Pharmacological actions of the South African medicinal and functional food plant Sceletium tortuosum and its principal alkaloids

Ethnopharmacological relevance: The South African plant Sceletium tortuosum has been known for centuries for a variety of traditional uses, and, more recently, as a possible source of anti-anxiety or anti-depressant effects. A standardised extract Zembrin (R) was used to test for pharmacological activities that might be relevant to the ethnopharmacological uses, and three of the main alkaloids were also tested. Materials and methods: A standardised ethanolic extract was prepared from dried plant material, along with the purified alkaloids mesembrine, mesembrenone and mesembrenol. These were tested on a panel of receptors, enzymes and other drug targets, and for cytotoxic effects on mammalian cells. Results: The extract was a potent blocker in 5-HT transporter binding assays (IC(50) 4.3 mu g/ml) and had powerful inhibitory effects on phosphodiesterase 4 (PDE4) (IC(50) 8.5 mu g/ml), but not other phosphodiesterases. There were no cytotoxic effects. Mesembrine was the most active alkaloid against the 5-HT transporter (K(i) 1.4 nM), while mesembrenone was active against the 5-HT transporter and PDE4 (IC(50)'s <1 mu M). Conclusions: The activity of the Sceletium tortuosum extract on the 5-HT transporter and PDE4 may explain the clinical effects of preparations made from this plant. The activities relate to the presence of alkaloids, particularly mesembrine and mesembrenone. (C) 2011 Elsevier Ireland Ltd. All right's reserved.