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Sceletium Tortuosum: Effects on Central Nervous System and Related Disease

Yangwen Luo, Jing Wen, Isadore Kanfer, Pei Yu, Srinivas Patnala

Abstract


Sceletium tortuosum is a well-known medicinal plant in South Africa with potential applications. Its raw material, extracts and isolated alkaloids are used as dietary supplements, natural medicines and health food. In this paper, methods of planting, extraction, isolation and identification of Sceletium tortuosum, as well as its chemical structure of main extracted alkaloids, their related pharmacological effects and mechanisms for treating the disease are reviewed. In general, Sceletium tortuosum is active to central nervous system (CNS) by inhibiting phosphodiesterase isozyme 4 (PDE4), serotonin (5-HT) uptake and acetylcholinesterase (AChE). It also acts as a monoamine releasing agent for antidepressant effects. Therefore, it is a useful therapeutic agent in clinical use.


Keywords


Sceletium tortuosum, alkaloids, phosphodiesterase isozyme 4, 5-hydroxytryptamine, central nervous system.

Full Text:

References


Smith CA. Common names of South African plants. 1966.

Hirabayashi M, Ichikawa K, Fukushima R, Uchino T, Shimada H. Clinical application of South African tea on dementia dog. Japanese Journal of Small Animal Practice. 2002;21:109-13.

Gericke N, Viljoen AM. Sceletium--a review update. J Ethnopharmacol. 2008;119(3):653-663. doi:10.1016/j.jep.2008.07.043.

Bennett A, Van Camp A, Lopez V, Smith C. Sceletium tortuosum may delay chronic disease progression via alkaloid-dependent antioxidant or anti-inflammatory action. J Physiol Biochem. 2018;74(4):539-47. doi: 10.1007/s13105-018-0620-6.

Gerbaulet M. Revision of the genus Sceletium NE Br.(Aizoaceae).(With 5 figures in the text). Botanische Jahrbucher fur Systematik Pflanzengeschichte und Pflanzengeographie. 1996;118(1):9-24.

Bodendorf K, Krieger W. Über die Alkaloide von Mesembryanthemum tortuosum L. Arch Pharm. 1957;290(10):441-8.

Shikanga EA, Viljoen A, Combrinck S, Marston A. Isolation of Sceletium alkaloids by high-speed countercurrent chromatography. Phytochemistry letters. 2011;4(2):190-3. doi: 10.1016/j.phytol.2011.03.003.

Patnala S, Kanfer I. HPLC analysis of mesembrine-type alkaloids in Sceletium plant material used as an African traditional medicine. J Pharm Pharm Sci. 2010;13(4):558-70. doi:10.18433/j3dk5f.

Shikanga E, Kamatou G, Chen W, Combrinck S, Viljoen A. Validated RP-UHPLC PDA and GC–MS methods for the analysis of psychoactive alkaloids in Sceletium tortuosum. S Afr J Bot. 2012;82:99-107.

Meyer GM, Wink CS, Zapp J, Maurer HH. GC-MS, LC-MS n, LC-high resolution-MS n, and NMR studies on the metabolism and toxicological detection of mesembrine and mesembrenone, the main alkaloids of the legal high “Kanna” isolated from Sceletium tortuosum. Anal Bioanal Chem. 2015;407(3):761-78. doi: 10.1007/s00216-014-8109-9.

Patnala S, Kanfer I. A capillary zone electrophoresis method for the assay and quality control of mesembrine in Sceletium tablets. J Pharm Biomed Anal. 2008;48(2):440-446. doi:10.1016/j.jpba.2008.01.002.

Roscher J, Posch TN, Pütz M, Huhn C. Forensic analysis of mesembrine alkaloids in Sceletium tortuosum by nonaqueous capillary electrophoresis mass spectrometry. Electrophoresis. 2012;33(11):1567-1570. doi:10.1002/elps.201100683.

Larive CK, Barding GA Jr, Dinges MM. NMR spectroscopy for metabolomics and metabolic profiling. Anal Chem. 2015;87(1):133-146. doi:10.1021/ac504075g.

Zhao J, Khan IA, Combrinck S, Sandasi M, Chen W, Viljoen AM. 1H-NMR and UPLC-MS metabolomics: Functional tools for exploring chemotypic variation in Sceletium tortuosum from two provinces in South Africa. Phytochemistry. 2018;152:191-203. doi: 10.1016/j.phytochem.2018.03.013.

Krstenansky JL. Mesembrine alkaloids: Review of their occurrence, chemistry, and pharmacology. J Ethnopharmacol. 2017;195:10-9. doi:10.1016/j.jep.2016.12.004.

Harvey AL, Young LC, Viljoen AM, Gericke NP. Pharmacological actions of the South African medicinal and functional food plant Sceletium tortuosum and its principal alkaloids. J Ethnopharmacol. 2011;137(3):1124-1129. doi:10.1016/j.jep.2011.07.035.

Harvey AL, Young LC, Viljoen AM, Gericke NP. Pharmacological actions of the South African medicinal and functional food plant Sceletium tortuosum and its principal alkaloids. J Ethnopharmacol. 2011;137(3):1124-1129. doi:10.1016/j.jep.2011.07.035.

Zhang H. Phosphodiesterase-4D knockout and RNAi-mediated knockdown enhance memory and increase hippocampal neurogenesis via increased cAMP signaling. J Neurosci. 2011;31:172183Lundquist. doi: 10.1523/JNEUROSCI.5236-10.2011.

Chiu S, Gericke N, Farina-Woodbury M, et al. 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. Evid Based Complement Alternat Med. 2014;2014:682014. doi:10.1155/2014/682014.

Blokland A, Menniti FS, Prickaerts J. PDE inhibition and cognition enhancement. Expert Opin Ther Pat. 2012;22(4):349-354. doi:10.1517/13543776.2012.674514.

Saura CA, Valero J. The role of CREB signaling in Alzheimer's disease and other cognitive disorders. Rev Neurosci. 2011;22(2):153-169. doi:10.1515/RNS.2011.018.

Gualtieri CT, Johnson LG. Reliability and validity of a computerized neurocognitive test battery, CNS Vital Signs. Arch Clin Neuropsychol. 2006;21(7):623-643. doi:10.1016/j.acn.2006.05.007.

Zimmerman M, Chelminski I, Posternak M. A review of studies of the Hamilton depression rating scale in healthy controls: implications for the definition of remission in treatment studies of depression. J Nerv Ment Dis. 2004;192(9):595-601. doi:10.1097/01.nmd.0000138226.22761.39.

Homberg JR. Serotonin and decision making processes. Neurosci Biobehav Rev. 2012;36(1):218-236. doi:10.1016/j.neubiorev.2011.06.001.

Rodríguez JJ, Noristani HN, Verkhratsky A. The serotonergic system in ageing and Alzheimer's disease. Prog Neurobiol. 2012;99(1):15-41. doi:10.1016/j.pneurobio.2012.06.010.

Dimpfel W, Schombert L, Gericke N. Electropharmacogram of Sceletium tortuosum extract based on spectral local field power in conscious freely moving rats. J Ethnopharmacol. 2016;177:140-147. doi:10.1016/j.jep.2015.11.036.

Klimesch W, Doppelmayr M, Pachinger T, Ripper B. Brain oscillations and human memory: EEG correlates in the upper alpha and theta band. Neurosci Lett. 1997;238(1-2):9-12. doi:10.1016/s0304-3940(97)00771-4.

Klimesch W. EEG alpha and theta oscillations reflect cognitive and memory performance: a review and analysis. Brain Res Brain Res Rev. 1999;29(2-3):169-195. doi:10.1016/s0165-0173(98)00056-3.

Zheng L-l, Jiang Z-y, Yu E-y. Alpha spectral power and coherence in the patients with mild cognitive impairment during a three-level working memory task. Journal of Zhejiang University SCIENCE B. 2007;8(8):584-92. doi: 10.1631/jzus.2007.B0584.

Georgiev V, Ilieva M, Bley T, Pavlov A. Betalain production in plant in vitro systems. Acta Physiologiae Plantarum. 2008;30(5):581-93. doi: 10.1007/s11738-008-0170-6.

Loria MJ, Ali Z, Abe N, Sufka KJ, Khan IA. Effects of Sceletium tortuosum in rats. J Ethnopharmacol. 2014;155(1):731-735. doi:10.1016/j.jep.2014.06.007.

Dimpfel W, Gericke N, Suliman S, Dipah GNC. Effect of Zembrin® on Brain Electrical Activity in 60 Older Subjects after 6 Weeks of Daily Intake. A Prospective, Randomized, Double-Blind, Placebo-Controlled, 3-Armed Study in a Parallel Design. World Journal of Neuroscience. 2016;7(1):140-71. doi: 10.4236/wjns.2017.71011.

Van W, Wink M. Medicinal Plants of the world. Portland, OR: Timber Press; 2004.

Coetzee DD, López V, Smith C. High-mesembrine Sceletium extract (Trimesemine™) is a monoamine releasing agent, rather than only a selective serotonin reuptake inhibitor. J Ethnopharmacol. 2016;177:111-116. doi:10.1016/j.jep.2015.11.034.

Wang Y, Liu M, Wang H, Bai Y, Zhang X, Sun Y, et al. Involvement of serotonin mechanism in methamphetamine-induced chronic pulmonary toxicity in rats. 2013;32(7):736-46. doi: 10.1177/0960327112468174.

Torres GE, Gainetdinov RR, Caron MG. Plasma membrane monoamine transporters: structure, regulation and function. Nat Rev Neurosci. 2003;4(1):13-25. doi:10.1038/nrn1008.

Bennett A, López V, van Camp A, Smith C. Sceletium tortuosum and depression: mechanisms elucidated. Planta Med. 2016;82(S 01):P853. doi: 10.1016/j.jep.2017.12.020.

Nell H, Siebert M, Chellan P, Gericke N. A randomized, double-blind, parallel-group, placebo-controlled trial of Extract Sceletium tortuosum (Zembrin) in healthy adults. J Altern Complement Med. 2013;19(11):898-904. doi:10.1089/acm.2012.0185.

Vecsey CG, Baillie GS, Jaganath D, et al. Sleep deprivation impairs cAMP signalling in the hippocampus. Nature. 2009;461(7267):1122-1125. doi:10.1038/nature08488.

Perrine SA, Hoshaw BA, Unterwald EM. Delta opioid receptor ligands modulate anxiety-like behaviors in the rat. Br J Pharmacol. 2006;147(8):864-872. doi:10.1038/sj.bjp.0706686.

Randall-Thompson JF, Pescatore KA, Unterwald EM. A role for delta opioid receptors in the central nucleus of the amygdala in anxiety-like behaviors. Psychopharmacology (Berl). 2010;212(4):585-595. doi:10.1007/s00213-010-1980-y.

Watson GS, Roach JT, Sufka KJ. Benzodiazepine receptor function in the chick social separation-stress procedure. Exp Clin Psychopharmacol. 1999;7(2):83-89. doi:10.1037//1064-1297.7.2.83.

Watson G, Sufka KJ. Chlordiazepoxide reverses social-separation-induced distress vocalizations and analgesia in young domestic fowl. Exp Clin Psychopharmacol. 1996;4(4):347. doi: 10.1037/1064-1297.4.4.347.

Smith C. The effects of Sceletium tortuosum in an in vivo model of psychological stress. J Ethnopharmacol. 2011;133(1):31-36. doi:10.1016/j.jep.2010.08.058.

Carpenter JM, Jourdan MK, Fountain EM, Ali Z, Abe N, Khan IA, et al. The effects of Sceletium tortuosum (L.) NE Br. extract fraction in the chick anxiety-depression model. J Ethnopharmacol. 2016;193:329-32. doi:10.1016/j.jep.2016.08.019.

Terburg D, Syal S, Rosenberger LA, Heany S, Phillips N, Gericke N, 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. 2013;38(13):2708. doi: 10.1038/npp.2013.183.

Swart A, S Swart AC, Smith C. Modulation of glucocorticoid, mineralocorticoid and androgen production in H295 cells by Trimesemine™, a mesembrine-rich Sceletium extract. J Ethnopharmacol. 2016;177:35-45. doi:10.1016/j.jep.2015.11.033.

Saccomano NA, Vinick FJ, Koe BK, et al. Calcium-independent phosphodiesterase inhibitors as putative antidepressants: [3-(bicycloalkyloxy)-4-methoxyphenyl]-2-imidazolidinones. J Med Chem. 1991;34(1):291-298. doi:10.1021/jm00105a045.

Fleischhacker WW, Hinterhuber H, Bauer H, et al. A multicenter double-blind study of three different doses of the new cAMP-phosphodiesterase inhibitor rolipram in patients with major depressive disorder. Neuropsychobiology. 1992;26(1-2):59-64. doi:10.1159/000118897.

Halene TB, Siegel SJ. PDE inhibitors in psychiatry–future options for dementia, depression and schizophrenia? Drug Discovery Today. 2007;12(19-20):870-8. doi: 10.1016/j.drudis.2007.07.023.

Pringle A, Browning M, Cowen PJ, Harmer CJ. A cognitive neuropsychological model of antidepressant drug action. Prog Neuropsychopharmacol Biol Psychiatry. 2011;35(7):1586-1592. doi:10.1016/j.pnpbp.2010.07.022.

Ye Y, Jackson K, O'Donnell JM. Effects of repeated antidepressant treatment of type 4A phosphodiesterase (PDE4A) in rat brain. J Neurochem. 2000;74(3):1257-1262. doi:10.1046/j.1471-4159.2000.741257.x.

Cashman JR, Voelker T, Johnson R, Janowsky A. Stereoselective inhibition of serotonin re-uptake and phosphodiesterase by dual inhibitors as potential agents for depression. Bioorg Med Chem. 2009;17(1):337-343. doi:10.1016/j.bmc.2008.10.065.

Fon EA, Pothos EN, Sun BC, Killeen N, Sulzer D, Edwards RH. Vesicular transport regulates monoamine storage and release but is not essential for amphetamine action. Neuron. 1997;19(6):1271-1283. doi:10.1016/s0896-6273(00)80418-3.

Rietjens SJ, Hondebrink L, Westerink RH, Meulenbelt J. Pharmacokinetics and pharmacodynamics of 3,4-methylenedioxymethamphetamine (MDMA): interindividual differences due to polymorphisms and drug-drug interactions. Crit Rev Toxicol. 2012;42(10):854-876. doi:10.3109/10408444.2012.725029.

Smilkstein MJ, Smolinske SC, Rumack BH. A case of MAO inhibitor/MDMA interaction: agony after ecstasy. J Toxicol Clin Toxicol. 1987;25(1-2):149-159. doi:10.3109/15563658708992620.

Pathak A, K Srivastava A, K Singour P, Gouda P. Synthetic and natural monoamine oxidase inhibitors as potential lead compounds for effective therapeutics. Central Nervous System Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry-Central Nervous System Agents). 2016;16(2):81-97. doi: 10.2174/1871524915666150624120516.

Bennett AC, Smith C. Immunomodulatory effects of Sceletium tortuosum (Trimesemine™) elucidated in vitro: Implications for chronic disease. J Ethnopharmacol. 2018;214:134-140. doi:10.1016/j.jep.2017.12.020.

Steinhoff BJ. The AMPA receptor antagonist perampanel in the adjunctive treatment of partial-onset seizures: clinical trial evidence and experience. Ther Adv Neurol Disord. 2015;8(3):137-147. doi:10.1177/1756285615575696.

Dimpfel W, Franklin R, Gericke N, Schombert L. Effect of Zembrin® and four of its alkaloid constituents on electric excitability of the rat hippocampus. J Ethnopharmacol. 2018;223:135-141. doi:10.1016/j.jep.2018.05.01.


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