Serotonin transporter affinity of (-)-loliolide, a monoterpene lactone from Mondia whitei

Mondia whitei (Apocynaceae) is used in traditional medicine to treat nervous disorders. Previous studies have shown in vivo antidepressant-like activity in the forced swimming test and affinity to the serotonin transporter of an ethanolic leaf extract of M. whitei. The aim of this study was to isolate the compound(s) responsible for in-vitro serotonin transporter affinity in M. whitei. Bioassay guided isolation lead to the identification of the monoterpene lactone (-)-loliolide. An ethanol extract was prepared from dry leaves. The residue was dissolved in ethyl acetate, extracted with water by liquid liquid partitioning. This was followed by VLC fractionation. Through HPLC-UV separation the active compound was isolated and characterized by GC-MS, LC-MS and H-1-NMR. The activity of (-)-loliolide was tested in a serotonin transporter binding assay using [H-3]citalopram as ligand, giving an IC50-value of 997 mu M, corresponding to a K-i-value of 409 mu M. Loliolide is a non-nitrogenous compound and might bind to the transporter in a different way to nitrogen-containing inhibitors. The results provide a rationale for the use of M. whitei in the treatment of depression and other central nervous system diseases in traditional medicine. (C) 2010 SAAB. Published by Elsevier B.V. All rights reserved.