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Sceletium tortuosum may delay chronic disease progression via alkaloid-dependent antioxidant or anti-inflammatory action


The link between obesity-induced systemic inflammation and decreased insulin signalling is well-known. It is also known that peripherally produced inflammatory cytokines can cross the blood-brain barrier, resulting in the release of neurotoxins that can ultimately lead to the demise of central nervous system integrity. A high-mesembrine Sceletium tortuosum extract was recently shown to possess cytoprotective and mild anti-inflammatory properties in monocytes and to target specific p450 enzymes to reduce adrenal glucocorticoid synthesis. This is significant since the aetiology of both obesity and diabetes is linked to inflammation and excess glucocorticoid production. Given the interlinked nature of glucocorticoid action and inflammation, central immunomodulatory effects of two Sceletium tortuosum extracts prepared by different extraction methods were investigated. Human astrocytes were pre-treated for 30 min, before exposure to Escherichia coli lipopolysaccharide for 23.5 h (in the presence of treatment). Cytotoxicity, mitotoxicity and cytokine responses (basally and in response to inflammatory stimulus) were assessed. In addition, total polyphenol content, antioxidant capacity and selected neural enzyme inhibition capacity were assessed for both extracts. The high-mesembrine Sceletium extract exerted cytoprotective and anti-inflammatory effects. In contrast, the high delta7-mesembrenone extract, rich in polyphenols, exhibited potent antioxidant effect, although with relatively higher risk of adverse effects with overdose. We conclude that both Sceletium tortuosum extracts may be employed as either a preventative supplement or complimentary treatment in the context of obesity and diabetes; however, current data also highlights the impact that extraction methods can have on plant product mechanism of action.

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Analysis of variance




Blood-brain barrier


Central nervous system


Dulbecco’s modified eagle’s medium


Dulbecco’s phosphate-buffered saline




Foetal bovine serum


Hank’s balanced salt solution


High-performance liquid chromatography








Monoamine oxidase A


Monocyte chemotactic protein-1


Phosphate-buffered saline


Propidium iodide


Reactive oxygen species


Revolutions per minute


Standard error of the mean


Type 2 diabetes


Type 3 diabetes


  1. Allen CL, Bayraktutan U (2009) Antioxidants attenuate hyperglycaemia-mediated brain endothelial cell dysfunction and blood-brain barrier hyperpermeability. Diabetes Obes Metab 11:480–490.

    Article  CAS  PubMed  Google Scholar 

  2. Anstey KJ, Cherbuin N, Budge M, Young J (2011) Body mass index in midlife and late-life as a risk factor for dementia: a meta-analysis of prospective studies. Obes Rev 12:426–437.

    Article  Google Scholar 

  3. Balkwill FR, Burke F (1989) The cytokine network. Immunol Today 10:299–304.

    Article  CAS  PubMed  Google Scholar 

  4. Belanger M, Magistretti PJ (2009) The role of astroglia in neuroprotection. Dialogues Clin Neurosci 11:281–296.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Bennett AC, Smith C (2018) Immunomodulatory effects of Sceletium tortuosum (Trimesemine™) elucidated in vitro: implications for chronic disease. J Ethnopharmacol 214:134–140.

    Article  PubMed  Google Scholar 

  6. Blanco AM, Valles SL, Pascual M, Guerri C (2005) Involvement of TLR4/type I IL-1 receptor signaling in the induction of inflammatory mediators and cell death induced by ethanol in cultured astrocytes. J Immunol 175:6893–6899.

    Article  CAS  PubMed  Google Scholar 

  7. Burkitt M (2001) Too much of a good thing? Nat Biotechnol 19:811–812.

    Article  CAS  PubMed  Google Scholar 

  8. Carvalho C, Cardoso S, Correia SC, Santos RX, Santos MS, Baldeiras I, Oliveira CR, Moreira PI (2012) Metabolic alterations induced by sucrose intake and Alzheimer’s disease promote similar brain mitochondrial abnormalities. Diabetes 61:1234–1242.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Cásedas G, Les F, Gómez-Serranillos MP, Smith C, López V (2017) Anthocyanin profile, antioxidant activity and enzyme inhibiting properties of blueberry and cranberry juices: a comparative study. Food Funct 8:4187–4193.

    Article  CAS  PubMed  Google Scholar 

  10. Chen YS, Liou HC, Chan CF (2013) Tyrosinase inhibitory effect and antioxidative activities of fermented and ethanol extracts of Rhodiola rosea and Lonicera japonica. Sci World J 2013:1–5.

    Article  Google Scholar 

  11. Coetzee DD, López V, Smith C (2016) High-mesembrine Sceletium extract (Trimesemine™) is a monoamine releasing agent, rather than only a selective serotonin reuptake inhibitor. J Ethnopharmacol 177:111–116.

    Article  CAS  PubMed  Google Scholar 

  12. Ellman GL, Courtney KD, Andres V, Featherstone RM (1961) A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 7:88–95.

    Article  CAS  Google Scholar 

  13. Gnatek Y, Zimmerman G, Goll Y, Najami N, Soreq H, Friedman A (2012) Acetylcholinesterase loosens the brain’s cholinergic anti-inflammatory response and promotes epileptogenesis. Front Mol Neurosci 5:1–10.

    Article  CAS  Google Scholar 

  14. Harvey AL, Young LC, Viljoen AM, Gericke NP (2011) Pharmacological actions of the South African medicinal and functional food plant Sceletium tortuosum and its principal alkaloids. J Ethnopharmacol 137:1124–1129.

    Article  CAS  PubMed  Google Scholar 

  15. Hassing LB, Dahl AK, Pedersen NL, Johansson B (2010) Overweight in midlife is related to lower cognitive function 30 years later: a prospective study with longitudinal assessments. Dement Geriatr Cogn Disord 29:543–552.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Kaushal V, Dye R, Pakavathkumar P, Foveau B, Flores J, Hyman B, Ghetti B, Koller BH, LeBlanc AC (2015) Neuronal NLRP1 inflammasome activation of Caspase-1 coordinately regulates inflammatory interleukin-1-beta production and axonal degeneration-associated Caspase-6 activation. Cell Death Differ 22:1676–1686.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Kim YJ, Uyama H (2005) Tyrosinase inhibitors from natural and synthetic sources: structure, inhibition mechanism and perspective for the future. Cell Mol Life Sci 62:1707–1723.

    Article  CAS  PubMed  Google Scholar 

  18. Ku SK, Kwak S, Kim Y, Bae JS (2014) Aspalathin and Nothofagin from rooibos (Aspalathus linearis) inhibits high glucose-induced inflammation in vitro and in vivo. Inflammation 38:445–455.

    Article  CAS  Google Scholar 

  19. De La Monte SM (2008) Alzheimer’s disease is type 3 diabetes—evidence reviewed. J Diabetes Sci Technol 2:1101–1113.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Nepal B, Brown LJ, Anstey KJ (2014) Rising midlife obesity will worsen future prevalence of dementia. PLoS One 9:1–5.

    Article  CAS  Google Scholar 

  21. Patnala S, Kanfer I (2013) Chemotaxonomic studies of mesembrine-type alkaloids in Sceletium plant species. S Afr J Sci 109:5–9.

    Article  CAS  Google Scholar 

  22. Petersen KS, Smith C (2016) Ageing-associated oxidative stress and inflammation are alleviated by products from grapes. Oxidative Med Cell Longev 2016:1–12.

    Article  CAS  Google Scholar 

  23. Pugazhenthi S, Qin L, Reddy PH (2017) Common neurodegenerative pathways in obesity, diabetes, and Alzheimer’s disease. Biochim Biophys Acta - Mol Basis Dis 1863:1037–1045.

    Article  CAS  PubMed  Google Scholar 

  24. Shikanga EA, Viljoen AM, Combrinck S, Marston A, Gericke N (2012) The chemotypic variation of Sceletium tortuosum alkaloids and commercial product formulations. Biochem Syst Ecol 44:364–373.

    Article  CAS  Google Scholar 

  25. Shoelson SE, Lee J, Goldfine AB (2006) Inflammation and insulin resistance. J Clin Invest 116:1793–1801.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Shytle RD, Mori T, Townsend K, Vendrame M, Sun N, Zeng J, Ehrhart J, Silver AA, Sanberg PR, Tan J (2004) Cholinergic modulation of microglial activation by α7 nicotinic receptors. J Neurochem 89:337–343.

    Article  CAS  PubMed  Google Scholar 

  27. Smith C (2011) The effects of Sceletium tortuosum in an in vivo model of psychological stress. J Ethnopharmacol 133:31–36.

    Article  CAS  PubMed  Google Scholar 

  28. Sorbara MT, Girardin SE (2011) Mitochondrial ROS fuel the inflammasome. Cell Res 21:558–560.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Streit WJ, Mrak RE, Griffin WST (2004) Microglia and neuroinflammation: a pathological perspective. J Neuroinflammation 1:1–4.

    Article  CAS  Google Scholar 

  30. Swart AC, Smith C (2016) Modulation of glucocorticoid, mineralocorticoid and androgen production in H295 cells by Trimesemine, a mesembrine-rich Sceletium extract. J Ethnopharmacol 177:35–45.

    Article  CAS  PubMed  Google Scholar 

  31. Szelényi J (2001) Cytokines and the central nervous system. Brain Res Bull 54:329–338.

    Article  PubMed  Google Scholar 

  32. Thomson CA, McColl A, Cavanagh J, Graham GJ (2014) Peripheral inflammation is associated with remote global gene expression changes in the brain. J Neuroinflammation 11:73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Tucsek Z, Toth P, Tarantini S, Sosnowska D, Gautam T, Warrington JP, Giles CB, Wren JD, Koller A, Ballabh P, Sonntag WE, Ungvari Z, Csiszar A (2014) Aging exacerbates obesity-induced cerebromicrovascular rarefaction, neurovascular uncoupling, and cognitive decline in mice. Journals Gerontol A Biol Sci Med Sci 2014 69:1339–1352. doi:

    Article  CAS  Google Scholar 

  34. Wild S, Roglic G, Green A, Sicree R, Hilary K (2004) Global prevalence of diabetes: estimates for the year 2000 and projection for 2030. Diabetes Care 27:1047–1053.

    Article  PubMed  Google Scholar 

  35. Wrona D (2006) Neural-immune interactions: an integrative view of the bidirectional relationship between the brain and immune systems. J Neuroimmunol 172:38–58.

    Article  CAS  PubMed  Google Scholar 

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We would like to acknowledge the South African National Research Foundation (NRF) for the funding, and Verve Dynamics for the preparation and kind donation of the extracts used in this study.

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Correspondence to C. Smith.

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Bennett, A., Van Camp, A., López, V. et al. Sceletium tortuosum may delay chronic disease progression via alkaloid-dependent antioxidant or anti-inflammatory action. J Physiol Biochem 74, 539–547 (2018).

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