W. Chen and A. M. Viljoen, “To Ferment or Not to Ferment Sceletium Tortuosum – Do Our Ancestors Hold the Answer?,” South African Journal of Botany, vol. 122, pp. 543–546, May 2019.
doi: 10.1016/j.sajb.2018.10.011.
The KhoiSan of southern Africa have used fermented Sceletium tortuosum preparations to induce psychoactive effects for centuries. It is claimed that the fermentation process changes the alkaloid composition, thereby increasing the potency of the psychoactive response. In this study, a validated ultra performance liquid chromatography–mass spectrometry method was used to quantify the content of alkaloids prior to, and after the controlled fermentation of samples of S. tortuosum. The results revealed that, despite only a slight change in the mesembrenol and mesembranol content during fermentation, the mesembrine content increased significantly from not detected – 1.6 μg/mL to 7.40–20.8 μg/mL. A corresponding decrease was found in the initial mesembrenone content of 8.00–33.0 μg/mL to 1.30–32.7 μg/mL after fermentation. The total alkaloid content also increased as a result of fermentation.
R. J. Faber, C. P. Laubscher, and M. O. Jimoh, The Importance of Sceletium Tortuosum (L.) N.E. Brown and Its Viability as a Traditional African Medicinal Plant. IntechOpen, 2021.
doi: 10.5772/intechopen.96473.
Sceletium tortuosum is a succulent plant that belongs to the family Mesembryanthemaceae (Aizoaceae). It is indigenous to South Africa, where it is well known by the indigenous people, especially in Namaqualand where the plant is utilized regularly for its medicinal and psycho-active properties. The main alkaloids responsible for these properties are mesembrine, mesembrenine (mesembrenone), and mesembrenol. The potential of the plant to be an alternative supplement in the promotion of health and treating a variety of psychological and psychiatric disorders such as depression and anxiety has stimulated interest in its pharmacological property and possibility of its commercialization. The economic value of indigenous medicinal plants in South Africa is approximately US$60 000 000 or R4 000 000 000 annually. Thus, interest in the knowledge and use of Traditional African Medicinal Plants (TAMP) as well as meeting pharmacological and economic needs of ever-increasing human population has led to the commercialization of traditional African medicines at a fast rate. It was found that S. tortuosum has clear pharmaceutical and economical importance and is one of the only known plants to contain the alkaloids mesembrenone and mesembrine which can be utilized for the promotion of health and/or treating a variety of psychological disorders such as anxiety and depression.
R. J. Faber, C. P. Laubscher, F. Rautenbach, and M. O. Jimoh, “Variabilities in Alkaloid Concentration of Sceletium Tortuosum (L.) N.E. Br in Response to Different Soilless Growing Media and Fertigation Regimes in Hydroponics,” Heliyon, vol. 6, no. 11, p. e05479, Nov. 2020.
doi: 10.1016/j.heliyon.2020.e05479.
This study was designed to investigate the variations in alkaloid concentrations of Sceletium tortuosum when grown in soilless media under different fertigation regimes and to examine the suitability of the plant for hydroponic cultivation. A mother plant obtained from Verve Dynamics (Pty) Ltd (a manufacturer and supplier of purified botanical extracts) was cultivated into three hundred plants used for this research study. Twenty treatments were evaluated with 15 sample replicates. Treatments were made up of 4 different soilless growing media, namely: pure silica sand, 50% silica sand with 50% coco-peat, 50% silica sand with 50% vermiculite, and 50% silica sand with 50% perlite. These growing media were tested in conjunction with 5 different fertigation regimes (FR). Plants grown in FR1 received aqueous nutrient solution once every week, FR2 received aqueous nutrient solution once every second week, FR3 received aqueous nutrient solution once every third week, FR4 received aqueous nutrient solution once every fourth week and FR5 received aqueous nutrient solution once every fifth week respectively. Results from this experiment showed that different soilless growing media and fertigation had varying effects on alkaloid concentrations in S. tortuosum. It was also observed that roots contained higher amounts of delta 7 mesembrenone and mesembrenone, while shoots contained higher amounts of the alkaloid mesembrine.
R. J. Faber, “Vegetative Growth and Alkaloid Concentration of Sceletium Tortuosum (L.) N.E. Br. in Response to Different Soilless Growing Media and Fertigation Regimes in Hydroponics,” Thesis, Cape Peninsula University of Technology, 2019.http://etd.cput.ac.za/handle/20.500.11838/3108.
The purpose for this study was to investigate whether Sceletium tortuosum was suitable for cultivation in hydroponics and to determine whether different soilless media and fertigation regimes would have an effect on the vegetative growth and alkaloid concentration of the plant. The experiment was conducted over a period of 6 weeks. Three hundred plants were cultivated from one initial mother plant obtained from Verve Dynamics (Pty) Ltd, Somerset West. Twenty treatments were evaluated with 15 sample replicates. Treatments were made up of 4 different soilless growing media, namely: pure silica sand (SS), 50% silica sand with 50% coco-peat (SC), 50% silica sand with 50% vermiculite (SV), and 50% silica sand with 50% perlite (SP). These growing media were tested in conjunction with 5 different fertigation regimes (FR), plants treated with fertigation regime 1 (FR1) received aqueous nutrient solution once every week, fertigation regime 2 (FR2) received aqueous nutrient solution once every second week, fertigation regime 3 (FR3) received aqueous nutrient solution once every third week, fertigation regime 4 (FR4) received aqueous nutrient solution once every fourth week and fertigation regime 5 (FR5) received aqueous nutrient solution once every fifth week respectively. Chapter 2 reviewed the importance of S. tortuosum and its viability as a Traditional African Medicinal Plant. It was found that S. tortuosum has clear pharmaceutical and economical importance and is one of the only known plants to contain the alkaloids mesembrenone and mesembrine which can be utilized for the promotion of health and treating a variety of psychological disorders such as anxiety and depression. In chapter 3 it was seen that the various treatments had significant effects in terms of plant root growth, shoot growth and dry weight. Treatment SCFR3 showed the highest individual mean value for root growth, while the average from treatments SVFR1-5 displayed the highest average value. The lowest individual value for root growth was observed in treatment SPFR5. Overall treatments with fertigation regime FR3 had better root growth, while fertigation regimes FR5 showed sub-optimal root growth. For shoot growth the highest individual mean value was found in treatment SVFR1, while the highest average value was observed in treatments SCFR1-5. In chapter 4 treatments also had a significant effect on alkaloid concentrations. It was observed that shoot extracts contained a higher concentration of total alkaloids than root extracts, however root extracts had an overall higher amount of delta 7 mesembrenone, and mesembrenone in terms of area %, while shoots had higher amounts of mesembrine. Further the mesembrine standard as mentioned in 4.4.5, shoots clearly have an overall higher concentration of mesembrine than roots. These results suggest that roots of S. tortuosum should be harvested for the purpose of extracting delta 7 mesembrenone and mesembrenone molecules, while the shoots should be harvested for extracting mesembrine. Chapter 5 further investigated the interaction between the vegetative growth and alkaloid concentration of S. tortuosum. There appears to be a clear trend that displays higher concentrations of mesembrine where shoot growth was more optimal, however more optimal growth did not display a higher concentration of total alkaloids. In terms of root growth and total alkaloid concentration, it did not appear that more optimal growth induced higher concentrations of total root alkaloids, meaning reasonable stress on plant root and shoot growth could possibly promote higher concentrations of total alkaloids. It is also clear that overall roots contain more delta 7 mesembrenone and mesembrenone than shoots, suggesting roots should be harvest for extracting these molecules specifically. In most cases high results of delta 7 mesembrenone in roots also had similar amounts of mesembrenone, however certain treatments resulted in higher concentrations of the former and the latter, therefore their similar molecular structure does not always permit similar manifestation in the plant material. Overall this study has found that S. tortuosum is suitable for cultivation in hydroponics, and that soilless media, fertigation regimes as well as soilless media in conjunction with fertigation regimes affected the vegetative growth and alkaloid concentration of S. tortuosum. This research has shown that some soilless media and fertigation regime treatments had more desirable results in terms of vegetative growth and/or alkaloid concentration of the plant.
C. D. Gaffney, “A Study of Mesembryanthemaceae Alkaloids,” Master's thesis, University of Johannesburg, 2006.https://core.ac.uk/display/18214579.
Since prehistoric times medicinal plants have been an invaluable source of medicinal preparations to mankind due to their respective chemical constituents. The family of the Mesembryanthemaceae is almost entirely endemic to southern Africa, and the subfamily Mesembryanthemoideae is a key source of previous reports of plants with traditional uses, both medicinal and culinary. In this thesis, phytochemical investigations were performed on a representative sample of the Mesembryanthemaceae genera and species, with emphasis on the subfamily Mesembryanthemoideae. The aims of this study were to record all ethnobotanical information on the medicinal and culinary uses of the Mesembryanthemaceae, and to isolate and identify alkaloids from selected taxa (especially those of medicinal interest) with specific emphasis on mesembrane alkaloids A review on the structural classification, biosynthesis and biological properties of the mesembrane alkaloids is presented in this dissertation. Experimentally, extracts of the 67 plants encompassing 15 genera and approximately 26 species which were investigated were prepared using one of two alkaloid extraction procedures, following which the extracts were screened for the presence of alkaloids by thin-layer chromatography. The extracts in which alkaloids were detected were analysed further using gas chromatography/mass spectrometry. Where possible, pure alkaloids were isolated from the crude alkaloid extracts and the pure compounds characterised using 1H and 13C nuclear magnetic resonance spectroscopy. Six of the mesembrane alkaloids as well as the tyrosine-derived non-mesembrane alkaloid hordenine were found to be distributed amongst the various genera and species of the Mesembryanthemoideae. The mesembrane alkaloids detected include mesembrine, mesembrenone, mesembrenol, mesembranol, 4’-Omethylsceletenone and 4,5-dihydro-4’-O-methylsceletenone. Within the genus Sceletium mesembrine, mesembrenone, mesembrenol, mesembranol and hordenine were identified. Mesembrine, mesembrenone, mesembranol and hordenine were also detected in Aridaria. The sceletenone derivatives 4’-Omethylsceletenone and 4,5-dihydro-4’-O-methylsceletenone as well as hordenine were identified as the major alkaloid constituents of the genus Aptenia. No alkaloids were detected in the species of Brownanthus and Prenia investigated in this study. Amongst the genera Mesembryanthemum, Phyllobolus and Psilocaulon, a random distribution of the alkaloid hordenine was observed. During the course of this study, the isolation and characterisation of 4’-O-methylsceletenone and 4,5-dihydro-4’-O-methylsceletenone from both Aptenia cordifolia and Aptenia lancifolia, as well as the non-mesembrane alkaloid hordenine from a number of species, was achieved. The two mesembrane alkaloids have been prepared synthetically, but this is the first report of the presence of the compounds in a natural source.
N. Gericke and A. M. Viljoen, “Sceletium—A Review Update,” Journal of Ethnopharmacology, vol. 119, no. 3, pp. 653–663, Oct. 2008.
doi: 10.1016/j.jep.2008.07.043.
It is probable that plants of the genus Sceletium (Mesembryanthemaceae) have been used as masticatories and for the relief of thirst and hunger, to combat fatigue, as medicines, and for social and spiritual purposes by San hunter-gatherers (historically referred to as Bushmen) and Khoi pastoralists (historically referred to as Hottentots) for millennia before the earliest written reports of the uses of these plants by European explorers and settlers. The oral-tradition knowledge of the uses of Sceletium by indigenous peoples has largely been eroded over the last three centuries due to conflicts with settlers, genocidal raids against the San, loss of land, the ravages of introduced diseases, and acculturation. Wild resources of Sceletium have also been severely diminished by over-harvesting, poor veld-management, and possibly also by plant diseases. Sceletium was reviewed almost a decade ago and new results have emerged substantiating some of the traditional uses of one of South Africa’s most coveted botanical assets, and suggesting dietary supplement, phytomedicine and new drug applications. This review aims to collate the fragmented information on past and present uses, the alkaloid chemistry and pharmacological evidence generated on Sceletium.
R. B. Herbert and A. E. Kattah, “The Biosynthesis of Sceletium Alkaloids in Sceletium Subvelutinum: L. Bolus,” Tetrahedron Letters, vol. 30, no. 1, pp. 141–144, Jan. 1989.
doi: 10.1016/S0040-4039(01)80346-4.
Six Sceletium (Mesembrine) alkaloids (1)–(6) are identified, together with N,N-dimethyltyramine (10) as constituents of Sceletium subvelutinum. The alkaloids (1)–(6) incorporate label from radioactive tyramine (8) and 4-hydroxyphenylpropionic acid (12) as expected; notably [3,5-3H]-4-hydroxydihydrocinnamaldehyde [as (13)] is a more efficient alkaloid precursor than the acid (12). Preliminary evidence locates the amine (16) potentially as a key precursor for Sceletium alkaloids; (14) is less efficiently incoporated.
N. T. Jambwa, J. Zhao, A. Viljoen, and I. A. Khan, “Chemical Variation of Sceletium Tortuosum Specimens – NMR Fingerprinting and Chemometric Approach,” Planta Medica, vol. 81, no. 05, p. PA10, Mar. 2015.
doi: 10.1055/s-0035-1545139.
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P. W. Jeffs and J. M. Karle, “Late Stages in the Biosynthesis of Mesembrine: Sceletenone as a Precursor to the Cis-3a-(3,4-Dimethoxyphenyl)Octahydroindole Alkaloids,” Journal of the Chemical Society, Chemical Communications, no. 2, pp. 60–61, Jan. 1977.
doi: 10.1039/C39770000060.
Radiolabelled tracer experiments with sceletenone (2), 4′-O-demethylmesembrenone (4), and mesembrenones (7) and (8) in Sceletium strictum reveal the sequence of reactions involved in the late stages of the biosynthesis of mesembrine (9) and mesembrenol (5).
P. W. Jeffs, W. C. Archie, R. L. Hawks, and D. S. Farrier, “Sceletium Alkaloids. IV. Biosynthesis of Mesembrine and Related Alkaloids. Amino Acid Precursors,” Journal of the American Chemical Society, vol. 93, no. 15, pp. 3752–3758, Jul. 1971.
doi: 10.1021/ja00744a032.
Z. Jin and G. Yao, “Amaryllidaceae and Sceletium Alkaloids,” Natural Product Reports, vol. 36, no. 10, pp. 1462–1488, 2019.
doi: 10.1039/C8NP00055G.
Covering: July 2015 to June 2017. Previous review: Nat. Prod. Rep., 2016, 33, 1318–1343 Recent progress on the isolation, identification, biological activity and synthetic studies of the structurally diverse alkaloids from plants of family Amaryllidaceae has been summarized in this review. In addition, the structurally related alkaloids isolated from Sceletium species are discussed.
C. Klak and P. V. Bruyns, “A New Infrageneric Classification for Mesembryanthemum (Aizoaceae: Mesembryanthemoideae),” Bothalia, vol. 43, no. 2, pp. 197–206, Jan. 2013.
doi: 10.4102/abc.v43i2.95.
We present a new infrageneric classification for Mesembryanthemum L. (Aizoaceae: Mesembryanthemoideae), based on a phylogeny of the genus published in 2007. We re-affirm that a broad generic circumscription for Mesembryanthemum (including all 103 species of the Mesembryanthemoideae) is the only group in the subfamily that can be recognized unambiguously by synapomorphies. We divide Mesembryanthemum into five subgenera, of which two are new: M. subg. Mesembryanthemum , M. subg. Cryophytum (N.E. Br.) Bittrich, M. subg. Opophytum (N.E. Br.) Bittrich, M. subg. Phyllobolus (N.E. Br.) Klak and M. subg. Volkeranthus (Gerbaulet) Klak. Furthermore, we recognize five sections in subg. Mesembryanthemum , six sections in subg. Phyllobolus and two sections in M. subg. Cryophytum . Descriptions and keys to all infrageneric taxa are provided.
C. Klak, P. V. Bruyns, and T. A. J. Hedderson, “A Phylogeny and New Classification for Mesembryanthemoideae (Aizoaceae),” TAXON, vol. 56, no. 3, pp. 737–756, 2007.
doi: 10.2307/25065857.
We present a phylogeny for Mesembryanthemoideae (Aizoaceae) based on sampling of nearly all species and subspecies of the subfamily and analysis of cptrnL-F, rbcL-atpB, rps16, nrITS1 and morphology. The larger genera Phyllobolus and Mesembryanthemum are not monophyletic. Although some clades can be circumscribed with morphological (often homoplasious) synapomorphies, several clades are impossible to characterise morphologically. We recognise a single genus, Mesembryanthemum, in Mesembryanthemoideae. The genera Aptenia, Aridaria, Aspazoma, Brownanthus, Caulipsolon, Dactylopsis, Phyllobolus, Prenia, Psilocaulon, Sceletium, and Synaptophyllum are reduced to synonymy. Mesembryanthemum, which now consists of 101 species without recognised sections, can be distinguished by several uniquely derived morphological characters. Mesembryanthemum longipapillosum, which had recently been reduced to synonymy, is reinstated.
J. L. Krstenansky, “Mesembrine Alkaloids: Review of Their Occurrence, Chemistry, and Pharmacology,” Journal of Ethnopharmacology, vol. 195, pp. 10–19, Jan. 2017.
doi: 10.1016/j.jep.2016.12.004.
Ethnopharmacological relevance Mesembrine alkaloids are considered to be the primary active constituents of the South African medicinal plant Sceletium tortuosum (L.) N.E.Br. (Aizoaceae), and it is used as the dried or fermented aerial material from the plant, which is known as kanna (aka, channa, kougoed). Traditional regional use ranged from relieving thirst, mild analgesia, and alteration of mood. Current interest has focused primarily on the antidepressant action of preparations based on the plant and commercialization is expanding the recognition and availability of these preparations. Materials and methods Searches for the keywords “Sceletium or mesembrine” were performed in “PubMed-NCBI”, “Chemical Abstracts SciFinder” and “Thomson Reuters Web of Science” databases in addition to the inclusion of references cited within prior reviews and scientific reports. Additionally the “SciFinder” database was searched using 3a-phenyl-cis-octahydroindole in the SciFinder Substructure Module (SSM). Plant taxonomy was validated by the database “The Plant List”. Results This review focuses on the chemistry, analysis, and pharmacology of the mesembrine alkaloids. Despite a long history of medicinal used and research investigation, there has been a renewed interest in the pharmacological properties of the mesembrine alkaloids and much of the pharmacology has only recently been published. The two major active alkaloids mesembrine and mesembrenone are still in the process of being more fully characterized pharmacologically. They are serotonin reuptake inhibitors, which provides a rationale for the plant’s traditional use as an antidepressant, but other actions are beginning to appear in the literature. Additionally, mesembrenone has reasonably potent PDE4 inhibitory activity. This review intends to provide an overview of the available literature, summarize the current findings, and put them in perspective with earlier studies and reviews.
F. Makolo, A. Viljoen, and C. G. L. Veale, “Mesembrine: The Archetypal Psycho-Active Sceletium Alkaloid,” Phytochemistry, vol. 166, p. 112061, Oct. 2019.
doi: 10.1016/j.phytochem.2019.112061.
(−)-Mesembrine is a chiral alkaloid that features an aryloctahydroindole skeleton and is most commonly found in species of the succulent genus Sceletium. Several Sceletium species are used by various ethnic groups in South Africa to manage disorders of the central nervous system. Binding assays have revealed that mesembrine is a more potent inhibitor of the serotonin transporter (SERT) than fluoxetine (Prozac) which has prompted the commercialization of mesembrine-containing consumer products. The congested all carbon quaternary stereocenter present at the bridgehead of mesembrine has rendered it a compound of interest for research in synthetic chemistry, which has assisted in the absolute configuration of the naturally occurring isomer to be assigned. Accordingly, this review will cover the recent literature pertaining to the distribution, structural elucidation, chemotaxonomy, biosynthesis, organic synthesis, as well as the biological activities of (−)-mesembrine. Recent synthetic procedures of the non-natural enantiomer as well as the racemate are also considered.
M. C. Manganyi, T. Regnier, C.-D. K. Tchatchouang, C. C. Bezuidenhout, and C. N. Ateba, “Antibacterial Activity of Endophytic Fungi Isolated from Sceletium Tortuosum L. (Kougoed),” Annals of Microbiology, vol. 69, no. 6, pp. 659–663, Jun. 2019.
doi: 10.1007/s13213-019-1444-5.
Endophytic fungi have the ability to co-exist with their host plants without causing any harm and are beneficial to both the plant and the fungi. The current study determined the antimicrobial properties and identify the chemical compounds of secondary metabolites produced by endophytic fungi isolated from Sceletium tortuosum L. A total of 60 endophytic fungi produced secondary metabolites that were detected after fermentation and extraction. Antibacterial properties of the secondary metabolites were determined using the disc diffusion assay against pathogenic environmental Gram-positive and Gram-negative bacteria as well as control stains. The chemical compounds were characterized by GC-MS. Overall, 15% of fungal extracts displayed narrow spectrum of activity against the bacteria strains. Despite this, none of the fungal extracts inhibited growth of Enterococcus faecalis (ATCC S1299) and Enterococcus gallinarum (ATCC 700425) while Bacillus cereus (ATCC 10876) was the most susceptible against the fungal extracts. Fusarium oxysporum (GG 008) with accession no. KJ774041.1 displayed significant antibacterial activity that was linked to high levels of 5-hydroxymethylfurfural (HMF) and octadecanoic acid as revealed by GC-MS. This study revealed the presence of bioactive secondary metabolites with antibacterial activities from fungi isolated from Sceletium tortuosum L.
M. C. Manganyi, T. Regnier, A. Kumar, C. C. Bezuidenhout, and C. N. Ateba, “Phylogenetic Analysis and Diversity of Novel Endophytic Fungi Isolated from Medicinal Plant Sceletium Tortuosum,” Phytochemistry Letters, vol. 27, pp. 36–43, Oct. 2018.
doi: 10.1016/j.phytol.2018.06.004.
Throughout history, mankind has used plants as their primary source of sustainability, in agricultural commodities, clothing, fragrances, fertilizers, flavours, and providing shelter. There is a strong symbiotic relationship between the plant and its endophytes. Endophytes are harboured within the living plant tissues without causing neither diseases nor symptoms. They produce bioactive compounds that protect the host plants against attack of insects, pathogens and herbivores. The bioactive compounds might be utilized for pharmaceutical, agricultural, or biotechnological applications.This paper reported on the various endophytic fungi strains that were isolated from isolated from a medicinal plant, Sceletium tortuosum. Fifty Sceletium tortuosum plants were collected from three different provinces in South Africa and leaves and roots used to isolate culturable endophytes. Morphological characteristics and a genus specific PCR designed to amplify fungal internal transcribe spacer (ITS) region (ITS1 and ITS4) and elongation factor (EF 1 and 2) was used for identification. A total of 60 fungal isolates belonging to 16 genera were identified and classified. Isolates were identified to species level based on similarities with known sequences in GenBank and a large proportion of the fungi were Fusarium species (37%) followed Aspergillus (25%) and Penicillium (7%) species. Phylogenetic analysis was performed using nuclear ribosomal DNA sequences and three potentially new isolates (DR 019 Fusarium penzigii, DR 010 Phomopsis columnaris, DR 007 Fusarium oxysporum f. sp. lycopersici) were identified in the phylogenic tree that was constructed. Our results offers basic data on the symbiotic/or mutualistic relationship between the medicinal plant Sceletium tortuosum and its endophytic fungi, as well as novel species.
T. L. Olatunji et al., “Sceletium Tortuosum: A Review on Its Phytochemistry, Pharmacokinetics, Biological and Clinical Activities,” Journal of Ethnopharmacology, vol. 280, p. 114476, Nov. 2021.
doi: 10.1016/j.jep.2021.114476.
Ethnopharmacological relevance 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. Conclusion As an important South African medicinal plant, S. tortuosum has garnered many research advances on its phytochemistry and biological activities over the last decade. These scientific studies have shown that S. tortuosum has various bioactivities. The findings have further established the link between the phytochemistry and pharmacological application, and support the traditional use of S. tortuosum in the indigenous medicine of South Africa.
S. Patnala and I. Kanfer, “Chemotaxonomic Studies of Mesembrine-Type Alkaloids in Sceletium Plant Species : Research Article,” South African Journal of Science, vol. 109, no. 3, pp. 1–5, Mar. 2013.
doi: 10.10520/EJC133140.
Complementary medicines containing the succulent herb Sceletium are being sold without information regarding their phytochemical contents, which is essential for the quality control of medicines. Furthermore, several different Sceletium species exist and little has been reported on the alkaloidal identities and contents of the various species. We therefore conducted phytochemical investigations on six selected Sceletium specimens, identified on the basis of their venation pattern as either ’emarcidum’ or ’tortuosum’ type. The tortuosum type consisted of S. tortuosum, S. expansum and S. strictum, whereas the emarcidum type consisted of S. emarcidum, S. exalatum and S. rigidum. Analysis was conducted by high-performance liquid chromatography with UV and alkaloids were identified by online mass spectroscopy. S. tortuosum and S. expansum samples contained mesembrine together with mesembrenone, mesembranol and epimesembranol, although the latter two alkaloids were present in low concentrations in S. expansum. S. strictum contained mesembrenone, mesembrine and either 4’-O-demethylmesembrenone or 4’-O-demethylmesembrenol. The emarcidum type specimens showed a complete absence of the major alkaloid mesembrine, as well as the other alkaloids usually associated with these species. In only one of the species of the emarcidum type - S. exalatum - two peaks corresponded to either 4’-O-demethylmesembrenone or O-methyljoubertiamine and either 4’-O-demethylmesembrenol or N-demethylmesembrenol, respectively. This study clearly indicates that not all Sceletium species contain the mesembrine-type alkaloids usually associated with Sceletium. It is thus important to identify the correct Sceletium species to ensure correct alkaloidal content for the manufacture and quality control of products containing this plant material.
S. Patnala and I. Kanfer, “Investigations of the Phytochemical Content of Sceletium Tortuosum Following the Preparation of ‘Kougoed’ by Fermentation of Plant Material,” Journal of Ethnopharmacology, vol. 121, no. 1, pp. 86–91, Jan. 2009.
doi: 10.1016/j.jep.2008.10.008.
Aim of the study Sceletium plant species that contain alkaloids are claimed to have mood elevation and anti-anxiety properties, especially after the plant material has been fermented. The fermented preparation is locally known as “kougoed” or “channa” and has been emphasized and advertised for its increased potency when incorporated in commercial products. The aim of the study was to investigate quantitative and qualitative changes in alkaloidal content following fermentation of plant samples carried out under controlled conditions and also on pure mesembrine hydrochloride (MHCl). Materials and methods Samples were prepared from the aerial parts of Sceletium tortuosum. Studies were also conducted on mesembrine hydrochloride (MHCl) in aqueous and methanolic solutions under similar conditions of exposure to sunlight as well as under ambient and elevated temperature (40±2°C). Quantitative and qualitative changes in alkaloidal content were monitored by HPLC and LC–MS, respectively. Results and Conclusions The initial fermentation study showed transformation of mesembrine to Δ7mesembrenone, where the content of the former decreased from a concentration of 1.33% to 0.05% whilst the latter increased from below its limit of quantitation (LoQ) to 0.11% on the 10th day. The experiments on pure MHCl revealed similar transformations in aqueous solutions whereas no change was seen in methanolic solutions. Sunlight and aqueous conditions appear necessary to facilitate the transformation, which was confirmed by the absence of such a transformation when solutions of MHCl were kept in the dark.
S. Patnala and I. Kanfer, Sceletium Plant Species: Alkaloidal Components, Chemistry and Ethnopharmacology. IntechOpen, 2017.
doi: 10.5772/66482.
The genus Sceletium, classified under the Aizoaceae family, is indigenous to the Western, Eastern and Northern Cape province of South Africa. There are currently eight reported species divided into tw
E. A. Shikanga, A. M. Viljoen, S. Combrinck, A. Marston, and N. Gericke, “The Chemotypic Variation of Sceletium Tortuosum Alkaloids and Commercial Product Formulations,” Biochemical Systematics and Ecology, vol. 44, pp. 364–373, Oct. 2012.
doi: 10.1016/j.bse.2012.06.025.
Commercial production and trade in Sceletium tortuosum and its products is on the rise due to an increase in consumer demand. Mesembrine-type alkaloids are the main active compounds responsible for the therapeutic properties of the plant. In this investigation, GC–MS was used to evaluate the variability in the mesembrine-type alkaloid content of 151 specimens of S. tortuosum growing wild in 31 localities in the south-western region of South Africa. In addition, the variability of the mesembrine-type alkaloid content of eight commercial products was determined. The total alkaloid content of wild plant material was found to vary between 0.11 and 1.99% of dry weight. Hierarchical cluster analysis and principal component analysis grouped the plants growing in the wild into five main chemotypes (A, B, C, D and E). Chemotype A is represented by samples devoid of mesembrine-type alkaloids, while chemotypes B, C and E are characterised by high levels of mesembrenol (64.96–95.55%), mesembrine (51.25–92.50%) and mesembrenone (50.86–72.51%), respectively. Chemotype D is an intermediate cluster representing specimens containing all four alkaloids in moderate amounts. Qualitative differences in the alkaloid profiles were observed between and within different populations of S. tortuosum, as well as among the investigated products. Mesembrine was identified as the main alkaloid constituent in most of the commercial products analysed. Mesembrenol, mesembrine and mesembrenone can be used as marker compounds for quality monitoring of S. tortuosum raw materials and products.
E. A. Shikanga, A. M. Viljoen, I. Vermaak, and S. Combrinck, “A Novel Approach in Herbal Quality Control Using Hyperspectral Imaging: Discriminating Between Sceletium Tortuosum and Sceletium Crassicaule,” Phytochemical Analysis, vol. 24, no. 6, pp. 550–555, 2013.
doi: 10.1002/pca.2431.
A. Sishuba, J. Leboko, C. N. Ateba, and M. C. Manganyi, “First Report: Diversity of Endophytic Fungi Possessing Antifungal Activity Isolated from Native Kougoed (Sceletium Tortuosum L.),” Mycobiology, vol. 49, no. 1, pp. 89–94, Jan. 2021.
doi: 10.1080/12298093.2020.1857009.
Forty-three (n = 43) endophytic fungi with different morphologic characteristics were from a medicinal plant Sceletium tortuosum, were utilized to investigate their antifungal effectiveness against pathogenic fungi. All fungal isolates exhibited antifungal activity against one or more pathogens in the dual culture test whereas only 33 fungal culture filtrates (77%) showed decent antifungal effect. Fusaria and Aspergillus were the dominate genus that displayed significant antifungal activity. Isolates GG02, GG09, ND15, and ND17 showed the broadest spectrum of antifungal activity. Furthermore, culture filtrate of Fusarium sp. DR08 exhibited a broad range of antifungal activity against all the pathogens. The results suggest endophytic fungi isolated from medicinal plant might be a source of novel bioactive molecules. To the best our knowledge, this is the first report on endophytic fungi isolated from native kougoed exhibiting antifungal activity against plant fungal pathogens.
M. T. Smith, C. R. Field, N. R. Crouch, and M. Hirst, “The Distribution of Mesembrine Alkaloids in Selected Taxa of the Mesembryanthemaceae and Their Modification in the Sceletium Derived ‘Kougoed,’” Pharmaceutical Biology, vol. 36, no. 3, pp. 173–179, Jan. 1998.
doi: 10.1076/phbi.36.3.173.6350.
Twenty species from nine genera of the Mesembryanthemaceae (Aptenia, Bergeranthus, Delosperma, Drosanthemum, Glottiphyllum, Lampranthus, Oscularia, Ruschia, and Sceletium) as well as the reportedly psychoactive preparation ‘kougoed’, prepared from ‘fermenting’ Sceletium tortuosum, were screened for the presence of the mesembrine alkaloids. Using gas chromatography (GC) with a nitrogen-phosphorous detector (NPD) three putative alkaloids were detected in Sceletium tortuosum whose mass spectra corresponded to those of 4’- O -demethylmesembrenol, mesembrine and mesembrenone. All the Mesembryanthemaceae plants investigated were shown to have Dragendorff-positive compounds on thin layer chromatograms (TLC); those containing mesembrine alkloids, as shown by later GC MS analysis, exhibited similar Rf values to the Sceletium alkaloids. However, using the technique employed in this study which encompassed the use of column and gas chromatography, the only genus containing mesembrine alkaloids to any significant extent was Aptenia. Alkaloid levels were found to be extremely low in all other taxa investigated. When a ‘modern’ technique for the preparation of a fermented Sceletium product, ‘kougoed’, was carried out it was found that levels, as well as the ratios, of the three alkaloids changed markedly. Substantial increases in total alkaloid levels were observed when the Sceletium material was crushed and bruised prior to drying for alkaloid extraction whereas no such changes occured when intact plants were oven dried at 80°C prior to alkaloid extraction. It is speculated that of the many potentially usable Mesembryanthemaceae plants available to the indigenous peoples, Sceletium was selected because it is the only genus with alkaloid levels high enough to elicit a psychoactive response. The traditional preparation technique also appears to have evolved as a method of producing a dry, stable, and relatively palatable preparation of increased pharmacological activity.
A. Sreekissoon, J. F. Finnie, and J. Van Staden, “Effects of Smoke Water on Germination, Seedling Vigour and Growth of Sceletium Tortuosum,” South African Journal of Botany, vol. 139, pp. 427–431, Jul. 2021.
doi: 10.1016/j.sajb.2021.01.025.
Sceletium tortuosum (L.) N. E. Br. is a South African protected species widely utilized in traditional medicine. The plants’ mesembrine-type alkaloids have immense potential in modern pharmacology as treatments for numerous medical and psychological disorders. Fresh plant material is paramount for researchers and pharmaceutical companies as it is presently the only available alkaloid source. Although S. tortuosum is a conservation concern and valuable to the pharmaceutical industry, information on germination behaviours of this species is scant. This study highlights the effects of the bio-stimulant smoke water (SW) on germination, seedling vigour and growth of Sceletium tortuosum in vitro. A standardized smoke extract was diluted to concentrations of 1:500, 1:1000, 1:1500, 1:2000, 1:2500 (v/v). Seeds were pulse-treated with SW solutions for 1, 2, 8 and 24 h. The study included positive and negative control treatments. The highest mean germination percentage and germination rate were recorded for 1:1000 SW for 24 h (83 ± 1.9%) and 1:2500 SW for 24 h (6.35 seeds germinated/day). Vigour index was highest for 1:1000 SW (24 h). Smoke water only improved seedling growth when germination occurred slowly. Although mean shoot length was optimal for 1:2500 (1 h) – 4.19 ± 0.15 mm – mean root length and seedling size were highest in the negative and positive (1 h) control treatments. This investigation showed that SW effectively improved germination and seedling vigour of S. tortuosum, however, alternatives must be investigated to optimize seedling growth when this biostimulant is applied.
A. Sreekissoon, L. Plačková, K. Doležal, J. F. Finnie, and J. Van Staden, “In Vitro and Ex Vivo Vegetative Propagation and Cytokinin Profiles of Sceletium Tortuosum (L.) N. E. Br.: A South African Medicinal Plant,” Plant Cell, Tissue and Organ Culture (PCTOC), vol. 145, no. 1, pp. 191–202, Apr. 2021.
doi: 10.1007/s11240-020-02001-2.
Sceletium tortuosum is a South African protected species with tremendous value in traditional and modern medicine. The plants’ mesembrine-type alkaloids are potential therapeutics for a plethora of psychological, neurological and inflammatory disorders. In our in vitro and ex vivo studies, vegetative propagation and growth of this species were investigated. Cytokinin (CK) profiles were also explored. Shoot multiplication was induced on Murashige and Skoog (MS) medium supplemented with 2.5 µM indole-3-butyric acid (IBA). In vitro-generated shoots were inoculated on MS medium supplemented with 0, 2.5, 5.0 and 10.0 µM IBA or indole-3-acetic acid (IAA). Optimal rooting (55%), mean number of roots (3.80\,± 0.83) and new leaf pairs (4.65\,± 0.67) were achieved by 10.0 µM IBA. After greenhouse acclimatization, 45–90% of plantlets survived. All ex vivo shoot cuttings rooted well (90–100%). The highest mean number of roots (11.20\,± 1.37) and root length (57.18\,± 3.85 mm) were obtained by 5.0 µM IBA. Although spontaneous rooting was observed in both experiments, auxins enhanced multiple growth parameters. Cytokinin analyses of tissue-cultured (auxin-treated) and greenhouse (untreated) plants revealed higher cytokinin levels in vitro. These investigations provide rapid and efficient propagation techniques for Sceletium tortuosum which will be valuable to conservationists and pharmaceutical companies.
J. Zhao, I. A. Khan, S. Combrinck, M. Sandasi, W. Chen, and A. M. Viljoen, “1H-NMR and UPLC-MS Metabolomics: Functional Tools for Exploring Chemotypic Variation in Sceletium Tortuosum from Two Provinces in South Africa,” Phytochemistry, vol. 152, pp. 191–203, Aug. 2018.
doi: 10.1016/j.phytochem.2018.03.013.
Sceletium tortuosum (Aizoaceae) is widely recognised for the treatment of stress, anxiety and depression, as well as for obsessive compulsive disorders. A comprehensive intraspecies chemotypic variation study, using samples harvested from two distinct regions of South Africa, was done using both proton nuclear magnetic resonance (1H-NMR) spectroscopy of methanol extracts (N\,= 145) and ultra performance liquid chromatography-mass spectrometry (UPLC-MS) of acid/base extracts (N\,= 289). Chemometric analysis of the 1H-NMR data indicated two main clusters that were region-specific (Northern Cape and Western Cape provinces). Two dimensional (2D) NMR was used to identify analytes that contributed to the clustering as revealed by the S-plot. The sceletium alkaloids, pinitol and two alkylamines, herein reported for the first time from S. tortuosum, were identified as markers that distinguished the two groups. Relative quantification of the marker analytes conducted by qNMR indicated that samples from the Northern Cape generally contained higher concentrations of all the markers than samples from the Western Cape. Quantitative analysis of the four mesembrine alkaloids using a validated UPLC-photo diode array (PDA) detection method confirmed the results of qNMR with regard to the total alkaloid concentrations. Samples from the Northern Cape Province were found to contain, on average, very high total alkaloids, ranging from 4938.0 to 9376.8 mg/kg dry w. Regarding the Western Cape samples, the total yields of the four mesembrine alkaloids were substantially lower (averages 16.4–4143.2 mg/kg). Hierarchical cluster analysis of the UPLC-MS data, based on the alkaloid chemistry, revealed three branches, with one branch comprising samples primarily from the Northern Cape that seemed somewhat chemically conserved, while the other two branches represented mainly samples from the Western Cape. The construction of an orthogonal projections to latent structures-discriminant analysis model and subsequent loadings plot, allowed alkaloid markers to be identified for each cluster. The diverse sceletium alkaloid chemistry of samples from the three clusters may facilitate the recognition of alkaloid profiles, rather than individual compounds, that exert targeted effects on various brain receptors involved in stress, anxiety or depression.