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® 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 (IC50 4.3 ug/ml) and had powerful inhibitory effects on phosphodiesterase 4 (PDE4) (IC50 8.5 ug/ml), but not other phosphodiesterases. There were no cytotoxic effects. Mesembrine was the most active alkaloid against the 5-HT transporter (Ki 1.4 nM), while mesembrenone was active against the 5-HT transporter and PDE4 (IC50 ’s < 1 uM). 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.