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Clinical application of South African tea on dementia dog

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... Watt and Breyer-Brandwijk (1962) report Zwicky's contradictory assertion from his research in 1914 that isolated mesembrine had a "cocaine-like activity", although weaker in action, and yet stated that it produced depression of the central nervous system in the frog, the rabbit, and man, rather than the stimulation one would expect from a cocaine-like action. Hirabayashi et al. (2002) reported a safety study of Sceletium tortuosum administration to canines. Milled dry Sceletium tortuosum was given at a dose of 10 mg/kg twice a day to seven healthy beagle dogs, as well as one dog with dementia for 6 days. ...
... The well-established history of use of Sceletium, extant longterm local use, and increasing use of manufactured Sceletium products with no known severe adverse effects, suggests that Sceletium is safe for human consumption. This is further supported by the documented safety in dogs treated with 10 mg/kg Sceletium given twice daily (Hirabayashi et al., 2002) and cats treated with 100 mg/kg per day (Hirabayashi et al., 2004), and dogs with dementia treated with up to 90 mg/kg per day. (Hirabayashi et al., 2005). ...
... The following individuals and institutions are thanked for their invaluable contribution; The South African Museum for permission to photograph and reproduce the painting of Sceletium in the collection known as the Codex Witsenii. Cornelia Klak at the Bolus Herbarium for comments on the taxonomy and nomenclature and Lyndy McGaw for sourcing dated literature in the library at Onderstepoort, David Gordon for providing a copy of his paper "From rituals of rapture to dependence: the political economy of Khoikhoi narcotic consumption", Anne Digby for providing a copy of her paper "Self-medication and the Trade in Medicine within a multi-ethnic context: A case study of South Africa from the mid-nineteenth to mid-twentieth Centuries", Edda Fiegert for hard work in sourcing a copy of Hartwich and Zwicky (1914), Olga Gericke for translating Hartwich and Zwicky (1914), Alan Harvey for providing the graph (Fig. 7) on the effect of synthetic mesembrine on monoamine uptake, Satoru Furukawa for providing copies and translations of the Japanese papers Hirabayashi et al. (2002), Hirabayashi et al. (2004), and Hirabayashi et al. (2005). ...
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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.
... Mesembrenone and mesembranol are less potent in competing for the 5-HT transport site in vitro III.b In vivo preclinical data in canine and feline AD model The efficacy of Zembrin extract in AD was first demonstrated by a group of Japanese veterinarians/pharmacologists in the canine and feline model of AD (80,81,82). In AD research, most of the studies used the rodent transgenic AD models: higher orders of mammals including subhuman primates and aged dogs and cats were seldom examined. ...
... A group of Japanese veterinarian-investigators reported for the first time on Zembrin effects on symptoms of canine cognitive dysfunction (CCD) and feline cognitive dysfunction (FCD ) mirroring AD in humans ( 80,81,82 ). The dog owners referred the aged dogs to the veterinarians for consultation, with the chief complaint of nocturnal excessive and almost continuous barking (80). ...
... A group of Japanese veterinarian-investigators reported for the first time on Zembrin effects on symptoms of canine cognitive dysfunction (CCD) and feline cognitive dysfunction (FCD ) mirroring AD in humans ( 80,81,82 ). The dog owners referred the aged dogs to the veterinarians for consultation, with the chief complaint of nocturnal excessive and almost continuous barking (80). The dogs were screened for core signs of dementia . ...
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Recently with the changing landscape of the aging population and the increase in incidence of Alzheimer’s disease (AD), there has been marked interest to develop strategies to prevent, delay and modify AD. We review the diverse lines of evidence in support of the emerging role of cAMP-mediated Phosphodiesterase (PDE) signalling with respect to aging, inflammation and depression. In view of the link of PDE to Epigenetic complex, targeting PDE through designing modulators and inhibitors of PDE may represent a novel approach in AD therapeutics. We review critically the translational studies of the proprietary Zembrin extract harvested and processed from the South African plant, Sceletium tortuosum, highlighting the dual property of Zembrin in targeting coupling of PDE and serotonin signaling mechanisms in vitro and in vivo models of AD and cognition. The promising clinical findings of Zembrin in cognition suggest that Zembrin extract may merit randomized controlled trials in AD to establish the efficacy and safety in AD.
... These products are sold as herbal teas, dietary supplements and other phytopharmaceutics. However, only some of these products have been scientifically investigated with the greatest quantity of information available for Zembrin R in terms of in vitro and in vivo pharmacological data (4,5) and more recently clinical studies focusing on this particular product as an anxiolytic and anti-depressant phytopharmaceutical (6)(7)(8)(9). In international markets, Sceletium products are classified as food supplements that are also sold in the complementary and alternative medicines sector. ...
... 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). ...
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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 .
... Three exploratory studies using milled M. tortuosum plant material in domestic cats and/or dogs brought to a veterinary clinic, both with and without mental disturbances, demonstrated no adverse reactions and positive effects on mood and behaviour at levels of 20-100 mg/kg bw orally daily for between 7 and 180 days [35][36][37]. ...
... Hirabayashi et al. [35,36] and Hirai et al. [37] found no adverse effects with sceletium powder (assuming 2% alkaloids) in dogs treated with 20 mg/kg per day, in dogs treated with up to 90 mg/kg per day, and in cats treated with 100 mg/kg per day. ...
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.
... Three exploratory studies using milled M. tortuosum plant material in domestic cats and/or dogs brought to a veterinary clinic, both with and without mental disturbances, demonstrated no adverse reactions and positive effects on mood and behaviour at levels of 20-100 mg/kg bw orally daily for between 7 and 180 days [35][36][37]. ...
... Hirabayashi et al. [35,36] and Hirai et al. [37] found no adverse effects with sceletium powder (assuming 2% alkaloids) in dogs treated with 20 mg/kg per day, in dogs treated with up to 90 mg/kg per day, and in cats treated with 100 mg/kg per day. ...
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.
... The veterinarians reported that the Sceletium reduced cage stress and travel stress in cats, and decreased the excessive nocturnal crying and barking of aged cats and dogs with a clinical diagnosis of dementia. These results have been published in Japanese (Hirabayashi et al., 2002;Hirabayashi et al., 2004;Hirabayashi et al., 2005). ...
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Part I The history of the use of kanna, the traditionally used plant material derived from a number of Sceletium species, is given from 1610-1971. This overview includes fragments of history documenting European ships docking in the Cape to search for kanna roots as a “ginseng” to trade in the Far East, and an ethnographic record from the 1700s transcribed directly from //Kabbo, a /Xam San “Bushman” from the Breakwater Convict Station in Cape Town, who gave us the name !k”waï for kaauwgoed, the Dutch name for kanna, and his own account of the uses of the plant. Part II The recent ethnobotany, ethnopharmacology and pre-clinical research on a commercialized standardized extract of Sceletium (trademarked Zembrin®) is given for the period 1995 to 2017. In vitro studies have demonstrated that the major alkaloids of kanna, including mesembrine, mesem- brenone and mesembrenol, are responsible for the psychoactivity of Sceletium, and have dual se- rotonin reuptake inhibitory (SRI) activity and phosphodiesterase-4 (PDE4) inhibitory activity. The effect of the extract of Sceletium tortuosum, Zembrin®, on brain electrical activity has been studied in vivo, demonstrating by discriminant analyses that the quantitative EEG electropharmacogram of the extract plots in close proximity to the plots for Ginkgo biloba, Rhodiola rosea, and also to the first-generation pharmaceutical PDE4 inhibitor Rolipram, indicating the potential of this extract for managing anxiety and depression and enhancing cognitive function. Part III Clinical experience with Sceletium is summarized and the results of pilot randomized, dou- ble-blind, placebo-controlled clinical studies on the extract of Sceletium tortuosum, Zembrin®, are presented, including: • A safety and tolerability study. • A pharmaco-Magnetic Resonance Imaging study. • A study on cognitive function domains using CNS Vital Signs, a computerized neu- rocognitive test battery. • A study looking at changes in brain electrical activity in response to cognitive and emotional challenges; changes in psychometric tests; and changes in the Hamilton Anxiety Scale (HAM-A). Part IV Scenarios on the future of kanna and alkaloids derived from kanna are considered.
... Ve studii na psech (Hirabayashi et al., 2002) nebyly po týdenním podávání Sceletium tortuosum zaznamenány žádné nežádoucí úèinky, u koèek pouze delší spánek a lehká elevace alkalické fosfatázy (Hirabayashi et al., 2004). ...
Article
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Sceletium tortuosum, also known as kanna, is a succulent plant from South Africa. Use of this plant by african indigenous people was recorded more than 300 years ago. Recent studies confirmed the effect of plant compounds on central nervous system, mainly serotonine re-uptake inhibition and antidepressant activity.
... Veterinarian studies in Japan demonstrated that Sceletium tortuosum reduced cage stress and travel stress in companion animal cats, and decreased the excessive crying and nocturnal barking of aged cats and dogs with a clinical diagnosis of dementia (Hirabayashi et al., 2002(Hirabayashi et al., , 2004(Hirabayashi et al., , 2005, while the first clinical case-reports on Sceletium tortuosum described rapid onset of anxiolytic and antidepressant activity, and mentioned anecdotal reports on the use of Sceletium in South Africa for the management of drug addiction at a community treatment centre (Gericke, 2001). ...
Article
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Ethnopharmacological relevance: The endemic succulent South African plant, Sceletium tortuosum (L.) N.E. Br. (synonym Mesembryanthemum tortuosum L.), of the family Mesembryathemaceae, has an ancient oral tradition history of use by San and Khoikhoi people as an integral part of the indigenous culture and materia medica. A special standardized extract of Sceletium tortuosum (Zembrin(®)) has been developed and tested pre-clinically in rats, and clinically in healthy subjects. Aim of the study: The present investigation aimed at the construction of electropharmacograms of Zembrin(®) in the presence of three dosages (2.5, 5.0 and 10.0mg/kg), and comparative electropharmacograms and discriminatory analyses for other herbal extracts, citicoline and rolipram. Material and methods: Seventeen adult Fischer rats were each implanted with a set consisting of four bipolar concentric steel electrodes fixed by dental cement and three screws driven into the scalp. After two weeks of recovery from surgery the animals were adapted to oral administration by gavage and to experimental conditions (45min pre-drug period and 5 hours of recording after a rest of 5 minutes for calming down). Data were transmitted wirelessly and processed using a Fast Fourier Transformation (FFT). Spectral power was evaluated for 8 frequency ranges, namely delta, theta, alpha1, alpha2, beta1a, beta1b, beta2 and gamma power. Results: Zembrin(®) dose dependently attenuated all frequency ranges, to varying degrees. The most prominent was the statistically significant reduction in alpha2 and beta1a waves, correlated with activation of the dopaminergic and glutamatergic transmitter systems respectively. This feature is common to all synthetic and herbal stimulants tested to date. The second strongest effects were reduction in both the delta and the theta frequency ranges, correlated with changes in the cholinergic and norepinephrine systems respectively, a pattern seen in preparations prescribed for neurodegenerative diseases. Theta wave reduction in common with the delta, alpha2 and beta1 attenuation has been noted for analgesic drugs. Attenuation of alpha1 waves emerged during the highest dosage in all brain areas, a feature seen in all antidepressants. Discussion: The electropharmacogram of Zembrin(®) was compared to the electropharmacograms of herbal extracts archived in our database. Extracts of Oenothera biennis and Cimicifuga racemosa gave a very similar electropharmacograms to that of Zembrin(®), and extracts of Ginkgo biloba and Rhodiola rosea gave rather similar electropharmacograms to Zembrin(®). Linear discriminant analysis confirmed these similarities and demonstrated that all three dosages of Zembrin(®) plotted in close neighbourhood to each other. Citocoline, a synthetic compound originally developed for cognitive enhancement, had a similar electropharmacogram to Zembrin(®). Similarity to the electropharmacograms of the synthetic phosphodiesterase-4 inhibitor, rolipram, suggests Zembrin(®) has antidepressant and cognitive function enhancing potentential. Conclusion: The combined results from the electropharmacograms and comparative discriminatory analyses suggest that Zembrin(®) has dose dependent activity, with potential applications as a cognitive function enhancer, as an antidepressant, and as an analgesic.
... No formal toxicological studies have been previously published on S. tortuosum or on extracts of S. tortuosum. Small-scale short-term studies in dogs and cats have been reported (Hirabayashi et al., 2002(Hirabayashi et al., , 2004 with no adverse effects noted after daily administration of dried S. tortuosum plant material for 6 or 7 days. ...
Article
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A well-characterized standardized hydroethanolic extract of a traditionally recognized mak (mild) variety of Sceletium tortuosum, a South African plant with a long history of traditional ingestion, is marketed under the trade name Zembrin® as an ingredient for use in functional foods and dietary supplements. It is standardized to contain 0.35–0.45% total alkaloids (mesembrenone and mesembrenol ≥60%, and mesembrine <20%). A 14-day repeated oral toxicity study was conducted at 0, 250, 750, 2500, and 5000 mg/kg bw/d. A 90-day subchronic repeated oral toxicity study was conducted at 0, 100, 300, 450, and 600 mg/kg bw/d. Because S. tortuosum has a long history of human use for relieving stress and calming, a functional observation battery, including spontaneous locomotor activity measured using LabMaster ActiMot light-beam frames system, was employed. Several parameters, such as locomotion, rearing behavior, spatial parameters, and turning behavior were investigated in the final week of the study. No mortality or treatment-related adverse effects were observed in male or female Crl:(WI)BR Wistar rats in the 14- or 90-day studies. In the 14- and 90-day studies, the NOAELs were concluded as 5000 and 600 mg/kg bw/d, respectively, the highest dose groups tested.
... There have also been a few published in vivo studies with Sceletium tortuosum. In animal studies, repeated oral doses of dry powdered plant material were shown to have no toxic effects in cats and dogs (Hirabayashi et al., 2002(Hirabayashi et al., , 2004. The authors also reported that the plant material had beneficial effects in cats with signs of stress and dogs showing signs clinically diagnosed as dementia. ...
Article
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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 main alkaloids were also tested. A standardised ethanolic extract was prepared from dried plant material, along with the purified alkaloids mesembrine, mesembrenone and mesembrenol. These were tested on a panel of receptors, enzymes and other drug targets, and for cytotoxic effects on mammalian cells. The extract was a potent blocker in 5-HT transporter binding assays (IC(50) 4.3 μg/ml) and had powerful inhibitory effects on phosphodiesterase 4 (PDE4) (IC(50) 8.5 μg/ml), but not other phosphodiesterases. There were no cytotoxic effects. Mesembrine was the most active alkaloid against the 5-HT transporter (K(i) 1.4 nM), while mesembrenone was active against the 5-HT transporter and PDE4 (IC(50)'s<1 μM). The activity of the Sceletium tortuosum extract on the 5-HT transporter and PDE4 may explain the clinical effects of preparations made from this plant. The activities relate to the presence of alkaloids, particularly mesembrine and mesembrenone.
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