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About 30% of epileptic patients continue to have seizures. The present study investigates the anticonvulsant and sedative effects of an aqueous extract of C. schweinfurthii in mice. Anticonvulsant effects of C. schweinfurthii aqueous extract (0.01-300 mg/kg, p.o.) were tested against 4-aminopyridine (4-AP, 15 mg/kg, i.p.) -, pilocarpine (PILO, 380 mg/kg, i.p.) - and pentylenetetrazole (PTZ, 75 mg/kg, i.p.) -induced seizures, while sedative effects were tested on diazepam (35 mg/kg, i.p.)-induced sleep. Afterward, the most effective dose of the extract (11.9 mg/kg) was antagonized with N-methyl-β-carboline-3-carboxamide or flumazenil. In another set of experiments, mice were sacrificed for the estimation of GABA content and GABA-T activity in the cerebral cortex. The dose of the extract that protected 50% of mice (ED 50 ) against 4-AP, PILO, and PTZ was respectively 4.43 mg/kg (versus 12.01 for phenobarbital), 9.59 mg/kg (vs 8.67 for diazepam), and 2.12 mg/kg (vs 0.20 for clonazepam). Further, the ED 50 of the extract that increased the duration of sleep was 0.24 mg/kg (vs 0.84 for phenobarbital). N-methyl-β-carboline-3-carboxamide or flumazenil antagonized (p < 0.001) the anticonvulsant effect of C. schweinfurthii in PTZ-induced seizures and diazepam-induced sleep when compared to the negative control group. The extract at all doses increased (p < 0.001) the GABA content and decreased (p < 0.001) GABA-T activity. These findings suggest that C. schweinfurthii possesses anticonvulsant and sedative effects. These effects seem to be mediated via the modulation of the GABA neurotransmission. These data explain the use of this plant to treat epilepsy in Cameroon traditional medicine., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Purpose: Characterization of sedative, possible anticonvulsant, and protective effects of Acacetin-7-O-glucoside (7-ACAG)., Methods: 7-ACAG was separated and its purity was analyzed. Its sedative and anti-seizure effects (1, 10, 20, and 40 mg/kg) were evaluated in male mice. Synaptic responses were acquired from area CA1 of hippocampal slices obtained from male Wistar rats. Rats were subjected to stereotaxic surgeries to allow Electroencephalographic (EEG) recordings. Functional recovery was evaluated by measuring the time rats spent in completing the motor task. Then the rats were subjected to right hemiplegia and administered 7-ACAG (40 mg/kg) 1 h or 24 h after surgery. Brains of each group of rats were prepared for histological analysis., Results: Effective sedative doses of 7-ACAG comprised those between 20 and 40 mg/kg. Latency and duration of the epileptiform crisis were delayed by this flavonoid. 7-ACAG decreased the synaptic response in vitro, similar to Gamma-aminobutyric acid (GABA) effects. The flavonoid facilitated functional recovery. This data was associated with preserved cytoarchitecture in brain cortex and hippocampus., Conclusions: 7-ACAG possesses anticonvulsive and sedative effects. Results suggest that GABAergic activity and neuroprotection are involved in the mechanism of action of 7-ACAG and support this compound's being a potential drug for treatment of anxiety or post-operative conditions caused by neurosurgeries.

This study investigated the hypnotic, anti-convulsant and anxiolytic effects of 1-nitro-2-phenylethane (BPNE) obtained from the oil of Dennettia tripetala G. Baker (Annonaceae) and established its mechanism of action. The essential oil (EO) from the leaf, fruit and seed was obtained by hydrodistillation, followed by isolation of BPNE purified to 99.2% by accelerated gradient chromatography on silica, and identified by NMR and GC-MS. The pure BPNE and EO of the dried seed (93.6%) were comparatively evaluated for hypnotic, anticonvulsant and anxiolytic effects in mice. The acute toxicity of BPNE was determined and the LD50 was 490 mg/kg, intrapritonealy. The hypnotic activities of the EO and BPNE (50-400 mg/kg, i.p.) were assessed by loss of righting reflex, while sodium pentobarbitone (PBS) and diazepam (DZM) were used as positive controls. The anticonvulsant and anxiolytic effects of the EO and BPNE were evaluated in mice. Both BPNE and EO at doses ≥100 mg/kg induced spontaneous hypnosis with loss of righting reflex, significantly decreased sleep latency (SL) and also increased total sleeping time (TST) dose-dependently. They had comparable activity with NAP in TST. The BPNE exhibited higher hypnotic potency than EO at the same dose levels. The EO and BPNE offered comparable dose-related protections against PTZ- and strychnine-induced convulsions. Flumazenil (2 mg/kg) blocked the hypnotic and anticonvulsant (PTZ-convulsions) effects of both EO and BPNE. The essential oil at 5-20 mg/kg dose levels significantly (p<0.05) increased the percentage time spent and number of entries into the open arms. While at the same dose range BPNE significantly (p<0.05) increased the percentage time spent and the number of entries into the open arms respectively. The study concluded that 1-nitro-2-phenylethane exhibited dose dependent significant hypnotic, anticonvulsant and anxiolytic effects and it is the compound largely responsible for the neuropharmacological effects of the oil., (Copyright © 2013 Elsevier GmbH. All rights reserved.)

The flowers or leaves of Chrysanthemum boreale (Compositae) have been traditionally used as herb tea to reduce anxiety, insomnia, and stress. Sedative and anticonvulsant activities were evaluated in mice using pentobarbital-induced sleeping assay and pentylenetetrazole (PTZ)-induced convulsion assay. The flower extract exhibited more potent activities than the extracts of the leaves and stems, and chromatographic isolation yielded the five compounds acacetin, linarin, acacetin 7-O-β-D-glucopyranosyl-(1 → 2)[α-L-rhamnopyranosyl-(1 → 6)]-β-D-glucopyranoside, chlorogenic acid, and 3,5-di-O-caffeoylquinic acid. These compounds were simultaneously analyzed by HPLC, and the method was validated. The contents of linarin, which were shown to be most abundant in C. boreale, were observed in the order of leaf (11.93 mg/g) > flower (8.50 mg/g) > stem (5.60 mg/g). Linarin and its aglycone, acacetin, exhibited sedative and anticonvulsant activities in the present in vivo assays. It can be considered that linarin is one of the active compounds effective against anxiety, insomnia, and stress, with acacetin as its active moiety.

On high performance liquid chromatography, the caffeoylquinic acid (CQ) occupying the highest proportion of the water-ethanol (7:3) extract of Aster glehni (Compositae) leaves was 3-Op-coumaroylquinic acid (46.10 ± 4.22 mg/g of dried weight) among CQs tested. The IC₅₀ of the water-ethanol (7:3) extract was 4.23 ± 0.24 μg/mL in the peroxynitrite (ONOO(-))-scavenging assay. Phytochemical isolation from A. glehni extract yielded three kaempferol glycosides. The water-ethanol (7:3) extract and both p-coumaric acid and caffeic acid, phenylpropanoid moieties of CQs, had sedative effects in pentobarbital-induced sleeping time in mice and anticonvulsant effects in pentylenetetrazole-induced mice. Furthermore, the phenolic substance-rich W-E (7:3) extract of A. glehni could be used to treat anxiety or convulsion partly due to its peroxynitrite-scavenging mechanism.

Context: Solanum sisymbriifolium Lam. (Solanaceae), commonly known as sticky nightshade, is traditionally used for central nervous system (CNS) disorders. Although solasodine has been isolated from this plant, little is known about its anticonvulsant and CNS depressant actions., Objective: We investigated anticonvulsant and CNS depressant effects of solasodine isolated from S. sisymbriifolium using several experimental models., Materials and Methods: Swiss albino mice (n=6) were employed for pentylenetetrazole (PTZ) and picrotoxin (PCT)-induced convulsions and thiopental-induced sleep time. Different groups of Wistar albino rats (n=6) were subjected to maximal electroshock (MES) test. Solasodine, a steroidal glycoalkaloid, was isolated from dried fruits of S. sisymbriifolium and identified by GC-MS., Results: The results showed that intraperitoneal (i.p.) injection of solasodine (25 mg/kg) significantly delayed (p < 0.01) latency of hind limb tonic extensor (HLTE) phase in the PCT-induced convulsions. In the MES model, solasodine significantly reduced (p < 0.001) duration of HLTE at 25, 50, and 100 mg/kg, i.p. in a dose-dependent manner. Interestingly, solasodine did not produce any significant reduction in PTZ-induced convulsions. Prior treatment of solasodine (25, 50, and 100 mg/kg, i.p.) significantly potentiated thiopental-provoked sleep in a dose-dependent manner (p < 0.001)., Discussion and Conclusion: Our study, for the first time, shows potent anticonvulsant and CNS depressant activities of solasodine. It is likely that solasodine, in part, is responsible for the anticonvulsant and sedative properties of S. sisymbriifolium. The future study should focus on the exact mechanism of action of solasodine.

Species of genus Ocimum (Lamiaceae) are economically important due to their essential oils and utilization as medicine for many disorders, including the central nervous system. A previous study showed seasonal variations in chemical profile and in central nervous system activities of essential oil from Ocimum gratissimum L. The preparation obtained in spring was able to protect the animals against tonic episodes induced by electroshock while those obtained in other seasons were effective in increasing barbiturate-induced sleeping time. The chemical analysis of essential oils showed eugenol and 1,8-cineole as principal compounds and trans-caryophyllene as a sesquiterpene in higher proportion. In the present study these three compounds were evaluated, separately or mixed in the same proportion detected in spring, in the open-field and rota-rod tests, against convulsions induced by pentylenetetrazole (PTZ; 60 mg/kg, subcutaneously, s.c.) or maximal electroshock (MES; 50 mA, 0.11 s) and in sodium pentobarbital (45 mg/kg, intraperitoneally, i.p.)-induced sleeping time. The compounds, isolated or in association, did not show efficaciousness in altering convulsive episodes, and only when in association were able to increase sleeping time duration. The absence of similar essential oil activity in the isolated compounds contributes to the idea that the major compounds are not always responsible for a biological effect observed in medicinal plant preparations. This view reinforces the concept of a multitargeted approach as a therapeutic strategy, contributing to an integrated understanding of the phenomena related to experimental activity of a complex herbal mixture.

Lavandula stoechas L. (Lamiaceae) has been used for a long time in traditional medicine as an anticonvulsant and antispasmodic. The aqueous-methanolic extract of L. stoechas flowers (LS) was studied for its possible anticonvulsant and antispasmodic activities. When tested in mice, LS (600 mg/kg) significantly reduced the severity and increased the latency of convulsions induced by pentylene tetrazole (PTZ). LS likewise reduced PTZ's lethality. LS up to a dose of 600 mg/kg was found devoid of any hypnotic effect in mice, however, animals were found to be dull, calm and relaxed. The sedative effect of the plant extract was confirmed, as it prolonged the pentobarbital sleeping time in mice similar to that of diazepam. In isolated rabbit jejunum preparations, LS caused a dose-dependent (0.1-1.0 mg/ml) relaxation of spontaneous contractions. LS also inhibited K(+)-induced contractions in a similar dose range, thereby suggesting calcium channel blockade. This effect was confirmed when pretreatment of the jejunum preparation with LS produced a dose-dependent shift of the Ca(2+) dose-response curve to the right, similar to the effect of verapamil, a standard calcium channel blocker. These data indicate that the plant extract exhibits anticonvulsant and antispasmodic activities. Its calcium channel blocking property may be mechanistically related to these activities. Its usefulness in folk medicine appears thus to be based on a sound mechanistic background.

Galphimia glauca Cav. (Malpighiaceae) is used in Mexican traditional medicine as a sedative in the treatment of mental disorders. Sedative properties of a methanolic extract of the aerial parts of this plant have been established in animal trials and an active compound, named galphimine B, has already been isolated. This compound was submitted to neuropharmacological testing, where it was shown that galphimine B had no significant effect as an anticonvulsant, while it exhibited a strong depressant activity on the nervous system.

The anticonvulsive, sedative and hypothermic effects of water and ethanol extracts of Periostracum Cicadae (PC), the cast off skin of Cryptotympana atrata were studied. The water-extract of whole Periostracum Cicadae (PCws) had anticonvulsive, sedative and hypothermic effects in rats. Orally, it decreased carrageenin-induced hyperthermia. The hypothermic effect of PCws was potentiated by 5-hydroxytryptophan and antagonized by p-chlorophenylalanine. PCws enhanced the decrease in locomotor activity induced by alpha-methyl-p-tyrosine or 5-hydroxytryptophan and reduced the increase in locomotor activity produced by levodopa plus benserazide or p-chlorophenylalanine. From these results, it was concluded that the sedative and hypothermic effect of PCws may be due to an increase in central serotonergic activity.