title: Pharmacological actions of the South African medicinal and functional food plant Sceletium tortuosum and its principal alkaloids.
abstract: BACKGROUND
  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.
  
  
  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 μg/ml) and had powerful inhibitory effects on phosphodiesterase 4 (PDE4) (IC(50) 8.5 μg/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 μM).
  
  
  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.
authors.affiliation: Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, UK. a.l.harvey@strath.ac.uk
authors.forename: Alan L
authors.initials: AL
authors.lastname: Harvey
authors.forename: Louise C
authors.initials: LC
authors.lastname: Young
authors.forename: Alvaro M
authors.initials: AM
authors.lastname: Viljoen
authors.forename: Nigel P
authors.initials: NP
authors.lastname: Gericke
mesh_terms: D035722:Aizoaceae / Q000737:chemistry; D000470:Alkaloids / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D055951:Functional Food; D056945:Hep G2 Cells; D006801:Humans; D026121:Indole Alkaloids / Q000494:pharmacology; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism; D008024:Ligands; D016488:Medicine, African Traditional; D058988:Phosphodiesterase 4 Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D035261:Plant Components, Aerial; D010946:Plants, Medicinal; D011869:Radioligand Assay; D050486:Serotonin Plasma Membrane Transport Proteins / Q000187:drug effects / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D013019:South Africa; D020298:U937 Cells
chemical_list: D000470:Alkaloids; D026121:Indole Alkaloids; D007473:Ion Channels; D008024:Ligands; D058988:Phosphodiesterase 4 Inhibitors; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; C011300:mesembrine