Multiple sclerosis (MS) is characterized as a chronic inflammatory demyelinating neurodegenerative disorder that leads to the deterioration of the myelin sheath and the loss of axons. Betaine, a trimethylglycine compound, is recognized for its ability to penetrate the blood-brain barrier (BBB) and exhibits properties that are antioxidant, anti-inflammatory, and neuroprotective. The cuprizone (CPZ) model serves as an effective tool for investigating the processes of demyelination and remyelination associated with MS. In our research, we examined the protective and therapeutic effects of betaine in a rat model of MS induced by CPZ. The experimental protocol involved administering 600 mg/kg of CPZ orally for 7 days, followed by 2 weeks with 200 mg/kg of CPZ. The protective group received a combination of betaine (1 g/kg/day, orally) and CPZ (200 mg/kg/day), while the therapeutic group was treated with CPZ (600 mg/kg) alongside betaine for three weeks. Behavioral assessments were conducted using inverted screen and rotarod tests to measure balance, motor coordination, and grasping ability. Following these evaluations, the rats were euthanized for analysis of oxidative stress and inflammatory biomarkers, toluidine blue staining, transmission electron microscopy (TEM) imaging, and myelin basic protein (MBP) immunostaining of the corpus callosum (CC). The results indicated that betaine significantly enhanced balance, motor coordination, and grasping ability, while decreasing oxidative stress, inhibiting interleukin (IL)-4 and IL-17 levels, and reversing the demyelination caused by CPZ. Notably, betaine also mitigated the increase in homocysteine (Hcy) levels and facilitated remyelination, evidenced by the presence of normal compacted myelin and increased expression of MBP in the CC. This study substantiates the remyelinating effects of betaine in the context of CPZ-induced demyelination. It suggests that it may contribute to the repair of myelin through the modulation of behavioral deficits, oxidative stress, neuroinflammation, ultrastructural changes, and MBP expression levels, indicating its potential as a complementary therapeutic agent in the management of MS.

Epilepsy is a complex neurological disorder characterized by recurrent seizures, significantly impacting patient health and quality of life. This study explores the neuroprotective effects of combining Eugenol (EUG), a natural bioactive compound administered at 100 mg/kg, with photobiomodulation (PBM), a non-invasive low-level laser therapy at 830 nm wavelength and 100 mW power, in a pentylenetetrazole (PTZ) kindling rat model of epilepsy. Fifty-nine adult male Wistar rats were assigned to five experimental groups: Control, PTZ (epilepsy model), PBM, EUG, and EUG + PBM. Seizure severity was assessed using a modified Racine scale following each PTZ injection. The study also evaluated cortical and hippocampal levels of brain-derived neurotrophic factor (BDNF), oxidative stress markers (MDA, NO, and GSH), activities of acetylcholinesterase (AChE) and Na + K + -ATPase, and monoamine neurotransmitters (DA, 5-HT, and NE). The results demonstrated that EUG and PBM, both individually and combined, significantly reduced seizure severity, mitigated oxidative stress, restored enzyme activities, and elevated BDNF levels. The combined treatment yielded superior neuroprotective effects compared to individual interventions, emphasizing its potential as a promising therapeutic strategy for epilepsy management.

Bisphenol A (BPA), a common endocrine-disrupting chemical, is found in a wide range of home plastics. Early-life BPA exposure has been linked to neurodevelopmental disorders; however, the link between neuroinflammation, pyroptosis, and the development of psychiatric disorders is rarely studied. The current study attempted to investigate the toxic effect of BPA on inflammatory and microglial activation markers, as well as behavioral responses, in the brains of male rats in a dose- and age-dependent manner. Early BPA exposure began on postnatal day (PND) 18 at dosages of 50 and 125 mg/kg/day. We started with a battery of behavioral activities, including open field, elevated plus- and Y-maze tests, performed on young PND 60 rats and adult PND 95 rats. BPA causes anxiogenic-related behaviors, as well as cognitive and memory deficits. The in vivo and in silico analyses revealed for the first time that BPA is a substantial activator of nuclear factor kappa B (NF-κB), interleukin (IL)-1β, -2, -12, cyclooxygenase-2, and the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, with higher beclin-1 and LC3B levels in BPA rats' PFC and hippocampus. Furthermore, BPA increased the co-localization of caspase-1 immunoreactive neurons, as well as unique neurodegenerative histopathological hallmarks. In conclusion, our results support the hypothesis that neuroinflammation and microglial activation are involved with changes in the brain after postnatal BPA exposure and that these alterations may be linked to the development of psychiatric conditions later in life. Collectively, our findings indicate that BPA triggers anxiety-like behaviors and pyroptotic death of nerve cells via the NF-κB/IL-1β/NLRP3/Caspase-1 pathway.

Epilepsy, affecting approximately 50 million individuals worldwide, is a neurological disorder characterized by recurrent seizures. Mitochondrial dysfunction and oxidative stress are critical factors in its pathophysiology, leading to neuronal hyperexcitability and cell death. Because of the multiple mitochondrial pathways that can be involved in epilepsy and mitochondrial dysfunction, it is optimal to treat epilepsy with multiple antioxidants in combination. Recent advancements highlight the potential of antioxidant therapy as a novel treatment strategy. This approach involves tailoring antioxidant interventions-such as melatonin, idebenone, and plant-derived compounds-based on individual mitochondrial health, including mitochondrial DNA mutations and haplogroups that influence oxidative stress susceptibility and treatment response. By combining antioxidants that target multiple pathways, reducing oxidative stress, modulating neurotransmitter systems, and attenuating neuroinflammation, synergistic effects can be achieved, enhancing therapeutic efficacy beyond that of a single antioxidant on its own. Future directions include conducting clinical trials to evaluate these combination therapies, and to translate preclinical successes into effective clinical interventions. Targeting oxidative stress and mitochondrial dysfunction through combination antioxidant therapy represents a promising adjunctive strategy to modify disease progression and improve outcomes for individuals living with epilepsy.

Along with accelerated aging, the prevalence of late-life depression (LLD) exacerbates. Older people are more vulnerable to the adverse effects of antidepressants than the young. Therefore, creating antidepressants from medicinal herbs that are more effective and safer is inevitable. Ginkgo biloba L. leaf extract (EGb761) is broadly applied for treating various neuronal dysfunctions. The present study aimed to evaluate the ameliorative and antidepressant effects of EGb761 against reserpine (RES)-induced depression like symptoms and associated comorbidities in aged female rats. Besides, it compared its efficacy with the antidepressant duloxetine (DULX), offering a more comprehensive understanding of therapeutic potential of EGb 761. Rats grouped into control group, EGb 761-H group, RES group, RES plus either EGb 761-L, EGb 761-H, or DULX groups. The antidepressant effects of EGb 761 were evaluated through a series of behavioral tests, measurement of depression biochemical markers, performing neuronal histopathology and immunohistochemical analyses. EGb 761 significantly attenuated behavioral deficits in the open field test and reduced immobility time in the forced swimming test. Moreover, EGb 761 exerted antidepressant-like actions by ameliorating neurotransmitter imbalances, restoring redox homeostasis in cortical region. Also, EGb 761 increased level of ATP, diminished DNA fragmentation, decreased caspase-3 immunoreactivity and increased immunoreactivity of synaptophysin in the cerebral cortex, besides it enhanced the histological architecture of this region. Overall, EGb 761 has the potential effects to manage LLD focus on the role of both serotonergic and noradrenergic systems in mediating these effects, alongside the impact on oxidative/nitrosative stress.

Arsenic is associated with various neurological disorders, notably affecting memory and cognitive functions. The current study examined the protective effects of vitamin D3 (Vit. D3) in countering oxidative stress, neuroinflammation and apoptosis induced by sodium arsenite (SA) in the cerebral cortex of rats. Male Wistar rats were subjected to a daily oral administration of sodium arsenite (NaAsO2, SA) at a dosage of 5 mg/kg, along with 500 IU/kg of Vit. D3, and a combination of both substances for four weeks. The results indicated that Vit. D3 effectively mitigated the SA-induced increase in oxidative stress markers, thiobarbituric acid reactive substances (TBARS) and nitric oxide (NO), the decrease in antioxidants (reduced glutathione; GSH, superoxide dismutase; SOD, catalase; CAT, and glutathione peroxidase; GPx), as well as the increase in pro-inflammatory markers including, tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and amyloid-beta (Aβ)1-42. Furthermore, Vit. D3 reversed the alterations in the neurochemicals acetylcholinesterase (AchE), monoamine oxidase (MAO), dopamine (DA), and acetylcholine (Ach) and ameliorated the histopathological changes in the cerebral cortex. Moreover, immunohistochemical analyses revealed that Vit. D3 reduced the SA-induced overexpression of cerebral cysteine aspartate-specific protease-3 (caspase-3) and glial fibrillary acidic protein (GFAP) in the cerebral cortex of male rats. Consequently, the co-administration of Vit. D3 can protect the cerebral cortex against SA-induced neurotoxicity, primarily through its antioxidant, anti-inflammatory, anti-apoptotic, and anti-astrogliosis effects.

Synthetic organic insecticides such as pyrethroids, organophosphates, neonicotinoids, and others have the potential to disrupt ecosystems and are often toxic to humans. Thiamethoxam (TMX), a neonicotinoid insecticide , is a widely used insecticide with neurotoxic potential. L-Carnitine (LC) is regarded as the "gatekeeper" in charge of allowing long-chain fatty acids into cell mitochondria. LC is an endogenous chemical that is renowned for its prospective biological activity in addition to its role in energy metabolism. This study investigated the protective effects of LC against TMX-induced neurotoxicity in male Wistar rats. For 28 days, animals were divided into four groups and treated daily with either LC (300 mg/kg), TMX (100 mg/kg), or both at the aforementioned doses. Our results revealed marked serum lipid profile and electrolyte changes, declines in brain antioxidants and neurotransmitters (acetylcholine, dopamine, and serotonin levels) with elevations in thiobarbituric acid reactive substances and proinflammatory cytokine levels, as well as acetylcholinesterase and monoamine oxidase brain activity in TMX-treated rats. TMX also increased the expression of caspase-3 and glial fibrillary acidic protein. In contrast, pretreatment with LC attenuated TMX-induced brain injury by suppressing oxidative stress and proinflammatory cytokines and modulating neurotransmitter levels. It also ameliorated the expression of apoptotic and astrogliosis markers. It could be concluded that LC has antioxidant, anti-inflammatory, anti-astrogliosis, and anti-apoptotic potential against TMX neurotoxicity.

Epilepsy is defined by an excessive level of activity in the neurons and coordinated bursts of electrical activity, resulting in the occurrence of seizure episodes. The precise cause of epileptogenesis remains uncertain; nevertheless, the etiology of epilepsy may involve neuroinflammation, oxidative stress, and malfunction of the neurotransmitter system.

The goal of this investigation was to assess barbaloin's protective properties with respect to pentylenetetrazol (PTZ)-)-induced cognitive deficits in rats via antioxidative, anti-inflammatory, and neurotransmitter-modulating effects.

Wistar rats were subjected to PTZ [40 mg/kg (i.p.)], which induced cognitive decline. Behavior assessment using a kindling score, open-field test (OFT), novel object recognition test (NORT), and assays for superoxide dismutase (SOD), reduced glutathione (GSH), catalase (CAT), malondialdehyde (MDA), acetylcholinesterase (AChE), caspase-3, nitric oxide (NO), interleukins-1β (IL-1β), tumor necrosis factor-α (TNF-α), IL-6, nuclear factor kappa-B (NF-κB), Bcl-2 and Bax, and neurotransmitter levels [GABA, DA, NE, and serotonin (5-HT)] were performed.

The treatment of rats with barbaloin resulted in behavior improvement and significant changes in the levels of GSH, SOD, CAT, MDA, AChE, NO, IL-6, IL-1β, TNF-α, NF-κB, caspase-3, Bcl-2, and Bax compared to the PTZ control group. Barbaloin treatment resulted in notable changes in neurotransmitter levels (GABA, NE, 5-HT, DA) compared to the PTZ group.

The ongoing study has gathered evidence indicating that the injection of barbaloin has resulted in significant improvements in cognitive performance in rats. This is achieved by inhibiting oxidative stress, enhancing the activity of natural antioxidant enzymes, reducing cytokine levels, and increasing the levels of neurotransmitters in the brain. These results were detected in comparison to a PTZ control and can be attributed to the potent anti-inflammatory and antioxidant capabilities of barbaloin, which could be linked to its neuroprotective properties. Barbaloin may potentially increase cognitive decline and boost neuronal survival by altering the expression of Bax, caspase-3, Bcl-2.

Treatment strategies for steatohepatitis are of special interest given the high prevalence of obesity and fatty liver disease worldwide. This study aimed to investigate the potential therapeutic mechanism of L-carnitine (LC) and Ginkgo biloba leaf extract (GB) supplementation in ameliorating the adverse effects of hyperlipidemia and hepatosteatosis induced by a high-cholesterol diet (HCD) in an animal model. The study involved 50 rats divided into five groups, including a control group, a group receiving only an HCD, and three groups receiving an HCD along with either LC (300 mg LC/kg bw), GB (100 mg GB/kg bw), or both. After eight weeks, various parameters related to lipid and glucose metabolism, antioxidant capacity, histopathology, immune reactivity, and liver ultrastructure were measured. LC + GB supplementation reduced serum total cholesterol, triglyceride, low-density lipoprotein cholesterol, glucose, insulin, HOMA-IR, alanine transaminase, and aspartate transaminase levels and increased high-density lipoprotein cholesterol levels compared with those in the HCD group. Additionally, treatment with both supplements improved antioxidant ability and reduced lipid peroxidation. The histological examination confirmed that the combination therapy reduced liver steatosis and fibrosis while also improving the appearance of cell organelles in the ultrastructural hepatocytes. Finally, the immunohistochemical analysis indicated that cotreatment with LC + GB upregulated the immune expression of GLP-1 and β-Cat in liver sections that were similar to those of the control animals. Mono-treatment with LC or GB alone substantially but not completely protected the liver tissue, while the combined use of LC and GB may be more effective in treating liver damage caused by high cholesterol than either supplement alone by regulating hepatic oxidative stress and the protein expression of GLP-1 and β-Cat.

Alzheimer's disease (ad) is a neurological condition that worsens over time and is characterized by the buildup of amyloid (Aβ) plaques in the brain parenchyma. Neuroprotection and cholinesterase inhibition have been the two primary techniques used in the creation of medications to date. In ad, a novel sort of programmed cell death known as ferroptosis takes place along with iron buildup, lipid peroxidation, and glutathione deficiency. The objective of the current investigation was to examine the neuroprotective and anti-ferroptotic role of nanocurcumin and Donepezil against model of aluminum chloride AlCl3 and D-galactose induced ad. The experiment was performed on 70 rats divided into (G1: control, G2: NCMN, G3: Donepezil, G4: ad-model, G5: Donepezil co-treatment, G6: NCMN co-treatment and G7: NCMN+Donepezil co-treatment). Hematological parameters and biochemical investigations as oxidative stress, liver function, kidney function, iron profile and plasma fibrinogen were evaluated. Treatment with Nanocurcumin alone or in combination with Donepezil improved oxidative stress, liver functions, and kidney functions, improve iron profile and decreased plasma fibrinogen.

Millions of individuals have used illicit anabolic-androgenic steroids (AAS), but the long-term cardiovascular associations of these drugs remain incompletely understood. Boldjan is AAS medication which is used in veterinary medicine and by young adults aiming to have a better appearance improving their self-esteem. Therefore; the objective of the current investigation was to examine any potential preventative effects of amygdalin extract against anabolic steroid Boldjan induced cardic toxicity, injury and oxidative stress in male rat. Forty adult male Wistar rats were classified into five groups (Gp1, Control Gp; Gp2, Amygdalin Gp in which rats treated with amygdalin (100 mg/kg body weight/day) daily for 2 weeks; Gp3, Boldjan Gp in which rats treated with Boldjan (10 mg/Kg BW/week) for 4 weeks; Gp4, Boldjan + Amygdalin). Boldjan induced a significant rises in serum lactate dehydrogenase (LDH), creatine kinase (CK) and creatine kinase MB (CK MB), aspartate aminotransferase (AST), total cholesterol (TC), triglycerides (TG), low-density lipoprotein-cholesterol (LDL-C), and very-low-density lipoprotein-cholesterol (VLDL-C), cardiac injury, and malondialdehyde (MDA) levels and a significant depletion in serum high-density lipoprotein-cholesterol (HDL-C), cardiac reduced glutathione (GSH), Superoxide dismutase (SOD) and catalase (Cat) activities as compared to control Gp. In contrast, Amygdalin significantly reversed the Boldjan induced cardiac toxicity in post treated rats Gp (Boldjan + Amygdalin). Amygdalin could be an efficient preventive supplement for mitigating Boldjan induced cardiac toxicity, possibly via controlling oxidative stress events.

Several anabolic androgenic steroids (ASSs) are a group of synthetic molecules derived from testosterone and developed mainly for veterinary use that classed as a Schedule III and sometimes utilized by athletes to enlarge their muscles. Abuse of anabolic androgenic steroids can result in severe organ damage that cannot be repaired. Therefore; the objective of the current investigation was to examine the therapeutic effects of vitamin B17 (VitB17) on the testicular toxicity caused by the anabolic steroid Trenorol in male rats. Rats were randomly assigned into control, VitB17 (50 mg/kg b.wt./day, orally), Trenorol (received 10 mg/kg b.wt./week, IM) and Trenorol + VitB17 treated groups. At the end of experiment, hormonal assay, semen evaluation, testicular enzymes, and DNA damage were assessed. Besides, the histopathological and immunohistochemical investigations of the P53 expression were performed. Current results revealed that; Trenorol induced significant depletion in relative weights of testis (RWT), total testosterone follicle stimulating hormone (FSH), and luteinizing hormone (LH), sperm count, morphology index, viability, progressive motility, and testicular injury and a significant increase sperm abnormalities, testicular DNA damage and P53 experssions. Treatment of rats with Trenorol + VitB17 decreased the testicular toxicity, sperm parameters, DNA damage and apoptosis. We can conclude that; Trenorol induced toxicity, DNA damage and apoptosis in rat testis and treatments with VitB1 improved these parameters.

Parkinson's disease (PD) is one of the most common neurodegenerative diseases worldwide. Currently applied therapeutic protocols are limited to improve the motor functions of patients. Therefore, seeking alternative regimes with better therapeutic impact is crucial. This study aims to validate the therapeutic impact of mesenchymal stem cell injection using two delivery methods, intracranial administration and intravenous administration, on rotenone (ROT)-induced PD model in rats. Our work included behavioral, biochemical, histological, and molecular investigations. Open field test (OFT) and rotarod tests were applied. Important oxidative stress, antioxidant and proinflammatory markers were monitored. Substantia Nigra and Striatum tissues were examined histologically and the molecular expression of DOPA decarboxylase, Tyrosine hydroxylase, and α-synuclein in neurons in these tissues were investigated. Our results showed that MSC grafting improved motor and memory impairments and oxidative stress status that were observed after ROT administration. Additionally, BM-MSCs application restored SOD and CAT activities and the levels of DA, L-Dopa, IL6, IL1β, and TNFα. Moreover, MSC grafting overwhelmed the pathological changes induced by ROT and normalized the expression of Tyrosine hydroxylase, DOPA decarboxylase, and α-synuclein towards the control values in the Nigral and Striatal tissues of male rats. Conclusively, both administration routes improved motor function, protection of the nigrostriatal system, and improved striatal dopamine release. The observed beneficial effect of applying MSCs suggests potential benefits in clinical applications. No significant differences in the outcomes of the treatment would favor a certain way of MSC application over the other. However, the intravenous delivery method seems to be safer and more feasible compared to the intrastriatal method.

Epilepsy is a neurological disorder that presents with recurring and spontaneous seizures. It is prevalent worldwide, affecting up to 65 million people, with 80% of cases found in lower-income countries. Medicinal plants are commonly employed for managing and treating epilepsy and convulsions due to their unique therapeutic properties. With increasing research and clinical application, medicinal plants are gaining attention globally due to their potent therapeutic effects and fewer side effects. The development of new plant-based antiepileptic/anticonvulsant agents has become a major focus in the pharmaceutical industry.

This article summarizes recent research on medicinal plants with reported antiepileptic/anticonvulsant effects. It provides pharmacological and molecular mechanism of action information for the crude extracts and related active constituents evaluated in preclinical research for the treatment of epilepsy and convulsions, and offers a reference for the development of future related studies in this area.

Articles related to ethnopharmacological and antiepileptic studies on plants or natural products from 2018 to 2023 were collected from PubMed, Web of Science and Scopus, etc. using keywords related to epilepsy, medicinal plants, and natural products, etc. RESULTS: Eighty plant species are commonly used to treat epilepsy and convulsions in African and Asian countries. Sixty natural products showing potential for antiepileptic/anticonvulsant effects have been identified from these medicinal plants. These products can be broadly classified as alkaloids, coumarins, flavonoids, saponins, terpenoids and other compounds. The antiepileptic action of plant extracts and their active ingredients can be classified according to their abilities to modulate the GABAergic and glutamatergic systems, act as antioxidants, exhibit anti-neuroinflammatory effects, and provide neuroprotection. In addition, we highlight that some medicinal plants capable of pharmacologically relieving epilepsy and cognition may be therapeutically useful in the treatment of refractory epilepsy.

The review highlights the fact that herbal medicinal products used in traditional medicine are a valuable source of potential candidates for antiepileptic drugs. This confirms and encourages the antiepileptic/anticonvulsant activity of certain medicinal plants, which could serve as inspiration for further development. However, the aspects of structural modification and optimization, metabolism, toxicology, mechanisms, and clinical trials are not fully understood and need to be further explored.

The use of additives, especially colorants, in food and pharmaceutical industry is increasing dramatically. Currently, additives are classified as contaminants of emerging concern (CECs). Concerns have been raised about the potential hazards of food additives to reproductive organs and fertility. The present study investigates the reproductive toxicity of tartrazine (TRZ), a synthetic colorant, in male rats and aims to explore the curative effect of Ginkgo biloba extract (EGb) against TRZ-induced testicular toxicity. Twenty-four rats were divided into four groups: the control (0.5 ml distilled water), the EGb group (100 mg/kg EGb alone), the TRZ group (7.5 mg/kg TRZ alone), and the TRZ-EGb group (7.5 mg/kg TRZ plus 100 mg/kg EGb). The doses were administered orally in distilled water once daily for 28 days. Toxicity studies of TRZ investigated testicular redox state, serum gonadotropins, and testosterone levels, testicular 17 ß-hydroxysteroid dehydrogenase activity, sperm count and quality, levels of inflammatory cytokines, and caspase-3 expression as an apoptotic marker. Also, histopathological alterations of the testes were examined. TRZ significantly affected the testicular redox status as indicated by the increase in malondialdehyde and the decrease in reduced glutathione, superoxide dismutase, and catalase. It also disrupted serum gonadotropins (follicle stimulating hormone and luteinizing hormone) and testosterone levels and the activity of testicular 17ß-hydroxysteroid dehydrogenase. Additionally, TRZ adversely affected sperm count, motility, viability, and abnormality. Levels of tumor necrosis factor-α, interleukin-1β, interleukin-6, and expression of caspase-3 were increased in the testes. Histopathological examination of the testes supported the alterations mentioned above. Administration of EGb significantly ameliorated TRZ-induced testicular toxicity in rats. In conclusion, EGb protected against TRZ-induced testicular toxicity through antioxidant, anti-inflammatory, and anti-apoptotic mechanisms.

Marine invertebrates represent a valuable reservoir of pharmaceutical bioactive compounds with potential relevance to various medical applications. These compounds exhibit notable advantages when compared to their terrestrial counterparts, in terms of their potency, activity, and mechanism of action. Within this context, the present work aimed to extract, chemically characterize, and investigate the bioactivity of the gonadal extract of the sea urchin Paracentrotus lividus (P. lividus) collected along the Mediterranean coast of Alexandria, Egypt. Fractions of the gonadal extract were characterized by Spectrophotometry and gas chromatography-mass spectrometry (GC-MS), and their bioactivities were investigated in vitro. The analysis supported the extract richness of carotenoids and bioactive compounds. The extract showed promising anticancer activity against three different breast cancer cell lines with different levels of aggressiveness and causative factors, namely MDA-MB-231, MDA-MB-453, and HCC-1954. Gene expression analysis using RT-qPCR showed that P. lividus extract inhibited the expression of crucial factors involved in cell cycle regulation and apoptosis. In addition, the extract significantly inhibited the lipo-polysaccharides (LPS) induced inflammation in the RAW264.7 macrophage cell line and exerted anti-bacterial activity against the Gram-negative bacteria Klebsiella pneumoniae and Pseudomonas aeruginosa. Collectively, these results demonstrated the chemical richness and the wide-scale applicability of P. lividus gonadal extract as an anti-cancer, anti-bacterial, and anti-inflammatory natural extract.

Epilepsy is a prevalent neurological disease, affecting approximately 1-2% of the global population. The hallmark of epilepsy is the occurrence of epileptic seizures, which are characterized by predictable behavioral changes reflecting the underlying neural mechanisms of the disease. Unfortunately, around 30% of patients do not respond to current pharmacological treatments. Consequently, exploring alternative therapeutic options for managing this condition is crucial. Two potential candidates for attenuating seizures are N-acetylcysteine (NAC) and Acetyl-L-carnitine (ALC), as they have shown promising neuroprotective effects through the modulation of glutamatergic neurotransmission.

This study aimed to assess the effects of varying concentrations (0.1, 1.0, and 10 mg/L) of NAC and ALC on acute PTZ-induced seizures in zebrafish in both adult and larval stages. The evaluation of behavioral parameters such as seizure intensity and latency to the crisis can provide insights into the efficacy of these substances.

Our results indicate that both drugs at any of the tested concentrations were not able to reduce PTZ-induced epileptic seizures. On the other hand, the administration of diazepam demonstrated a notable reduction in seizure intensity and increased latencies to higher scores of epileptic seizures.

Consequently, we conclude that, under the conditions employed in this study, NAC and ALC do not exhibit any significant effects on acute seizures in zebrafish.

Epilepsy is a neurological disorder characterized by epileptic seizures resulting from neuronal hyperexcitability, which may be related to failures in Na,K-ATPase activity and oxidative stress participation. We conducted this study to investigate the impact of antioxidant therapy on oxidative stress, Na,K-ATPase activity, seizure factors, and mortality in rodent seizure/epilepsy models induced by pentylenetetrazol (PTZ), pilocarpine (PILO), and kainic acid (KA). After screening 561 records in the MEDLINE, EMBASE, Web of Science, Science Direct, and Scopus databases, 22 were included in the systematic review following the PRISMA guidelines. The meta-analysis included 14 studies and showed that in epileptic animals there was an increase in the oxidizing agents nitric oxide (NO) and malondialdehyde (MDA), with a reduction in endogenous antioxidants reduced glutathione (GSH) and superoxide dismutase (SO). The Na,K-ATPase activity was reduced in all areas evaluated. Antioxidant therapy reversed all of these parameters altered by seizure or epilepsy induction. In addition, there was a percentage decrease in the number of seizures and mortality, and a meta-analysis showed a longer seizure latency in animals using antioxidant therapy. Thus, this study suggests that the use of antioxidants promotes neuroprotective effects and mitigates the effects of epilepsy. The protocol was registered in the Prospective Register of Systematic Reviews (PROSPERO) CRD42022356960.

Tiagabine (Tia), a new-generation antiseizure drug that mimics the GABAergic signaling by inhibiting GABA transporter type-1, is the least studied molecule in chronic epilepsy models with comorbid neurobehavioral and neuroinflammatory parameters. Therefore, the current study investigated the effects of Tia in a real-time manner on electroencephalographic (EEG) activity, behavioral manifestations and mRNA expression in pentylenetetrazole (PTZ)-kindled mice. Male BALB/c mice were treated with tiagabine (0.5, 1 and 2 mg/kg) for 21 days with simultaneous PTZ (40 mg/kg) injection every other day for a total of 11 injections and monitored for seizure progression with synchronized validation through EEG recordings from cortical electrodes. The post-kindling protection from anxiety and memory deficit was verified by a battery of behavioral experiments. Isolated brains were evaluated for oxidative alterations and real-time changes in mRNA expression for BDNF/TrkB, GAT-1 and GAT-3 as well as neuroinflammatory markers. Experimental results revealed that Tia at the dose of 2 mg/kg maximally inhibited the development of full bloom seizure and reduced epileptic spike discharges from the cortex. Furthermore, Tia dose-dependently exerted the anxiolytic effects and protected from PTZ-evoked cognitive impairment. Tia reduced lipid peroxidation and increased superoxide dismutase and glutathione levels in the brain via augmentation of GABAergic modulation. PTZ-induced upregulated BDNF/TrkB signaling and pro-inflammatory cytokines were mitigated by Tia with upregulation of GAT-1 and GAT-3 transporters in whole brains. In conclusion, the observed effects of Tia might have resulted from reduced oxidative stress, BDNF/TrkB modulation and mitigated neuroinflammatory markers expression leading to reduced epileptogenesis and improved epilepsy-related neuropsychiatric effects.

Copper oxide nanoparticles (CuO NPs) have developed as a significant class of nanomaterial with potential dangers to organisms and the environment in a variety of applications. This study aimed to investigate the impact of costus root extract against CuO NPs induced oxidative stress, alterations in heart structure and functions. 40 adult male rats were assigned randomly to four groups: first; control, second; costus (300 mg/kg body weight/day) orally for 2 weeks, third; CuO NPs (100 mg/kg body weight/day) intraperitoneally for 4 weeks and fourth; CuO NPs + costus. Current results revealed, significant increases in serum levels of creatine kinase-MB, creatine kinase enzyme, lactate dehydrogenase, myoglobin, aspartate aminotransferase, alkaline phosphatase, cardiac TBIRS, total thiol, nitric oxide, and cardiac proliferating cell nuclear antigen after CuO NPs administration when compared with control group. Conversely, statistical significant decreases were detected in cardiac reduced glutathione, catalase, and superoxide dismutase in CuO NPs group as compared with control group. Interestingly, treatment of CuO NPs with costus root extract was associated with significant improvements of the studied parameters, heart structure and functions. CuO NPs-induced toxicity, injury and oxidative stress in rat heart and treatment with Costus root extract could scavenge free radicals producing beneficial effects against CuO NPs.