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This study revisits the seminal question of the effectiveness of education for sustainable development (ESD) by using a novel longitudinal approach. Scholarly attention in the past decade has been increasingly directed towards the concept of action competence for sustainability. However, little is still known about the effects of ESD as a teaching approach to help develop students' action competence for sustainability. This study therefore adopts a three-wave longitudinal design, tapping into the development of 760 Swedish upper secondary students' self-perceived action competence for sustainability as related to their experience of ESD teaching at their school. We can conclude that ESD has effect on students' action competence for sustainability. Our longitudinal growth models show that it is possible to develop students' action competence, which is affected by their experience of ESD teaching at their school. However, the students did not significantly develop the action competence component confidence under their own influence. Our findings reveal that developing students' action competence by implementing ESD in formal education takes time, and they shed light on the need for longitudinal research studies in the field of ESD.

During the past decade, numerous schools in Sweden have implemented education for sustainable development (ESD) as an explicit guiding approach in teaching. In this paper, we investigate the effect of this approach in comparison with that of pupils taught in ordinary schools. Accordingly, we introduce the concept of sustainability consciousness to represent the holistic view of sustainability. Within the concept of sustainability consciousness, we combine and investigate the environmental, economic, and social dimensions of sustainable development in terms of sustainability knowingness, attitudes, and behavior. A Likert-scale questionnaire with 50 items was developed to evaluate pupils' sustainability consciousness through a nationwide study in Sweden. A total of 1773 pupils from the 6th and 9th grades participated. The results indicated that the ESD profile schools had a small positive effect on the pupils' sustainability consciousness, while in grade 9 the effect was negative. The implications for further ESD implementation are discussed.

Teachers' pro-environmental behaviour, conceptions and attitudes towards nature and the environment were investigated using 47 questions from the BIOHEAD-Citizen questionnaire. The sample included 1,109 pre- and in-service teachers from Sweden and France. Analyses showed only few significant differences between female and male teachers. Forty-one questions were further analysed in terms of ecofeminism. Ecofeminism claims that women and men's conceptions and attitudes towards nature and the environment differ, in the sense that women show higher awareness of environmental issues than men. Our study finds quite poor support for this claim and therefore challenges ecofeminism. This may have implications for environmental education and the perspectives of sustainable development at schools, as our results indicate that there is no reason to fear that male teachers are less engaged with environmental education than female teachers.

This article describes the results of a nationwide questionnaire study of 3229 Swedish upper secondary school teachers' conceptual understanding of sustainable development in relation to their subject discipline and teaching experience. Previous research has shown that teachers have difficulties understanding the complex concept of sustainable development. According to the Swedish curriculum, all teachers in all subjects should integrate a holistic perspective of sustainable development including economic, ecological, and social dimensions. This study shows that teachers differ in their understanding of the concept mostly according to their subject traditions. Social science teachers emphasize social dimensions and science teachers' ecological dimensions, respectively. Teachers are aware of the relevance of the three dimensions to various degrees, but do not generally have a holistic understanding. The greatest uncertainty in teachers' understanding is related to the economic dimension. Science and social science teachers are critical of incorporating economic growth into the concept of sustainable development while language, vocational, and esthetical-practical teachers are not. No experience-bound differences of the teachers' understanding could be found, but recently qualified teachers consider their understanding of sustainable development to be poorer in comparison with more experienced teachers' self-evaluation. The study highlights the need for further training in sustainable development since more than 70% of the questioned teachers stated that they need such training.

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. [ABSTRACT FROM AUTHOR]

‘Open schooling’ has become in recent years a burgeoning theme in the discourse on how to rethink education for the 21st century. This paper addresses a gap between calls for implementing an open schooling approach in policy papers and international reports and the scarcity of rigorous academic discourse on what open schooling theoretically means and practically entails in terms of school organization and curriculum. To this end, the paper presents an ecological model of school openness that is composed of eight interrelated dimensions: shared governance, ‘open’ curriculum, inner-school communities, learning communities, student participation, social engagement, parental involvement, and community collaborations. These dimensions are organized into three categories, accounting for organizational, pedagogical and communal aspects of school openness. The multidimensional nature of the model presented here provides a more intricate and nuanced account of open schooling that acknowledges the complexities and challenges that the movement towards greater openness yields for school communities. From an educational research perspective, this model functions to inform the understanding and examination of the multidimensionality of opening schools to their community. From an educational practice perspective, it can instigate in-depth and meaningful dialogue within school teams on what open schooling is and its ensuing merits. [ABSTRACT FROM AUTHOR]

Teaching about the nervous system has become a challenging task in secondary biology and science education because of the fast development in the field of neuroscience. A major challenge is to determine what content to teach. Curricula goals are often too general to guide instruction, and information about the nervous system has become overwhelming and diverse with ubiquitous relevance in society. In addition, several misconceptions and myths are circulating in educational communities causing world-wide confusion as to what content is correct. To help teachers, textbook authors, and curricula developers in this challenging landscape of knowledge, the aim of the present study is to identify the expert view on what knowledge is important for understanding the nervous system in the context of secondary biology and science education. To accomplish this, we have conducted a thematic content analysis of textbooks followed by a Delphi study of 15 experts in diverse but relevant fields. The results demonstrate six curriculum themes including gross anatomy and function, cell types and functional units, the nerve signal, connections between neurons, when nerve signals travel through networks of neurons, and plasticity in the nervous system, as well as 26 content principles organized in a coherent curriculum progression from general content to more specific content. Whereas some of the principles clarify and elaborate on traditional school biology knowledge, others add new knowledge to the curriculum. Importantly, the new framework for teaching about the nervous system presented here, meets the needs of society, as expressed by recent international policy frameworks of OECD and WHO, and it addresses common misconceptions about the brain. The study suggests an update of the biology and science curriculum., Competing Interests: The authors have declared that no competing interests exist.

Animal Welfare Attitudes (AWA) are defined as human attitudes towards the welfare of animals in different dimensions and settings. Demographic factors, such as age and gender are associated with AWA. The aim of this study was to assess gender differences among university students in a large convenience sample from twenty-two nations in AWA. A total of 7914 people participated in the study (5155 women, 2711 men, 48 diverse). Participants completed a questionnaire that collected demographic data, typical diet and responses to the Composite Respect for Animals Scale Short version (CRAS-S). In addition, we used a measure of gender empowerment from the Human Development Report. The largest variance in AWA was explained by diet, followed by country and gender. In terms of diet, 6385 participants reported to be omnivores, 296 as pescatarian, 637 ate a vegetarian diet and 434 were vegans ( n = 162 without answer). Diet was related with CRAS-S scores; people with a vegan diet scored higher in AWA than omnivores. Women scored significantly higher on AWA than men. Furthermore, gender differences in AWA increased as gender inequality decreased.

Thermally processed food is an important part of the human diet. Heat-treatment, however, promotes the formation of so-called Amadori rearrangement products, such as fructoselysine. The gut microbiota including Escherichia coli can utilize these compounds as a nutrient source. While the degradation route for fructoselysine is well described, regulation of the corresponding pathway genes frlABCD remained poorly understood. Here, we used bioinformatics combined with molecular and biochemical analyses and show that fructoselysine metabolism in E. coli is tightly controlled at the transcriptional level. The global regulator CRP (CAP) as well as the alternative sigma factor σ32 (RpoH) contribute to promoter activation at high cAMP-levels and inside warm-blooded hosts, respectively. In addition, we identified and characterized a transcriptional regulator FrlR, encoded adjacent to frlABCD, as fructoselysine-6-phosphate specific repressor. Our study provides profound evidence that the interplay of global and substrate-specific regulation is a perfect adaptation strategy to efficiently utilize unusual substrates within the human gut environment., (© 2020 The Authors. Molecular Microbiology published by John Wiley & Sons Ltd.)

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 that 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., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Ethnobotanical Relevance: Leaves of Mangifera indica L. have folk-uses in tropical regions of the world as health teas, as a remedy for exhaustion and fatigue, as a vegetable, and as a medicine. Mangifera indica leaf extract (MLE) had previously been demonstrated to alter brain electrical activity in-vivo. The aim of the present series of studies was to investigate whether mangiferin, a major compound in leaves and in MLE, is responsible for the neurocognitive activity of MLE, and if the CNS activities of MLE have translational potential., Materials and Methods: MLE, tradename Zynamite, is produced by Nektium Pharma, Spain. Isolated mangiferin was tested in-vitro in radioligand binding and enzyme inhibition studies against 106 CNS targets. Changes in the electroencephalograms (EEG's) of MLE and mangiferin were recorded in-vivo from four brain regions. Two double blind randomized placebo-controlled crossover clinical trials were conducted, each with 16 subjects. At 90 min and at 60 min respectively, after oral intake of 500 mg MLE, EEG recordings, psychometric tests, mood state, and tolerability were studied., Results: Isolated mangiferin is a selective inhibitor of catechol-O-methyltransferase (COMT) with an IC50 of 1.1 μM, with no activity on the CNS targets of caffeine. Both mangiferin and MLE induce similar changes in long-term potentiation (LTP) in the hippocampus in-vitro, and induce a similar pattern of EEG changes in-vivo. In both translational clinical trials MLE was well tolerated, with no cardiovascular side-effects. In both studies MLE caused significant spectral changes in brain electrical activity in cortical regions during cognitive challenges, different to the attenuated spectral changes induced by caffeine. There were no significant changes in the psychometric tests other than reaction time for all groups. In the second study there was a trend to faster reaction time within group for MLE (p = 0.066) and the percentage improvement in reaction time for MLE compared to placebo was significant (p = 0.049). In the first study MLE improved all scores for Profile of Mood States (POMS), with the score for "fatigue" significantly improved (p = 0.015); in the second study the POMS score for "dejection" was improved in the caffeine group, p = 0.05., Conclusions: Mangiferin is a COMT inhibitor of moderate potency and is the major CNS-active compound in MLE. Both mangiferin and MLE increase hippocampal LTP in-vitro, and induce a similar pattern of changes in brain electrical activity in-vivo. While the translational clinical trials of MLE are limited by being single dose studies in a small number of subjects, they provide the first clinical evidence that the extract is well tolerated with no cardiovascular side-effects, can induce changes in brain electrical activity, may give a faster reaction time, and decrease fatigue. These CNS activities support the reported folk-uses use of mango leaf tea as a substitute for tea and as a traditional remedy for fatigue and exhaustion. Extract Mangifera indica L., Zynamite, has nootropic potential, and larger clinical studies are needed to realise this potential., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Extracts made from the leaves of the mango food plant ( Mangifera indica L., Anacardiaceae ) have a long history of medicinal usage, most likely due to particularly high levels of the polyphenol mangiferin. In rodent models, oral mangiferin protects cognitive function and brain tissue from a number of challenges and modulates cerebro-electrical activity. Recent evidence has confirmed the latter effect in healthy humans following a mangiferin-rich mango leaf extract using quantitative electroencephalography (EEG). The current study therefore investigated the effects of a single dose of mango leaf extract, standardised to contain >60% mangiferin (Zynamite ® ), on cognitive function and mood. This study adopted a double-blind, placebo-controlled cross-over design in which 70 healthy young adults (18 to 45 years) received 300 mg mango leaf extract and a matched placebo, on separate occasions, separated by at least 7 days. On each occasion, cognitive/mood assessments were undertaken pre-dose and at 30 min, 3 h and 5 h post-dose using the Computerised Mental Performance Assessment System (COMPASS) assessment battery and the Profile of Mood States (POMS). The results showed that a single dose of 300 mg mango leaf extract significantly improved performance accuracy across the tasks in the battery, with domain-specific effects seen in terms of enhanced performance on an 'Accuracy of Attention' factor and an 'Episodic Memory' factor. Performance was also improved across all three tasks (Rapid Visual Information Processing, Serial 3s and Serial 7s subtraction tasks) that make up the Cognitive Demand Battery sub-section of the assessment. All of these cognitive benefits were seen across the post-dose assessments (30 min, 3 h, 5 h). There were no interpretable treatment related effects on mood. These results provide the first demonstration of cognition enhancement following consumption of mango leaf extract and add to previous research showing that polyphenols and polyphenol rich extracts can improve brain function.

We report here the results of the study of the chemical composition of Cyperus esculentus rhizomes. Ethanolic extracts have been separated by column chromatography and analyzed by magnetic resonance spectroscopy and mass spectrometry. Quercetin, stigmasterol, and linoleic and oleic acid glycerol esters, together with 4-chlorobutyl oleate, oleamide, myricetin, tyramine and N-feruloyltyramine, found for the first time in Cyperus esculentus rhizomes, have been isolated and quantified in the extracts. Alkaloids have not been detected, and the presence of flavonoids and sterols is moderate., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Ethnopharmacological Relevance: Sceletium tortuosum (Mesembryanthemaceae), a succulent plant indigenous to South Africa. is consumed in the form of teas, decoctions and tinctures and is sometimes smoked and used as snuff. In recent years, Sceletium has received a great deal of commercial interest for relieving stress in healthy people, and for treating a broad range of psychological, psychiatric and inflammatory conditions., Material and Methods: The whole extract (Zembrin®) was tested ex vivo in the hippocampus slice preparation after one week of daily oral administration of 5 and 10 mg/kg. Four alkaloids - mesembrine, mesembranol, mesembrenol and mesembrenone - were tested directly in vitro. All four were also tested in the presence of different glutamate receptor agonists., Results: Zembrin® ex vivo as well as all alkaloids in vitro attenuated the amplitude of the population spike during electric stimulation as single shock as well as theta burst stimulation. Only Mesembranol and Mesembrenol having a hydroxyl group at position C6 instead of carbonyl group as in mesembrine and mesembrenone acted by attenuation of AMPA receptor mediated transmission as documented for the whole extract., Discussion: The current experimental series revealed a new physiological effect of Zembrin ® on the electric activity of the hippocampus. Attenuation of AMPA mediated transmission has been related to successful adjunctive treatment of epileptic patients. Administered doses of 5 and 10 mg/kg are in line with a dosage of 50 mg/subject as tested clinically., Conclusion: We have discovered a new structure activity relationship for Sceletium alkaloids. Since attenuation of AMPA mediated transmission has been related to successful adjunctive treatment of epileptic patients), Mesembrenol and Mesembranol may serve as new chemical leads for the development of new drugs for the treatment of epilepsy., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

It remains unknown whether polyphenols such as luteolin (Lut), mangiferin and quercetin (Q) have ergogenic effects during repeated all-out prolonged sprints. Here we tested the effect of Mangifera indica L. leaf extract (MLE) rich in mangiferin (Zynamite®) administered with either quercetin (Q) and tiger nut extract (TNE), or with luteolin (Lut) on sprint performance and recovery from ischemia-reperfusion. Thirty young volunteers were randomly assigned to three treatments 48 h before exercise. Treatment A: placebo (500 mg of maltodextrin/day); B: 140 mg of MLE (60% mangiferin) and 50 mg of Lut/day; and C: 140 mg of MLE, 600 mg of Q and 350 mg of TNE/day. After warm-up, subjects performed two 30 s Wingate tests and a 60 s all-out sprint interspaced by 4 min recovery periods. At the end of the 60 s sprint the circulation of both legs was instantaneously occluded for 20 s. Then, the circulation was re-opened and a 15 s sprint performed, followed by 10 s recovery with open circulation, and another 15 s final sprint. MLE supplements enhanced peak (Wpeak) and mean (Wmean) power output by 5.0-7.0% ( P < 0.01). After ischemia, MLE+Q+TNE increased Wpeak by 19.4 and 10.2% compared with the placebo ( P < 0.001) and MLE+Lut ( P < 0.05), respectively. MLE+Q+TNE increased Wmean post-ischemia by 11.2 and 6.7% compared with the placebo ( P < 0.001) and MLE+Lut ( P = 0.012). Mean VO 2 during the sprints was unchanged, suggesting increased efficiency or recruitment of the anaerobic capacity after MLE ingestion. In women, peak VO 2 during the repeated sprints was 5.8% greater after the administration of MLE, coinciding with better brain oxygenation. MLE attenuated the metaboreflex hyperpneic response post-ischemia, may have improved O 2 extraction by the Vastus Lateralis (MLE+Q+TNE vs. placebo, P = 0.056), and reduced pain during ischemia ( P = 0.068). Blood lactate, acid-base balance, and plasma electrolytes responses were not altered by the supplements. In conclusion, a MLE extract rich in mangiferin combined with either quercetin and tiger nut extract or luteolin exerts a remarkable ergogenic effect, increasing muscle power in fatigued subjects and enhancing peak VO 2 and brain oxygenation in women during prolonged sprinting. Importantly, the combination of MLE+Q+TNE improves skeletal muscle contractile function during ischemia/reperfusion.

In this paper we present the development and validation a comprehensive questionnaire to assess college students' knowledge about modern genetics and genomics, their belief in genetic determinism, and their attitudes towards applications of modern genetics and genomic-based technologies. Written in everyday language with minimal jargon, the Public Understanding and Attitudes towards Genetics and Genomics (PUGGS) questionnaire is intended for use in research on science education and public understanding of science, as a means to investigate relationships between knowledge, determinism and attitudes about modern genetics, which are to date little understood. We developed a set of core ideas and initial items from reviewing the scientific literature on genetics and previous studies on public and student knowledge and attitudes about genetics. Seventeen international experts from different fields (e.g., genetics, education, philosophy of science) reviewed the initial items and their feedback was used to revise the questionnaire. We validated the questionnaire in two pilot tests with samples of university freshmen students. The final questionnaire contains 45 items, including both multiple choice and Likert scale response formats. Cronbach alpha showed good reliability for each section of the questionnaire. In conclusion, the PUGGS questionnaire is a reliable tool for investigating public understanding and attitudes towards modern genetics and genomic-based technologies., Competing Interests: The authors have declared that no competing interests exist.

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 10.0 mg/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 (45 min pre-drug period and 5h of recording after a rest of 5 min 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 potential., 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., (Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.)

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/day. A 90-day subchronic repeated oral toxicity study was conducted at 0, 100, 300, 450, and 600 mg/kg bw/day. 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., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction. Converging evidence suggests that PDE-4 (phosphodiesterase subtype 4) plays a crucial role in regulating cognition via the PDE-4-cAMP cascade signaling involving phosphorylated cAMP response element binding protein (CREB). Objective. The primary endpoint was to examine the neurocognitive effects of extract Sceletium tortuosum (Zembrin) and to assess the safety and tolerability of Zembrin in cognitively healthy control subjects. Method. We chose the randomized double-blind placebo-controlled cross-over design in our study. We randomized normal healthy subjects (total n = 21) to receive either 25 mg capsule Zembrin or placebo capsule once daily for 3 weeks, in a randomized placebo-controlled 3-week cross-over design. We administered battery of neuropsychological tests: CNS Vital Signs and Hamilton depression rating scale (HAM-D) at baseline and regular intervals and monitored side effects with treatment emergent adverse events scale. Results. 21 subjects (mean age: 54.6 years ± 6.0 yrs; male/female ratio: 9/12) entered the study. Zembrin at 25 mg daily dosage significantly improved cognitive set flexibility (P < 0.032) and executive function (P < 0.022), compared with the placebo group. Positive changes in mood and sleep were found. Zembrin was well tolerated. Conclusion. The promising cognitive enhancing effects of Zembrin likely implicate the PDE-4-cAMP-CREB cascade, a novel drug target in the potential treatment of early Alzheimer's dementia. This trial is registered with ClinicalTrials.gov NCT01805518.

The South African endemic plant Sceletium tortuosum has a long history of traditional use as a masticatory and medicine by San and Khoikhoi people and subsequently by European colonial farmers as a psychotropic in tincture form. Over the past decade, the plant has attracted increasing attention for its possible applications in promoting a sense of wellbeing and relieving stress in healthy individuals and for treating clinical anxiety and depression. The pharmacological actions of a standardized extract of the plant (Zembrin) have been reported to be dual PDE4 inhibition and 5-HT reuptake inhibition, a combination that has been argued to offer potential therapeutic advantages. Here we tested the acute effects of Zembrin administration in a pharmaco-fMRI study focused on anxiety-related activity in the amygdala and its connected neurocircuitry. In a double-blind, placebo-controlled, cross-over design, 16 healthy participants were scanned during performance in a perceptual-load and an emotion-matching task. Amygdala reactivity to fearful faces under low perceptual load conditions was attenuated after a single 25 mg dose of Zembrin. Follow-up connectivity analysis on the emotion-matching task showed that amygdala-hypothalamus coupling was also reduced. These results demonstrate, for the first time, the attenuating effects of S. tortuosum on the threat circuitry of the human brain and provide supporting evidence that the dual 5-HT reuptake inhibition and PDE4 inhibition of this extract might have anxiolytic potential by attenuating subcortical threat responsivity.

Objectives: The objective of the study was to evaluate the safety and tolerability of two doses (8 mg and 25 mg once daily) of a 2:1 standardized extract of the South African medicinal plant Sceletium tortuosum (L.) N.E. Br., trademarked Zembrin,(®) in healthy adult volunteers over a three-month period., Design: This was a randomized, double-blind, parallel-group, placebo-controlled single center study., Setting: Tiervlei Trial Centre, Karl Bremer Hospital, Bellville, Cape Town, South Africa., Participants: The study took place between February 2 and July 27, 2009. Thirty-seven healthy adults were recruited from the general population., Intervention: Participants were randomized to receive either one of two doses of study medication, or an identical placebo, taken once daily for 3 months. Of the 37 subjects, 12, 12, and 13 subjects received 8 mg extract Sceletium tortuosum (Zembrin), 25 mg extract Sceletium tortuosum (Zembrin), and placebo treatment, respectively., Outcome Measures: No efficacy variables were assessed. The safety and tolerability variables comprised of vital signs, physical examination, 12-lead electrocardiogram (ECG), laboratory assessments (hematology, biochemistry, and urinalysis), and the recording of adverse events (AEs)., Results: There were no apparent differences between the three treatments with regard to vital signs, 12-lead ECG, body weight, and physical examination from screening to the end of the 3-month treatment period. No significant changes were observed in hematology or biochemistry parameters between initial screening and the end of the study. Both doses of extract Sceletium tortuosum (Zembrin) were well-tolerated. The most commonly reported AE was headache, followed by abdominal pain and upper respiratory tract infections, all with greater incidence in the placebo group than in the treatment groups. Unsolicited positive effects on well-being were noted in patient diaries by some participants taking extract Sceletium tortuosum (Zembrin), including improved coping with stress and sleep., Conclusion: Both doses of extract Sceletium tortuosum (Zembrin) (8 mg and 25 mg) were well tolerated when used by healthy human subjects once daily for 3 months.

Ethnopharmacological Relevance: Harpagophytum procumbens subps. procumbens (Burch.) DC. ex Meisn. (Pedaliaceae) is an important traditional medicine growing in the Kalahari region of southern Africa where it is consumed as a general health tonic and for treating diverse ailments including arthritis, pain, fever, ulcers and boils., Aim of the Review: To provide a comprehensive overview of the ethnobotany, phytochemistry and biological activity of H. procumbens and possibly make recommendations for further research., Materials and Methods: Peer-reviewed articles on H. procumbens were acquired on Scopus, ScienceDirect and SciFinder, there was no specific timeline set for the search. A focus group discussion was held with different communities in Botswana to further understand ethnobotanical uses of the plant., Results: Harpogophytum procumbens is used for a wide variety of health conditions in the form of infusions, decoctions, tinctures, powders and extracts. In addition to the common local use for arthritis and pain, other ethnomedicinal uses include dyspepsia, fever, blood diseases, urinary tract infections, postpartum pain, sprains, sores, ulcers and boils. Scientific studies revealed that H. procumbens exhibits analgesic, anti-oxidant, anti-diabetic, anti-epileptic, antimicrobial and antimalarial activities amongst others. Iridoid glycosides and phenylpropanoid glycosides have been the focus of phytochemical investigations as the biological activity has been ascribed to the iridoid glycosides (such as harpagoside and harpagide), which are common in nature and are known to possess anti-inflammatory activity. In addition, it has been shown that the hydrolysed products of harpagoside and harpagide have more pronounced anti-inflammatory activity when compared to the unhydrolysed compounds. Harpagophytum zeyheri is a close taxonomic ally of H. procumbens but H. procumbens is the favoured species of commerce, and contains higher levels of the pharmacologically active constituents. The two are used interchangeably and H. procumbens raw material is often intentionally adulterated with H. zeyheri and this may impact on the efficacy of inadequately controlled health products. The main exporter of this highly commercialised plant is Namibia. In 2009 alone, Harpagophytum exports were worth approximately €1.06 million. The high demand for health products based on this plant has led to over-harvesting, raising concerns about sustainability. Although only the secondary tubers are utilised commercially, the whole plant is often destroyed during harvesting., Conclusions: Harpagophytum procumbens is used to treat a wide range of ailments. Some of the ethnobotanical claims have been confirmed through in vitro studies, however, when the constituents deemed to be the biologically active compounds were isolated the efficacy was lower than that of the whole extract. This necessitates the use of a different approach where all the metabolites are considered using a robust method such as spectroscopy; the phytochemical data can then be superimposed on the biological activity. Furthermore, there is a need to develop rapid and efficient quality control methods for both raw materials and products because the orthodox methods in current use are time-consuming and labour intensive., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Sceletium tortuosum is an indigenous South African plant that has traditionally been used for its mood-enhancing properties. Recently, products containing S. tortuosum have become increasingly popular and are commonly administered as tablets, capsules, teas, decoctions, or tinctures, while traditionally the dried plant material has been masticated. This study evaluated the in vitro permeability of the four major S. tortuosum alkaloids (i.e., mesembrine, mesembrenone, mesembrenol, and mesembranol) across porcine intestinal, sublingual, and buccal tissues in their pure form and in the form of three different crude plant extracts, namely water, methanol, and an acid-base alkaloid-enriched extract. The permeability of mesembrine across intestinal tissue was higher than that of the highly permeable reference compound caffeine (which served as a positive control for membrane permeability) both in its pure form, as well as in the form of crude extracts. The intestinal permeability of mesembranol was similar to that of caffeine, while those of mesembrenol and mesembrenone were lower than that of caffeine, but much higher than that of the poorly permeable reference compound atenolol (which served as a negative control for membrane permeability). In general, the permeabilities of the alkaloids were lower across the sublingual and the buccal tissues than across the intestinal tissue. However, comparing the transport of the alkaloids with that of the reference compounds, there are indications that transport across the membranes of the oral cavity may contribute considerably to the overall bioavailability of the alkaloids, depending on pre-systemic metabolism, when the plant material is chewed and kept in the mouth for prolonged periods. The results from this study confirmed the ability of the alkaloids of S. tortuosum in purified or crude extract form to permeate across intestinal, buccal, and sublingual mucosal tissues., (© Georg Thieme Verlag KG Stuttgart · New York.)

Aerosolized perfluorocarbon (PFC) improves gas exchange, lung mechanics, and pulmonary artery pressure. The objective of this intervention was to study the dose-response effect to aerosolized perfluorooctylbromide (PFOB; perflubron, LiquiVent, Alliance Pharmaceutical Corp.) in surfactant-depleted piglets. After induction of lung injury by saline lavage, 25 newborn piglets were randomly assigned to receive 0, 1.25, 2.5, 5.0, or 7.5 mL/kg aerosolized PFOB per hour. A 2-h therapy period was followed by a 3-h observation period. In all animals, respiratory support was performed with intermittent mandatory ventilation. After aerosol treatment and 3 h of observation, arterial oxygen pressure was similarly improved in the 2.5-, 5.0-, and 7.5-mL. kg(-1). h(-1) aerosol-PFOB groups and higher compared with the 1.25-mL. kg(-1). h(-1) aerosol-PFOB (P < 0.01) and the control groups (P < 0.001). Compared with the control group, arterial carbon dioxide pressure was significantly reduced with 2.5-, 5.0-, and 7.5-mL. kg(-1). h(-1) aerosol-PFOB (P < 0.001). Treatment with 1.25 mL. kg(-1). h(-1) aerosol-PFOB did not significantly affect arterial carbon dioxide pressure. The 20% terminal dynamic compliance/dynamic compliance was significantly improved in the groups that received 2.5, 5.0, and 7.5 mL. kg(-1). h(-1) aerosol-PFOB compared with control animals. Mean pulmonary artery pressure was lower after therapy with 5.0 and 7.5 mL. kg(-1). h(-1) aerosol-PFOB (P < 0.01) than in the control group. IL-1beta gene expression in lung tissue was significantly reduced with PFOB 1.25 mL. kg(-1). h(-1). In summary, aerosolized PFOB improved terminal dynamic compliance, pulmonary gas exchange, and pulmonary artery pressure in a dose-dependent manner. In terms of oxygenation and lung mechanics, the optimum dose was between 2.5 and 5 mL. kg(-1). h(-1).

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.