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Effects of mesembrine, mesembrenone and mesembrenol (all at 3 M) in binding and PDE assays. Values are mean of 2 separate assays with bars indicating the upper range. a, 100% block at 5-HT transporter; b, 100% block at PDE4A.

Effects of mesembrine, mesembrenone and mesembrenol (all at 3 M) in binding and PDE assays. Values are mean of 2 separate assays with bars indicating the upper range. a, 100% block at 5-HT transporter; b, 100% block at PDE4A.

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The South African plant Sceletium tortuosum has been known for centuries for a variety of traditional uses, and, more recently, as a possible source of anti-anxiety or anti-depressant effects. A standardised extract Zembrin(®) was used to test for pharmacological activities that might be relevant to the ethnopharmacological uses, and three of the m...

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... mesembrenone and mesembrine were tested at 3 M in the binding and enzymatic assays in which the Sceletium extract had previously been shown to have activity. The results are summarised in Fig. 5. All three alkaloids blocked binding to the 5-HT transporter, but had little effect on binding at GABA- A and GABA-B receptors, 2 -opioid receptors, -opioid receptors, cholecystokinin-1 (or -A) receptors, EP4 prostaglandin receptors and melatonin-1 receptors. Only mesembrenone had potent effects at PDE4A and ...

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... Bulb infusions of this plant are drank by South African traditional healers and patients (Neergaard et al., 2009), and weak decoctions made from the bulb scales of are taken by mouth or as enemas for headache (Hutchings et al., 1996;Van Wyk et al., 1997). Sceletium tortuosum has recently attracted attention for its long history of use in traditional medicine and its possible use in promoting well-being and treating depression and/ or stress (Sobiecki, 2002;Harvey et al., 2011). It was likely to have been used in the prehistoric times by hunter-gatherers and pastoralists as a mood-altering substance (Van Wyk and Gericke, 2000). ...
... Several biological assays have been used to investigate the antidepressant-like effects of South African medicinal plants, including in vitro biological assays (Nielsen et al., 2004;Sandager et al., 2005;Neergaard et al., 2009;Harvey et al., 2011;Stafford et al., 2013) and in vivo assays conducted using rodent models of depression (Machado et al., 2007;Machado et al., 2009;El-Alfy et al., 2010;Ahmadpoor et al., 2019;Rabiei and Setorki, 2019). The mechanism of action of most psychoactive compounds involves endocrine modulation of specific molecules in the CNS, modification of multiple biological effects on reuptake and/or receptor binding of various monoamines and interacting with neuronal receptors (Saki et al., 2014;Alrashedy and Molina, 2016). ...
... The observed antidepressant pharmacological activities of H. perforatum appear to be attributed to adhyperforin, hypericin and pseudohypericin, previously isolated from dry extracts, with antidepressant activities as effective as conventional antidepressants desipramine and trimipramine (Öztürk et al., 1996;Tian et al., 2014). An ethanol extract from Sceletium tortuosum, with alkaloids mesembrine, mesembrenone and mesembrenol, has shown to inhibit serotonin uptake (Harvey et al., 2011). ...
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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.
... An approach of using metabolomic tools to tentatively identify key metabolites in Sceletium was used initially to generate a list of molecules that may be responsible for the mood elevation activity of Sceletium (2,22). These molecules could then be tested in silico against a number of receptors that assist in the modulation of Alzheimer's, Parkinson's, anxiety and depression. ...
... The proteins that were investigate for in silico screening were the 5-HT serotonin transporter (5I75) (23), the GABA-A receptor (6D6T) (24), and the acetylcholinesterase (AChE) enzyme (1QTI) (25). These proteins and enzymes were selected on the basis that they respond best to mesembrine alkaloids in a wide screening of a receptor binding assay performed by Harvey et al. (22). The acetylcholinesterase enzyme was selected on the basis of previously reported activity of Sceletium to assist with cognitive enhancement (Alzheimer's) (7,26,27). ...
... There have been no assays testing any alkaloids other than the mesembrine-type phytochemicals. Harvey et al. (22) reported little to no inhibition by isolated alkaloids (mesembrenol, mesembrenone and mesembrine alkaloids) on the GABA-A system. However, it was reported that the standardized extract Zembrin R , showed >80% inhibition of binding in that particular study. ...
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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 MS E 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 .
... total Sceletium alkaloids. The reported pharmacological effects of Zembrin® include inhibition of the phosphodiester-4 (PDE4) enzyme as well as the inhibition of the serotonin (5-hydroxytryptamine, 5-HT) transporter (5-HTT, also known as SERT) (Harvey et al., 2011). Inhibition of PDE4 results in the elevation of the intracellular cyclic adenosine monophosphate (cAMP) levels with resultant modulation of second messenger effects and has been implicated in the regulation of anxiety and depression in animals models (O'Donnell and Zhang, 2004). ...
... 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). ...
... The application of multiple predictive tools was to allow for the reproducibility of the results while validating the methods. Harvey et al. (2011), in a study of the effects of a standardised ethanolic extract of M. tortuosum, commercially available as Zembrin® and the purified isolated alkaloids, found that the extract exhibited potent inhibitory effects on the SERT (IC 50 4.3 μg/mL) as well as on PDE4 (IC 50 8.5 μg/mL), but no effect was observed on other PDEs. Mesembrenol, mesembrenone, and mesembrine inhibited binding to the SERT but showed minimal effect at GABA receptors. ...
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.
... They could identify most of these metabolites in both rat urine and human liver preparations. Harvey et al. (2011) tested the pharmacological effects of the ethanolic extracts of S. tortuosum along with the pure mesembrine, mesembrenone and mesembrenol. The plant extract and the purified alkaloids were tested individually on a panel of receptors, enzymes, other drug targets, and for cytotoxic activities on mammalian cells using radioligand binding, phosphodiesterase activity, cholinesterase activity, and cytotoxicity assays. ...
... The actions of S. tortuosum on serotonin and GABA (Harvey et al., 2011) may allow it credible utility in treating anxiety states (Brand et al., 2015). Indeed, the Koi-San of Africa have long since used S. tortuosum plant extracts to promote a sense of calm and relieve stress, reduce anxiety, improve mood, and enhance concentration . ...
... serotonin syndrome when SSRIs are co-administered with for instance Saint John's wort (Sarris, 2018). Given the serotonergic actions of ST (Table 4) (Harvey et al., 2011), and similar supportive evidence from our laboratory (Gericke, 2020), such studies need to be undertaken. These real-world issues, plus that plant constituents may have interacting effects with one another, warrant dedicated research into the pharmacokinetic and pharmacological profiles of herbal medicines (Sarris, 2018). ...
... They could identify most of these metabolites in both rat urine and human liver preparations. Harvey et al. (2011) tested the pharmacological effects of the ethanolic extracts of S. tortuosum along with the pure mesembrine, mesembrenone and mesembrenol. The plant extract and the purified alkaloids were tested individually on a panel of receptors, enzymes, other drug targets, and for cytotoxic activities on mammalian cells using radioligand binding, phosphodiesterase activity, cholinesterase activity, and cytotoxicity assays. ...
... The actions of S. tortuosum on serotonin and GABA (Harvey et al., 2011) may allow it credible utility in treating anxiety states (Brand et al., 2015). Indeed, the Koi-San of Africa have long since used S. tortuosum plant extracts to promote a sense of calm and relieve stress, reduce anxiety, improve mood, and enhance concentration . ...
... serotonin syndrome when SSRIs are co-administered with for instance Saint John's wort (Sarris, 2018). Given the serotonergic actions of ST (Table 4) (Harvey et al., 2011), and similar supportive evidence from our laboratory (Gericke, 2020), such studies need to be undertaken. These real-world issues, plus that plant constituents may have interacting effects with one another, warrant dedicated research into the pharmacokinetic and pharmacological profiles of herbal medicines (Sarris, 2018). ...
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]. ...
... Eight species were recognized in a revision of the genus Sceletium (which now forms part of the genus Mesembryanthemum) namely S. crassicaule, S. emarcidum, S. exalatum, S. expansum, S. rigidum, S. strictum, S. tortuosum and S. varians [2,9]. Klak et al. [10] provided an alternative classification of the Sceletium group which is shown below, with all major synonyms indicated. ...
... Zem-brin® was found to also be an inhibitor of the phosphodiesterase-4 (PDE4) enzyme. Isolated pure mesembrine, mesembrenone and mesembrenol were found to inhibit PDE4B with IC 50 values of 7.8 μg/ml, 0.47 μg/ml and 16 μg/ml, respectively [2]. While Harvey et al. [2] did not find a significant activity of Zembrin® or isolated mesembrine alkaloids on acetylcholinesterase or cannabinoid receptors, Lubbe et al. [30] reported activity of a sceletium extract on a cannabinoid receptor 1 (CB-1) receptor binding assay, and compounds other than the alkaloids were thought to contribute to this activity. ...
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.
... Although the physiological mechanisms for the anxiolytic and mood-enhancing actions of ZEM have not been fully elucidated, multiple studies have reported underpinning mechanisms to be the inhibition of phosphodiesterase-4 (PDE-4) and the blockade of 5-hydoxytryptamine (5HT) reuptake [3,8]. Previous investigations have shown that PDE-4 inhibition results in increased cyclic-adenosine monophosphate (cAMP) signaling in neural tissue, thereby increasing cellular signal transduction [9,10]. ...
... Bolstering this, psychological disorders, such as depression, have been shown to have diminished neuronal cAMP signaling [11]. ZEM has been shown by multiple groups to be a strong PDE-4 inhibitor [8,12]. For example, Harvey et al. reported that ZEM potently inhibited human myeloid cell-derived PDE-4 activity [8]. ...
... ZEM has been shown by multiple groups to be a strong PDE-4 inhibitor [8,12]. For example, Harvey et al. reported that ZEM potently inhibited human myeloid cell-derived PDE-4 activity [8]. 5HT reuptake and transport has also been shown to be blunted by ZEM treatment [8,13]. ...
Article
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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.
... 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). ...
... 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). ...
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.
... They could identify most of these metabolites in both rat urine and human liver preparations. Harvey et al. (2011) tested the pharmacological effects of the ethanolic extracts of S. tortuosum along with the pure mesembrine, mesembrenone and mesembrenol. The plant extract and the purified alkaloids were tested individually on a panel of receptors, enzymes, other drug targets, and for cytotoxic activities on mammalian cells using radioligand binding, phosphodiesterase activity, cholinesterase activity, and cytotoxicity assays. ...
... The actions of S. tortuosum on serotonin and GABA (Harvey et al., 2011) may allow it credible utility in treating anxiety states (Brand et al., 2015). Indeed, the Koi-San of Africa have long since used S. tortuosum plant extracts to promote a sense of calm and relieve stress, reduce anxiety, improve mood, and enhance concentration . ...
... serotonin syndrome when SSRIs are co-administered with for instance Saint John's wort (Sarris, 2018). Given the serotonergic actions of ST (Table 4) (Harvey et al., 2011), and similar supportive evidence from our laboratory (Gericke, 2020), such studies need to be undertaken. These real-world issues, plus that plant constituents may have interacting effects with one another, warrant dedicated research into the pharmacokinetic and pharmacological profiles of herbal medicines (Sarris, 2018). ...
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.
... Modern pharmacology has established that the plants' mesembrine-type alkaloids are responsible for its medicinal properties. These compounds are drug candidates for various neurological, psychological and medical disorders (Gericke and Van Wyk, 2001;Harvey et al., 2011;Coetzee et al., 2016;Kapewangolo et al., 2016;Bennett et al., 2018;Dimpfel et al. 2018). Fresh plant material is the only available alkaloid source for pharmaceutical research, development and manufacture (Elev8 TM , 2017;Krstenansky, 2017). ...
Article
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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.