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.
Neobeguea mahafalensis is used as a medicinal plant in Madagascar. A decoction of the stem bark of this species is reported to treat back pain. Recently, it was reported that a decoction of the root bark, containing two novel phragmalin limonoids as identified active constituents, exhibited an extraordinarily high potency and remarkably long duration in augmenting sexual activity in male rodents.From the dichloromethane extract of the root barks of N. mahafalensis, nine phragmalin limonoids were isolated, of which eight were novel compounds. The structures were established mainly by extensive use of 2D NMR spectroscopic techniques and high-resolution mass spectrometry. One of the new compounds named dodoguin displayed sleep-inducing activity in Swiss albino mice. The amount of 3-10 mg/kg of this compound induced sleep 18-22 min after its administration with a duration of 16-18 min.
Libiguins are limonoids with highly potent sexual activity enhancing effects, originally isolated from the Madagascarian Meliaceae species Neobeguea mahafalensis, where they exist in only minute quantities. Their low natural abundance has hampered mapping of their biological effects. Here we describe an approach to the semisynthesis of libiguin A and its close analogues 1-3 starting from phragmalin, which is a limonoid present in high amounts in a commercially cultivated Meliaceae species, Chukrasia tabularis, allowing the preparation of libiguins in appreciable quantities.
Gas chromatography/mass spectroscopy analysis (GC/MS) of essential oils obtained from populations of the resurrection plant Myrothamnus moschatus, growing in different areas of Madagascar, allowed identification of three main chemotypes in the species. The first one was provided by plants with a high content of trans-pinocarveol and pinocarvone; the second one involved plants with high percentages of limonene, cis- and trans-p-mentha-1(7),8-dien-2-ol, and β-selinene; and the third chemotype was characterized by plants with high levels of oxygenated sesquiterpenes such as caryophyllene oxide and α- and β-isomers of caryophylla-4(12),8(13)-dien-5-ol. Chemical data were supported by chemometric technique as the principal component analysis. Furthermore, the relationship between the dioecy and phytochemistry within one population was also considered. Finally, correlations between chemical variations and ethnobotanical data were assessed.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.