G.I. Stafford

Review on plants with CNS-effects used in traditional South African medicine against mental diseases

The majority of the population in South Africa use traditional health care to treat various mental conditions. In this review, we present ethnobotanical information on plants used by the traditional healers in South Africa to treat mental illnesses, specifically epilepsy, depression, age-related dementia and debilitative mental disorders. Details of the recent scientific studies conducted on some of these plants are reviewed. Extracts of Searsia chirindensis, Cotelydon orbiculata and Leonotis leonurus have shown in vivo anticonvulsant activity. Extracts from Searsia dentata and Searsia pyroides showed spontaneous epileptiform discharge in mouse cortical slices, and acted as NMDA-receptor antagonists. Apigenin, amentoflavone and agathisflavone with affinity to the benzodiazepine site on the GABA(A)-receptor were isolated from Searsia pyroides. Naringenin with affinity to the GABA(A)-benzodiazepine receptor was isolated from Mentha aquatica. Agapanthus campanulatus, Boophone disticha, Mondia whitei and Xysmalobium undulatum exhibited antidepressant-like activity in three in vivo models for depression. Amaryllidaceae alkaloids with activity to the serotonin transporter were isolated from Boophone disticha. The alkaloid mesembrine, which act as a serotonin reuptake inhibitor, was isolated from Sceletium tortuosum. Investigations of plants used to treat age-related dementia and debilitative mental disorders lead to the isolation of a number of Amaryllidaceae alkaloids with acetylcholinesterase inhibitory activity from Boophone disticha and Crinum species. Extracts of Mentha aquatica, Gasteria croucheri, Ruta graveolens and Scotia brachypetala inhibited MAO-B. Naringenin was isolated from Mentha aquatica as a MAO inhibitor. Only a small number of the more than 300 southern African plant species reported to treat or affect the CNS have been scientifically evaluated. Very few of the active compounds have been isolated and identified.

Isolation of the MAO-inhibitor naringenin from Mentha aquatica L.

AIMS OF THE STUDY To isolate the compound(s) responsible for the MAO-inhibitory activity. MATERIALS AND METHODS Six extracts of varying polarity of Mentha aquatica L. were tested in a photometric peroxidase linked MAO bioassay. The 70% ethanol extract had highest inhibitory activity. (S)-Naringenin was isolated from the extract by bioassay guided fractionation on VLC and preparative TLC. The structure of the compound was determined by (1)H, (13)C and (13)C-DEPT NMR and optical rotation. RESULTS The IC(50) values for MAO inhibition by naringenin were 342+/-33 microM for the rat liver mitochondrial fraction, 955+/-129 microM for MAO-A and 288+/-18 microM for MAO-B. CONCLUSIONS The content of naringenin in Mentha aquatica might explain its use in traditional medicine for depression-like conditions.

Can phylogeny predict chemical diversity and potential medicinal activity of plants? A case study of amaryllidaceae

BackgroundDuring evolution, plants and other organisms have developed a diversity of chemical defences, leading to the evolution of various groups of specialized metabolites selected for their endogenous biological function. A correlation between phylogeny and biosynthetic pathways could offer a predictive approach enabling more efficient selection of plants for the development of traditional medicine and lead discovery. However, this relationship has rarely been rigorously tested and the potential predictive power is consequently unknown.ResultsWe produced a phylogenetic hypothesis for the medicinally important plant subfamily Amaryllidoideae (Amaryllidaceae) based on parsimony and Bayesian analysis of nuclear, plastid, and mitochondrial DNA sequences of over 100 species. We tested if alkaloid diversity and activity in bioassays related to the central nervous system are significantly correlated with phylogeny and found evidence for a significant phylogenetic signal in these traits, although the effect is not strong.ConclusionsSeveral genera are non-monophyletic emphasizing the importance of using phylogeny for interpretation of character distribution. Alkaloid diversity and in vitro inhibition of acetylcholinesterase (AChE) and binding to the serotonin reuptake transporter (SERT) are significantly correlated with phylogeny. This has implications for the use of phylogenies to interpret chemical evolution and biosynthetic pathways, to select candidate taxa for lead discovery, and to make recommendations for policies regarding traditional use and conservation priorities.

In vitro pharmacological effects of manufactured herbal concoctions used in KwaZulu-Natal South Africa

ETHNOPHARMACOLOGY RELEVANCE Manufactured and packaged herbal mixtures, known locally as muthi concoctions, have become a new feature of traditional medicine in South Africa. These herbal concoctions are often claimed to cure several diseases ranging from minor illness to life threatening conditions. AIM OF THE STUDY To document the prevalence, variety and evaluate the efficacy of selected herbal concoctions sold in KwaZulu-Natal. MATERIALS AND METHODS Nine herbal concoctions were evaluated for their effects as antibacterial and antifungal agents as well as their ability to inhibit the cyclooxygenase (COX-1 and COX-2) enzymes using standard in vitro methods. RESULTS Imbiza ephuzwato and Ibhubezi, both multipurpose mixtures showed high abilities to inhibit bacterial and fungal growth as well as inhibit the COX-1 and COX-2 enzymes. Umzimba omubi and Umuthi wekukhwehlela ne zilonda, both remedies for wounds, boils and chest infections were not active against the two Gram-positive and two Gram-negative bacterial strains tested. Vusa umzimba and Supreme one hundred were active against Candida albicans. CONCLUSIONS Four of the herbal concoctions showed no activity in all of the assays tested while only two showed good activity. Activity cannot be ruled out as there are many mechanisms upon which natural products can act.

Effects of South African traditional medicine in animal models for depression

ETHNOPHARMACOLOGICAL RELEVANCE The four South African medicinal plants Agapanthus campanulatus (AC), Boophone distica (BD), Mondia whitei (MW) and Xysmalobium undulatum (XU) are used in traditional medicine to treat depression. AIM To evaluate the effect of ethanolic extracts of the plants in models for depression. MATERIALS AND METHODS The extracts were screened for affinity for the serotonin transporter (SERT) in the [(3)H]-citalopram-binding assay. The inhibitory potency of the extracts towards the SERT, the noradrenalin transporter (NAT) and the dopamine transporter (DAT) were determined in a functional uptake inhibition assay. Antidepressant-like effects of the extracts were investigated using the tail suspension test (TST) and the forced swim test in both rats (rFST) and mice (mFST). RESULTS All four plants showed affinity for SERT in the binding assay. AC and BD showed functional inhibition of SERT, NAT and DAT, MW affected SERT while XU showed no effect. BD showed significant effect in the TST and in the mFST/rFST, AC showed significant effect in mFST, MW showed significant effect in the rFST and XU showed significant effect in the mFST. CONCLUSION In this study we have demonstrated the antidepressant activity of four South African medicinal plants in vitro and in vivo, supporting their rational use in traditional medicine.

Antimicrobial, anti-inflammatory and mutagenic investigation of the South African tree aloe (Aloe barberae)

ETHNOPHARMACOLOGY RELEVANCE In recent times, many products ranging from aloe drinks to aloe gels, powders, capsules, and creams have appeared on the commercial market prepared from different aloe species including Aloe barberae. These products are used in ethnomedicine to treat various conditions including gastrointestinal disorders, insect bites, skin burns and other skin injuries by traditional communities. AIM OF THE STUDY This study was aimed at evaluating the antibacterial, antifungal and anti-inflammatory activities as well as genotoxic effects of different extracts of Aloe barberae. MATERIALS AND METHODS Organic and water extracts of the upper stem, young bark, mature bark, leaves and roots of the South African tree aloe (Aloe barberae) were evaluated for their antimicrobial [gram-positive (Bacillus subtilis and Staphylococcus aureus), gram-negative (Escherichia coli and Klebsiella pneumoniae) bacteria as well as the fungus Candida albicans], anti-inflammatory (COX-1 and COX-2) and mutagenic properties (Ames test). Thin layer chromatography (TLC) was used to compare the phytochemical profiles of different extracts of Aloe barberae. RESULTS The petroleum ether (PE) and dichloromethane (DCM) extracts of the mature bark, leaves and roots exhibited good activity against all the bacteria and fungus Candida albicans with minimum inhibitory concentrations (MIC) ranging from 0.195 to 1.56 mg/ml. All the PE extracts evaluated showed a high activity (>70%) in both COX-1 and COX-2 assays. Apart from the organic extracts of the root with consistently good activity (>70%), all the remaining extracts showed moderate activity (40-69%) in COX-1 assay. The PE extracts also showed a dose dependent increase in activity. Ultraviolet (UV) spectrum of the leaves and root EtOH extracts indicated the presence of compounds that could absorb UV light (wavelength: 190-820 nm). None of the extracts had a mutagenic effect in the Salmonella/microsome assay against a tester strain, TA98. CONCLUSION Activity observed in the bark, leaves and roots of Aloe barberae validates its use in commercial herbal products, ethnobotany and ethnoveterinary medicine by South African communities and small scale farmers to treat various conditions.

Amides from Piper capense with CNS Activity – A Preliminary SAR Analysis

Piper capense L.f. (Piperaceae) is used traditionally in South Africa as a sleep inducing remedy. Bioassay-guided fractionation of the roots of P. capense led to the isolation of piperine (1) and 4,5-dihydropiperine (2), which showed moderate affinity for the benzodiazepine site on the GABAA receptor (IC50 values of 1.2 mM and 1.0 mM, respectively). The present study suggests that strict structural properties of the amides are essential for affinity. Taken together, these observations suggest that the carbon chain must contain not less than four carbons, and that a conjugated double bond, adjacent to the amide group, is necessary for binding to the receptor and that the amine part should be bulky.

The effect of extracts of Searsia species on epileptiform activity in slices of the mouse cerebral cortex.

ETHNOPHARMACOLOGICAL RELEVANCE Searsia dentata and Searsia pyroides are used in traditional South African medicine to treat convulsions and epilepsy. Previous studies have demonstrated that extracts of these plants comprise compounds that bind to the flumazenil-sensitive site on the GABA(A) receptor. However, their use as anticonvulsant medicinal plants cannot be adequately explained by these findings. AIMS The aim of this study was to examine the possible involvement of the glutamatergic system of extracts from the plants. MATERIALS AND METHODS The mouse cortical wedge preparation was used for functional characterization of the extracts. The affinity towards the NMDA and the AMPA receptor was investigated using classical [(3)H]-GP39653 and [(3)H]-AMPA binding assays, respectively. RESULTS The extracts of Searsia dentata and Searsia pyroides inhibited the spontaneous epileptiform discharges in mouse cerebral cortical slices with ED(50) of 0.62 and 1.67mg dry extract/mL, respectively. Both extracts displaced [(3)H]-GP39653 binding and significantly inhibited the NMDA-induced response during co-administration in cortical slices. CONCLUSION In this study, the NMDA receptor antagonistic effect of the crude ethanolic extracts of these two South African medicinal plants was demonstrated.

Antimicrobial activity of South African Podocarpus species.

ETHNOPHARMACOLOGICAL RELEVANCE Several species of Podocarpus (Podocarpaceae) are utilized in treating ailments across the world. In Africa, four species are used traditionally in both animal and human health. AIM OF THE STUDY To investigate the antimicrobial activity of Podocarpus species against Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae and Candida albicans. MATERIALS AND METHODS Six solvents of varying polarity were used for extraction. Antibacterial activity was assessed using the microdilution bioassay and for antifungal activity, the microdilution bioassay and (M27-P) broth dilution were used. RESULTS All species exhibited antimicrobial activity with MIC values of less than 1mg/ml. Inhibition against Gram-positive bacteria was stronger with an MIC value of 98 microg/ml while for Gram-negative bacteria, the highest inhibition was against Klebsiella pneumoniae with an MIC value of 0.33 mg/ml. All species exhibited strong antifungal activity with the best MIC being 30 microg/ml after 48 h. CONCLUSIONS All four species exhibited strong inhibition against all tested microbials, based on Aligiannis et al. [Aligiannis, N., Kalpotzakis, E., Mitaku, S., Chinou, I.B., 2001. Composition and antimicrobial activity of the essential oils of two Origanum species. Journal of Agricultural and Food Chemistry 40, 4168-4170] classification they can be classified as strong inhibitors.

Best practice in research: Consensus Statement on Ethnopharmacological Field Studies – ConSEFS

BACKGROUND Ethnopharmacological research aims at gathering information on local and traditional uses of plants and other natural substances. However, the approaches used and the methods employed vary, and while such a variability is desirable in terms of scientific diversity, research must adhere to well defined quality standards and reproducible methods OBJECTIVES: With ConSEFS (the Consensus Statement on Ethnopharmacological Field Studies) we want to define best-practice in developing, conducting and reporting field studies focusing on local and traditional uses of medicinal and food plants, including studies using a historical approach. METHODS After first developing an initial draft the core group invited community-wide feedback from researchers both through a web-based consultation and a series of workshops at conferences during 2017. OUTCOMES The consultation resulted in a large number of responses. Feedback was received via a weblink on the Journal of Ethnopharmacologys website (ca. 100 responses), other oral and written responses (ca. 50) and discussions with stakeholders at four conferences. The main outcome is a checklist, covering best practice for designing, implementing and recording ethnopharmacological field studies and historical studies. CONCLUSIONS Prior to starting ethnopharmacological field research, it is essential that the authors are fully aware of the best practice in the field. For the first time in the field of ethnopharmacology a community-wide document defines guidelines for best practice on how to conduct and report such studies. It will need to be updated and further developed. While the feedback has been based on responses by many experienced researchers, there is a need to test it in practice by using it both in implementing and reporting field studies (or historical studies), and peer-review.