonins; D010936:Plant Extracts; C000592852:libiguin A; C000592853:libiguin B