title: High-mesembrine Sceletium extract (Trimesemine™) is a monoamine releasing agent, rather than only a selective serotonin reuptake inhibitor.
abstract: BACKGROUND
  Extracts from and alkaloids contained in plants in the genus Sceletium have been reported to inhibit ligand binding to serotonin transporter. From this, the conclusion was made that Sceletium products act as selective serotonin-reuptake inhibitors. However, other mechanisms which may similarly result in the anxiolytic or anti-depressant effect ascribed to Sceletium, such as monoamine release, have not been investigated.
  
  
  OBJECTIVE
  The current study investigated simultaneously and at two consecutive time points, the effect of high-mesembrine Sceletium extract on both monoamine release and serotonin reuptake into both human astrocytes and mouse hippocampal neurons, as well as potential inhibitory effects on relevant enzyme activities.
  
  
  METHODS
  Human astrocytes and mouse hippocampal cells were treated with citalopram or Sceletium extract for 15 and 30min, after which protein expression levels of serotonin transporter (SERT) and vesicular monoamine transporter-2 (VAMT-2) was assessed using fluorescent immunocytochemistry and digital image analysis. Efficacy of inhibition of acetylcholinesterase (AChE) and monoamine oxidate-A (MAO-A) activity were assessed using the Ellman and Olsen methods (and appropriate controls) respectively.
  
  
  RESULTS
  We report the first investigation of mechanism of action of Sceletium extract in the context of serotonin transport, release and reuptake in a cellular model. Cell viability was not affected by Sceletium treatment. High-mesembrine Sceletium extract down-regulated SERT expression similarly to citalopram. In addition, VMAT-2 was upregulated significantly in response to Sceletium treatment. The extract showed only relatively mild inhibition of AChE and MAO-A.
  
  
  CONCLUSIONS
  We conclude that the serotonin reuptake inhibition activity ascribed to the Sceletium plant, is a secondary function to the monoamine-releasing activity of high-mesembrine Sceletium extract (Trimesemine(TM)).
authors.affiliation: Department of Physiological Sciences, Science Faculty, Stellenbosch University, Stellenbosch, South Africa.
authors.forename: Dirk D
authors.initials: DD
authors.lastname: Coetzee
authors.affiliation: Department of Pharmacy, Faculty of Health Sciences, San Jorge University, Villanueva de Gállego, Zaragoza, Spain.
authors.forename: Víctor
authors.initials: V
authors.lastname: López
authors.affiliation: Department of Physiological Sciences, Science Faculty, Stellenbosch University, Stellenbosch, South Africa. Electronic address: csmith@sun.ac.za.
authors.forename: Carine
authors.initials: C
authors.lastname: Smith
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects; D015306:Biogenic Monoamines / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D026121:Indole Alkaloids / Q000737:chemistry / Q000494:pharmacology*; D035723:Mesembryanthemum / Q000737:chemistry*; D051379:Mice; D008995:Monoamine Oxidase / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors; D009474:Neurons / Q000187:drug effects; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*
chemical_list: D015306:Biogenic Monoamines; D026121:Indole Alkaloids; D008995:Monoamine Oxidase; D008996:Monoamine Oxidase Inhibitors; D010936:Plant Extracts; D017367:Selective Serotonin Reuptake Inhibitors; C011300:mesembrine
keywords: Alkaloid; Alternative medicine; Anxiolytic; Depression; Sceletium tortuosum; Stress