M. E. Pedersen

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.

An epidermal microRNA regulates neuronal migration through control of the cellular glycosylation state.

Extracellular Regulation During Caenorhabditis elegans development, the hermaphrodite-specific neurons (HSNs) migrate and then extend axons toward their functional targets. Posttranslational modification of heparan sulfate proteoglycans are important for HSN development, and so Pedersen et al. (p. 1404) tested the effect of disrupting or reducing chondroitin and heparan sulfate synthesis during C. elegans development. The results suggest that proteoglycan biosynthesis is tightly regulated by a microRNA pathway to shape the cell surface glycosylation architecture required to direct neuronal migration. A conserved microRNA affects the characteristics of extracellular proteoglycans that direct migrating neurons in nematodes. An appropriate balance in glycosylation of proteoglycans is crucial for their ability to regulate animal development. Here, we report that the Caenorhabditis elegans microRNA mir-79, an ortholog of mammalian miR-9, controls sugar-chain homeostasis by targeting two proteins in the proteoglycan biosynthetic pathway: a chondroitin synthase (SQV-5; squashed vulva-5) and a uridine 5′-diphosphate–sugar transporter (SQV-7). Loss of mir-79 causes neurodevelopmental defects through SQV-5 and SQV-7 dysregulation in the epidermis. This results in a partial shutdown of heparan sulfate biosynthesis that impinges on a LON-2/glypican pathway and disrupts neuronal migration. Our results identify a regulatory axis controlled by a conserved microRNA that maintains proteoglycan homeostasis in cells.

Pharmacological screening of Malian medicinal plants used against epilepsy and convulsions.

ETHNOPHARMACOLOGICAL RELEVANCE Several medicinal plants are used in Mali to treat epilepsy and convulsions. So far, no studies have investigated the pharmacological effect of these plants. AIMS The aim of this study was to investigate the in vitro and in vivo antiepileptic potential of the ethanolic extracts of 11 Malian medicinal plants. MATERIALS AND METHODS The extracts were screened for antiepileptic properties in the mouse cortical wedge preparation and in the [3H]-flumazenil binding assay. Two of the plant extracts were investigated for anticonvulsive properties in the pentylenetetrazol (PTZ) kindling model in mice. Possible side effects on motor impairment were evaluated using the rota-rod test. RESULTS Extracts of 10 of the 11 medicinal plants showed affinity to the benzodiazepine binding site on the GABAA receptor. Seven of the 11 extracts inhibited the spontaneous discharges (SEDs) in the mouse cortical wedge preparation, with the extracts of Flueggea virosa and Psorospermum senegalense being the most potent. However, when tested for in vivo anticonvulsive properties these two extracts failed to show any effect on PTZ-induced seizures in mice. CONCLUSIONS The pharmacological screening of the ethanolic extracts of 11 Malian medicinal plants in vitro lead to the identification of several extracts with potential anticonvulsant properties.

Transmembrane proteoglycans control stretch-activated channels to set cytosolic calcium levels

Syndecans regulate members of the transient receptor potential family to control cytosolic calcium levels with impact on cell adhesion, junction formation, and neuronal guidance.

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.

Hypoglycemic activity of Iraqi Rheum ribes root extract

Rheum ribes Linn (Polygonaceae) root is used traditionally to treat diabetes, hemorrhoids, ulcers, and diarrhea. Here, the hypoglycemic effect of R. ribes root extract in healthy mice was investigated. Fasted mice were given a single dose of 50 mg/kg of three extracts of different polarity from R. ribes by gastric feeding and the blood glucose was measured 0, 1, 2, 4, and 24 h later. The aqueous extract showed a significant hypoglycemic effect. In vitro, the aqueous extract stimulated insulin release from INS-1E cells at both stimulatory (20 mM) and non-stimulatory (1 mM) glucose concentrations, thus suggesting a mechanism for the in vivo effect. The hypoglycemic active fraction was found to contain anthraquinone glycosides of aloe emodin, emodin, physcion, and chrysophanol derivatives.

Cinnamamides from Piper capense with affinity to the benzodiazepine site on the GABAA receptor

Epilepsy is among the most prevalent of the serious neurological disorders, affecting from 0.5–1.0% of the worlds population and the prevalence of epilepsy in developing countries is generally higher than in developed countries [1]. Recently, plants used in South African traditional medicine for treatment of epilepsy and convulsion were examined for their pharmacological properties in the search for new and better anti-epileptic drugs [2, 3, 4]. The root of Piper capense L.f. (Piperaceae) is used in traditional South African medicine. A bioassay guided fractionation of an ethanolic extract using VLC, HPLC-UV, GC-MS and 1H-NMR led to the isolation and identification of cinnamamides with affinity to the benzodiazepine site on the GABAA receptor in the [3H]flumazenil receptor binding assay. The isolated cinnamides piperine and 4,5 dihydropiperine binded to the receptor with IC50 values of 0.9 and 1.7±mM respectively. . References: 1. Sander and Shorvon (1996)J Neurol Neurosurg Psych 65:433–443. 2. Svenningsen et al. (2006)J Ethnopharmacol. 103: 276–280. 3. Stafford, et al. (2005)J Ethnopharmacol 100: 210–215. 4. Risa, et al. (2004)J Ethnopharmacol 93:177–182