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
