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

Abstract 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 1 H-NMR. The activity of (−)-loliolide was tested in a serotonin transporter binding assay using [ 3 H]-citalopram as ligand, giving an IC 50 -value of 997 µM, corresponding to a K i -value of 409 µM. 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.