J Ethnopharmacol, 2016 Jan 11;177:111-6. doi: 10.1016/j.jep.2015.11.034. Epub 2015 Nov 23.
High-mesembrine Sceletium extract is a monoamine releasing agent, rather than only a selective serotonin reuptake inhibitor
Dirk D Coetzee 1, Víctor López 2, Carine Smith 3
Affiliations expand
- PMID: 26615766
- DOI: 10.1016/j.jep.2015.11.034
Abstract
Ethnopharmacological relevance: 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.
Aims of the study: 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.
Materials and 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)).
Keywords: Alkaloid; Alternative medicine; Anxiolytic; Depression; Sceletium tortuosum; Stress.
Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Journal of Ethnopharmacology
Volume 280, 15 November 2021, 114476
Sceletium tortuosum: A review on its phytochemistry, pharmacokinetics, biological and clinical activities
Author links open overlay panelT.L. Olatunji a
, F. Siebert a, A.E. Adetunji b, B.H. Harvey cde, J. Gericke ce, J.H. Hamman c, F. Van der Kooy cShow moreAdd to MendeleyShareCite
https://doi.org/10.1016/j.jep.2021.114476Get rights and content
Abstract
Sceletium tortuosum (L.) N.E.Br, the most sought after and widely researched species in the genus Sceletium is a succulent forb endemic to South Africa. Traditionally, this medicinal plant is mainly masticated or smoked and used for the relief of toothache, abdominal pain, and as a mood-elevator, analgesic, hypnotic, anxiolytic, thirst and hunger suppressant, and for its intoxicating/euphoric effects. Sceletium tortuosum is currently of widespread scientific interest due to its clinical potential in treating anxiety and depression, relieving stress in healthy individuals, and enhancing cognitive functions. These pharmacological actions are attributed to its phytochemical constituents referred to as mesembrine-type alkaloids.
Aim of the review
The aim of this review was to comprehensively summarize and critically evaluate recent research advances on the phytochemistry, pharmacokinetics, biological and clinical activities of the medicinal plant S. tortuosum. Additionally, current ongoing research and future perspectives are also discussed.
Methods
All relevant scientific articles, books, MSc and Ph.D. dissertations on botany, behavioral pharmacology, traditional uses, and phytochemistry of S. tortuosum were retrieved from different databases (including Science Direct, PubMed, Google Scholar, Scopus and Web of Science). For pharmacokinetics and pharmacological effects of S. tortuosum, the focus fell on relevant publications published between 2009 and 2021.
Results
Twenty-five alkaloids belonging to four structural classes viz: mesembrine, Sceletium A4, joubertiamine, and tortuosamine, have been identified from S. tortuosum, of which the mesembrine class is predominant. The crude extracts and commercially available standardized extracts of S. tortuosum have displayed a wide spectrum of biological activities (e.g. antimalarial, anti-oxidant, immunomodulatory, anti-HIV, neuroprotection, enhancement of cognitive function) in in vitro or in vivo studies. This plant has not yet been studied in a clinical population, but has potential for enhancing cognitive function, and managing anxiety and depression.
Pharmacology
Kanna contains about 1–1.5% total alkaloids. Mesembrine and mesembrenone are the main components and have been isolated in yields of 0.86% and 0.2% respectively. Half a dozen other alkaloids, including tortuosamine, occur in very small quantities [7][9] . The alkaloids mesembrine, mesembrenone, mesembrenol, and tortuosamine are thought to be the psychoactive components. It is possible that tryptamines may occur in the plant as well, with Methyltryptamine (MMT) and N,N-DMT having been detected in a Delosperma species, a close relative from the same family [7]. The leaves also contain oxalic acid [10] ().
Mesembrine (empirical formula C17H23NO3) can be found in the leaves and stalks of the plant with 0.3% found in the roots and 0.86% in the leaves, stems, and flowers of the plant [7]. Mesembrine acts as a serotonin reuptake inhibitor with less prominent inhibitory effects on phosphodiesterase 4 (PDE4). In an in-vitro study, a high-mesembrine Sceletium extract showed monoamine releasing activity by up-regulation of vesicular monoamine transporter 2 (VMAT2) [11]. VMAT2 is a protein that transports neurotransmitters out of the cell, where they can have their effects. In the brain, VMAT2 transports—and thereby activates—molecules like dopamine, serotonin, and GABA.
Mesembrenone has been reported to serve as a more balanced serotonin reuptake inhibitor and also boosts energy use in the body by blocking an enzyme called phosphodiesterase 4, or PDE4.
Kanna is also reported to be an acetylcholinesterase inhibitor and cannabinoid agonist. In rats, active compounds of Sceletium tortuosum extract also activated the receptors for GABA, opioids, cholecystokinin, prostaglandins, and melatonin.
