Activity of traditional South African sedative and potentially CNS-acting plants in the GABA-benzodiazepine receptor assay

https://doi.org/10.1016/j.jep.2005.04.004Get rights and content

Abstract

Several plants are traditionally used to treat mental diseases in South Africa. Forty-six ethanol extracts from 35 species, both indigenous and exotic that are traditionally used predominantly as sedatives or to treat various CNS-related ailments were tested in the GABAA-benzodiazepine receptor-binding assay. In this assay, the binding of 3H-Ro 15-1788 (flumazenil) to the benzodiazepine site is measured. The GABAA-benzodiazepine receptor complex is involved in sedation, epilepsy and convulsions. Out of the 46 extracts tested, seven showed good activity and 10 showed moderate activity. The most active extracts were the ethanolic leaf extracts of Arctopus echinatus, Artemisa afra, four Helichrysum species and Mentha aquatica which all showed good dose-dependent activity.

Introduction

Traditional health care is utilized by the majority of the population in Southern Africa; this is especially true of treatment for mental health problems. This is partly due to a severe lack of facilities for treatment of mental disease in the Western health care system, but also because these diseases in their cultural context are better handled by a traditional healer. In many African cultures, diseases, mental or otherwise, are largely believed to be the result of a disregard for the ancestors, who in turn are believed to inflict an individual with illness as a punishment. Swift and Asuni (1975) suggest that healers, because of their knowledge of the ways of their people and the power conferred upon them by their people, can often provide peace of mind to the distressed and thus provide a feeling of protection to the threatened. Southern Africa is exceptionally rich in plant diversity with an estimated 30,000 species of flowering plants that is almost one tenth of the world's higher plants. There are 10 endemic families, while 80% of the species and 29% of the genera are endemic (Goldblatt, 1978).

Epilepsy can be caused by imbalance in the GABAnergic system. γ-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the mammalian central nervous system, where it exerts its physiological effects by binding to three different receptor types in the neuronal membrane: GABAA, GABAB and GABAC receptors. The GABAA receptor, which is involved in epilepsy, has a binding site for compounds, such as benzodiazepines, β-carbolines, barbiturates and certain steroids that allosterically modifies the chloride channel gating of GABA. In addition, it has been found that flavones bind with high affinity to the benzodiazepine site of the GABAA receptor (Kahnberg et al., 2002). The pharmacological effects of benzodiazepines (anxiolytic, anti-convulsant, muscle relaxant and sedative-hypnotic) make them the most important GABAA modulating drugs (Doble and Martin, 1996).

Recently, several southern African plants have been shown to exhibit GABAA-benzodiazepine receptor-binding (Jäger et al., 2005, Risa et al., 2004). Notable plants were aqueous and ethanol extracts of Aptosimum procumbens (Lehm.) Steud. and Asparagus suaveolens Burch. and the aqueous extract of Commiphora marlothii Engl. which are included in the traditional Northern Sotho remedy for epilepsy, Sehlare sa Seebana (Jäger et al., 2005). Risa et al. (2004) detected good activity in ethanolic extracts of Rhus species, Hoslundia opposita Vahl and ethanolic corm extract of Hypoxis colchicifolia Bak.

In the present study, 46-ethanol extracts from 35 species, both indigenous and exotic that is traditionally used predominantly as sedatives or to treat various CNS-related ailments (Table 1), was tested in the GABAA-benzodiazepine receptor-binding assay.

Section snippets

Plant materials

Plant species traditionally used as sedatives or to treat various CNS-related ailments, were selected based on information in a database on plants used to treat mental diseases, constructed at the Research Centre for Plant Growth and Development, University of KwaZulu-Natal. The information in the database largely originates from published literature (Iwu, 1993, Sobiecki, 2002, Van Wyk et al., 1997, Watt, 1967). Table 1 contains information pertaining to the plants’ traditional use as well as

Results and discussion

Out of the 46 extracts tested, seven extracts showed good dose dependant activity (Table 2). These extracts were Arctopus echinatus, Artemisia afra, Helichrysum hesbaceum, Helichrysum ruderale, Helichrysum simillimum, Helichrysum umbraculigerum and Mentha aquatica ethanolic leaf extracts. Several plants showed moderate dose dependant activity. These plants include the ethanolic root extract of Scadoxus puniceus, the ethanolic leaf extracts of Helichrysum rugulosum, Millettia grandis, Mentha

Acknowledgements

The Danish Medical Research Council (Denmark) and the National Research Foundation's IKS fund (South Africa), University of KwaZulu-Natal Research Fund (South Africa) are thanked for financial assistance. G.I. Stafford thanks the Danish University of Pharmaceutical Sciences for the use of their facilities.

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