Acteoside Isolated from Colebrookea oppositifolia Smith Attenuates Epilepsy in Mice Via Modulation of Gamma-Aminobutyric Acid Pathways.

The present study was aimed to evaluate the anticonvulsant activity of acteoside and explore its mechanism of action. Initially, the acteoside was evaluated in maximal electroshock (MES) and pentylenetetrazole (PTZ)-induced convulsions, and later it was evaluated against N-methyl-D-aspartic acid (NMDA)-induced mortality in Swiss albino mice. Based on the response in these models, further evaluations were performed to explore the mechanism of action. In the results, the acteoside (10, 25, and 50 mg/kg) has shown significant anticonvulsant activity in the PTZ model (p < 0.01 for all doses); however, there was no protection observed in MES and NMDA models. Therefore, further mechanism-based studies were performed on the PTZ model, and the outcomes have revealed that there was a significant reduction in GABA (p < 0.01 for both regions) and elevation of glutamate (p < 0.01 for both regions) in the cortex and hippocampus regions of PTZ-treated animals. Further, the antioxidant levels (SOD, catalase, GPx, GR, GSH, LPO) were altered significantly (p < 0.01 for all parameters), with reduced GABAA mRNA levels (p < 0.01) in the PTZ control compared with the normal control. Interestingly, co-administration of acteoside (25 mg/kg) (p < 0.01 for all parameters) has restored all the PTZ-induced alterations compared to PTZ-control. Moreover, the anti-PTZ action of acteoside was completely blocked in the presence of flumazenil, and thus confirmed the GABAergic mechanism behind the anticonvulsant activity of acteoside. Besides, actophotometer and rotarod tests have confirmed that the acteoside is free from central side effects like motor incoordination and locomotor deficits.

Poisoning due to water hemlock.

INTRODUCTION: Water hemlock, which encompasses a range of species divided across two genera (Cicuta and Oenanthe), are regarded as being among the most poisonous plants both in North America and in the United Kingdom. Despite their toxicity, the literature consists almost entirely of case reports. AIM: The aim of this review is to summarize this literature by covering all aspects of taxonomy and botanical characterization, principal toxins, basic pharmacology including mechanisms of toxicity, and the clinical features, diagnosis, and management of poisoning. MECHANISMS OF TOXICITY: The principal toxins, cicutoxin and oenanthotoxin, belong to a group of C17 conjugated polyacetylenes. They act as (noncompetitive) gamma-aminobutyric acid antagonists in the central nervous system (CNS), resulting in unabated neuronal depolarization that can lead to seizures. Ingestion of even a small amount of plant matter may result in severe intoxication. FEATURES: After ingestion, the patient is most likely to experience CNS stimulatory effects including seizures that, in the absence of aggressive supportive care, can result in death. Other features include nausea, vomiting, diarrhea, tachycardia, mydriasis, rhabdomyolysis, renal failure, coma, respiratory impairment, and cardiac dysrhythmias. MANAGEMENT: Treatment consists mainly of prompt airway management and seizure control, plus decontamination if achieved early and after stabilization. In the event of renal failure, the use of hemodialysis has been employed successfully. CONCLUSIONS: The ingestion of water hemlock can lead to serious complications that may be fatal. Prognosis is good, however, if prompt supportive care is provided.

Polyacetylenes from sardinian Oenanthe fistulosa: a molecular clue to risus sardonicus.

An investigation of Oenanthe fistulosa from Sardinia afforded oenanthotoxin (1a) and dihydrooenanthotoxin (1b) from the roots and the diacetylenic epoxydiol 2 from the seeds. The absolute configuration of 1a and 1b was established as R by the modified Mosher's method, and the structure of 2 by chemical correlation with (+)-(3R,8S)-falcarindiol. Oenanthotoxin (1a) and dihydrooenanthotoxin (1b) were found to potently block GABAergic responses, providing a molecular rationale for the symptoms of poisoning from water-dropwort (Oenanthe crocata) and related plants. These observations bear relevance for a series of historical and ethnopharmacological observations on the identification of the Sardonic herb and the molecular details of the facial muscular contraction caused by its ingestion (risus sardonicus).

Inhibition of MAO and GABA: probable mechanisms for antidepressant-like activity of Nardostachys jatamansi DC. in mice.

Ethanolic extract (100, 200 and 400 mg/kg, po) of N. jatamansi administered for 14 successive days to Swiss young albino mice (either sex) produced significant antidepressant-like effect in both tail suspension and forced swim tests. The efficacy of the extract was found to be comparable to imipramine (15 mg/kg, po) and sertraline (20 mg/kg, po). Ethanolic extract (200 mg/kg, po) did not show any significant change on locomotor activity of mice as compared to control; hence it did not produce any motor effects. Further, the extract decreased the whole brain MAO-A and MAO-B activities as compared tocontrol, thus increased the levels of monoamines. The antidepressant effect of the extract was also significantly reversed by pretreatment of animals with baclofen (GABAB agonist); when tested in tail suspension test. The results suggested that the antidepressant-like effect of the extract may also be due to interaction with GABAB receptors, resulting in decrease in the levels of GABA in mouse brain. Thus, the extract may have potential therapeutic value for the management of mental depression.

Two flavonoids from Artemisia herba-alba Asso with in vitro GABAA-benzodiazepine receptor activity.

An ethyl acetate extract of Artemisia herba-alba was partitioned by HPLC in 10 fractions that were tested in the [(3)H]-flumazenil radioligand assay, for affinity to the GABA(A)-benzodiazepine receptor. Two fractions showed activity from which hispidulin and cirsilineol were isolated. The structures were confirmed by (1)H NMR. The IC(50) values were 8 microM for hispidulin and 100 microM for cirsilineol.