stigmasterol and Seizures

Gamma-aminobutyric acid A (GABA. This study aimed to investigate the effects of stigmasterol, a plant sterol (phytosterol) isolated from Artemisia indica Linn on neurological disorders.. Stigmasterol was evaluated on various recombinant GABA. To our knowledge, this is the first study reporting the positive modulation of GABA

Topics: Animals; Anti-Anxiety Agents; Anticonvulsants; GABA Modulators; Oocytes; Receptors, GABA-A; Seizures; Stigmasterol; Xenopus laevis

α-Spinasterol is a plant-derived compound which was reported to act as a selective antagonist for the transient receptor potential vanilloid 1 (TRPV1) receptor. Several studies revealed that the TRPV1 receptors might modulate seizure activity in animal models of seizures and epilepsy. The aim of the present study was to investigate the effect of α-spinasterol on the seizure threshold in three acute models of seizures, i.e., in the intravenous (i.v.) pentylenetetrazole (PTZ) seizure test, in the maximal electroshock seizure threshold (MEST) test and in the model of psychomotor seizures induced by 6 Hz stimulation in mice. Our results revealed significant anticonvulsant effect of α-spinasterol in all the used seizure tests. In the i.v. PTZ test, statistically significant elevation was noted in case of the threshold for myoclonic twitches (doses of 0.1-1 mg/kg) and generalized clonus seizures (doses of 0.5 and 1 mg/kg) but not for tonic seizures. The studied TRPV1 antagonist also increased the threshold for tonic hindlimb extension in the MEST (doses of 0.5 and 1 mg/kg) and 6 Hz psychomotor seizure (doses of 0.1 and 0.5 mg/kg) tests in mice. Furthermore, α-spinasterol did not produce any significant impairment of motor coordination (assessed in the chimney test) and muscular strength (investigated in the grip-strength test) and it did not provoke significant changes in body temperature in mice. Based on the results of our study and the fact that α-spinasterol is characterized by good blood-brain permeability, we postulate further investigation of this compound to precisely evaluate mechanism of its anticonvulsant action and opportunity of its usage in clinical practice.

Topics: Animals; Anticonvulsants; Body Temperature; Disease Models, Animal; Dose-Response Relationship, Drug; Electric Stimulation; Male; Mice; Motor Activity; Muscle Strength; Pentylenetetrazole; Random Allocation; Seizures; Stigmasterol; Treatment Outcome; TRPV Cation Channels

We previously showed that extracts of Sargassum fusiforme significantly reduce immobility time in the forced swim test and tail suspension test, suggesting that these extracts possess antidepressant-like effects. Here, fucosterol extracted from S. fusiforme was evaluated for antidepressant and anticonvulsant activities in mice. Fucosterol (10, 20, 30 and 40mg/kg) significantly shortened immobility time in the forced swim test and tail suspension test for30min after treatment but had no effect on locomotor activity in the open field test. Fucosterol significantly increased serotonin, norepinephrine and the metabolite 5-hydroxyindoleacetic acid in mouse brain, suggesting that the effects of fucosterol may be mediated through these neurotransmitters. As assessed using maximal electroshock, fucosterol (20, 40, 100mg/kg) possessed anticonvulsant activity, whereas rotarod toxicity test results indicated that fucosterol did not induce neurotoxicity at the same dose levels in mice. Thus, fucosterol may be a useful antidepressant adjunct candidate for treating depression in patients with epilepsy. A significant increase in hippocampal brain-derived neurotrophic factor (BDNF) levels was found in the fucosterol 20mg/kg group (P<0.05). Our findings suggested that fucosterol may possess an antidepressant-like effect, which may be mediated by increasing central BDNF levels.

Topics: Animals; Anticonvulsants; Antidepressive Agents; Biogenic Monoamines; Brain; Depression; Male; Mice; Mice, Inbred BALB C; Motor Activity; Neurotransmitter Agents; Sargassum; Seizures; Stigmasterol; Swimming