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Evidence-Based Complementary and Alternative Medicine
Volume 2014, Article ID 682014, 9 pages
http://dx.doi.org/10.1155/2014/682014
Research Article

Proof-of-Concept Randomized Controlled Study of Cognition Effects of the Proprietary Extract Sceletium tortuosum (Zembrin) Targeting Phosphodiesterase-4 in Cognitively Healthy Subjects: Implications for Alzheimer’s Dementia

1Lawson Health Research Institute, Lab FB125, 268 Grosvenor Street, London, ON, Canada N6A 4V2
2Department of Psychiatry, University of Western Ontario, London, ON, Canada N6A 3K7
3Medical and Scientific of HG & H Pharmaceuticals (Pty) Ltd., 193 Bryanston Drive, Bryanston 2192, South Africa
4Department of Psychiatry, School of Medicine, University of Puerto Rico, San Juan, PR 00936-5067, USA
5Medical and Scientific Affairs, P L Thomas & Co., Inc., Morristown, NJ 07960, USA
6Department of Psychiatry, Island Medical Program, University of Victoria, University British Columbia Extended Medical Campus, Victoria, BC, Canada V8W 2Y2
7Department of Psychiatry, Northern Ontario School of Medicine, Thunder Bay, ON, Canada P7B 5E1

Received 21 May 2014; Revised 16 August 2014; Accepted 2 September 2014; Published 19 October 2014

Academic Editor: Kuzhuvelil B. Harikumar

Copyright © 2014 Simon Chiu et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. P. Ljubuncic, A. Globerson, and A. Z. Reznick, “Evidence-based roads to the promotion of health in old age,” Journal of Nutrition, Health and Aging, vol. 12, no. 2, pp. 139–143, 2008. View at Publisher · View at Google Scholar · View at Scopus
  2. L. Nyberg, M. Lövdén, K. Riklund, U. Lindenberger, and L. Bäckman, “Memory aging and brain maintenance,” Trends in Cognitive Sciences, vol. 16, no. 5, pp. 292–305, 2012. View at Publisher · View at Google Scholar · View at Scopus
  3. K. R. Daffner, “Promoting successful cognitive aging: a comprehensive review,” Journal of Alzheimer's Disease, vol. 19, no. 4, pp. 1101–1122, 2010. View at Publisher · View at Google Scholar · View at Scopus
  4. B. T. Hyman, C. H. Phelps, T. G. Beach et al., “National Institute on Aging-Alzheimer's Association guidelines for the neuropathologic assessment of Alzheimer's disease,” Alzheimer's and Dementia, vol. 8, no. 1, pp. 1–13, 2012. View at Publisher · View at Google Scholar · View at Scopus
  5. S. Hatashita and H. Yamasaki, “Diagnosed mild cognitive impairment due to Alzheimer's disease with PET biomarkers of beta amyloid and neuronal dysfunction,” PLoS ONE, vol. 8, no. 6, Article ID e66877, 2013. View at Publisher · View at Google Scholar · View at Scopus
  6. A. Otaegui-Arrazola, P. Amiano, A. Elbusto, E. Urdaneta, and P. Martínez-Lage, “Diet, cognition, and Alzheimer's disease: food for thought,” European Journal of Nutrition, vol. 53, no. 1, pp. 1–23, 2014. View at Publisher · View at Google Scholar · View at Scopus
  7. J. N. Laditka, S. B. Laditka, E. M. Tait, and M. M. Tsulukidze, “Use of dietary supplements for cognitive health: results of a national survey of adults in the United States,” The American Journal of Alzheimer's Disease and other Dementias, vol. 27, no. 1, pp. 55–64, 2012. View at Publisher · View at Google Scholar · View at Scopus
  8. E. Benito and A. Barco, “CREB's control of intrinsic and synaptic plasticity: implications for CREB-dependent memory models,” Trends in Neurosciences, vol. 33, no. 5, pp. 230–240, 2010. View at Publisher · View at Google Scholar · View at Scopus
  9. E. Bollen and J. Prickaerts, “Phosphodiesterases in neurodegenerative disorders,” IUBMB Life, vol. 64, no. 12, pp. 965–970, 2012. View at Publisher · View at Google Scholar · View at Scopus
  10. Y.-F. Li, Y.-F. Cheng, Y. Huang et al., “Phosphodiesterase-4D knock-out and RNA interference-mediated knock-down enhance memory and increase hippocampal neurogenesis via increased cAMP signaling,” Journal of Neuroscience, vol. 31, no. 1, pp. 172–183, 2011. View at Publisher · View at Google Scholar · View at Scopus
  11. Y.-F. Cheng, C. Wang, H.-B. Lin et al., “Inhibition of phosphodiesterase-4 reverses memory deficits produced by Aβ25-35 or Aβ1-40 peptide in rats,” Psychopharmacology, vol. 212, no. 2, pp. 181–191, 2010. View at Publisher · View at Google Scholar · View at Scopus
  12. C. A. Saura and J. Valero, “The role of CREB signaling in Alzheimer's disease and other cognitive disorders,” Reviews in the Neurosciences, vol. 22, no. 2, pp. 153–169, 2011. View at Publisher · View at Google Scholar · View at Scopus
  13. A. Blokland, F. S. Menniti, and J. Prickaerts, “PDE Inhibition and cognition enhancement,” Expert Opinion on Therapeutic Patents, vol. 22, no. 4, pp. 349–354, 2012. View at Publisher · View at Google Scholar · View at Scopus
  14. J. H. Chung, “Metabolic benefits of inhibiting cAMP-PDEs with resveratrol,” Adipocyte, vol. 1, no. 4, pp. 256–258, 2012. View at Publisher · View at Google Scholar
  15. M. Rivera-Oliver and M. Díaz-Ríos, “Using caffeine and other adenosine receptor antagonists and agonists as therapeutic tools against neurodegenerative diseases: a review,” Life Sciences, vol. 101, no. 1-2, pp. 1–9, 2014. View at Publisher · View at Google Scholar · View at Scopus
  16. C. Santos, J. Costa, J. Santos, A. Vaz-Carneiro, and N. Lunet, “Caffeine intake and dementia: systematic review and meta-analysis,” Journal of Alzheimer's Disease, vol. 20, no. 1, pp. S187–S204, 2010. View at Publisher · View at Google Scholar · View at Scopus
  17. M. H. Eskelinen and M. Kivipelto, “Caffeine as a protective factor in dementia and Alzheimer's disease,” Journal of Alzheimer's Disease, vol. 20, supplement 1, pp. S167–S174, 2010. View at Publisher · View at Google Scholar · View at Scopus
  18. M. H. Eskelinen, T. Ngandu, J. Tuomilehto, H. Soininen, and M. Kivipelto, “Midlife coffee and tea drinking and the risk of late-life dementia: a population-based CAIDE study,” Journal of Alzheimer's Disease, vol. 16, no. 1, pp. 85–91, 2009. View at Publisher · View at Google Scholar · View at Scopus
  19. A. L. Harvey, L. C. Young, A. M. Viljoen, and N. P. Gericke, “Pharmacological actions of the South African medicinal and functional food plant Sceletium tortuosum and its principal alkaloids,” Journal of Ethnopharmacology, vol. 137, no. 3, pp. 1124–1129, 2011. View at Publisher · View at Google Scholar · View at Scopus
  20. H. Raheb, Y. B. M. Woodbury-Farina, V. Badmaev et al., “Translational study of standardized Zembrin extract and mesembrenone targeting PDE-4 (phosphodiesterase subtype for regulation of cognition and mood),” in Proceedings of International Conference on Bioactive Naturals, London, Canada, July 2012.
  21. H. Nell, M. Siebert, P. Chellan, and N. Gericke, “A randomized, double-blind, parallel-group, placebo-controlled trial of extract Sceletium Tortuosum (Zembrin) in healthy adults,” Journal of Alternative and Complementary Medicine, vol. 19, no. 11, pp. 898–904, 2013. View at Publisher · View at Google Scholar · View at Scopus
  22. DSM-IV-TR American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, DSM-IV-TR American Psychiatric Association, 4th edition, 2000.
  23. M. Zimmerman, I. Chelminski, and M. Posternak, “A review of studies of the Hamilton depression rating scale in healthy controls: implications for the definition of remission in treatment studies of depression,” Journal of Nervous and Mental Disease, vol. 192, no. 9, pp. 595–601, 2004. View at Publisher · View at Google Scholar · View at Scopus
  24. C. T. Gualtieri and L. G. Johnson, “Reliability and validity of a computerized neurocognitive test battery, CNS vital signs,” Archives of Clinical Neuropsychology, vol. 21, no. 7, pp. 623–643, 2006. View at Publisher · View at Google Scholar · View at Scopus
  25. A. Martyr and L. Clare, “Executive function and activities of daily living in Alzheimer's disease: a correlational meta-analysis,” Dementia and Geriatric Cognitive Disorders, vol. 33, no. 2-3, pp. 189–203, 2012. View at Publisher · View at Google Scholar · View at Scopus
  26. M. S. Albert, “Changes in cognition,” Neurobiology of Aging, vol. 32, supplement 1, pp. S58–S63, 2011. View at Publisher · View at Google Scholar · View at Scopus
  27. G. A. Marshall, D. M. Rentz, M. T. Frey, J. J. Locascio, K. A. Johnson, and R. A. Sperling, “Executive function and instrumental activities of daily living in mild cognitive impairment and Alzheimer's disease,” Alzheimer's and Dementia, vol. 7, no. 3, pp. 300–308, 2011. View at Publisher · View at Google Scholar · View at Scopus
  28. L. R. Clark, D. M. Schiehser, G. H. Weissberger, D. P. Salmon, D. C. Delis, and M. W. Bondi, “Specific measures of executive function predict cognitive decline in older adults,” Journal of the International Neuropsychological Society, vol. 18, no. 1, pp. 118–127, 2012. View at Publisher · View at Google Scholar · View at Scopus
  29. P. Allain, F. Etcharry-Bouyx, and C. Verny, “Executive functions in clinical and preclinical Alzheimer's disease,” Revue Neurologique, vol. 169, no. 10, pp. 695–708, 2013. View at Publisher · View at Google Scholar · View at Scopus
  30. M. N. Braskie and P. M. Thompson, “Understanding cognitive deficits in alzheimer's disease based on neuroimaging findings,” Trends in Cognitive Sciences, vol. 17, no. 10, pp. 510–516, 2013. View at Publisher · View at Google Scholar · View at Scopus
  31. M. L. Schroeter, B. Vogt, S. Frisch et al., “Executive deficits are related to the inferior frontal junction in early dementia,” Brain, vol. 135, no. 1, pp. 201–215, 2012. View at Publisher · View at Google Scholar · View at Scopus
  32. A. B. Burgin, O. T. Magnusson, J. Singh et al., “Design of phosphodiesterase 4D (PDE4D) allosteric modulators for enhancing cognition with improved safety,” Nature Biotechnology, vol. 28, no. 1, pp. 63–70, 2010. View at Publisher · View at Google Scholar · View at Scopus
  33. N. Gericke and A. M. Viljoen, “Sceletium—a review update,” Journal of Ethnopharmacology, vol. 119, no. 3, pp. 653–663, 2008. View at Publisher · View at Google Scholar · View at Scopus
  34. K. Rutten, J. L. Basile, J. Prickaerts, A. Blokland, and J. A. Vivian, “Selective PDE inhibitors rolipram and sildenafil improve object retrieval performance in adult cynomolgus macaques,” Psychopharmacology, vol. 196, no. 4, pp. 643–648, 2008. View at Publisher · View at Google Scholar · View at Scopus
  35. R. T. Hansen III and H.-T. Zhang, “Senescent-induced dysregulation of cAMP/CREB signaling and correlations with cognitive decline,” Brain Research, vol. 1516, pp. 93–109, 2013. View at Publisher · View at Google Scholar · View at Scopus
  36. J. R. Homberg, “Serotonin and decision making processes,” Neuroscience and Biobehavioral Reviews, vol. 36, no. 1, pp. 218–236, 2012. View at Publisher · View at Google Scholar · View at Scopus
  37. Y. I. Sheline, T. West, K. Yarasheski et al., “An antidepressant decreases CSF Aβ production in healthy individuals and in transgenic AD mice,” Science Translational Medicine, vol. 6, no. 236, Article ID 236re4, 2014. View at Publisher · View at Google Scholar · View at Scopus
  38. J. J. Rodríguez, H. N. Noristani, and A. Verkhratsky, “The serotonergic system in ageing and Alzheimer's disease,” Progress in Neurobiology, vol. 99, no. 1, pp. 15–41, 2012. View at Publisher · View at Google Scholar · View at Scopus
  39. D. Terburg, S. Syal, L. A. Rosenberger et al., “Acute effects of sceletium tortuosum (Zembrin), a dual 5-HT reuptake and PDE4 inhibitor, in the human amygdala and its connection to the hypothalamus,” Neuropsychopharmacology, vol. 38, no. 13, pp. 2708–2716, 2013. View at Publisher · View at Google Scholar · View at Scopus
  40. C. G. Vecsey, G. S. Baillie, D. Jaganath et al., “Sleep deprivation impairs cAMP signalling in the hippocampus,” Nature, vol. 461, no. 7267, pp. 1122–1125, 2009. View at Publisher · View at Google Scholar · View at Scopus
  41. T. L. Schaefer, A. A. Braun, R. M. Amos-Kroohs, M. T. Williams, E. Ostertag, and C. V. Vorhees, “A new model of Pde4d deficiency: genetic knock-down of PDE4D enzyme in rats produces an antidepressant phenotype without spatial cognitive effects,” Genes, Brain and Behavior, vol. 11, no. 5, pp. 614–622, 2012. View at Publisher · View at Google Scholar · View at Scopus