Ethnopharmacology of Q'eqchi' Maya antiepileptic and anxiolytic plants: effects on the GABAergic system.

ETHNOPHARMACOLOGICAL RELEVANCE: The Q'eqchi' Maya possess a large selection of plants to treat neurological disorders, including epilepsy and susto (fright), a culture-bound illness related to anxiety disorders. AIM OF THE STUDY: To investigate the activity of antiepileptic and anxiolytic plants in the GABAergic system, and determine if there is a pharmacological basis for plant selection. MATERIALS AND METHODS: Ethanol extracts of 34 plants were tested in vitro for their ability to inhibit GABA-transaminase (GABA-T) or bind to the GABA(A)-benzodiazepine (BZD) receptor, two principal drug targets in epilepsy and anxiety. Pharmacological activity was correlated with relative frequency of use, based on informant consensus. RESULTS: Ten plants showed greater than 50% GABA-T inhibition at 1mg/ml, while 23 showed greater than 50% binding to the GABA(A)-BZD receptor at 250 microg/ml. Piperaceae, Adiantaceae and Acanthaceae families were highly represented and active in both assays. There was a significant positive correlation between GABA-T inhibition and relative frequency of use for epilepsy, and an even stronger correlation between GABA(A) binding and relative frequency of use for susto (fright). CONCLUSIONS: Clearly, Q'eqchi' traditional knowledge of antiepileptic and anxiolytic plants is associated with the use of pharmacologically active plants. Based on the evidence, it is suggested that the mechanism of action for some traditionally used plants may be mediated through the GABAergic system.

Bioassay-guided fractionation of lemon balm (Melissa officinalis L.) using an in vitro measure of GABA transaminase activity.

A novel pharmacological mechanism of action for the anxiolytic botanical Melissa officinalis L. (lemon balm) is reported. The methanol extract was identified as a potent in vitro inhibitor of rat brain GABA transaminase (GABA-T), an enzyme target in the therapy of anxiety, epilepsy and related neurological disorders. Bioassay-guided fractionation led to the identification and isolation of rosmarinic acid (RA) and the triterpenoids, ursolic acid (UA) and oleanolic acid (OA) as active principles. Phytochemical characterization of the crude extract determined RA as the major compound responsible for activity (40% inhibition at 100 microg/mL) since it represented approximately 1.5% of the dry mass of the leaves. Synergistic effects may also play a role.

Glutamic acid decarboxylase 65, 67, and GABA-transaminase mRNA expression and total enzyme activity in the goldfish (Carassius auratus) brain.

GAD65 and GAD67 are the two major isoforms of the enzyme that converts glutamate into GABA in a single step reaction. Despite studies describing GAD65 and GAD67 mRNA expression in the mammalian brain, both GAD65 and GAD67 mRNA expression has not yet been fully described for a non-mammalian vertebrate model. Similarly, the expression patterns of GABA-T mRNA, the major enzyme involved in metabolizing GABA, have not been described for any vertebrate. In the present study, we utilized non-radioactive in situ hybridization to localize GAD65, GAD67, and GABA-T in the adult goldfish brain and complimented this with an in vitro assessment of total GAD and GABA-T enzyme activities. A partial fragment of goldfish GABA-T was cloned for a riboprobe that showed approximately 92% deduced amino acid identity to zebrafish GABA-T and 78% identity to human GABA-T. Transcripts for GAD65, GAD67, and GABA-T were detected throughout the brain and were detected largely in the medial and ventral regions of the telencephalon, nucleus preopticus, nucleus recessus lateralis of the hypothalamus, and Purkinje cell layer of the cerebellum. GAD65 mRNA was significantly more abundant in the nucleus recessus posterioris of the hypothalamus than GAD67 and GABA-T mRNA. Total GAD and GABA-T specific enzyme activity was highest in the hypothalamus and optic tectum and GABA-T activity was significantly higher than total GAD enzyme activity. Our results show that GAD65, GAD67, and GABA-T mRNAs are generally correlated with total GAD and GABA-T activity and all three transcripts have a largely overlapping mRNA distribution in the goldfish forebrain.

Ethnopharmacological investigation of plants used to treat susto, a folk illness.

Selected plants used to treat susto, a folk illness recognized by various groups of Latin America, were screened for anxiolytic and/or fear suppression activity in behavioral assays. We found that the plant used by most of the healers interviewed (Adiantum tetraphyllum Humb. & Bonpl. ex Willd.; Adiantaceae) suppressed certain components of anxiety and fear. To our knowledge, this is the first report on the biological activity of Adiantum tetraphyllum. This finding supports the contention that susto may represent what in the Western culture is defined as fear or anxiety, and hence may share the same psychological, biological or neural underpinnings. In light of the available literature, this represents the first experimental investigation of the biological activity of plants specifically in the perspective of their use in treating a culture-bound syndrome.