Polysaccharide-rich extract of Genipa americana leaves protects seizures and oxidative stress in the mice model of pentylenetetrazole-induced epilepsy.

Plant polysaccharides have biological activities in the brain and those obtained from Genipa americana leaves present antioxidant and anticonvulsant effects in the mice model of pentylenetetrazole (PTZ)-induced acute seizures. This study aimed to evaluate the polysaccharide-rich extract of Genipa americana leaves (PRE-Ga) in the models of acute seizures and chronic epilepsy (kindling) induced by PTZ. In the acute seizure model, male Swiss mice (25-35 g) received PRE-Ga (1 or 9 mg/kg; intraperitoneal- IP), alone or associated with diazepam (0.01 mg/kg), 30 min before induction of seizures with PTZ (70 mg/kg; IP). In the chronic epilepsy model, seizures were induced by PTZ (40 mg/kg) 30 min after treatment and in alternated days up to 30 days and evaluated by video. Brain areas (prefrontal cortex, hippocampus, striatum) were assessed for inflammatory and oxidative stress markers. Diazepam associated to PRE-Ga (9 mg/kg; i.p.) increased the latency of seizures in acute (222.4 ± 47.57 vs. saline: 62.00 ± 4.709 s) and chronic models (6.267 ± 0.502 vs. saline: 4.067 ± 0.407 s). In hippocampus, PRE-Ga (9 mg/kg) inhibited TNF-α (105.9 ± 5.38 vs. PTZ: 133.5 ± 7.62 pmol/g) and malondialdehyde (MDA) (473.6 ± 60.51) in the chronic model. PTZ increased glial fibrillar acid proteins (GFAP) and Iba-1 in hippocampus, which was reversed by PRE-Ga (GFAP: 1.9 ± 0.23 vs PTZ: 3.1 ± 1.3 and Iba-1: 2.2 ± 0.8 vs PTZ: 3.2 ± 1.4). PRE-Ga presents neuroprotector effect in the mice model of epilepsy induced by pentylenetetrazole reducing seizures, gliosis, inflammatory cytokines and oxidative stress.

Electroencephalographic profile of Salvia amarissima Ortega and amarisolide A in the absence and presence of PTZ-induced seizures in mice.

Salvia amarissima Ortega is a plant used in traditional medicine to treat CNS's affections. Despite its depressant properties in anxiety and fibromyalgia, there is no scientific evidence about its capability to control seizure activity. This study aimed to investigate the effects of the S. amarissima aqueous extract (SAAE) and its metabolite amarisolide A (AMA) on the electrocorticographic (ECoG) activity. The ECoG profiles were previously and concurrently analyzed to the pentylenetetrazole (85 mg/kg, i.p.)-induced seizure behavior after thirty min of the administration of several doses of the SAAE (1, 10, 30, and 100 mg/kg, i.p.) and two doses of AMA (0.5 and 1 mg/kg, i.p.). A dosage of AMA (1 mg/kg,i.p.) was selected to explore a possible mechanism of action by using antagonists of inhibitory receptors such as GABAA (picrotoxin, 1 mg/kg, i.p.) or 5-HT1A of serotonin (WAY100635, 1 mg/kg, i.p.). Significant changes in the frequency bands and the spectral power were observed after the treatment alone. Additionally, SAAE and AMA produced significant and dose-dependent anticonvulsant effects by reducing the incidence and severity of seizures and increasing latency or survival. Both antagonists prevented the effects of AMA in the severity score of seizures and survival during the tonic-clonic seizures. In conclusion, our preclinical data support that S. amarissima possesses anticonvulsant properties, in part due to the presence of amarisolide A, mediated by different inhibitory mechanisms of action. Our scientific evidence suggests that this Salvia species and amarisolide A are potential neuroprotective alternatives to control seizures in epilepsy therapy.

Therapeutic potential of CB1R activation by Qingyangshen glycoside M1 for seizure relief.

ETHNOPHARMACOLOGICAL RELEVANCE: Cynanchum otophyllum C.K.Schneid.PI.Wilson, commonly referred as ''Qingyangshen'' (QYS), is a traditional folk medicine from Yunnan, renowned for its efficacy in neurological and psychiatric disorders. Glycosides isolated from QYS have shown promise in alleviating epilepsy, however, mechanisms of action and specific molecular targets remain to be elucidated. AIM OF THE STUDY: The study aimed to evaluate the anticonvulsant effects of Qingyangshen glycosides M1 (M1), a C21 steroidal glycoside from QYS, on pentylenetetrazol (PTZ)-induced convulsions in zebrafish (Danio rerio), and its neuroprotective effect on Glutamate (Glu)-induced damage to PC12 cells, and importantly to identify its potential molecular targets. MATERIALS AND METHODS: To evaluate anticonvulsant activity of M1, 7 days-post-fertilization (7-dpf) animals were pretreated (by immersion) and then exposed to PTZ (10 mM) solution. Furthermore, Glu-induced PC12 cell damage was employed to investigate the neuroprotective and anti-apoptotic capacity. Cells were pretreated with various concentrations of M1 (0-10 µM) for 12 h and then co-treated with Glu (15 mM) for an additional 24 h. The cell viability, apoptosis rate and apoptosis-related proteins (p-PI3K, PI3K, Akt, p-Akt, CREB, p-CREB, BDNF, Bax and Bcl-2) were measured using CCK-8, annexin V/PI and Western blot assays. To model the expected interaction between M1 and candidate cannabinoid receptor type 1 (CB1R), ERK phosphorylation, molecular docking, and drug affinity responsive target stability (DARTS) techniques were employed. Finally, CB1R antagonist Rimonabant (Rim) was validated by co-administration in both zebrafish and cells to confirm the requirement of CB1R for M1 efficacy. RESULTS: At a concentration of 400 µM, M1 dramatically reversed PTZ-induced convulsive-like behaviors in zebrafish, as evidenced by a significant reduction in locomotor activity. In the context of Glu-induced cytotoxicity, M1 (10 µM) demonstrated a notable increase in cell viability and suppressed apoptosis through modulation of the Bax/Bcl-2 ratio and activation of the PI3K/Akt/CREB/BDNF signaling axis. These effects were facilitated through CB1R activation. In contrast, Rim dampened the beneficial activities of M1 as a cannabinoid agonist. CONCLUSIONS: These results demonstrated that M1 as a potential CB1R activator, exhibiting anticonvulsive effects in a PTZ-induced zebrafish model and neuroprotective properties via the PI3K/Akt/CREB/BDNF signaling axis in a Glu-induced PC12 cell injury model. Notably, the observed seizure relief attenuated by CB1R chemical antagonism.

Effectiveness of Shugan Jieyu capsules for psychiatric symptoms of epilepsy: a systematic review and meta-analysis.

BACKGROUND: The relationship between epilepsy and depression is bidirectional. One condition exacerbates the other. However, there are no current guidelines for treating depression in epilepsy patients. In some cases, seizures worsen when antidepressants (AD) are prescribed or when they are discontinued due to adverse events. The Shugan Jieyu capsule, composed of Acanthopanax senticosus and Hypericum perforatum, is a widely used herbal medicine for treating depression. This study aimed to explore the effectiveness and safety of Shugan Jieyu capsules (SJC) in relieving depression in patients with epilepsy. METHODS: We searched English, Korean, Japanese, and Chinese databases in October 2023 to collect all relevant randomized clinical trials (RCTs). The primary outcomes were the depression scale scores and seizure frequency. The secondary outcomes were quality of life (QoL) and adverse events. RESULTS: Nine RCTs were included in this meta-analysis. Compared with AD, SJC showed significant differences in the improvement of depression (SMD: 3.82, 95% CI: 3.25, 4.39) and reduction in seizure frequency (MD: 0.39 times/month, 95% CI: 0.28, 0.50). SJC showed more beneficial results than antiepileptic drugs (AED) in terms of antidepressant effects (SMD: 1.10, 95% CI: 0.69, 1.51) and QoL (MD: 11.75, 95% CI: 10.55, 12.95). When patients were prescribed AED, the additional administration of SJC improved depression symptoms (SMD: 0.96, 95% CI: 0.28, 1.63). The SJC treatment group had a lower incidence of side effects than the control group. However, the difference was not statistically significant. CONCLUSIONS: Our results suggest that SJC may be effective in treating depression in patients with epilepsy. Additionally, SJC has the potential to help reduce seizure frequency in epilepsy patients with depression.

Integrated non-targeted metabolomics and network pharmacology to reveal the mechanisms of berberine in the long-term treatment of PTZ-induced epilepsy.

AIMS: The increasing resistance to anti-seizure medications (ASMs) and the ambiguous mechanisms of epilepsy highlight the pressing demand for the discovery of pioneering lead compounds. Berberine (BBR) has received significant attention in recent years within the field of chronic metabolic disorders. However, the reports on the treatment of epilepsy with BBR are not systematic and the mechanism remains unclear. MAIN METHODS: In this study, the seizure behaviors of mice were recorded following subcutaneous injection of pentetrazol (PTZ). Non-targeted metabolomics was used to analyze the serum metabolites based on ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). Meanwhile, multivariate statistical methods were used for metabolite identification and pathway analysis. Furthermore, network pharmacology, molecular docking, and quantitative real-time PCR assay were used for the target identification. KEY FINDINGS: BBR had anti-seizure effects on PTZ-induced seizure mice after long-term treatment. Tryptophan metabolism and phenylalanine metabolism were involved in regulating the therapeutic effects of BBR. SIGNIFICANCE: This study reveals the potential mechanism of BBR for epilepsy treatment based on non-targeted metabolomics and network pharmacology, which provides evidence for uncovering the pathogenesis of epilepsy, suggesting that BBR is a potential lead compound for anti-epileptic treatment.

A Compared Study of Eicosapentaenoic Acid and Docosahexaenoic Acid in Improving Seizure-Induced Cognitive Deficiency in a Pentylenetetrazol-Kindling Young Mice Model.

Epilepsy is a chronic neurological disorder that is more prevalent in children, and recurrent unprovoked seizures can lead to cognitive impairment. Numerous studies have reported the benefits of docosahexaenoic acid (DHA) on neurodevelopment and cognitive ability, while comparatively less attention has been given to eicosapentaenoic acid (EPA). Additionally, little is known about the effects and mechanisms of DHA and EPA in relation to seizure-induced cognitive impairment in the young rodent model. Current research indicates that ferroptosis is involved in epilepsy and cognitive deficiency in children. Further investigation is warranted to determine whether EPA or DHA can mitigate seizure-induced cognitive deficits by inhibiting ferroptosis. Therefore, this study was conducted to compare the effects of DHA and EPA on seizure-induced cognitive deficiency and reveal the underlying mechanisms focused on ferroptosis in a pentylenetetrazol (PTZ)-kindling young mice model. Mice were fed a diet containing DHA-enriched ethyl esters or EPA-enriched ethyl esters for 21 days at the age of 3 weeks and treated with PTZ (35 mg/kg, i.p.) every other day 10 times. The findings indicated that both EPA and DHA exhibited ameliorative effects on seizure-induced cognitive impairment, with EPA demonstrating a superior efficacy. Further mechanism study revealed that supplementation of DHA and EPA significantly increased cerebral DHA and EPA levels, balanced neurotransmitters, and inhibited ferroptosis by modulating iron homeostasis and reducing lipid peroxide accumulation in the hippocampus through activating the Nrf2/Sirt3 signal pathway. Notably, EPA exhibited better an advantage in ameliorating iron dyshomeostasis compared to DHA, owing to its stronger upregulation of Sirt3. These results indicate that DHA and EPA can efficaciously alleviate seizure-induced cognitive deficiency by inhibiting ferroptosis in PTZ-kindled young mice.

The standardized extract of Centella asiatica L. Urb attenuates the convulsant effect induced by lithium/pilocarpine without affecting biochemical and haematological parameters in rats.

BACKGROUND: Status epilepticus (SE) is a type of epileptic activity characterized by a failure of the inhibitory mechanisms that limit seizures, which are mainly regulated by the GABAergic system. This imbalance increases glutamatergic neurotransmission and consequently produces epileptic activity. It is also associated with oxidative stress due to an imbalance between reactive oxygen species (ROS) and antioxidant defences. Unfortunately, long-term treatment with anti-epileptic drugs (AEDs) may produce hepatotoxicity, nephrotoxicity, and haematological alterations. In this way, some secondary metabolites of plants have been used to ameliorate the deterioration of nervous system disorders through their antioxidant properties, in addition to their anticonvulsant effects. An example is Centella asiatica, a plant noted to have a reputed neuroprotective effect related to its antioxidant activity. However, similar to conventional drugs, natural molecules may produce side effects when consumed in high doses, which could occur with Centella asiatica. Therefore, we aimed to evaluate the effect of a standardized extract of Centella asiatica L. Urb with tested anticonvulsant activity on biochemical and haematological parameters in rats subjected to lithium/pilocarpine-induced seizures. METHODS: Twenty-eight adult male Wistar rats were randomly divided into four groups (n = 7 each): vehicle (purified water), Centella asiatica (200 and 400 mg/kg), and carbamazepine (CBZ) (300 mg/kg) as a pharmacological control of anticonvulsant activity. Treatments were administered orally every 24 h for 35 consecutive days. On Day 36, SE was induced using the lithium/pilocarpine model (3 mEq/kg, i.p. and 30 mg/kg s.c., respectively), and the behavioural and biochemical effects were evaluated. RESULTS: Centella asiatica 400 mg/kg increased the latency to the first generalized seizure and SE onset and significantly reduced the time to the first generalized seizure compared to values in the vehicle group. Biochemical parameters, i.e., haematic cytometry, blood chemistry, and liver function tests, showed no significant differences among the different treatments. CONCLUSION: The dose of Centella asiatica that produces anticonvulsant activity in the lithium/pilocarpine model devoid of hepatotoxicity, nephrotoxicity, and alterations in haematological parameters suggests that the standardized extract of this plant could be of utility in the development of new safe therapies for the treatment of convulsions associated with epilepsy.

Behavioral and electrophysiological (ECoG) effects of haplophyllum robustum and TRPA1 antagonist in adult male wistar rats.

This article aimed to investigate the effects of Haplophyllum robustum hydroalcoholic extract on animals' behavioral and electrocorticographic changes. This plant is mainly found in Turkey, Iran, and Central Asia, and is reported to have convulsive effects. In this article, we worked on the effects of its hydroalcoholic extract on electrocorticography (ECoG), along with changes induced by intracerebroventricular administration of GABAA antagonists. Furthermore, the effects of low doses of this extract on behavioral depression were examined. Four animal sets were used to compare ECoG in Wistar rats. A group of negative control, a group of positive control (PTZ), and two groups received an injection of plant extract (500 mg/kg, ip), with or without administration of Diazepam (5 mg/kg). Also, three sets were applied to compare receiving and not receiving intracerebroventricular (icv) injection of Transient receptor potential ankyrin 1 antagonist (HC-030031) (2 µg/kg) on plant-induced seizure delay and animal death. Two groups of control and a group with plant extract together with TRPA1 antagonist were administrated. Furthermore, in the present study, the forced swimming test (FST) was used as a model of depression. The behaviors of animals in three groups of negative control and positive control (Fluoxetine) and plant extract (200 mg/kg, ip) were compared. According to the ECoG, high doses of extract of plants led to seizures similar to PTZ, which were then reduced by diazepam injection. At this dose, injection of TRPA1 antagonist did not significantly delay the onset of seizures or the death of the animals. Further, a subconvulsive dose of hydroalcoholic plant extracts was equally effective in treating depression as Fluoxetine injections.

A Comparative Analysis of Prehospital Emergency Treatments: Midazolam Intramuscularly, Diazepam Enema, and Chloral Hydrate Enema for Pediatric Convulsions.

Objective: This study aimed to compare the effectiveness of prehospital emergency treatments using midazolam (MDL) intramuscularly, diazepam (DZP) enema, and chloral hydrate (CH) enema in managing pediatric convulsions. Methods: A comparative observational study was conducted, and a total of 140 children with acute convulsions treated with prehospital anti-convulsions at Qinhuangdao First Hospital's emergency department between June 2015 and May 2019 were included in this study. The children were categorized based on the prehospital anti-convulsion measures received: group M (n = 48) received MDL intramuscularly, group D (n = 46) received DZP enema, and group C (n = 46) received CH enema. The emergency effects of the three treatment groups were compared. Results: 1. Group M showed significantly shorter treatment preparation time and total rescue time compared to groups C and D (both P < .05); no significant difference was observed between groups C and D (both P > .05), including convulsion control time in the effective cases (45 in group M, 42 in group C, and 43 in group D) (all P > .05 Group M had effective rates of 93.75%, while group C and group D had rates of 91.3% and 93.48%, respectively (all P > .05); Group M had more controlled cases at 1 min, 3 min, 5 min, and 10 min than group C and group D (all P > .05). Group M had significantly fewer relapses, cases requiring intravenous maintenance treatment, and faster convulsion control after intravenous maintenance compared to groups C and D (P < .05), with no significant differences between groups C and D in time to recovery of consciousness and length of hospitalization (P > .05). 4. Systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), respiratory (R) frequency, and peripheral oxygen saturation (SpO2) showed no significant differences before and 10 minutes after medication in all three groups (P > .05); SBP and DBP levels fluctuated within the normal range, while HR decreased, R frequency decreased, and SpO2 increased significantly 10 minutes after medication compared to before treatment (P < .05). 5. No significant adverse effects were observed in the three patient groups. Conclusions: MDL intramuscular injection, DZP enema, and CH enema were effective prehospital treatments for pediatric acute convulsions. MDL intramuscular injection demonstrated advantages such as fast onset, reliable efficacy, ease of use, and high safety, making it more suitable for the prehospital treatment of pediatric convulsions.

Herb pair of Polygala tenuifolia Willd and Acorus tatarinowii Schott decoction attenuates seizures and alleviates anxiety in mice: Evidence for modulating inflammation, alleviating oxidative stress and mediating GABA pathway.

Currently, prolong use of standard anti-epileptics may cause tolerance and ineffective for about 30% of epileptic patients. Medicinal plants provide an attractive therapeutic effect in preventing and treating seizures in traditional and folk medicine. In this study, we investigate the antiepileptic effects of PTAT decoction on acute and chronic seizure models in mice and explore the potential mechanisms. PTAT decoction dose-dependently protected mice against MES and PTZ induced seizure. Meanwhile, it decreased the seizure severity and reduced seizure-caused anxious behavior in the PTZ-kindling mice, suggesting a significant antiepileptic activity and anxiolytic/anxiogenic potential. PTAT decoction dose-dependently increased the levels of GSH and the activity SOD and CAT, while decreased the level of MDA in the hippocampi of treated mice. Furthermore, a significant decrease in the proinflammatory cytokine levels, including TNF-α, IL-1ß, IL-6 and MCP-1 was found in treated mice compared with the mice in the vehicle + PTZ group. Moreover, PTAT decoction dose-dependently reversed the alterations induced by PTZ in GABA, GABA-T, L-GAD and glutamate levels in kindling mice, showing an effect on the modulation of the GABA neurotransmission. Thus, PTAT decoction has a promising anticonvulsant activity mediated via multiple mechanisms, which might be used as an up-and-coming phytotherapy strategy in the management of epilepsy and its complications.

Ameliorative effects of Albizia adianthifolia aqueous extract against pentylenetetrazole-induced epilepsy and associated memory loss in mice: Role of GABAergic, antioxidant defense and anti-inflammatory systems.

Albizia adianthifolia (Schumach.) (Fabaceae) is a medicinal herb used for the treatment of epilepsy and memory impairment. This study aims to investigate the anticonvulsant effects of Albizia adianthifolia aqueous extract against pentylenetetrazole (PTZ)-induced spontaneous convulsions in mice; and determine whether the extract could mitigate memory impairment, oxidative/nitrergic stress, GABA depletion and neuroinflammation. Ultra-high performance liquid chromatography/mass spectrometry analysis was done to identify active compounds from the extract. Mice were injected with PTZ once every 48 h until kindling was developed. Animals received distilled water for the normal group and negative control groups, doses of extract (40, 80, or 160 mg/kg) for the test groups and sodium valproate (300 mg/kg) for the positive control group. Memory was measured using Y maze, novel object recognition (NOR) and open field paradigms, while the oxidative/nitrosative stresses (MDA, GSH, CAT, SOD and NO), GABAergic transmission (GABA, GABA-T and GAD) and neuro-inflammation (TNF-α, IFN-γ, IL- 1ß, and IL-6) were determined. Brain photomicrograph was also studied. Apigenin, murrayanine and safranal were identified in the extract. The extract (80-160 mg/kg) significantly protected mice against seizures and mortality induced by PTZ. The extract significantly increased the spontaneous alternation and the discrimination index in the Y maze and NOR tests, respectively. PTZ kindling induced oxidative/nitrosative stress, GABA depletion, neuroinflammation and neuronal cells death was strongly reversed by the extract. The results suggest that the anticonvulsant activity of Albizia adianthifolia extract is accompanied by its anti-amnesic property, and may be supported by the amelioration of oxidative stress, GABAergic transmission and neuroinflammation.

Anticonvulsant potential of Grewia tiliaefolia in pentylenetetrazole induced epilepsy: insights from in vivo and in silico studies.

Epilepsy, a chronic neurological condition, impacts millions of individuals globally and remains a significant contributor to both illness and mortality. Available antiepileptic drugs have serious side effects which warrants to explore different medicinal plants used for the management of epilepsy reported in Traditional Indian Medicinal System (TIMS). Therefore, we explored the antiepileptic potential of the Grewia tiliaefolia (Tiliaeceae) which is known for its neuroprotective properties. Aerial parts of G. tiliaefolia were subjected to extraction with increasing order of polarity viz. hexane, chloroform and methanol. Antioxidant potential of hexane, chloroform and methanol extracts of G. tiliaefolia was evaluated by 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) assay, total antioxidant capacity (TAC) assay, reducing power assay (RPA) and DNA nicking assay. Additionally, quantitative antioxidant assays were also conducted to quantify total phenolic (TPC) and total flavonoid content (TFC). As revealed by in vitro assays, methanol extract was found to contain more phenolic content. Hence, the methanol extract was further explored for its anticonvulsant potential in pentylenetetrazole (PTZ) induced acute seizures in mice. The methanol extract (400 mg/kg) significantly increased the latency to occurrence of myoclonic jerks and generalized tonic clonic seizures (GTCS). Additionally, it also reduced duration and seizure severity score associated with GTCS. The Grewia tiliaefolia methanol extract was further screened by Ultra High-Performance Liquid Chromatography (UHPLC) for presence of polyphenolic compounds, among which gallic acid and kaempferol were present in higher amount and were further analysed by in silico study to predict their possible binding sites and type of interactions these compounds show with gamma amino butyric acid (GABA) receptor and glutamate α amino-3- hydroxyl-5-methyl-4-isoxazolepropionic acid (Glu-AMPA) receptor. It was revealed that gallic acid and kaempferol had shown agonistic interaction for GABA receptor and antagonistic interaction for Glu-AMPA receptor. We concluded that G. tiliaefolia showed anticonvulsant potential possibly because of gallic acid and kaempferol possibly mediated through GABA and Glu-AMPA receptor.

Effects of probiotics on GABA/glutamate and oxidative stress in PTZ- induced acute seizure model in rats.

Studies conducted in recent years have indicated a relationship between epilepsy and gut microbiota. Ion channels, excitatory/inhibitory balance and regulatory systems play a role in the pathophysiology of epilepsy. In addition, gut dysbiosis is also involved in the pathophysiology of epilepsy. This research investigated the impacts of probiotic mixture on epileptic seizures, Gamma aminobutyric acid (GABA), glutamate, and TAS and TOS levels in hippocampal tissue in the PTZ-induced acute seizure model in rats. Four groups were formed with male Wistar albino rats. The first and second groups were given 1 ml/day saline solution, and the other groups were given 0.05 mg/1 ml/day vehicle or 109cfu/1 ml/day probiotic supplementation, respectively via gavage for 21 days. A single-dose PTZ (45 mg/kg) was administered to induce seizure. The stages of seizure were analyzed according to the Racine scale. While ELISA was used to determine GABA and glutamate levels in the hippocampus, an automated colorimetric method was utilized to measure oxidant/antioxidant biomarkers. It was found that by delaying the first myoclonic jerk (FMJ), and the onset of the generalized tonic-clonic seizures, the probiotic mixture demonstrated anticonvulsant effects against seizures. The probiotic mixture was found to increase the inhibitory neurotransmitter GABA. It was also found to decrease TOS levels and increase TAS concentration. The findings of this study showed that probiotic mixture reduced oxidative stress with its positive effects against PTZ-induced epileptic seizures. Further studies are needed to reveal potentially related mechanisms.

Supplementation of n-3 PUFAs in Adulthood Attenuated Susceptibility to Pentylenetetrazol Induced Epilepsy in Mice Fed with n-3 PUFAs Deficient Diet in Early Life.

The growth and development of the fetus and newborn throughout pregnancy and lactation are directly related to the nutritional status of the mother, which has a significant impact on the health of the offspring. The purpose of this experiment was to investigate the susceptibility of n-3 polyunsaturated fatty acid deficiency in early life to seizures in adulthood. The n-3 PUFAs-deficient mice's offspring were established and then fed with α-LNA diet, DHA-enriched ethyl ester, and DHA-enriched phospholipid-containing diets for 17 days at the age of eight weeks. During this period, animals received intraperitoneal injections of 35 mg/kg of pentylenetetrazol (PTZ) every other day for eight days. The results showed that dietary n-3 PUFA-deficiency in early life could aggravate PTZ-induced epileptic seizures and brain disorders. Notably, nutritional supplementation with n-3 PUFAs in adulthood for 17 days could significantly recover the brain n-3 fatty acid and alleviate the epilepsy susceptibility as well as raise seizure threshold to different levels by mediating the neurotransmitter disturbance and mitochondria-dependent apoptosis, demyelination, and neuroinflammation status of the hippocampus. DHA-enriched phospholipid possessed a superior effect on alleviating the seizure compared to α-LNA and DHA-enriched ethyl ester. Dietary n-3 PUFA deficiency in early life increases the susceptibility to PTZ-induced epilepsy in adult offspring, and nutritional supplementation with n-3 PUFAs enhances the tolerance to the epileptic seizure.

Ceftriaxone and selenium mitigate seizures and neuronal injury in pentylenetetrazole-kindled rats: Oxidative stress and inflammatory pathway.

Epilepsy is one of the most serious worldwide neurological disorders that lead to the cognitive-psychosocial insults in recurrent seizures. About one third of the patients are drug-resistant, so innovative drugs are needed to manage seizures to improve the quality of life. Ceftriaxone is a cephalosporin antibiotic that increases the expression of glutamate transporters-1 and improves the neurobehavioral effects caused by increased glutamate level in the CNS. Selenium is well known antioxidant. The present study aimed to investigate ceftriaxone and selenium therapeutic effects against epilepsy in rats. Epilepsy was induced by PTZ given at a dose (50 mg/kg I.P) on alternative days for 13 days. Eighty rats were randomly divided into 8 groups: Group1-2; normal and vehicle control, Group 3; PTZ group, Group 4-8; kindled rats received selenium, ceftriaxone100, ceftriaxone200, selenium + ceftriaxone100 and selenium + ceftriaxone200 mg/kg/day respectively for a week. At the end of the study, behavioral tests were performed. Oxidative stress, inflammatory markers, neurotransmitters and GLT-1 were measured in brain tissue homogenate. Brain histopathological investigation was also done. PTZ-kindled rats exhibited increased Racine score, besides behavioral tests and histopathological changes, significant elevation in oxidative stress and inflammatory markers, with decrease in serotonin, dopamine, GABA levels and GLT-1 expressions. Selenium and Ceftriaxone alone or combined treatment decreased Racine score with remarkable improvement in behavioral and histopathological changes. The antioxidant enzymes, neurotransmitters and GLT-1 expressions were increased, along with reduced TNF-α, IL-1 levels. Current study showed that selenium + ceftriaxone100 group represents a possible approach to improve epilepsy particularly through inhibiting oxidative stress and inflammation.

Acute pancreatitis during valproic acid administration in a patient with vascular dementia, epileptic seizures, and psychiatric symptoms: a case report.

BACKGROUND: Valproic acid (VPA) is a relatively safe drug widely used for the treatment of epileptic seizures and mania in bipolar disorder, as well as the prevention of migraine headaches. Here, we present a case of VPA-induced pancreatitis in a patient with vascular dementia, epileptic seizures, and psychiatric symptoms. He had no distinctive abdominal symptoms. CASE PRESENTATION: A 66-year-old Japanese man was treated with VPA for agitation and violent behavior due to vascular dementia, epileptic seizures, and psychiatric symptoms. During admission, he experienced a sudden decrease in consciousness and blood pressure. Abdominal findings were unremarkable; however, blood tests showed an inflammatory response and elevated amylase levels. Contrast-enhanced abdominal computed tomography showed diffuse pancreatic enlargement and inflammation extending to the subrenal pole. VPA-induced acute pancreatitis was diagnosed, VPA was discontinued, and high-dose infusions were administered. Acute pancreatitis resolved after treatment initiation. CONCLUSIONS: Clinicians should be aware of this relatively rare side effect of VPA. Diagnosis may be challenging in elderly people and patients with dementia as they may present with non-specific symptoms. Clinicians should consider the risk of acute pancreatitis when using VPA in patients who cannot report spontaneous symptoms. Blood amylase and other parameters should be measured accordingly.

Pharmacognostic profiles, evaluation of analgesic, anti-inflammatory and anticonvulsant activities of Newbouldia laevis (P. Beauv.) Seem. ex Bureau leaf and root extracts in Wistar rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Newbouldia laevis is a popular medicinal plant whose leaves and roots are used in Nigeria as ethnomedicinal prescriptions for pain, inflammation, convulsion, and epilepsy. These claims have not been scientifically verified prior to this study. AIM OF THE STUDY: To determine pharmacognostic profiles of the leaves and roots and evaluate the analgesic, anti-inflammatory, and anticonvulsant activities of methanol leaf and root extracts in Wistar rats. MATERIAL AND METHODS: The pharmacognostic profiles of the leaves and roots were determined using standard procedures to serve as fingerprints for the plant. The methanol leaf and root extracts of Newbouldia laevis were tested for acute toxicity using the OECD's up and down method at the maximum dose of 2000 mg/kg (orally) in Wistar rats. Analgesic studies were carried out in acetic acid-induced writhing in rats and tail immersion. The anti-inflammatory activity of the extracts was evaluated using carrageenan-induced rat paw-oedema and formalin-induced inflammation in rats' mode. The anticonvulsant activity was determined using strychnine-induced, pentylenetetrazol-induced, and maximal electroshock-induced rat convulsion models. For each of these studies, the extracts doses of 100, 200 and 400 mg/kg were administered to the rats following the oral route. RESULTS: The pharmacognostic profiles showed that the leaves possessed deep-sunken paracytic stomata (5-8-16 mm2; adaxial, 8-11-24 mm2; abaxial epidermis), vein islets (2-4-10 mm2; adaxial), vein terminations (10-14-18 mm2; adaxial), palisade ratio (8.3-12.5-16.4 mm2; adaxial, 2.5-6.8-12.2 mm2; adaxial), covering unicellular trichome (8-14; adaxial), spheroidal calcium oxalate crystals (3-5 µm), and oval-shaped striated starch grain with no hilum (0.5-4.3 µm). The transverse section of the leaf showed the presence of spongy and palisade parenchyma as well as a closed vascular bundle. The root powder showed the presence of brachy sclereid, fibers without lumen, and lignin. All physicochemical parameters fall within the acceptable limits, phytochemical contents showed mainly glycosides, alkaloids, and steroids while acute oral toxicity (LD50) of the parts for 14 days did not produce any toxicity signs or mortality in the rats. The extracts produced dose-dependent (100-400 mg/kg) analgesic involving opioid receptors, anti-inflammatory, and anticonvulsant activities in the rats which were significant (p ≤ 0.05) when compared to the standard drugs. The leaf extract possessed the most potent analgesic and anti-inflammatory effects in the rats, while the most anticonvulsant effects were observed in rats treated with the leaf extract. Both extracts showed elevated levels of protection against strychnine-induced, pentylenetetrazol-induced, and maximal electroshock-induced seizure in rats. CONCLUSION: Our study revealed some pharmacognostic profiles of Newbouldia laevis leaves and roots that are vital for its identification from closely related species often used for adulteration in traditional medicine. The study further showed that the leaf and root extracts of the plant possessed dose-dependent analgesics, anti-inflammatory and anti-convulsant activities in rats, thus, justifying its use for the treatment of these diseases in Nigerian traditional medicine. There is a need to further study its mechanisms of action towards drug discovery.

Chemical composition and anticonvulsant activities of herb pair of Gastrodia elata Blume-Acorus tatarinowii Schott decoction on experimentally induced seizures in mice.

Epilepsy is a serious public health problem in the world. At present, over 30% of affected patients remain refractory to currently available treatment. Medicinal plants as pharmaceuticals and healthcare treatments have been frequently used in the management of epilepsy in China for many centuries. Gastrodia elata-Acous tatarinowii (GEAT), as a classic and most commonly used herb pair in traditional Chinese medicine (TCM), has been employed to control seizures for thousands of years. However, the animal experiment data on its anticonvulsant effect is limited in the literature. Thus, this study aimed to reveal the therapeutic actions of GEAT decoction against seizures in mice. UHPLC-MS/MS was performed to analyze the chemical components of GEAT decoction. The mice were given GEAT decoction for 7 days, and MES, PTZ, and 3-MP injection was given 30 min after the last administration. Video monitoring was performed for comparisons. In addition, the PTZ-induced kindling models were conducted to investigate the seizure severity, anxiety and cognitive profile, inflammation, and oxidative stress parameters in mice. The results showed that GEAT decoction dose-dependently protected mice against MES, 3-MP, and PTZ-induced acute seizures. Furthermore, GEAT decoction significantly ameliorated seizure severity, decreased the accumulation of inflammatory mediators TNF-α, IL-1ß, and IL-6, mitigated oxidative stress, as well as alleviated anxious-like behavior and cognitive deficits in PTZ-kindled mice. These results suggest that GEAT decoction possesses certain anticonvulsant properties, which might be clinically useful as phytotherapy alone or as an adjunct therapy for the prevention and treatment of seizures and epilepsy.

In Vivo Neuropharmacological Effects of Neophytadiene.

Neophytadiene (NPT) is a diterpene found in the methanolic extracts of Crataeva nurvala and Blumea lacera, plants reported with anxiolytic-like activity, sedative properties, and antidepressant-like actions; however, the contribution of neophytadiene to these effects is unknown. This study determined the neuropharmacological (anxiolytic-like, antidepressant-like, anticonvulsant, and sedative) effects of neophytadiene (0.1-10 mg/kg p.o.) and determined the mechanisms of action involved in the neuropharmacological actions using inhibitors such as flumazenil and analyzing the possible interaction of neophytadiene with GABA receptors using a molecular docking study. The behavioral tests were evaluated using the light-dark box, elevated plus-maze, open field, hole-board, convulsion, tail suspension, pentobarbital-induced sleeping, and rotarod. The results showed that neophytadiene exhibited anxiolytic-like activity only to the high dose (10 mg/kg) in the elevated plus-maze and hole-board tests, and anticonvulsant actions in the 4-aminopyridine and pentylenetetrazole-induced seizures test. The anxiolytic-like and anticonvulsant effects of neophytadiene were abolished with the pre-treatment with 2 mg/kg flumazenil. In addition, neophytadiene showed low antidepressant effects (about 3-fold lower) compared to fluoxetine. On other hand, neophytadiene had no sedative or locomotor effects. In conclusion, neophytadiene exerts anxiolytic-like and anticonvulsant activities with the probable participation of the GABAergic system.

Antiepileptic therapy in a patient with star fruit intoxication: A case report.

RATIONALE: It is rare for uremia patients to have epileptic seizures after eating star fruit, only a dozen cases are reported worldwide. Such patients usually have poor prognoses. Few patients had good prognoses, all of them were treated with expensive renal replacement therapy. At present, there is no report on the addition of drug therapy to these patients based on the initial renal replacement therapy. PATIENT CONCERNS: A 67-year-old male patient with star fruit intoxication who had a history of diabetic nephropathy, hypertension, polycystic kidney, and chronic kidney disease in the uremic phase, and regular hemodialysis 3 times a week for 2 years. Initial clinical manifestations include hiccups, vomiting, speech disturbances, delayed reactions, and dizziness, which gradually progress to hearing and visual impairment, seizures, confusion, and coma. DIAGNOSES: This patient was diagnosed with seizures caused by star fruit intoxication. The experience of eating star fruit and the electroencephalograms can prove our diagnosis. INTERVENTIONS: We performed intensive renal replacement therapy according to the recommendations in the literature. However, his symptoms did not improve significantly until he received an extra dose of levetiracetam and resumed his previous dialysis schedule. OUTCOMES: The patient was discharged after 21 days without neurologic sequelae. Five months after discharge, he was readmitted due to poor seizure control. LESSONS: To improve the prognosis of these patients and to reduce their financial burden, the use of antiepileptic drugs should be emphasized.