ArticleLiterature Review

Sceletium-A review update

Authors:
To read the full-text of this research, you can request a copy directly from the authors.

Abstract

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.

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the authors.

... Sceletium tortuosum) (L.) N.E.Br. has well-documented medicinal activity and ethnopharmacology (Smith et al., 1998;Gericke and Viljoen, 2008) and is thus the most popular from the Sceletium genus (Family: Aizoaceae, subfamily: Mesembryanthemoideae). S. tortuosum is also referred to as kanna, channa, kougoed, or 'sceletium' (Smith et al., 1998). ...
... The seeds of Sceletium species are brown to black kidney-shaped, and these are small in diameter ranging from 1 mm to 2 mm ( Figure 1F). The plant is indigenous to southern Africa where it has been traditionally used in folk medicine by the Khoekhoen and San (Khoe-San/KhoiSan) people as a masticatory agent or as a mood elevator (Gericke and Viljoen, 2008). More recently, S. tortuosum has been commercialised as an antidepressant or anxiolytic and it is also recommended for attention-deficit disorders, as it aids in mental alertness (Harvey et al., 2011). ...
... Thus far, there have been several comprehensive reviews based on the chemistry of alkaloids found in Sceletium (Jeffs et al., 1982;Lewis, 1995;Jin, 2016;Jin and Yao, 2019). Although this list may not necessarily be comprehensive as it is based on a Scopus database search, other reviews that focus on Sceletium and its phytochemistry and pharmacology include the work of Gericke and Viljoen (2008); Stafford et al. (2008); Van Wyk (2011); Van Wyk (2015); Krstenansky (2017); Makolo et al. (2019), and Faro et al. (2020). These reviews discuss 1) the ethnobotanical history and chemical diversity in the genus (Smith et al., 1998); 2) the pharmacological and chemical evidence of ethnobotanical use in Sceletium (Gericke and Viljoen, 2008); 3) plants from South Africa with CNS effects used for mental health purposes (Stafford et al., 2008); 4) the commercial potential of medicinal plants in South Africa (Van Wyk, 2011, 2015; 5) the occurrence, chemistry, and pharmacology of mesembrine alkaloids (Krstenansky, 2017); 6) the distribution, structural elucidation, biosynthesis, organic synthesis, chemotaxonomy, and biological activities of (−)-mesembrine from Sceletium species (Makolo et al., 2019); and 7) the biomedical activities of new psychoactive substances from natural origins (Faro et al., 2020). ...
Article
Full-text available
Plants from the Sceletium genus (Aizoaceae) have been traditionally used for millennia by the Khoe and Khoen people in southern Africa, as an appetite suppressant as well as a mood elevator. In more recent times, this mood-elevating activity has been commercialised in the South African natural products industry for the treatment of anxiety and depression, with several products available both locally and abroad. Research on this species has seen rapid growth with advancements in analytical and pharmacological tools, in an effort to understand the composition and biological activity. The Web of Science (WoS) database was searched for articles related to ‘Sceletium’ and ‘Mesembrine’. These data were additionally analysed by bibliometric software (VOSviewer) to generate term maps and author associations. The thematic areas with the most citations were South African Traditional Medicine for mental health (110) and anxiolytic agents (75). Pioneer studies in the genus focused on chemical structural isolation, purification, and characterisation and techniques such as thin layer chromatography, liquid chromatography (HPLC, UPLC, and more recently, LC-MS), gas chromatography mass spectrometry (GC-MS), and nuclear magnetic resonance (NMR) to study mesembrine alkaloids. Different laboratories have used a diverse range of extraction and preanalytical methods that became routinely favoured in the analysis of the main metabolites (mesembrine, mesembranol, mesembranone, and Sceletium A4) in their respective experimental settings. In contrast with previous reviews, this paper identified gaps in the research field, being a lack of toxicology assays, a deficit of clinical assessments, too few bioavailability studies, and little to no investigation into the minor alkaloid groups found in Sceletium. Future studies are likely to see innovations in analytical techniques like leaf spray mass spectrometry and direct analysis in real-time ionisation coupled with high-resolution time-of-flight mass spectrometry (DART-HR-TOF-MS) for rapid alkaloid identification and quality control purposes. While S. tortuosum has been the primary focus, studying other Sceletium species may aid in establishing chemotaxonomic relationships and addressing challenges with species misidentification. This research can benefit the nutraceutical industry and conservation efforts for the entire genus. At present, little to no pharmacological information is available in terms of the molecular physiological effects of mesembrine alkaloids in medical clinical settings. Research in these fields is expected to increase due to the growing interest in S. tortuosum as a herbal supplement and the potential development of mesembrine alkaloids into pharmaceutical drugs.
... The use of Sceletium-type alkaloids mesembrine and mesembrenone in pharmaceutical formulations has been disclosed in US Patent 6288,104 and WO2010106494 [7] for the management of depression, anxiety, drug dependence, bulimia, and obsessive-compulsive disorder. Their anxiolytic and antidepressant activities are attributed to their potent inhibitory effects on the serotonin transporter (SERT) and phosphodiesterase 4 (PDE-4) [8,9]. Mesembrine is a more potent SERT inhibitor than fluoxetine (Prozac) [8]. ...
... Their anxiolytic and antidepressant activities are attributed to their potent inhibitory effects on the serotonin transporter (SERT) and phosphodiesterase 4 (PDE-4) [8,9]. Mesembrine is a more potent SERT inhibitor than fluoxetine (Prozac) [8]. ...
... In sprouting bulbs (Phase 2), the alkaloid pattern of roots was dominated by pretazettine (12), followed by lycorine (8), sanguinine (7), and of 6-epi-mesembrenol (2). No alkaloids of haemanthamine type and galanthamine (6) were detected. ...
Article
The Sceletium -type alkaloids, known for their anxiolytic and antidepressant activities, have been recently found to be biosynthesized in Narcissus cv. Hawera, which is largely used as an ornamental plant. An alkaloid fraction enriched with Sceletium -type alkaloids from the plant has shown promising antidepressant and anxiolytic activities. In the present study, qualitative and quantitative analyses of the alkaloids in the plant organs were performed during one vegetation season by GC-MS. The alkaloid pattern and total alkaloid content was found to depend strongly on the stage of development and plant organ. The alkaloid content of bulbs was found to be highest during the dormancy period and lowest in sprouting bulbs. The leaves showed the highest alkaloid content during the intensive vegetative growth and lowest during flowering. In total, 13 alkaloids were detected in the methanol extracts of Narcissus cv. Hawera, six Sceletium -type and seven typical Amaryllidaceae alkaloids. Major alkaloids in the alkaloid pattern were lycorine, 6- epi -mesembrenol, mesembrenone, sanguinine, and galanthamine. The leaves of flowering plants were found to have the highest amount of 6- epi -mesembrenol. Mesembrenone was found to be dominant alkaloid in the leaves of sprouting bulbs and in the flowers. Considering the biomass of the plant, the dormant bulbs are the best source of alkaloid fractions enriched with 6- epi -mesembrenol. The flowers and the young leaves can be used for preparation of alkaloid fractions enriched with mesembrenone. The results indicates that Narcissus cv. Hawera is an emerging source of valuable bioactive compounds and its utilization can be extended as a medicinal plant.
... Sceletium tortuosum) (L.) N.E.Br. has well-documented medicinal activity and ethnopharmacology (Smith et al., 1998;Gericke and Viljoen, 2008) and is thus the most popular from the Sceletium genus (Family: Aizoaceae, subfamily: Mesembryanthemoideae). S. tortuosum is also referred to as kanna, channa, kougoed, or 'sceletium' (Smith et al., 1998). ...
... The seeds of Sceletium species are brown to black kidney-shaped, and these are small in diameter ranging from 1 mm to 2 mm ( Figure 1F). The plant is indigenous to southern Africa where it has been traditionally used in folk medicine by the Khoekhoen and San (Khoe-San/KhoiSan) people as a masticatory agent or as a mood elevator (Gericke and Viljoen, 2008). More recently, S. tortuosum has been commercialised as an antidepressant or anxiolytic and it is also recommended for attention-deficit disorders, as it aids in mental alertness (Harvey et al., 2011). ...
... Thus far, there have been several comprehensive reviews based on the chemistry of alkaloids found in Sceletium (Jeffs et al., 1982;Lewis, 1995;Jin, 2016;Jin and Yao, 2019). Although this list may not necessarily be comprehensive as it is based on a Scopus database search, other reviews that focus on Sceletium and its phytochemistry and pharmacology include the work of Gericke and Viljoen (2008); Stafford et al. (2008); Van Wyk (2011); Van Wyk (2015); Krstenansky (2017); Makolo et al. (2019), and Faro et al. (2020). These reviews discuss 1) the ethnobotanical history and chemical diversity in the genus (Smith et al., 1998); 2) the pharmacological and chemical evidence of ethnobotanical use in Sceletium (Gericke and Viljoen, 2008); 3) plants from South Africa with CNS effects used for mental health purposes (Stafford et al., 2008); 4) the commercial potential of medicinal plants in South Africa (Van Wyk, 2011, 2015; 5) the occurrence, chemistry, and pharmacology of mesembrine alkaloids (Krstenansky, 2017); 6) the distribution, structural elucidation, biosynthesis, organic synthesis, chemotaxonomy, and biological activities of (−)-mesembrine from Sceletium species (Makolo et al., 2019); and 7) the biomedical activities of new psychoactive substances from natural origins (Faro et al., 2020). ...
Preprint
Plants from the Sceletium genus (Aizoaceae) have been traditionally used by the Khoe-Sān people in southern Africa, mainly for thirst and hunger relief, pain reduction and spiritual purposes, particularly Sceletium tortuosum . The research on this species has seen rapid growth with advancements in analytical and pharmacological tools. The Web of Science (WoS) database was searched for articles related to ‘Sceletium’ and ‘Mesembrine’. These data were additionally analysed by bibliometric software (VOSviewer) to generate term maps and author associations. The thematic areas with the most citations were, South African Traditional Medicine for mental health (110) and anxiolytic agents (75). Pioneer studies in the genus focused on chemical structural isolation, purification and characterization and techniques such as thin layer chromatography, liquid chromatography (HPLC, UPLC and more recently, LC-MS), gas chromatography mass spectrometry (GC-MS) and nuclear magnetic resonance (NMR) to study mesembrine alkaloids. Different laboratories have used a diverse range of extraction and pre-analytical methods that become routinely favoured in the analysis of the main metabolites (mesembrine, mesembranol, mesembranone and Sceletium A4) in their respective experimental settings. In contrast with previous reviews, this paper identified gaps in the research field, being a lack of toxicology assays, a deficit of clinical assessments, too few bioavailability studies and little to no investigation into the minor alkaloid groups found in Sceletium . Future studies are likely to see innovations in analytical techniques like leaf spray mass spectrometry and direct analysis in real-time ionization coupled with high-resolution time-of-flight mass spectrometry (DART-HR-TOF-MS) for rapid alkaloid identification and quality control purposes. While S. tortuosum has been the primary focus, studying other Sceletium species may aid in establishing chemotaxonomic relationships and addressing challenges with species misidentification. This research can benefit the nutraceutical industry and conservation efforts for the entire genus. At present, little to no pharmacological information is available in terms of the molecular physiological effects of mesembrine alkaloids in medical clinical settings. Research in these fields is expected to increase due to the growing interest in S. tortuosum as a herbal supplement and the potential development of mesembrine alkaloids into pharmaceutical drugs.
... Of the eight species in the genus, only S. tortuosum (commonly known as "kougoed", "kanna" or "channa") is used in the emergent phytopharmaceutics industries in South Africa and this use stems from the ethnobotany of the Khoi-San. The plant has been administered in a dried or fermented form for traditional uses ranging from pain and thirst relief to mood elevation (1). The mood-elevating activity of S. tortuosum has been attributed to the mesembrine alkaloids (particularly mesembrine and mesembrenone), acting as serotonin reuptake inhibitors (2), amongst other observed activities. ...
... With this in mind, we chose to also explore molecular networking as a dereplication tool. Metabolomics paired with molecular networking may assist in distinguishing populations from each other with a great deal of phytochemical detail, especially where the chemistry is still largely unresolved (1). The feature identification capabilities of molecular networking act as a dereplication tool through identifying coeluting isobaric compounds and reducing redundancy by identifying isomers across samples from MS 2 fragmentation patterns (14). ...
... This is the first evidence put forward that minor alkaloids may be responsible for neurological activity observed in vitro. Current reports where isolated extracts have negligible activity as compared to extracts may suggest other phytochemicals responsible for the mood-elevation and cognitive enhancement activity in Sceletium (1,22). Further in vitro and in vivo studies would have to be conducted on isolated metabolites to corroborate these findings. ...
Article
Full-text available
The Sceletium genus has been of medicinal importance in southern Africa for millennia and Sceletium tortuosum (Aizoaceae), one of eight species in the genus has gained pharmaceutical importance as an anxiolytic and anti-depressant due to the presence of mesembrine alkaloids. S. tortuosum is used for the manufacture of herbal teas, dietary supplements and other phytopharmaceutical products. This study aimed to provide a metabolomic characterization of S. tortuosum and its sister species as these are not easy to distinguish using morphology alone. Plant samples were thus collected from various locations in the succulent Karoo (South Africa) and analyzed through liquid chromatography-mass spectrometry (LC-MS), using MSE fragmentation as a putative tool for chemical identities. Metabolomics-based analyses in combination with molecular networking were able to distinguish between the four species of Sceletium based on the presence of 4-(3,4-dimethyoxyphenyl)-4-[2-acetylmethlamino)ethyl]cyclohexanone (m/z 334.2020; RT 6.60 min), mesembrine (m/z 290.1757; RT 5.10 min) and 4'-O-demethylmesembrenol (m/z 276.1597; RT 4.17 min). Metabolomic profiles varied according to the different localities and metabolites occurred at variable quantitative levels in Sceletium ecotypes. Molecular networking provided the added advantage of being able to observe mesembrine alkaloid isomers and coeluting metabolites (from the joubertiamine group) that were difficult to discern without this application. By combining high-throughput metabolomics together with global and feature based-molecular networking, a powerful metabolite profiling platform that is able to discern chemical patterns within and between populations was established. These techniques were able to reveal chemotaxonomic relationships and allowed for the discovery of chemical markers that may be used as part of monitoring protocols during the manufacture of phytopharmaceutical and dietary products based on Sceletium.
... Mesembryanthemum tortuosum L. (Aizoaceae) is a succulent plant indigenous to the southwestern parts of South Africa (Loria et al., 2014) and is of scientific interest due to its possible therapeutic effects, such as the enhancement of physical well-being and the treatment of anxiety, stress, and depression (Gericke and Viljoen, 2008). Traditionally, pastoralists and hunter-gatherers have used this plant for managing mood-swings and improving general well-being (Van Wyk and Gericke, 2000). ...
... Mesembryanthemum tortuosum, known as 'kougoed' or 'channa' in South Africa, traditionally used for its tranquillizing and anxiolytic properties (Gericke and Viljoen, 2008;Smith, 2011), is marketed as Zembrin®, a standardized ethanolic extract (Shikanga et al., 2012). Since 2010 M. tortuosum has been the subject of much in vitro and in vivo research, as well as clinical studies, with respect to its CNS activity. ...
... Since 2010 M. tortuosum has been the subject of much in vitro and in vivo research, as well as clinical studies, with respect to its CNS activity. All these studies, with the exception of Fountain (2016), corroborated its mood elevation, antidepressant or antiepileptic activity (Gericke and Viljoen, 2008;Harvey et al., 2011;Loria et al., 2014;Schell, 2014;Carpenter et al., 2014;Dimpfel et al., 2018). The anxiolytic-like effects of M. tortuosum have also been studied and substantiated by some research groups (Dimpfel et al., 2018;Fountain, 2016). ...
Article
Ethnopharmacological relevance Mesembryanthemum tortuosum L. (previously known as Sceletium tortuosum (L.) N.E. Br.) is indigenous to South Africa and traditionally used to alleviate anxiety, stress and depression. Mesembrine and its alkaloid analogues such as mesembrenone, mesembrenol and mesembranol have been identified as the key compounds responsible for the reported effects on the central nervous system. Aim of the study To investigate M. tortuosum alkaloids for possible anxiolytic-like effects in the 5-dpf in vivo zebrafish model by assessing thigmotaxis and locomotor activity. Materials and methods Locomotor activity and reverse-thigmotaxis, recognised anxiety-related behaviours in 5-days post fertilization zebrafish larvae, were analysed under simulated stressful conditions of alternating light-dark challenges. Cheminformatics screening and molecular docking were also performed to rationalize the inhibitory activity of the alkaloids on the serotonin reuptake transporter, the accepted primary mechanism of action of selective serotonin reuptake inhibitors. Mesembrine has been reported to have inhibitory effects on serotonin reuptake, with consequential anti-depressant and anxiolytic effects. Results All four alkaloids assessed decreased the anxiety-related behaviour of zebrafish larvae exposed to the light-dark challenge. Significant increases in the percentage of time spent in the central arena during the dark phase were also observed when larvae were exposed to the pure alkaloids (mesembrenone, mesembrenol, mesembrine and mesembrenol) compared to the control. However, mesembrenone and mesembranol demonstrated a greater anxiolytic-like effect than the other alkaloids. In addition to favourable pharmacokinetic and physicochemical properties revealed via in silico predictions, high-affinity interactions characterized the binding of the alkaloids with the serotonin transporter. Conclusions M. tortuosum alkaloids demonstrated an anxiolytic-like effect in zebrafish larvae providing evidence for its traditional and modern day use as an anxiolytic.
... (Aizoaceae) commonly called "kanna" or "kougoed", is a succulent medicinal herb indigenous to South Africa (Carpenter et al., 2016). Aerial parts of the plant are commonly masticated or chewed, taken as tea or tincture, and occasionally smoked (Gericke and Viljoen, 2008). The plant is chewed for the relief of abdominal pain, toothache, and hunger, and fresh juice from the plant is given to induce sleep in young children (Gericke and Viljoen, 2008). ...
... Aerial parts of the plant are commonly masticated or chewed, taken as tea or tincture, and occasionally smoked (Gericke and Viljoen, 2008). The plant is chewed for the relief of abdominal pain, toothache, and hunger, and fresh juice from the plant is given to induce sleep in young children (Gericke and Viljoen, 2008). It is currently used commercially to treat different central nervous system (CNS) related disorders, including stress, depression, and anxiety (Yin et al., 2019). ...
... Over two decades ago, Smith et al. (1996), published the first ethnopharmacological review on the genus Sceletium and more than a decade later, in 2008, Gericke and Viljoen (2008), published the second review focusing on the chemistry, pharmacology, clinical and veterinary applications of Sceletium, with much emphasis on S. tortuosum. Gericke (2018) provided a review of the historical uses, ethno-pharmacology and pre-clinical studies of Zembrin® and quite recently, a review was published on the biological and pharmaceutical properties of S. tortuosum (Manganyi et al., 2021). ...
... (Aizoaceae) commonly called "kanna" or "kougoed", is a succulent medicinal herb indigenous to South Africa (Carpenter et al., 2016). Aerial parts of the plant are commonly masticated or chewed, taken as tea or tincture, and occasionally smoked (Gericke and Viljoen, 2008). The plant is chewed for the relief of abdominal pain, toothache, and hunger, and fresh juice from the plant is given to induce sleep in young children (Gericke and Viljoen, 2008). ...
... Aerial parts of the plant are commonly masticated or chewed, taken as tea or tincture, and occasionally smoked (Gericke and Viljoen, 2008). The plant is chewed for the relief of abdominal pain, toothache, and hunger, and fresh juice from the plant is given to induce sleep in young children (Gericke and Viljoen, 2008). It is currently used commercially to treat different central nervous system (CNS) related disorders, including stress, depression, and anxiety (Yin et al., 2019). ...
... Over two decades ago, Smith et al. (1996), published the first ethnopharmacological review on the genus Sceletium and more than a decade later, in 2008, Gericke and Viljoen (2008), published the second review focusing on the chemistry, pharmacology, clinical and veterinary applications of Sceletium, with much emphasis on S. tortuosum. Gericke (2018) provided a review of the historical uses, ethno-pharmacology and pre-clinical studies of Zembrin® and quite recently, a review was published on the biological and pharmaceutical properties of S. tortuosum (Manganyi et al., 2021). ...
Article
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, 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, pre-clinical 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, neuromodulatory, immunomodulatory, anti-HIV, neuroprotection) in in vitro or in vivo studies. While the plant has been studied in clinical populations, this has only been in healthy subjects, so that further study in pathological states remains to be done. Nevertheless, the aforementioned studies have demonstrated that S. tortuosum 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.
... A number of potential mechanisms for its observed clinical effects have been described. The main active constituents have been identified as mesembrine alkaloids and some of their individual properties have been investigated [1][2][3]. ...
... In 1738, Kolben noted kanna (or channa) to be the "greatest Chearer of the Spirits, and the noblest Restorative in the World" [12]. In 1924, Kolben was referencing a plant used by the Khoi for enjoyment, which they "chewed, kept in their mouth for some time, thus becoming excited…" [1]. The traditional use as masticatory is also described by Commelin in 1692 [13], Thunberg ca. ...
... The traditional use as masticatory is also described by Commelin in 1692 [13], Thunberg ca. 1770 [4], and numerous other sources [1,6,12,[14][15][16][17][18][19][20][21][22][23]. ...
Article
Modern-day regulatory systems governing conditions for how health products enter national markets constitute a barrier of access for traditional herbal medicines on an international level. Regulatory intentions are focused on ensuring consumers are being provided with safe, efficacious and high-quality products that, however, collaterally limit opportunities for traditional herbal medicinal products, especially those that do not already have a long-standing tradition of use established in the respective national marketplaces. This case study investigates and compares how a Southern African herbal medicine with great potential as an anxiolytic and mild antidepressant – Mesembryanthemum tortuosum L. [syn. Sceletium tortuosum (L.) N.E.Br.] aerial parts – fares internationally in today’s regulatory environments. It is argued that inadvertent regulatory favoritism combined with the lack of means for adequate protection of intellectual property may obstruct innovation by creating an almost insurmountable economical hurdle for successful product development and introduction of botanicals from developing countries into most of the world’s health product markets.
... For generations, the indigenous Khoisan people have used ST as a mood-elevator, analgesic, hypnotic, anxiolytic, thirst and hunger suppressant, and for its intoxicating/euphoric effects (Gericke and Viljoen, 2008;Brendler et al., 2021). The characteristic alkaloid profile of Sceletium tortuosum, including mesembrine, mesembrenone, mesembrenol, and mesembranol (Krstenansky, 2017), presents with subtly different neuro-psycho-pharmacological actions (Olatunji et al., 2021) that may underlie the above-mentioned therapeutic properties. ...
... In vitro studies by Harvey et al. (2011) andZhong et al. (2012) suggest that ST shares some mechanistic properties of SSRIs as both target 5-HT through potent inhibition of SERT (Harvey et al., 2011;Brendler et al., 2021). In fact, alkaloid components of ST, specifically mesembrine, mesembrenol and mesembrenone, present with dose-dependent inhibitory actions on SERT, similar to that of citalopram and fluoxetine (Coetzee et al., 2016;Gericke and Viljoen, 2008;Krstenansky, 2017). ST also possesses monoamine releasing properties by increasing VMAT-2 and is also a mild MAO-A inhibitor (Coetzee et al., 2016;Gericke and Viljoen, 2008;Krstenansky, 2017). ...
... In fact, alkaloid components of ST, specifically mesembrine, mesembrenol and mesembrenone, present with dose-dependent inhibitory actions on SERT, similar to that of citalopram and fluoxetine (Coetzee et al., 2016;Gericke and Viljoen, 2008;Krstenansky, 2017). ST also possesses monoamine releasing properties by increasing VMAT-2 and is also a mild MAO-A inhibitor (Coetzee et al., 2016;Gericke and Viljoen, 2008;Krstenansky, 2017). Although not immediately evident with respect to the actions of Zembrin® on serotonergic-based swimming behaviour (Fig. 3B), ESC and Zembrin® can broadly be regarded as serotonergic drugs, indirectly activating pre-and post-synaptic 5-HT 1A and 5-HT 2A/C receptors via SERT inhibition. ...
Article
Ethnopharmacological relevance Sceletium tortuosum (L.) N.E.Br. (ST) has been used by the Khoisan people of South Africa as a mood elevator. Its various pharmacological mechanisms of action suggest distinct potential as an antidepressant. Clinical studies in healthy individuals suggest beneficial effects on mood, cognition, and anxiety. Aim of the study To obtain a chromatographic fingerprint of a standardized extract of S. tortuosum (Zembrin®), and to evaluate the acute antidepressant-like properties of Zembrin® versus the reference antidepressant, escitalopram, in the Flinders Sensitive Line (FSL) rat, a genetic rodent model of depression. Materials and methods The chemical profile of Zembrin® was determined by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) chromatogram method using alkaloid standards. Twelve saline treated FSL and six Flinders Resistant Line (FRL) control rats were used to confirm face validity of the FSL model using the forced swim test (FST). Thereafter, FSL rats (n = 10) received either 5, 10, 25, 50 or 100 mg/kg of Zembrin®, or 5, 10 or 20 mg/kg escitalopram oxalate (ESC), both via oral gavage, and subjected to the open field test (OFT) and FST. Results Four main ST alkaloids were identified and quantified in Zembrin® viz. mesembrenone, mesembrenol, mesembrine, and mesembranol (47.9%, 32%, 13.2%, and 6.8% of the total alkaloids, respectively). FSL rats showed significantly decreased swimming and climbing (coping) behaviours, and significantly increased immobility (despair), versus FRL controls. ESC 5 mg/kg and Zembrin® 25 mg/kg and 50 mg/kg showed significant dose-dependent reversal of immobility in FSL rats and variable effects on coping behaviours. Zembrin® 50 mg/kg was the most effective antidepressant dose, showing equivalence to ESC 5. Conclusions Zembrin® (25 and 50 mg/kg) and ESC (5 mg/kg) are effective antidepressants after acute treatment in the FST. Moreover, Zembrin® 50 mg/kg proved equivalent to ESC 5. Further long-term bio-behavioural studies on the antidepressant properties of Zembrin® are warranted.
... (Aizoaceae) commonly called "kanna" or "kougoed", is a succulent medicinal herb indigenous to South Africa (Carpenter et al., 2016). Aerial parts of the plant are commonly masticated or chewed, taken as tea or tincture, and occasionally smoked (Gericke and Viljoen, 2008). The plant is chewed for the relief of abdominal pain, toothache, and hunger, and fresh juice from the plant is given to induce sleep in young children (Gericke and Viljoen, 2008). ...
... Aerial parts of the plant are commonly masticated or chewed, taken as tea or tincture, and occasionally smoked (Gericke and Viljoen, 2008). The plant is chewed for the relief of abdominal pain, toothache, and hunger, and fresh juice from the plant is given to induce sleep in young children (Gericke and Viljoen, 2008). It is currently used commercially to treat different central nervous system (CNS) related disorders, including stress, depression, and anxiety (Yin et al., 2019). ...
... Over two decades ago, Smith et al. (1996), published the first ethnopharmacological review on the genus Sceletium and more than a decade later, in 2008, Gericke and Viljoen (2008), published the second review focusing on the chemistry, pharmacology, clinical and veterinary applications of Sceletium, with much emphasis on S. tortuosum. Gericke (2018) provided a review of the historical uses, ethno-pharmacology and pre-clinical studies of Zembrin® and quite recently, a review was published on the biological and pharmaceutical properties of S. tortuosum (Manganyi et al., 2021). ...
Article
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.
... In addition to the fact that it is part of their cultural heritage, the traditional health care system provides an affordable, personalized, and culturally accepted alternative to the costly modern clinical system. The South African health care system is overwhelmed by the private and public health care system, however, the ratio of traditional healers to allopathic doctors is estimated at 10 to 1 [1][2][3]. ...
... It was identified as a ginseng-like herb by the European population. However, prior to this, South African pastoralists and hunter-gatherers had been using the plant as a mood-altering substance from prehistoric times [1,14,15]. S. tortuosum is a small succulent plant with trimmed branches that thicken along and become slightly woody with age. The succulent plant consists of water cells. ...
... Hence, the botanical name, Sceletium, comes from the Latin word "sceletus", due to the prominent leaf veins. Sceletium genera consists of eight species, known for their persistent dry leaves that become skeletonized ( Figure 2a) [1,17]. The Sceletium genera, although native to southwestern parts of South Africa, has attracted global attention since it enhances a sense of well-being and healing properties for anxiety, depression, and stressed individuals. ...
Article
Full-text available
Sceletium tortuosum (L.) N.E.Br. (Mesembryanthemaceae), commonly known as kanna or kougoed, is an effective indigenous medicinal plant in South Africa, specifically to the native San and Khoikhoi tribes. Today, the plant has gained strong global attraction and reputation due to its capabilities to promote a sense of well-being by relieving stress with calming effects. Historically, the plant was used by native San hunter-gatherers and Khoi people to quench their thirst, fight fatigue and for healing, social, and spiritual purposes. Various studies have revealed that extracts of the plant have numerous biological properties and isolated alkaloids of Sceletium tortuosum are currently being used as dietary supplements for medicinal purposes and food. Furthermore, current research has focused on the commercialization of the plant because of its treatment in clinical anxiety and depression, psychological and psychiatric disorders, improving mood, promoting relaxation and happiness. In addition, several studies have focused on the isolation and characterization of various beneficial bioactive compounds including alkaloids from the Sceletium tortuosum plant. Sceletium was reviewed more than a decade ago and new evidence has been published since 2008, substantiating an update on this South African botanical asset. Thus, this review provides an extensive overview of the biological and pharmaceutical properties of Sceletium tortuosum as well as the bioactive compounds with an emphasis on antimicrobial, anti-inflammatory, anti-oxidant, antidepressant, anxiolytic, and other significant biological effects. There is a need to critically evaluate the bioactivities and responsible bioactive compounds, which might assist in reinforcing and confirming the significant role of kanna in the promotion of healthy well-being in these stressful times.
... A number of potential mechanisms for its observed clinical effects have been described. The main active constituents have been identified as mesembrine alkaloids and some of their individual properties have been investigated [1][2][3]. ...
... In 1738, Kolben noted kanna (or channa) to be the "greatest Chearer of the Spirits, and the noblest Restorative in the World" [12]. In 1924, Kolben was referencing a plant used by the Khoi for enjoyment, which they "chewed, kept in their mouth for some time, thus becoming excited…" [1]. The traditional use as masticatory is also described by Commelin in 1692 [13], Thunberg ca. ...
... The traditional use as masticatory is also described by Commelin in 1692 [13], Thunberg ca. 1770 [4], and numerous other sources [1,6,12,[14][15][16][17][18][19][20][21][22][23]. ...
Article
Full-text available
Modern-day regulatory systems governing conditions for how health products enter national markets constitute a barrier of access for traditional herbal medicines on an international level. Regulatory intentions are focused on ensuring consumers are being provided with safe, efficacious and high-quality products that, however, collaterally limit opportunities for traditional herbal medicinal products, especially those that do not already have a long-standing tradition of use established in the respective national marketplaces. This case study investigates and compares how a Southern African herbal medicine with great potential as an anxiolytic and mild antidepressant – Mesembryanthemum tortuosum L. [syn. Sceletium tortuosum (L.) N.E.Br.] aerial parts – fares internationally in today’s regulatory environments. It is argued that inadvertent regulatory favoritism combined with the lack of means for adequate protection of intellectual property may obstruct innovation by creating an almost insurmountable economical hurdle for successful product development and introduction of botanicals from developing countries into most of the world’s health product markets.
... The psychoactivity of this relatively little studied plant and its "fermentation" product ("kougoed" in Afrikaans) is attributed to a structurally related group of alkaloids of which the most abundant is mesembrine (Figure 1). Mesembrine was isolated by Zwicky in 1914 and its structure identified in 1960 (see [181,182]). Laboratory experiments with various plant preparations have revealed anti-stress, antidepressant, narcotic, anxiolytic and anti-addictive but not hallucinogenic effects [182,183]. ...
... Mesembrine was isolated by Zwicky in 1914 and its structure identified in 1960 (see [181,182]). Laboratory experiments with various plant preparations have revealed anti-stress, antidepressant, narcotic, anxiolytic and anti-addictive but not hallucinogenic effects [182,183]. Screening in vitro a range of potential pharmacological targets revealed that mesembrine was an effective inhibitor of 5-HT reuptake, while its unsaturated derivative (i.e., mesembrenone) inhibited both 5-HT reuptake and phosphodiesterase type 4 isoenzyme [184,185]. These results, at least partly, support the observed psychoactive properties of the plant. ...
Article
(corrected* abstract from the 2023 Annual Meeting of the College on Problems of Drug Dependence) Aim New synthetic opioids continue to emerge on recreational drug markets. Recently, opioids with a 2-benzylbenzimidazole core (‘nitazenes’, e.g. isotonitazene) have become increasingly prevalent, the potency of some members dwarfing that of fentanyl. The aim of our work is to in vitro and in vivo characterize existing, as well as 'prophetic' nitazenes, to allow risk prioritization based on structure activity relationships. As a case example, the pharmacological characterization of ethyleneoxynitazene, which we predicted to emerge, and which was first found in January 2023, will be presented. Methods In vitro pharmacological characterization (experiments performed in quintuplicate) encompassed assessment of mu opioid receptor (MOR) activation via a β-arrestin2 recruitment assay to derive the potency and efficacy, as well as radioligand binding assays performed in rat brain tissue. Pharmacodynamic effects were evaluated in male C57BL/6J mice and included assessment of antinociception, locomotor activity, and thermic effects. Results Radioligand binding assays revealed a Ki of 57.9 nM at MOR; only slightly higher than the Ki of etonitazene (38.4 nM), the most potent nitazene. Despite a similar affinity, ethyleneoxynitazene had a >100-fold lower potency in the MOR-β-arrestin2 recruitment assay (EC50 etonitazene 0.588 nM; ethyleneoxynitazene 70 nM). Also its efficacy (relative to the reference hydromorphone) was lower than that of etonitazene (Emax 187% vs. 254%). The strongly reduced MOR activation potential was also evident from the in vivo antinociception (mouse hot plate) assay, with an ED50 of 0.0223 mg/kg and 11.1 mg/kg for etonitazene and ethyleneoxynitazene, repectively. The hypothermia and locomotor activity assays revealed the same pattern. Conclusions The a priori availability of pharmacological (in vitro and in vivo) data by the time the 'prophetic' opioid ethyleneoxynitazene hit the recreational drug market allowed us to predict that, compared to several other nitazenes, this is not the opioid of highest concern. Similarly, pharmacological data for other 'prophetic' nitazenes are now readily available. *: in the text of the ‘Methods’ and ‘Results’ section, the original abstract inadvertently makes referral to Sprague Dawley rats and cataleptic effects rather than C57/BL/6J mice and locomotor activity effects. This was corrected in the abstract above. The rest of the abstract is correct.
... Sceletium tortuosum (ST), a succulent plant native to Southern Africa (Gericke and Viljoen, 2008), has been used by the indigenous Khoisan people for many ailments and purposes, including appetite and thirst suppression, mood elevation, sedation, analgesia, and euphoric effects (Gericke and Viljoen, 2008;Gericke et al., 2018). Due to its local popularity, unchecked wild harvesting of ST for local trade initially led to a scarcity in habitat (Gericke et al., 2018). ...
... Sceletium tortuosum (ST), a succulent plant native to Southern Africa (Gericke and Viljoen, 2008), has been used by the indigenous Khoisan people for many ailments and purposes, including appetite and thirst suppression, mood elevation, sedation, analgesia, and euphoric effects (Gericke and Viljoen, 2008;Gericke et al., 2018). Due to its local popularity, unchecked wild harvesting of ST for local trade initially led to a scarcity in habitat (Gericke et al., 2018). ...
... Sceletium tortuosum (ST), a succulent plant native to Southern Africa (Gericke and Viljoen, 2008), has been used by the indigenous Khoisan people for many ailments and purposes, including appetite and thirst suppression, mood elevation, sedation, analgesia, and euphoric effects (Gericke and Viljoen, 2008;Gericke et al., 2018). Due to its local popularity, unchecked wild harvesting of ST for local trade initially led to a scarcity in habitat (Gericke et al., 2018). ...
... Sceletium tortuosum (ST), a succulent plant native to Southern Africa (Gericke and Viljoen, 2008), has been used by the indigenous Khoisan people for many ailments and purposes, including appetite and thirst suppression, mood elevation, sedation, analgesia, and euphoric effects (Gericke and Viljoen, 2008;Gericke et al., 2018). Due to its local popularity, unchecked wild harvesting of ST for local trade initially led to a scarcity in habitat (Gericke et al., 2018). ...
Article
Full-text available
Ethnopharmacology relevance: Sceletium tortuosum (L.) N.E.Br. (ST) is an alkaloid-rich succulent plant with various mechanisms of action that infer psychotropic effects. These actions correlate with clinical evidence suggesting efficacy in the treatment of depression and anxiety, in line with its use by indigenous populations. Its low side effect profile suggests potential of ST to improve the overall wellbeing and compliance of millions of patients that experience severe side effects and/or do not respond to current prescription medication. However, to elucidate specific physiological effects of ST extracts, it is necessary to first understand which of its constituents are the major contributors to beneficial effects demonstrated for ST in this context. Aim of the study: To determine an anxiolytic- and antidepressant-like effective concentration of a ST extract by means of a dose response in zebrafish (ZF) larvae, and to assess relative contributions of equivalent concentrations of isolated alkaloids contained in the effective concentration(s). Materials and methods: A dose response study employing a light-dark transition test (LDTT) was done in ZF larvae (<5 days post fertilization) to track locomotor activity in terms of anxiety-like (hyperlocomotion) and depression-like (hypolocomotion) behaviour. Larvae were treated for 1 h directly before the LDTT with escalating concentrations of a ST extract commercially known as Zembrin® (Zem) ranging from 0.25 to 500 μg/mL and compared to an untreated control group (n = 12 per treatment concentration). LDTT was repeated after 24 h to evaluate long-term exposure toxicity. The concentration that best attenuated hyperlocomotion during the dark phase following light-dark transition was identified as the anxiolytic-like concentration. This concentration, plus one higher and one lower concentration, were used for subsequent tests. The percentage content of each alkaloid (mesembrine, mesembrenone, mesembrenol, and mesembranol) in these concentrations were calculated and applied to additional larvae to identify the most effective anxiolytic-like alkaloid in the LDTT. To identify antidepressant-like therapeutic concentration and equivalent alkaloid concentration, the same treatment concentrations were tested in larvae (n = 12 per treatment concentration) pre-exposed to reserpine for 24 h. Depending on normality of data distribution, Brown-Forsythe and Welch, or Kruskal-Wallis ANOVA were used, with Dunnett or Dunn's multiple comparisons tests. Results: Only the extreme concentration of Zem (500 μg/mL) elicited toxicity after treatment for 24 h. Zem 12.5 μg/mL was the most effective anxiolytic-like concentration as it significantly decreased locomotor activity (P = 0.05) in the LDTT. Low (5 μg/mL), optimal (12.5 μg/mL) and high (25 μg/mL) Zem concentrations, as well as treatment solutions of single alkaloids (mesembrine, mesembrenone, mesembranol and mesembrenol), prepared to contain equivalent concentrations of each major alkaloid contained within these three concentrations of Zem, were tested further. Only mesembrine concentrations equal to that contained within the optimal and high dose of Zem (12.5 and 25 μg/mL) showed significant anxiolytic-like effects (P < 0.05). Only the highest Zem concentration (25 μg/mL) reversed the effects of reserpine - indicating antidepressant-like properties (P < 0.05) - while isolated alkaloids failed to induce such effects when administered in isolation. Conclusions: Current data provide evidence of both anxiolytic- and antidepressant-like effect of whole extract of Zem, with relatively higher concentrations required to achieve antidepressant-like effect. Of all alkaloids assessed, only mesembrine contributed significantly to the anxiolytic-like effects of Zem. No alkaloid alone could be pinpointed as a contributor to the antidepressant-like activity observed for higher concentration Zem. This may be due to synergistic effects of the alkaloids or may be due to other components not tested here. Current data warrants further investigation into mechanisms of action, as well as potential synergy, of ST alkaloids in suitable mammalian in vivo models.
... The aim of this chapter was therefore, to highlight pharmaceutical and economic viability of S. tortuosum and relate the medicinal value of the plant with respect to the bioactive compound found in it and suggest ways of cultivating the plant in a soilless systems. Sceletium plant and its "skeletonised appearance" of the dried leaves [9]. ...
... Sceletium tortuosum plant surrounded by its white flowers [13]. [9]). This family has received a large amount of attention in the present century both in herbaria collections and in the field. ...
Chapter
Full-text available
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.
... The Sceletium-type alkaloids mesembrine (IC50 = 29 µM) and mesembrenone (IC50 < 1 µM) are potent inhibitors of phosphodiesterase 4 (PDE-4). [3][4][5][6] Mesembrine (IC50 = 27 µM) is a more potent inhibitor of the serotonin transporter (SERT) than fluoxetine (Prozac) which has prompted the commercialization of mesembrine-containing consumer products. 7 Mesembrenone was also found to affect a human T cell lymphoma line (Molt4 cells) with an EC50 of 2 µM (0.6 µg/ml), but to have little effect on a hepatoma cell line (Hep G2) or on a mouse fibroblast line (LMTK cells). ...
... prolonging the action of cAMP as a second messenger in the neurons. 3 Figure 5B). We could assume that lower immobility time might be due to the motor stimulation of MZM, especially in male mice. ...
Article
Rationale: Narcissus cv. Hawera has been found to biosynthesize some Sceletium-type alkaloids with antidepressant and anxiolytic activities. This ornamental plant has been poorly studied as a source of bioactive alkaloids including some contraversive reports on in vitro and intact plants. Here, a detailed GC-MS characterization of its alkaloid fractions is presented. Methods: GC-MS was used for identification of compounds in the alkaloid fractions. Both, underivatized and silylated samples were analyzed in parallel. Elevated plus maze and tail suspension tests were used to assay the anxiolytic and antidepressant activities. Ellman's and MTT-dye reduction assays were used to evaluate the AChE inhibitory and cytotoxicity activities, respectively. Results: Twenty-nine alkaloids, 13 of them of Sceletium-type were detected. Two new alkaloids were identified as 2-oxo-mesembrine and 2-oxo-epi-mesembrenol. Lycorine was found as a major compound (43.5%) in the crude silylated methanol extract. After elimination of lycorine by pre-crystallization, the major alkaloids were 40.8% 6-epi-mesembranol, 16.2% 6-epi-mesembrenol, and 13.8% sanguinine. This fraction showed anxiolytic and antidepressant-like activities as well as potent AChE inhibitory and antineoplastic activities. Conclusions: Silylation of the alkaloid fractions from Narcissus cv. Hawera provides better separation, structural information and improved sensitivity for compounds with two and more hydroxyl groups. The lycorine-free alkaloid fraction shows a great potential for further pharmacological studies.
... Sceletium tortuosum (L.) N. E. Br. is a succulent shrub from the Aizoaceae family (subfamily Mesembryanthemoideae) (Gericke and Viljoen, 2008;Klak and Bruyns, 2013). It is predominantly found in the Succulent Karoo of the Greater Cape Floristic Region (GCFR) of South Africa (Chesselet, 2005;Snijman, 2013). ...
... In recent years, natural populations of S. tortuosum have deteriorated and the species is now protected (Gericke and Viljoen, 2008;Elev8 TM , 2017). Despite this, and the pressing need for fresh plant material, the scientific literature is deficient on the germination and post-germination behaviour of this species. ...
Article
Full-text available
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.
... Many studies have shown promising antimicrobial, cytotoxic, and enzyme inhibitory effects, correlated with the diversity of their phytoconstituents [1,2] Aizoaceae, the "ice plant", is the largest family of succulent leaves, consisting of 135 genera and 2499 species. Aizoaceae is characterized by its flavonoids, as reported in Aptenia [3,4] and Trianthema [5,6], and alkaloids, as identified in Sceletium species [7], in addition to sterols and triterpenes [8]. Alkaloids of the family Aizoaceae are characterized by their phenolic alkaloid nature [7,9]. ...
... Aizoaceae is characterized by its flavonoids, as reported in Aptenia [3,4] and Trianthema [5,6], and alkaloids, as identified in Sceletium species [7], in addition to sterols and triterpenes [8]. Alkaloids of the family Aizoaceae are characterized by their phenolic alkaloid nature [7,9]. Six genera and ten species are recognized from Aizoaceae in Egypt, however are poorly studied [10]. ...
Article
Full-text available
Aizoaceae is a large succulent family characterized by many psychoactive species. Aizoon canariense L., a wild neglected plant traditionally used in gastrointestinal ailments, has been the subject of a limited number of phytochemical and biological studies. Therefore, herein, we investigated the in vitro cytotoxic, antimicrobial, and anticholinesteraseactivity of the aerial parts of A. canariense L. and analyzed the phytochemical compositions of the lipoidal and alkaloidal fractions. Petroleum ether extract showed the presence of behenic and tricosylic acid, while an in-depth investigation of the alkaloidal fraction revealed the identification of new adenine based alkaloids (1–5), which were isolated and identified for the first time from Aizoon canariense L. Their structures were elucidated based on extensive spectroscopic analyses. The alkaloidal extract showed a powerful cytotoxic effect (IC50 14–28 μg/mL), with the best effect against colon carcinoma, followed by liver and breast carcinomas. The alkaloidal extract also had a potent effect against Candida albicans and Escherichia coli, with minimum inhibitory concentrations (MIC) values of 312.5 and 625 µg/mL. The in vitro anticholinesterase activity was potent, with IC50 < 200 ng/mL for the tested extracts compared with 27.29 ± 0.49 ng/mL for tacrine.
... (7 of 11) e2000834 ase by more than 5-10 %. [30] However, these alkaloids showed remarkable in vitro activity as serotonin reuptake inhibitors, giving them potential applications as antidepressants in the treatment of stress and anxiety. [31,32] Mesembrane-type alkaloids were firstly studied because several species of Sceletium (currently Mesembryanthemun L.) -Aizoaceae, subfamily Mesembryanthemoideae, are part of a preparation used in traditional medicine in South Africa, known as 'Kanna'. [33,34] For millennia, species of the genus Sceletium have been used for the relief of thirst and hunger, to combat fatigue, as medicines, and for social and spiritual purposes by African ethnic groups. ...
... [33,34] For millennia, species of the genus Sceletium have been used for the relief of thirst and hunger, to combat fatigue, as medicines, and for social and spiritual purposes by African ethnic groups. [32] The presence of 3'-demethoxy-6-epimesembranol (1) in Zephyranthes fosteri suggests that the 'smiling, laughing or pleasing flower Huetzcanixochitl' depicted in folium 38r of the Libellus was probably used in pre-Columbian times in Mexico as a 'restorative, stimulant and euphoriant', alike Sceletium tortuosum by several ethnic groups in South Africa. However, more historical, ethnobotanical, chemical, and pharmacological studies are needed to support this hypothesis. ...
Article
The Libellus de Medicinalibus Indorum Herbis (Booklet of Indian Medicinal Plants) is the first book of medicinal plants written in the American continent. It was first published in 1939 as 'An Aztec Herbal'. One of the depicted plants is Huetzcanixochitl (laughing flower) interpreted as Zephyranthes fosteri (Amaryllidaceae). No chemical or pharmacological studies are reported for this species; so, we decide to investigate it. The GC/MS of the bulbs and aerial parts extracts indicated that they contain Amaryllidaceae alkaloids, among them: lycorine, 3-O-acetylpowelline, and norlycoramine. An unknown major alkaloid was isolated and identified by 1 H, 13 C-NMR and MS, as 3'-demethoxy-6-epimesembranol (1). The methanolic extract, the alkaloid fraction, and compound 1 inhibited acetylcholinesterase in vitro. Mesembrine alkaloids are found in Sceletium species (Aizoaceae). Several are known as serotonin recapture inhibitors and have been proposed as potential antidepressant drugs. The presence of 1 suggests that Z. fosteri was probably used in pre-Columbian times in Mexico as a 'stimulant and euphoriant', alike Sceletium tortuosum by several ethnic groups in South Africa.
... Sceletium tortuosum (L.) N. E. Br. (Aizoaceae) is a succulent decumbent shrub native to the south-western regions of South Africa (Gericke and Viljoen 2008). It is utilized in traditional medicine to treat a variety of ailments, including pain, insomnia and anxiety. ...
... Unfortunately, a pure commercial source of mesembrinetype alkaloids does not exist, thus researchers and pharmaceutical companies are reliant upon fresh plant material (Elev8™ 2017;Krstenansky 2017;Wild 2015). Sceletium tortuosum is now a protected species due to diminished natural populations (Elev8™ 2017; Gericke and Viljoen 2008). Its value and conservation status suggest that rapid and efficient propagation techniques would be a credit to this species and the pharmacological industry. ...
Article
Full-text available
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.
... Despite the plant's long recorded history of use as a masticatory, health tea, and herbal medicine, there have been few reports on its pharmacological activity. Its reported ef cacy in cases of depression has been connected to inhibitory effects on 5-HT reuptake, yet these effects have not been well explored (Gericke and Viljoen, 2008). Mesembrine, isolated from Sceletium tortuosum, was found to be a powerful inhibitor of 5-hydroxytryptamine (5-HT) reuptake, which was veri ed with synthetic mesembrine (Gericke and Van Wyk, 2001). ...
... The alkaloid changes in the plant biomass of fermentation A coincided with an increase in pH (Table S3), a relative decrease in the dominant bacterial taxa (Fig. 5; Table S4), and an increase in the representatives of a few fusarioid fungal genera ( Fig. 6; Table S5). Initially the bacterial community associated with the plant biomass was dominated by Tentative identifications proposed according to structures and exact masses published by Gericke and Viljoen (2008). a Patnala and Kanfer (2010). ...
Article
Full-text available
Sceletium tortuosum, a medicinal plant used as a natural antidepressant, has been fermented traditionally to yield what is believed by its users to be a stronger more potent product. The question persists if fermenting is changing the actives (mesembrine alkaloids) in the plant material or if it is just a natural way of concentrating it and increasing its bioavailability. In this study the plant material was macerated and incubated over a period of 9 days with regular sampling to monitor any chemical and metagenomic changes over time. Ultra-high pressure liquid chromatography-mass spectrometry (UHPLC-MS) analysis showed that the first significant changes in the chemical composition occurred after 5 days when Fusarium species became the predominant species in the microflora. To confirm whether fusaroid taxa do play a role in the alkaloid production and/or changes in the alkaloid profile, the sterilized plant bio-mass was inoculated with three Fusarium species as monocultures and the fermentation monitored. The alkaloid profile in the control did not change over time, but similarly to the natural fermentation, one of the Fusarium species yielded an increase in epimesembranol and decreases in some of the other alkaloids which indicates that the microbiome indeed plays a role.
... This has paid rich dividends and a suite of new benefit-sharing agreements has since been negotiated. Sceletium tortuosum for example, also known as kougoed or kanna, is a succulent plant well known for its moodenhancing properties and long used among indigenous San and Khoi as a mild narcotic or intoxicant and to treat pain and other ailments (Gericke & Viljoen 2008). Using knowledge from Nama-speaking traditional healers from two villages in the Northern Cape, Nourivier and Paulshoek, a researcher was guided towards the plant's use and patented an extract that is now incorporated into medication to improve cognitive function and treat anxiety and depression (Chennells 2013;Modise 2018). ...
... Traditionally, it's related to treatments involving toothache, abdominal pains, hypnotic, analgesic, thirst and hunger inhibition, and anxiolytic, the aim of this meta-analysis [6]. Historically associated with indigenous societies within the same region, the substance was first reported by the end of the 17th century [3]. Recently, some authors have sought to understand how using the plant medicinally, usually made from chewable powder or smoke [5], can attenuate anxiety symptoms, such as heart rate, mean arterial pressure, or subjective outcomes collected from questionnaires. ...
Article
Full-text available
Introduction: Sceletium tortuosum is a South African succulent associated with traditional medicine. Despite this, its effect on anxiety treatment is not consolidated. Thus, this study aims to investigate whether the compound reduces anxiety symptoms. Objective: This study will evaluate how Sceletium tortuosum affects anxiety symptoms compared to placebo in adult patients by analyzing randomized clinical trials. Methods: We performed comprehensive literature searches using Pubmed, Cochrane, and Embase databases. The assessed outcome was Anxiety. Statistical analysis was conducted using RevMan 5.4. Results: In our analysis, we included four studies; one randomized clinical trial and three randomized cross-over trials, comprising a total of 117 patients, in which Sceletium tortuosum was the treatment strategy in 29 (49,15%) patients in RCT and in 51 individuals among cross-over trials. Anxiety (RR 1.01; 95% Cl 0.56–1.83; p = 0.98; I2 = 0%) had no clinical difference between intervention or control group. Conclusion: At the end of the study, it was not possible to guarantee Sceletium tortuosum affects anxiety.
... This has paid rich dividends and a suite of new benefit-sharing agreements has since been negotiated. Sceletium tortuosum for example, also known as kougoed or kanna, is a succulent plant well known for its moodenhancing properties and long used among indigenous San and Khoi as a mild narcotic or intoxicant and to treat pain and other ailments (Gericke & Viljoen 2008). Using knowledge from Nama-speaking traditional healers from two villages in the Northern Cape, Nourivier and Paulshoek, a researcher was guided towards the plant's use and patented an extract that is now incorporated into medication to improve cognitive function and treat anxiety and depression (Chennells 2013;Modise 2018). ...
... Channaine (70, Figure 4), which is an AA with an unusual cage-like ring structure at the interface of two aryl-hydroindole subunits, was isolated from Sceletium tortuosum [64]. This species was collected from St. Helena in the Western Cape Province of South Africa and belongs to the Sceletium genus, which is endemic to South Africa and which is a well-known producer of alkaloids [65,66]. Alkaloid 70 was previously isolated from the same Amaryllidaceae [67], but only its empirical formula and some functional groups were assigned. ...
Article
Full-text available
The alkaloids are one of the most represented family of natural occurring biological active compounds. Amaryllidaceae are also very well known for their beautiful flower and are thus used as ornamental plants in historic and public gardens. The Amaryllidacea alkaloids constitute an important group that is subdivided into different subfamilies with different carbon skeletons. They are well known from ancient times for their long application in folk medicine, and in particular, Narcissus poeticus L. was known to Hippocrates of Cos (ca. B.C. 460–370), who treated uterine tumors with a formulate prepared from narcissus oil. To date, more than 600 alkaloids of 15 chemical groups exhibiting various biological activities have been isolated from the Amaryllidaceae plants. This plant genus is diffused in regions of Southern Africa, Andean South America and the Mediterranean basin. Thus, this review describes the chemical and biological activity of the alkaloids collected in these regions in the last two decades as weel those of isocarbostyls isolated from Amaryllidaceae in the same regions and same period.
... For example, Sceletium tortuosum, known commonly as kougoed or kanna, is a succulent plant recognized for its mood-enhancing and calming properties. It has been long used among Indigenous San and Khoi as a mild narcotic or intoxicant and to treat pain and other ailments (Gericke and Viljoen, 2008). Knowledge from Nama-speaking traditional healers from two villages in the Northern Cape province of South Africa, Nourivier and Paulshoek, guided researchers towards its use, and the patented extract 7 is now incorporated into medications to improve cognitive function and treat anxiety and depression (Chennells, 2013;Modise, 2018;Brendler et al., 2021). ...
Article
Full-text available
Access and benefit sharing (ABS) is a central approach to address biopiracy – the misappropriation of genetic resources and traditional knowledge without consent or compensation, often tied to patenting. Benefit-sharing agreements comprise a core element of ABS and are intended to leverage greater social and economic justice, create incentives for biodiversity conservation, and strengthen the rights of indigenous and local communities. However, emerging evidence suggests otherwise. Through review of four cases of biodiversity commercialization in South Africa – Hoodia gordonii, Aspalathus linearis (rooibos), Sceletium tortuosum (kougoed) and Pelargonium sidoides, each with histories of biopiracy charges and associated benefit-sharing agreements, this paper aims to explain this apparent contradiction. The cases reveal that while ABS has succeeded in recognizing holders of traditional knowledge, the wider political and economic struggles faced by communities remain neglected. Power relations and economic disparities have not changed, and control remains vested in land, with ownership remaining highly skewed towards industry partners who have market dominance; and intellectual property, the benefits of which are disassociated from traditional knowledge holders and biodiversity custodians. ABS processes have also led to a clamor for representation, favoring groups that are politically connected, well organized and resourced, while excluding more marginalized groups who are less capacitated. Moreover, despite significant biodiversity concerns in each case, there are few conservation benefits. Such trends, combined with new forms of “digital biopiracy” and opportunities opening through the post 2020 Global Biodiversity Framework, emphasize the need to reconceptualize ABS to leverage more equitable and sustainable outcomes.
... Mesembryathemaceae has a long history of medicinal and traditional use by San and Khoikhoi people as a masticatory and medicine [2][3] and after by colonial farmers as a psychotropic in nature in tincture form [4]. From the last 15 years, the plant has attracted attention for its theorised applications in endorsing a sense of wellbeing and relieving stress in human beings and for the treatment of anxiety and depression in clinically anxious and depressed patients [5][6] 539 modulators. Enzymes found in the PDE4 family catalyze the hydrolysis of cyclic Adenosine monophosphate (cAMP) and have a critical role in controlling the intracellular concentration of cAMP and increasing phosphorylation of cAMP-response element-binding protein [7]. ...
Article
Full-text available
Background: Depression is a disorder that leads to disability worldwide and its liability seems to increase in the future. The Phytoconstituents as medicinal drugs obtained from various plants have remarkable attention towards drug discovery for various disease treatments using different techniques. Mesembrine, Mesembrenone, and Mesembranol obtained from a plant extract of Sceletium tortuosum were reported as potent Antidepressants. Objective: The current effort deals with computational study of a few Phytoconstituents obtained from plant extract as potent Phosphodiesterase 4 inhibitors in the treatment of depression and their comparison with standard drug Imipramine. Methods: In silico methods were adopted to study the interactions between Phosphodiesterase 4 as receptor and mesembrine, mesembrenone, and mesembranolas ligands. Docking studies of selected Phytoconstituentswere carried using autodock 4.2 and autodock vina (PyRxtool) to assess and compare the binding energies of these Phytoconstituents with receptor to the binding energy of Imipramine. Analysis of docking results was done using a discovery studio visualizer. The validation of the receptor was carried out by a pro-check validation tool. For the drug likeliness, the drulito tool was used. Results: Analysis of docking result showed that all Phytoconstituents found to have better binding energy with Phosphodiesterase 4 receptor and can act as potent antidepressant agents. Mesembrenone, Mesembrine, and Mesembranol showed the estimated free binding energy of-8.2 kcal/mol,-8.1kcal/mol, and-8.0kcal/mol respectively with Phosphodiesterase 4. All selected Phytoconstituents showed better binding energy than imipramine (-7.9 kcal/mol) with Phosphodiesterase 4. Conclusion: Based on the computational study, it was concluded that compounds from a medicinal plant with promising biological activity can recognize as a valuable and alternative drug lead for depression treatment.
... Sceletium tortuosum (sold as a standardized extract under the name Zembrin ® (ZEM)) is a succulent plant native to the South African region [1]. In traditional folk medicine, leaves from the plant have been chewed or used in teas and implicated in the amelioration of thirst, staving hunger, and decreasing fatigue [2]. As of late, ZEM has been identified as a promising nutraceutical with potent anxiolytic and anti-depressant actions [3,4]. ...
Article
Full-text available
The purpose of this study was to investigate acute Zembrin® (Sceletium tortuosum) supplementation on muscle soreness, markers of muscle damage, mood, and exercise performance following unaccustomed resistance exercise. Untrained females (n = 16) were divided into two groups with a different three-day treatment regimen: (1) placebo (PL) and (2) Zembrin® (ZEM). During the initial visit, baseline perceived soreness, range of motion (ROM), mood state (profile of mood states (POMS) questionnaire), and plasma lactate dehydrogenase concentrations (LDH) were measured followed by the performance of an eccentric bicep curl protocol with their non-dominant arm. The total repetitions and rate of perceived exertion (RPE) were recorded throughout the exercise. The participants then supplemented with the corresponding treatment immediately following, the subsequent day, and 30 min prior to completing a 48 h follow-up visit. For the 48 h visit, all procedures were repeated and comparisons were drawn for perceived soreness, ROM, LDH, mood scores, total repetitions, and RPE. The findings indicate that short-term ZEM supplementation resulted in lower perceived soreness (p = 0.020) and a greater preservation of ROM (p = 0.028) at 48 h versus the PL group. Mood worsened from the baseline to 48 h regardless of the treatment (p = 0.043) but the decrements were exacerbated in the PL group compared with the ZEM group (p < 0.001). LDH levels (p = 0.019) and RPE (p = 0.008) were higher and total repetitions were lower (p < 0.001) at 48 h irrespective of the treatment. Although short-term dietary enrichment with ZEM did not alter the exercise performance or biomarkers of muscle damage, the current results suggest ZEM supplementation may be effective in reducing the markers of soreness and preserve mood following unaccustomed eccentric exercise.
... This raises questions about bio-prospecting and the ethics of phyto-extraction, as well as questions about access and benefit sharing. Many studies have been driven by the commercial potential, including in vitro pharmacology experimentation, pre-clinical studies, clinical case studies and pilot randomized controlled clinical trials (Gericke & Viljoen 2008;Nell et al. 2013;Chiu et al. 2014;Dimpfel et al. 2016;Krstenansky 2017). These studies are concentrated on Sceletium and extracts of the plant material per se, in particular the alkaloids. ...
Presentation
Three ingredients exist inside any honeybee hive, wild or domesticated – yeast, beebread (transformed floral pollen) and honey (fructose and glucose). If combined with water these ingredients produce alcohol. Success depends on an accumulation of pharmacological knowledge, keen observation and an astute, flexible cognitive ability. Archaeological evidence from Border Cave, South Africa suggests that honey bee products were being used and consumed by early people 40, 000 years ago. In this presentation, Neil Rusch draws on the archaeological record in support of a long-term chronology involving bees, bow-hunting and arrow poison production. This better explains the early appearance of intentional fermentation. A deep time perspective also accounts for the occurrence of bees in the ethnography, rock paintings and mythology of the region. This presentation and others in the NC State University Seminar Series are published in: Jewell, M., Dunn, R.R., Vandegrift, M., Nichols, L.M., Ciccone, K., Dufresne, K., Gannon, K., Hill, C., Kittinger, A., Kittleson, S., & O'Reilly, R. (Eds.). (2021). Fermentology. Raleigh, NC: NC State University Libraries. https://doi.org/10.52750/679579
... The psychoactivity is attributed to alkaloids, mainly mesembrine. It was isolated by Zwicky in 1914, and structurally solved in 1960 [73,74]. In vitro experiments reveal various pharmacological roles, such as an effective inhibition of 5-HT reuptake, while mesembrenone inhibits both phosphodiesterase type 4 isoenzyme and 5-HT reuptake [75,76]. ...
Article
Full-text available
The misuse of psychoactive substances is attracting a great deal of attention from the general public. An increase use of psychoactive substances is observed among young people who do not have enough awareness of the harmful effects of these substances. Easy access to illicit drugs at low cost and lack of effective means of routine screening for new psychoactive substances (NPS) have contributed to the rapid increase in their use. New research and evidence suggest that drug use can cause a variety of adverse psychological and physiological effects on human health (anxiety, panic, paranoia, psychosis, and seizures). We describe different classes of these NPS drugs with emphasis on the methods used to identify them and the identification of their metabolites in biological specimens. This is the first review that thoroughly gives the literature on both natural and synthetic illegal drugs with old known data and very hot new topics and investigations, which enables the researcher to use it as a starting point in the literature exploration and planning of the own research. For the first time, the conformational analysis was done for selected illegal drugs, giving rise to the search of the biologically active conformations both theoretically and using lab experiments.
... The psychotropic effect is due to the substances extracted into saliva by chewing a dried plant (Kanna) or a fermented plant (Kougoed). [72,86] Acute oral consumption of 25 mg of an S. tortuosum extract is reported to affect the amygdala in humans and reduce anxiety. [87] Supplementation of S. tortuosum extract (0.4 % of total alkaloids) for 3 weeks led to an increase in executive functions. ...
... This set a tone in the investigation of significantly important microbial community that has a symbiotic interactions with plants [6]. S. tortuosum L. commonly known as kougoed is a native medicinal plant that has been used in indigenous tribes for stress relief, depression, as a painkiller, alleviate hunger and overall mood-enhancer [7]. Hence, S. tortuosum L. was selected in the current study for the screening of endophytic fungi that exhibit antifungal activity against fungal pathogens. ...
Article
Full-text available
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.
... The psychotropic effect is due to the substances extracted into saliva by chewing a dried plant (Kanna) or a fermented plant (Kougoed). [72,86] Acute oral consumption of 25 mg of an S. tortuosum extract is reported to affect the amygdala in humans and reduce anxiety. [87] Supplementation of S. tortuosum extract (0.4 % of total alkaloids) for 3 weeks led to an increase in executive functions. ...
Article
This review focuses on four new product categories of food supplements: pre‐workout, fat burner/thermogenic, brain/cognitive booster, and hormone/testosterone booster. Many food supplements have been shown to be contaminated with unauthorized substances. In some cases, the ingredients in the new categories of dietary supplements were medicinal products or new synthetic compounds added without performing clinical trials. Some of the new ingredients in dietary supplements are plant materials that are registered in the pharmacopoeia as herbal medicines. In other cases, dietary supplements may contain plant materials that have no history of human use and are often used as materials to “camouflage” stimulants. In the European Union, new ingredients of dietary supplements, according to European Food Safety Authority or unauthorized novel food. Furthermore, selected ingredients in dietary supplements may be prohibited in sports and are recognized as doping agents by World Anti‐Doping Agency.
... Moreover, it has been shown that celecoxib significantly reduced TNF-α and IL-6 cytokine levels in mice infected with influenza-A when compared to controls [302], further emphasizing the anti-inflammatory role of COX-2 inhibitors in viral infections. Celecoxib also has potential beneficial mood elevating effects, as an adjunctive treatment [78], that could contribute towards clinical improvement of neuropsychiatric Sceletium tortuosum ↓ anxiety, depression [379] anti-inflammatory [284] ↓ viral enzymes and proteases [285] Thymoquinone ↑ spatial memory and slowdown of Alzheimer's disease complications [289,380] ↓ NO and ROS; modulating (inhibit) NF-κB and antioxidant enzyme nuclear factor 2 heme oxygenase-1 (Nrf2/HO-1) [289,290,381] ↓ viral entry into host cell [291] Alpha-2-AR modulators Clonidine ↓ psychosis, anxiety [298,299] -↓ viral replication [ ...
Article
Full-text available
The recent outbreak of the corona virus disease (COVID-19) has had major global impact. The relationship between severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection and psychiatric diseases is of great concern, with an evident link between corona virus infections and various central and peripheral nervous system manifestations. Unmitigated neuro-inflammation has been noted to underlie not only the severe respiratory complications of the disease but is also present in a range of neuro-psychiatric illnesses. Several neurological and psychiatric disorders are characterized by immune-inflammatory states, while treatments for these disorders have distinct anti-inflammatory properties and effects. With inflammation being a common contributing factor in SARS-CoV-2, as well as psychiatric disorders, treatment of either condition may affect disease progression of the other or alter response to pharmacological treatment. In this review, we elucidate how viral infections could affect pre-existing psychiatric conditions and how pharmacological treatments of these conditions may affect overall progress and outcome in the treatment of SARS-CoV-2. We address whether any treatment-induced benefits and potential adverse effects may ultimately affect the overall treatment approach, considering the underlying dysregulated neuro-inflammatory processes and potential drug interactions. Finally, we suggest adjunctive treatment options for SARS-CoV-2-associated neuro-psychiatric symptoms.
Article
Full-text available
This study emphasizes the critical role of antioxidants in protecting human health by counteracting the detrimental effects of oxidative stress induced by free radicals. Antioxidants-found in various forms such as vitamins, minerals, and the phytochemicals abundant in fruits and vegetables-neutralize free radicals by stabilizing them through electron donation. Specifically, flavonoid compounds are highlighted as robust defenders, addressing oxidative stress and inflammation to avert chronic illnesses like cancer, cardiovascular diseases, and neurodegenerative diseases. This research explores the bioactive potential of flavonoids, shedding light on their role not only in safeguarding health, but also in managing conditions such as diabetes, cancer, cardiovascular diseases, and neurodegenerative diseases. This review highlights the novel integration of South African-origin flavonoids with nanotechnology, presenting a cutting-edge strategy to improve drug delivery and therapeutic outcomes. This interdisciplinary approach, blending traditional wisdom with contemporary techniques, propels the exploration of flavonoid-mediated nanoparticles toward groundbreaking pharmaceutical applications, promising revolutionary advancements in healthcare. This collaborative synergy between traditional knowledge and modern science not only contributes to human health, but also underscores a significant step toward sustainable and impactful biomedical innovations, aligning with principles of environmental conservation.
Article
Full-text available
The intranasal route of drug administration offers an opportunity to bypass the blood–brain barrier and deliver compounds directly into the brain. Scientific evidence exists for medicinal plants (e.g., Centella asiatica and Mesembryanthemum tortuosum) to treat central nervous system conditions such as anxiety and depression. The ex vivo permeation of selected phytochemicals (i.e., asiaticoside and mesembrine) has been measured across excised sheep nasal respiratory and olfactory tissue. Permeation studies were conducted on individual phytochemicals and C. asiatica and M. tortuosum crude extracts. Asiaticoside exhibited statistically significantly higher permeation across both tissues when applied alone as compared to the C. asiatica crude extract, while mesembrine permeation was similar when applied alone or as M. tortuosum crude extract. Permeation of all the phytocompounds was similar or slightly higher than that of the drug atenolol across the respiratory tissue. Permeation of all the phytocompounds was similar to or slightly lower than that of atenolol across the olfactory tissue. In general, the permeation was higher across the olfactory epithelial tissue than across the respiratory epithelial tissue and therefore showed potential for direct nose-to-brain delivery of the selected psychoactive phytochemicals.
Article
With the readily prepared iron porphyrin complex as a catalyst and starting with alkyl azides, a panel of nitrogen-containing skeletons representing the families of natural alkaloids and bioactive compounds could be prepared in good yields.
Chapter
Mesembryanthemum tortuosum L. (Aizoaceae) was previously classified as Sceletium tortuosum and is still widely referred to under that name in literature. Locally, the plant is known as ‘kanna’. The small scrambling succulent is endemic to South Africa and is found in the arid areas of the Western, Eastern and Northern Cape provinces. For centuries, the Khoi and San people used the aerial parts in the form of a masticant or infusion, as a mood enhancer, to promote sleep and to soothe digestive conditions. After traditional fermentation to boost its psychoactive properties, the remedy is referred to as ‘kougoed’. The plant has been fully commercialised and selected chemotypes are cultivated as a source of raw material. Products are used for the management of mild depression, anxiety, insomnia, weak appetite, stress, bulimia, obsessive compulsive disorder and to alleviate drug-dependence. The psychoactive properties of the plant are attributed to the presence of mesembrine-type alkaloids. This monograph is a record of the ethnobotany, and the extensive research carried out to study the phytochemistry, in vitro and in vivo biological and pharmacological properties of M. tortuosum, as well as its toxicity profile. High-performance thin-layer chromatography (HPTLC) and ultra-performance liquid chromatography coupled to mass spectrometry (UPLC–MS) were used to establish typical chemical fingerprints of the plant. The marker compounds, mesembrenol, mesembranol, mesembrenone and mesembrine, were identified after both HPTLC and UPLC–MS analyses.
Article
Ethnopharmacological relevance The Aizoaceae is one of the largest succulent plant families. Most members of the family are ornamental and form part of specialist succulent collections. The exceptional diversity of the Aizoaceae is not only limited to its growth forms, habitat, and chemistry, but is also reflected in its many traditional uses. Selected species are well known for their use in traditional medicines, with recent scientific studies validating their biological activity. Aim of the study Herein, this review aimed to articulate foundational and current global research endeavors related to the traditional uses and pharmacological activities of the Aizoaceae. Materials and methods Research articles and search terms related to the ethnopharmacology and bioactivities of the Aizoaceae between 1940-2022 were evaluated using electronic databases such as Google Scholar, PubMed, ScienceDirect, Scopus, JSTOR, and Web of Science. Results Popular Aizoaceae genera including Mesembryanthemum, Trianthema, and Tetragonia are noted for their cultural value and are key components in herbal medicines for the treatment of a myriad of disorders. Isolated bioactive compounds isolated from selected species demonstrated varied antimicrobial, antioxidant, and neuroprotective functions in basic pharmacological studies. However, most studies lacked reliable correlation to in vivo activity and did not adequately validate the safety and efficacy of potential therapeutic compounds. Conclusions While the cultural and therapeutic value of popular Aizoaceae species have been highlighted in the literature, there remains glaring inconsistencies among other related species. Data deficiency may be ameliorated by further studies focused on taxonomic markers, chemical characterization and underlying molecular mechanisms of activity of a wider pool of species to enhance our knowledge of this hyperdiverse family.
Article
Phosphodiesterase 4 (PDE4), the largest member of PDE family, is highly expressed in mammalian brain. It selectively hydrolyzes the second messenger cyclic adenosine monophosphate (cAMP), a correlate of brain functions including learning, memory and cognitive abilities. Its inhibition is beneficial to counteract cognitive deficits. Thus, targeting PDE4 may be a viable strategy for cognitive improvement. Currently, many PDE4 inhibitors have been discovered but with a great hurdle in clinical development due to adverse effects such as emesis. Analysis of PDE4 subtypes and discovery of subtype specific regulators indicate therapeutic benefits with improved safety in preclinical and clinical models. Herein, we summarize PDE4 structure, describe PDE4 mediated signaling pathways, review the role of individual PDE4 subtypes and discuss the development of PDE4 inhibitors for cognitive improvement, trying to give an insight into the strategy for cognitive improvement with PDE4 inhibitors in future.
Article
Full-text available
The relationship between man and substances that have abuse potentials, and whose use has been associated with the development or progression of substance use disorders has continued to evolve in terms of geography, economic implications, and time. History shows that local plants with psychoactive constituents can get exported worldwide through global travel, commerce, or even conquest. Time and globalization also change people's relationship with substances of abuse; hence, an area that was initially alien to certain substances might evolve to becoming a trafficking hub, and then a destination. A case in point is Africa where a rapidly increasing prevalence of substance use/abuse and substance use disorder among adolescents and young adults is putting enormous strain on the economy, healthcare system, and society at large. However, there appears to be a paucity of scientific literature and data on the epidemiology, risk assessment, and contributing factors to substance use and the development of substance use disorders across Africa. In this narrative review, we examine extant literature (PubMed, Google scholar, Medline) for information on the prevalence, trends, and influencers of substance use and the development of substance use disorders. This is with a view of understanding the determinants of substance use and factors that influence the development of substance use disorders in the region, and how this information can be channeled towards developing a comprehensive intervention and treatment program.
Article
Full-text available
Globally, the search for safe and potent natural-based treatment for depression is receiving renewed interest given the numerous side-effects associated with many existing drugs. In South Africa, the use of plants to manage depression and related symptoms is fairly documented among different ethnic groups. In the current study, we reviewed existing ethnobotanical, ethnopharmacological and phytochemical studies on South African medicinal plants used to manage depression. Electronic databases were accessed for scientific literature that meets the inclusion criteria. Plants with ethnobotanical evidence were subjected to a further pharmacological review to establish the extent (if any) of their effectiveness as antidepressants. Critical assessment resulted in 20 eligible ethnobotanical records, which generated an inventory of 186 plants from 63 plant families. Due to the cultural differences observed in the definition of depression, or lack of definition in some cultures, most plants are reported to treat a wide range of atypical symptoms related to depression. Boophone disticha, Leonotis leonurus and Mentha longifolia were identified as the three most popular plants, with over eight mentions each from the ethnobotanical records. The dominant families were Asteraceae (24), Fabaceae (16), Amaryllidaceae (10), and Apocynaceae (10) which accounted for about 32% of the 186 plants. Only 27 (≈14.5%) of the plants have been screened for antidepressant activity using in vitro and in vivo models. Agapanthus campanulatus, Boophone disticha, Hypericum perforatum, Mondia whitei and Xysmalobium undulatum, represent the most studied plants. Phytochemical investigation on nine out of the 27 plants revealed 24 compounds with antidepressant-like effects. Some of these included buphanidrine and buphanamine which were isolated from the leaves of Boophone disticha, Δ⁹-tetrahydrocannabinol, cannabidiol and cannabichromene obtained from the buds of Cannabis sativa and carnosic acid, rosmarinic acid and salvigenin from Rosmarinus officinalis, A significant portion (≈85%) of 186 plants with ethnobotanical records still require pharmacological studies to assess their potential antidepressant-like effects. This review remains a valuable reference material that may guide future ethnobotanical surveys to ensure their robustness and validity as well as database to identify promising plants to screen for pharmacology efficacy.
Article
Different routes of access to mesembrine alkaloids uniquely produced by the medicinal succulent Sceletium tortuosum (Aizoaceae) are thus highly sought after in the natural products sector. In order to develop a biotechnological method, the establishment of in vitro microshoot and callus suspension cultures was investigated using in vitro seedlings of S. tortuosum. The production of mesembrine and other alkaloid derivatives in vitro was monitored using high-throughput ultra-high performance liquid chromatography-mass spectrometry in regenerated microplant and callus cultures. Microshoots were transferred to a shoot multiplication medium after initiation on media with factorial combinations of 1-naphthylacetic acid and N⁶-benzyladenine at 0–1 mg/L and 1–5 mg/L, respectively. Persistent carryover effects associated with the initiation procedures led to four dominant morphotypes. A drier Micropore™ seal environment reduced the number of propagules but the cultures exhibited greater proportions of healthy plantlets (88%) even though the incidence of a red coloured pigment was higher, recorded at 100% in some of the lines. Using a semi-in vitro technique, 96% of in vitro derived plants survived ex vitro. Microshoot cultures, pre-treated with a dehydration step, accumulated four key biomarkers with mesembrine (3270.9 mg/kg), mesembranol (4738.8 mg/kg), mesembrenol (333.1 1 mg/kg), and Δ⁴- mesembrenone (29.9 mg/kg) (dry weight) at levels comparable to wild types. Δ⁷-Mesembrenone, while detected in the microshoots, was not present in callus cultures. The reported mass propagation strategies are opportune for offering an alternative source to the mesembrine alkaloids currently used in clinical herbal formulations.
Article
Asymmetric total synthesis of (−)-sila-mesembranol, the silicon analog of the natural alkaloid (−)-mesembranol has been achieved in 3.3% yield over 11 steps. The chiral silicon center was enantioselectively constructed via...
Chapter
Central nervous system disorders such as anxiety, depression, and Alzheimer’s occur as a result of the imbalance of neurotransmitters such as acetylcholine (Ach), dopamine (DA), serotonin (5-HT), and/or γ-aminobutyric acid (GABA). Such disorders may lead to emotional changes as well as impaired cognitive functions. Plants have been the predominant source of medicines throughout the vast majority of human history and remain so today outside of industrialized societies. Many plants are known for their anxiolytic, antidepressant, and memory-enhancing properties. Moreover, phytoconstituents, particularly alkaloids, have proven effectiveness as psychoactive lead drugs. In this chapter, we will have an overview of the most important psychoactive, neuroprotective, and antidepressant plants and phytoconstituents with emphasis on their mechanism of action.
Article
Full-text available
The article analyses the distinctive experience of self-medication in South Africa, where the preferences of racial and ethnic groups structured a differentiated consumption of herbs, home and folk remedies, patent and proprietary medicines, and pharmaceuticals. Also examined are the interlocking agencies of missionaries, traders, storekeepers and pharmacists in the creation of regional diversity within an evolving medical market. The article indicates that sufferers developed hybrid and plural forms of self-medication that were historically and culturally variable as a result of natural and manufactured products becoming increasingly accessible and affordable. These provided attractive substitutes and/or complements to the medicines of both 'western' and traditional doctors. © The Society for the Social History of Medicine 2005, all rights reserved.
Article
Full-text available
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.
Article
Full-text available
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.
Article
Full-text available
25 Amaryllidaceae alkaloids belonging to different skeletal types were evaluated for their cytotoxic activity against one murine non-tumoral cell line (LMTK) and two human tumoral cell lines (Molt4 and HepG2) according to established protocols. Significant differences of activity related with the type of skeleton of the tested alkaloids could be observed. Pretazettine (22) was among the most active compound among the 25 tested alkaloids on the Molt4 lymphoid cells, but was inactive against HepG2 hepatoma. On the other hand, lycorenine (11) was found to be the most cytotoxic compound against HepG2 hepatoma, even though it appears to be active against Molt4 cells. Almost all of the tested alkaloids showed cytotoxic activity against fibroblastic LMTK cells. Only mesembrenone (25) showed some specificity against Molt4 cells in comparison to LMTK cells.
Patent
There is disclosed the use of mesembrine and related compounds (e.g. mesembranol, mesembranone) as scrotonin-uptake inhibitors, pharmaceutical compositions comprising such compounds or dry material or an extract of plants from the Mesembryanthemaceae family (e.g. Sceletium Sceletium (Aizoaceae) tortuosum) containing a standardized content of said compounds, for use in the treatment of depressive states, psychological or psychiatric disorders with an anxiety component, alcohol and drug dependence, bulimia nervosa and obsessive-compulsive disorders. Also disclosed are new derivatives of mesembrine.
Article
From S. namaquense L. Bolus, we have isolated the known base tortuosamine (7) and two new alkaloids, 3′-methoxy-4′-O-methyljoubertiamine (6) and (-)-mesembrane (2) the structures of which have been established by spectroscopic and X-ray methods. Previous suggestions concerning the absolute configuration of alkaloids of the 3a-aryl-cis-octahydroindole ring system are confirmed by an X-ray analysis of (-)-mesembrane hydrochloride monohydrate which crystallizes in the monoclinic system, space group P21, with a = 14.50(1), b = 8.02(1), c = 7.57(1) Å, β= 93.4(1)°, Z = 2. The crystal structure was solved by direct methods and refined by least-squares calculations to R 0.055 over 1 158 reflections from diffractometer measurements. The absolute configuration was established by the anomalous dispersion effect. The c.d. spectrum of (-)-mesembrine, considered as an axial β-aminoketone, is shown to exhibit normal octant behaviour.
Chapter
This chapter focuses on mesembrine alkaloids. The mesembrine alkaloids are a group of alkaloids named after the most important representative, mesembrine. The basic skeleton of these alkaloids is formed by mesembrane, an N-methyl-3a-(3′4′-dimethoxyphenyl)-cis-octahydroindole. The mesembrine alkaloids are closely related to the 5,10b-ethanophenanthridine group of the Amaryllidaceae alkaloids, which are derived from crinane. Mesembrine, N-methyl-3a-3′4′-dimethoxyphenyl)-6-oxo-cis-octahydroindole, is the most important alkaloid of the mesembrine group. It was isolated as the hydrochloride because the base is an uncrystallizable oil. Mesembrine gives a number of color reactions. The mesembrine alkaloids can be separated chromatographically by the ascending method on paper, impregnated with a solution of formamide in acetone (1: 4), with the solvent systems A (methyl ethyl ketone:heptane = 2 : 3) and B (methyl ethyl ketone:xylene = 1:l), in an atmosphere saturated with ammonia. After spraying with Dragendorff reagent, an extract from S. namaquense showed at least nine alkaloids. The Rf values of the mesembrine alkaloids are also presented in the chapter.
Article
The structures of partial racemic Sceletium alkaloid A4 and tortuosamine are shown by spectral and chemical evidence to represent a new structural type of Sceletium alkaloid.
Article
From S. namaquense L. Bolus, we have isolated the known base tortuosamine (7) and two new alkaloids, 3′methoxy-4′-O-methyljoubertiamine (6) and (–)-mesembrane (2) the structures of which have been established by spectroscopic and X-ray methods. Previous suggestions concerning the absolute configuration of alkaloids of the 3a-aryl-cis-octahydroindole ring system are confirmed by an X-ray analysis of (–)-mesembrane hydrochloride monohydrate which crystallizes in the monoclinic system, space group P21, with a= 14.50(1), b= 8.02(1), c= 7.57(1)Å, β= 93.4(1)°, Z= 2. The crystal structure was solved by direct methods and refined by least-squares calculations to R 0.055 over 1 158 reflections from diffractometer measurements. The absolute configuration was established by the anomalous dispersion effect. The c.d. spectrum of (–)-mesembrine, considered as an axial β-aminoketone, is shown to exhibit normal octant behaviour.
Article
The structure of the title alkaloid is shown by spectral evidence and direct method X-ray analysis to embody a 2,3-disubstituted pyridine ring in a novel variant of the known alkaloid ring system of the mesembrine series.
Article
The structures of five new alkaloids are reported. Sceletium alkaloid A4 (3) is a new type of Sceletium alkaloid containing a tetracyclic ring system and N-formyltortuosamine (8) is a ring C seco derivative of 3. Three additional members of the 3a-aryloctahydroindole class are described by the structures of the phenolic base, 4′-O-demethylmesembrenone (12), Δ7-mesembrenone (7), and sceletenone (15). The latter constitutes the prototype of a monooxyaryl member of this class. A unified biogenetic scheme which accounts for the origins of the various ring systems of the different classes of Sceletium alkaloids is presented.
Article
The structures of five new alkaloids are reported. These include N-acetyltortuosamine (6), the dihydropyridone base (5) related to Sceletium alkaloid A4 (3), and three new alkaloids with the joubertiamine (2) skeleton represented by 4-(3,4-dimethoxyphenyl)-4-[2-(acetylmethylamino)ethyl]cyclohexanone (20), 4-(3-methoxy-4-hydroxyphenyl)-4-[2-(acetyhnethylamino)ethyl]cyclohexadienone (24), and (-)-3′-methoxy-4′-O-methyljoubertiaminol (13). The stereochemistry of joubertinamine (18) is suggested by 1H NMR spectral data.
Article
The relative configurations of the epimeric alcohols, (-)-mesembranol (2) and (-)-6-epimesembranol (3), have been established by spectral studies of the alcohols and their O-acetyl derivatives 4 and 5. Supporting evidence for the configurational assignments is presented from the saponification rates of 4 and 5 and rates of acetylation of the alcohols. In the latter reaction an unusually facile acetylation of 6-epimesembranol is consistent with neighboring group participation by the nitrogen to account for the rate enhancement. Analysis of the nmr spectrum of the alkaloid mesembrine indicates that it also exists predominantly with ring B in the chair conformation 1A in which the aryl substituent is quasi-axial. Interpretation of the CD spectrum of mesembrine on the basis of this conformation for ring B leads to a reassignment of the absolute configuration of mesembrine as indicated by structure 1. A discussion of the conformational features of mesembrine is presented.
Article
Six Sceletium (Mesembrine) alkaloids (l)-(6) are identified together with NN-dimethyltyramine (10) as constituents of Sceletium subvelutinum. The alkaloids (l)-(6) incorporate label from [7-14C]tyramine [as (8)]and 3-([35-3H2]-4-hydroxyphenyl)propionic acid (13) as expected; notably 3-([35-3H2]-4-hydroxyphenyl)propanal (15) is a more efficient alkaloid precursor than is the acid (13) and the aldehyde is deduced to be a key intermediate in the biosynthesis of Sceletium alkaloids. The N-methylamine (21) is an important late intermediate in the biosynthesis of Sceletium alkaloids or is closely related to that intermediate. The amine (20) is less efficiently incorporated than (22)=(21) is.
Article
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.
Article
This paper provides an overview of the expansive South African biodiversity, which contributes to the historical use of medicinal plants and the large existence of traditional healers. It also underscores the lack of acknowledgment that traditional medicines are given by local authorities and the flaws that exist within present validation systems. The author also briefly highlights a few indigenous South African medicinal plants to draw attention to some recent developments.
Article
The use by the Khoisan of South Africa of Sceletium plants in psychoactive preparations has often been alluded to in the literature. However, much of it is fragmentary and contradictory. The current review reassembles the historical data recorded over a 300-year period, describes techniques for the preparation and use of "kougoed' from plants of Sceletium and documents the subjective experiences of a number of contemporary users. Apart from chewing the dried product, after "fermentation', there are reports of uses as tinctures for sedation and analgesia, chewing the material directly and smoking the residue after chewing. The symbolic connections of Sceletium with eland antelopes, the "trance animals' par excellence of the San hunter-gatherers is noted. Observations by Paterson (1789) and reports of contemporary users indicate a synergism and potentiation with smoked Cannabis. There is no evidence to support the view that "kougoed' or Sceletium alkaloids are hallucinogenic. The alkaloid distribution in Sceletium and other members of the family Mesembryanthemaceae are considered. Chemical studies have indicated as many as nine alkaloids in Sceletium which fall into three distinct structural categories. Mesembrine, the alkaloid first isolated and named is not the dominant constituent of plants and is weakly narcotic. Evidence is assembled to suggest that traditional and contemporary methods of preparation serve to reduce levels of potentially harmful oxalates, which are found in Sceletium and other Mesembryanthemaceae. It is concluded that there is a need for further pharmacological studies on these alkaloids, based on their narcotic-anxiolytic properties, strong synergism with other psychomimetics, moderate toxicity and anti-cancer activity.
Article
Cyclic AMP (cAMP) is a key second messenger in all cells. It is compartmentalized within cells and its levels are controlled, as a result of spatially discrete signaling cassettes controlling its generation, detection and degradation. Underpinning compartmentalized cAMP signaling are approximately 20 members of the phosphodiesterase-4 (PDE4) family. The selective inhibition of this family generates profound, functional effects and PDE4 inhibitors are currently under development to provide potential, novel therapeutics for the treatment of inflammatory diseases, such as asthma, chronic obstructive pulmonary disease and psoriasis, as well as treating depression and serving as cognitive enhancers. Here, we delineate the range of PDE4 isoforms, their role in signaling, their structural biology and related preclinical and clinical pharmacology.
Article
The earliest inhabitants of South Africa are believed to be the Khoi-Khoi and San peoples, whose knowledge of economic botany is extensive. Their ethnomedical practice, based on the plant species indigenous to the region, is an oral tradition and particularly susceptible to disruption. The culture of both peoples has during the past 350 years come under increasing threat of extinction, resulting in the likely loss to science of important ethnomedical knowledge. While written records of Khoi-San traditional medical practice are preserved in English, they mainly cover the period from 1800 onward. Earlier written records do exist, but do not appear to have been adequately screened. The present study was undertaken in order to complete the historical written record by critically examining all potential sources of Khoi and San ethnomedical information, for the years 1650-1800. These sources comprised journals of exploratory expeditions, herbarium specimens, published academic works and archival records associated with the activities of the former Dutch East India Company (VOC) at the Cape. The results of the search show that the VOC had a great interest in Khoi and San traditional medicines and attempted to record this knowledge. The VOC archives in particular represent a largely untapped source of ethnomedical information with potential application in health care, new drug development and intellectual property protection.
Governor of the Cape of Good Hope, found on his great journey, 1685
  • Simon
Simon van der Stel, Governor of the Cape of Good Hope, found on his great journey, 1685. Zwicky, E., 1914. “Über channa”. Dissertation. Zurich.
Handbook of Succulent Plants
  • H Jacobsen
Jacobsen, H., 1960. Handbook of Succulent Plants. Vol. III. Mesembryanthemums (Ficoidaceae). Blandford Press, London
Origins and Meanings of Names of South African Plant Genera
  • W P U Jackson
Jackson, W.P.U., 1990. Origins and Meanings of Names of South African Plant Genera. University of Cape Town Ecolab, Cape Town.
Phantastica Meiring, I., 1898. Notes on some experiments with the active principle of Mesembri-anthemum tortuosum
  • L Lewin
Lewin, L., 1998. Phantastica. Park Street Press, Rochester, Vermont. Meiring, I., 1898. Notes on some experiments with the active principle of Mesembri-anthemum tortuosum, L. Transactions of the South African Philosophical Society 9, 48–50.
Personal communication to Dr Nigel Gericke
  • L Mories
Mories, L., 1995. Personal communication to Dr Nigel Gericke. Interview recorded in Afrikaans on analogue audiotape near the farm Ratelkraal in Namaqualand.
Wissenschaftliche Mitteilungen
  • C Hartwich
  • E Zwicky
Hartwich, C., Zwicky, E., 1914. Wissenschaftliche Mitteilungen. Ueber Channa, ein Guussmittel der Hottentotten (Mesembrythanthemum expansum L. und M. tortuosum L.). Apotheker-Zeitung 94, 925-926.
Narcotic Plants. Revised and Enlarged
  • W Emboden
Emboden, W., 1979. Narcotic Plants. Revised and Enlarged. Macmillan Publishing Co., Inc., New York.
Simon van der Stel's Journey to Namaqualand in 1685
  • G Waterhouse
  • G C De Wet
Waterhouse, G., De Wet, G.C., Pheiffer, R.H. (Eds.), 1979. Simon van der Stel's Journey to Namaqualand in 1685. Human & Rousseau, Cape Town.
The Plains of Cambdeboo
  • E Palmer
Palmer, E., 1966. The Plains of Cambdeboo, Revised edition. Jonathan Ball Publishers.
C. Notes upon the isolation of the alkaloidal constituent of the drug ‘channa’ or ‘kougoed’ (Mesembryanthemum anatomicum and M. tortuosum
  • Rimington
Rimington, C., Roets, G.C.S., 1937. C. Notes upon the isolation of the alkaloidal constituent of the drug 'channa' or 'kougoed' (Mesembryanthemum anatomicum and M. tortuosum. Onderstepoort Journal of Veterinary Science and Animal Industry 9, 187-191.