Search Results (266)

Essential oils have attracted increasing attention due to their bioactive properties. This review focuses on their anticonvulsant potential by exploring the relation between the chemical composition of essential oils and the mechanism of action underlying this effect. Evidence from in vivo and ex vivo studies is presented to identify structure–activity relations and to distinguish well-supported effects from preliminary findings. Moreover, as essential oil’s quality is vital to ensure safety and efficacy in pharmacotherapeutic approaches. For this reason, factors including extraction and analytical methods as well as authenticity assessment are discussed due to their impact on pharmacological consistency and reproducibility. Overall, this review highlights key compounds and mechanisms contributing to anticonvulsant activity, identifies current limitations in the literature, and outlines priorities for future research aimed at validating essential oils as potential complementary therapeutic agents in seizure management. Full article

Introduction: Spontaneous and recurrent epileptic seizures cause neuroinflammation, whereas the chronic administration of antiepileptic drugs may lead to hepatotoxicity and nephrotoxicity. Investigating natural compounds such as naringenin, which exhibits antioxidant, anti-inflammatory, and neuroprotective properties, could mitigate these toxic effects. However, whether naringenin delays seizure onset through anti-inflammatory mechanisms remains unclear. Objective: We evaluated the anticonvulsant effect of subchronic naringenin administration and its impact on inflammatory biomarkers in rats. Methods: Thirty-two male Wistar rats were divided into four groups (n = 8 each): vehicle (10% DMSO), naringenin (50 mg/kg), naringenin (100 mg/kg), and diazepam (4 mg/kg). Treatments were administered once daily for ten days through the intraperitoneal route. On day 11, status epilepticus (SE) was induced via the lithium-pilocarpine model. One hour after SE onset, cardiac blood was collected, and the serum was analyzed via ELISA to quantify the following inflammatory markers: superoxide dismutase (SOD), C-reactive protein (CRP), carbonyl protein, and nitrite/nitrate. Results: We found that 100 mg/kg naringenin increased the latency to SE and the first generalized seizure and shortened the duration of generalized seizures. Fifty percent of the rats in the 100 mg/kg naringenin group did not develop SE. The group treated with 100 mg/kg naringenin demonstrated reduced levels of CRP, protein carbonyls, and nitrates; conversely, the inhibition of SOD activity increased. Conclusions: Naringenin exerted anticonvulsant activity associated with a reduction in oxidative stress and inflammatory plasma biomarkers, suggesting its potential utility in the future development of alternative treatments to reduce epilepsy symptoms. Full article

Pharmacotherapy of neuropathic pain (NP) remains challenging due to its heterogeneous etiology, lack of objective diagnostic tools, and the limited efficacy of currently available treatments, including antidepressants, anticonvulsants, and local anesthetics. Therefore, the search for novel therapies with improved analgesic efficacy and reduced adverse effects is of growing importance. In this context, natural alkaloids have emerged as promising candidates, demonstrating analgesic potential in both diabetes-induced neuropathy and various experimental models of NP. This review outlines NP pathophysiology, emphasizing maladaptive changes within the somatosensory nervous system, including peripheral and central sensitization, as well as glial cell activation. Furthermore, it discusses the mechanisms through which alkaloids may modulate NP-related pathways, with particular focus on their interactions with ion channels, signaling pathways, inflammatory responses, and oxidative stress. A literature search was conducted using the Scopus, Google Scholar and PubMed databases for papers published between 2015 and 2026, using the keywords “alkaloids” and “neuropathic pain”, and focused on recent findings regarding the antinociceptive effects of berbamine, tetrandrine, fangchinoline, and sinomenine, and their derivatives. The analysis indicates that, despite promising preclinical evidence, further rigorous preclinical and clinical studies are necessary to fully assess their therapeutic potential in the treatment of NP. Full article

As global demand grows for natural health-promoting food ingredients, the agri-food industry’s organic wastes are emerging as promising alternatives thanks to attributes such as biocompatibility, nutritional value and nutraceutical effect. During saffron (Crocus sativus L.) production, approximately 53 kg of petals are obtained as a by-product for every 1 kg of saffron spice. The use of saffron petals and petal extracts in bakery products improves products’ shelf life due to the petals’ high content of nutraceuticals and minerals acting as natural preservatives. Petal-enriched bakery products contain high levels of fiber, minerals and antioxidants. Addition of saffron petals into bread dough reduces gluten network strength, increases crumb hardness, enhances acidity, improves water retention, alters color profiles and increases the duration of the shelf life. The formulation for incorporating saffron petals or petal extracts into food products must address three primary criteria: the maximum concentration of bioactive compounds per 100 g of the finished matrix, the thermal stability of these compounds during the baking process, and their bioavailability (in the food matrix) within the human gastrointestinal tract. Nutraceuticals with pharmacological potential are also influenced by the compositional profile: the proximate composition, minerals, phenolic content, flavonols, and antioxidant capacity of saffron petals and bakery products containing saffron petals. Saffron petals exhibit diverse therapeutic potentials, acting as antidepressants, anxiolytics, anticonvulsants, and neuroprotective agents. They also offer metabolic, cardiovascular, hepatoprotective, and renoprotective benefits, along with anti-inflammatory, antimicrobial, and antitumor activities. This article proposes a roadmap for developing bakery products enriched with saffron petals or petal extracts, targeting both pharmacological applications and consumer goods focused on disease prevention and general wellness. This study investigates the biochemical composition of saffron petals and their integration into bakery products. It evaluates the influence of petal-derived additives on rheological properties, shelf stability, and organoleptic characteristics, alongside an assessment of their bioactivity and toxicological profiles. Furthermore, the analytical methodologies employed for ingredient and biological sample characterization are discussed, emphasizing their role in verifying the authenticity, safety, and nutritional functionality of both raw materials and finished formulations. Full article

Background: Connexins (Cx) are a family of transmembrane proteins that form gap junctions and connexin hemichannels (HCs), enabling direct intercellular communication within the nervous system. Connexin 43 (Cx43), the principal astrocytic connexin, exhibits a context-dependent dual role: under physiological conditions it maintains tissue homeostasis and metabolic support, whereas under pathological conditions excessive activation of Cx43 hemichannels promotes neuroinflammation, excitotoxicity, blood–brain barrier disruption, and secondary neural tissue damage. Other connexin isoforms also contribute to the pathogenesis of neurological and psychiatric disorders through alterations in neuronal synchronization, glial signaling, and myelin integrity. Objective: To systematize current evidence on the role of key connexin isoforms in acute nervous system injuries—including stroke, traumatic brain injury, spinal cord injury, and peripheral nerve injury—as well as chronic disorders such as neurodegenerative diseases, epilepsy, and psychiatric disorders, with particular emphasis on the functional duality of connexin channels and the therapeutic potential of their selective modulation. Methods: A systematic literature search was conducted in the PubMed, Scopus, and Web of Science databases in accordance with the PRISMA framework and the PRISMA Extension for Scoping Reviews guidelines. The review included data from experimental models, postmortem brain studies, genetic association analyses, and pharmacological intervention studies. The retrieved studies were screened, assessed for eligibility, and integrated using a qualitative narrative synthesis approach. Results: In acute neural injuries, hyperactivation of Cx43 hemichannels amplifies inflammatory signaling, edema formation, and neuronal death, whereas selective HCs inhibitors reduce lesion volume and improve functional outcomes in experimental models. Connexin 36 (Cx36) contributes to cortical spreading depolarization and seizure propagation, while Connexin 32 (Cx32) and Connexin 47 (Cx47) are critically involved in oligodendrocyte function and white-matter demyelination. In PNI, Cx43 upregulation contributes to neuropathic pain, whereas mutations in Cx32 cause hereditary demyelinating neuropathies. In neurodegenerative diseases—including Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis—Cx43 hemichannel activity promotes neuroinflammation and pathological protein accumulation, while reduced Cx32/Cx47 expression disrupts metabolic support of axons. In psychiatric disorders such as major depressive disorder, bipolar disorder, and schizophrenia, decreased astrocytic connexin expression (Cx43 and Cx30) has been associated with impaired glial–neuronal communication and cognitive–emotional dysfunction. In epilepsy, increased Cx43/Cx30 expression contributes to neuronal hypersynchronization and blood–brain barrier dysfunction, whereas selective hemichannel blockade suppresses seizure activity. Conclusions: Cx—particularly Cx43—occupies a central position in the molecular mechanisms of secondary neural injury and network dysfunction. The dual functional properties of gap junctions and hemichannels determine their context-dependent effects across neurological and psychiatric diseases. Selective inhibition of pathological HCs activity shows significant neuroprotective and anticonvulsant potential and represents a promising direction for the development of targeted therapeutic strategies. Further studies are required to determine optimal therapeutic time windows, tissue-specific effects, and the long-term safety of Cx modulation. Full article

Currently, poly- and monophenol antioxidants should be considered not only as inhibitors that interact with free radicals, but also take into account that they are biologically active substances that affect specific targets in cells and can induce the activity of certain genes or stimulate various signaling pathways. The phenols can directly influence different points of the apoptotic process, and/or the expression of regulatory proteins. In our present study the effect of two antioxidants, sterically hindered monophenols sodium anphene (ANa) and potassium phenosan (PhK), on cell apoptosis of splenocytes was studied by fluorescence and confocal microscopy. PhK has already been introduced into medical practice in the Russian Federation because it proved effective as an anticonvulsant and was useful in treating neonatal hypoxia. The study of ANa continues; it may be a promising anticancer drug for some types of tumors. The fluorescent and confocal microscopy methods demonstrate that ANa in combination with H₂O₂ enhances apoptosis in suspension of Lewis carcinoma cells and to a lesser extent in splenocyte culture. We also discovered that autofluorescence of FAD and immunofluorescence of NADPH enzymatic complexes (with the AV-FITC fluorophore) in splenocytes of normal cells increases symbatically. The autofluorescence of FAD in splenocytes of Lewis carcinoma cells significantly exceeded that of splenocytes of healthy animals. The exact distinctive result was obtained when using potassium phenozan. It turned out that PhK prevents the development of apoptosis in mouse splenocyte cell culture (F1(CBA×C57B)). The combined use of ANa and PhK had no effect on splenocyte apoptosis. We show that fluorescence and confocal microscopy allow observing and quantifying the apoptotic effect of ANa and hydrogen peroxide, and make it possible to visualize metabolic changes in the cell, increased FAD fluorescence in tumor cells and NADPH -oxidase complexes in splenocytes. The data obtained indicate the possibility of using ANa in combination with hydrogen peroxide as an antitumor drug acting on certain types of cells. The different effects of sterically hindered monophenols ANa and PhK on the level of the anti-apoptotic protein Bcl-2 in the cell were established. ANa acts to lower Bcl-2 levels, signaling apoptosis, while PhK prevents the development of apoptosis and induces repair processes. Full article

Background: We investigated whether a water extract of Lilii bulbus (Lilium lancifolium Thunberg; WELB) could modulate inhibitory synaptic organization in a mouse model of pentylenetetrazol (PTZ)-induced kindling. Methods: Starting 14 days prior to the initial PTZ challenge, WELB (500 mg/kg) was delivered via oral gavage once daily. This treatment regimen was maintained for a total of 40 days, spanning the entire period until the animals reached the fully kindled state. Results: Behavioral assessments revealed that WELB treatment significantly reduced seizure severity and Racine scores, prolonged the latency to clonic seizures, and shortened seizure duration, demonstrating potent anticonvulsant activity. Two-photon calcium imaging further showed that WELB markedly suppressed PTZ-induced neuronal hyperexcitability in the posterior parietal cortex, accompanied by decreased expression of neuronal activation markers, including c-fos, phosphorylated-calcium/calmodulin-dependent protein kinase IIα (p-CaMKIIα), and N-methyl-D-aspartate receptor 1 (NR1). In the hippocampus, WELB modulated the expression of GABAergic interneuron markers [glutamate decarboxylase 67 (GAD67), vesicular GABA transporter (VGAT), parvalbumin (PV), somatostatin (SOM)] and upregulated GABAergic gene transcripts [GABA-A receptor α1 subunit (Gabra1), GABA-A receptor α2 subunit (Gabra2), GABA transporter 1 (Gat1), GABA transporter 3 (Gat3), PV, SOM, cholecystokinin (CCK)] that were downregulated by PTZ kindling. Moreover, WELB enhanced the expression of GABAergic synaptic organization-related proteins (gephyrin, collybistin, neurexin-1β, neuroligin-2, and neuropilin-2), indicating its regulatory effect on inhibitory synaptic integrity. Conclusions: Collectively, these findings suggest that WELB may exert its anticonvulsant effects by functionally remodeling GABAergic synaptic organization-related factors, thereby restoring inhibitory circuit integrity and providing a mechanism-based therapeutic strategy for epilepsy and seizure-related neurological disorders. Full article

Epilepsy is a neurological disorder characterized by a long-lasting predisposition to recurrently generate unprovoked seizures. Epilepsy affects over 70 million people worldwide, with approximately one-third suffering from pharmacoresistant seizures. Currently, the clinical antiseizure drugs lack efficacy in preventing epileptogenesis. Adenosine, as an endogenous anticonvulsant, inhibits the development of epilepsy via interaction with the molecular epileptogenic network on several levels: (i) Activation of A1 receptor inhibits glutamate release via presynaptic inhibition, and hyperpolarizes the synaptic potentials in postsynaptic neurons. (ii) The A2A receptor on astrocytes interacts with astroglial glutamate transporter GLT-1, controlling glial glutamate homeostasis. (iii) Activation of the A3 receptor inhibits GABA transporter type 1-mediated GABA uptake. (iv) Adenosine kinase (ADK) is highlighted as a pathological hallmark of epilepsy, with its distinct isoforms driving different mechanisms. The cytoplasmic short isoform (ADK-S) in astrocytes controls extracellular adenosine and receptor-mediated pathways, whereas the nuclear long isoform (ADK-L) in astrocytes and specific neurons regulates epigenetic mechanisms without relying on adenosine receptors. Collectively, this review clarifies the adenosine system’s critical regulatory role in the epileptogenic network, highlights adenosine receptors and ADK isoforms as promising therapeutic targets for epilepsy, and provides a theoretical basis for developing novel disease-modifying therapies for pharmacoresistant epilepsy while laying a foundation for subsequent preclinical and clinical translation. Full article

Chemotherapy-induced neuropathic pain (CINP) can be caused by several chemotherapeutic drugs, including paclitaxel, oxaliplatin, and vincristine, which is difficult to treat with several drugs, including antidepressants and anticonvulsants. The patho-mechanisms of CINP are not completely understood. However, they showed oxidative stress, mitochondrial damage, ion channel damage, and immunological dysfunction. Acting as a key regulator of antioxidant responses, nuclear factor erythroid 2-related factor 2 (Nrf2) decreased oxidative stress and mitochondrial damage. In addition, it plays a role in inhibiting nuclear factor kappa B (NF-κB). A systematic, English-only search of MEDLINE (PubMed) was performed for studies on Nrf2, chemotherapy, and neuropathic pain from database inception through 1 December 2024. Several Nrf2 activators, including tempol, oltipraz, rosiglitazone, pristimerin, cannabidiol, daidzein, bardoxolone methyl, curcumin, resveratrol, and mitoquinone, demonstrated analgesic effects in CINP animal models. Furthermore, in clinical studies, curcumin demonstrated significant efficacy in reducing vincristine-induced neuropathy in pediatric leukemia patients, while the combined administration of alpha-lipoic acid with ipidacrin hydrochloride prevented paclitaxel-induced motor neuropathy and improved axonal function in breast cancer patients. Thus, the purposes of our review article were to summarize the analgesic effects of Nrf2 activators and the patho-mechanisms of Nrf2 in CINP animal, and then the consequences for clinical trials were presented. Full article

Background: Epilepsy comprises a range of disorders affecting the central nervous system (CNS) characterized by recurrent seizures, impacting approximately 60 million individuals globally. In this study, we designed and derived a series of peptide analogs 1–30 of 3,4,5-trimethoxycinnamic acid (TMCA) from the herbal combinations of Polygala tenuifolia and Gastrodia elata, recognized in Traditional Chinese Medicine (TCM). Methods: All the analogs were synthesized, and their anticonvulsant efficacy was subsequently assessed. The anticonvulsant activity of all TMCA analogs was evaluated using two acute seizure models in mice: the maximal electroshock (MES) and the sc-pentylenetetrazole (PTZ) models. Furthermore, we explored the electroencephalogram (EEG) and double-labeling immunofluorescence experiments were carried out as well. Results: Our findings indicated that compounds 11, 19, 22, and 23 demonstrated favorable anticonvulsant activities during the initial assessment. Compounds 19 and 23 also played roles in controlling the onset of epilepsy in EEG, modulating levels of GABA aminotransferase (GABA-AT)/gamma-aminobutyric acid type A receptor (GABA_AR), interacting with active sites of GABA-AT and GABA_AR obtained from docking simulation methods. Conclusions: Novel derivatives in this study provide new cores for further design and optimization inspired by TCM herb pair drugs P. tenuifolia and G. elata, with the aim of exploring new anticonvulsant agents. Full article

Agmatine is a biogenic amine that functions as a neurotransmitter and exhibits anticonvulsant, antineurotoxic, and antidepressant properties. It can be metabolized into putrescine and urea by canonical agmatinases or by the agmatinase-like protein (ALP), which corresponds to the C-terminal region of the LIMCH1 protein. The amino acid sequence of ALP/LIMCH1 diverges significantly from that of canonical agmatinases and lacks the conserved residues typically required for coordination with Mn²⁺, an essential cofactor for ureohydrolase activity. The three-dimensional structure of ALP/LIMCH1 remains unresolved, and predictive artificial intelligence algorithms such as AlphaFold have failed to model it reliably. As a result, the configuration of its active site and the identity of potential metal-coordinating ligands remain elusive. In this study, we purified recombinant full-length rat LIMCH1 (119.5 kDa) and a truncated ALP variant, ΔLIM-ALP (51 kDa), and analyzed their secondary structures using circular dichroism spectroscopy. Our results indicate that both proteins differ markedly from known ureohydrolases, exhibiting a high proportion of disordered regions (~60%) and β-structures (~30%). In contrast, Escherichia coli agmatinase displays a well-defined α/β/α sandwich fold. Despite these structural differences, ALP/LIMCH1 remain the only known mammalian proteins exhibiting agmatinase activity. To gain insight into the putative active site of ALP, we proposed candidate Mn²⁺-binding residues and generated single-point mutants (N213A, Q215A, D217A, E288A, K290A). Although these mutations did not significantly alter Mn²⁺ binding or its overall content in the protein samples, four mutants exhibited a decreased K_m for agmatine and a reduced V_max when normalized to protein concentration. Full article

An important class of heterocyclic chemicals are pyrimidine derivatives, providing a wide spectrum of biological activities in the form of antibacterial, antifungal, anti-HIV, anti-hypertensive, anti-inflammatory, anti-cancer, anti-convulsant, anti-depressant, and anti-tuberculosis acts. The chalcone group also has a significant impact on the pharmacological activity of compounds used for therapeutic purposes, acting as antibiotics, antioxidants, and anti-cancer agents. In this research, the derivative 1-(4-(4-(dimethylamino)-2-hydroxyphenyl)-6-methyl-2-thioxo-1,2,3,4-tetrahydropyrimidin-5-yl) ethan-1-one was prepared. From the reaction of thiourea with acetyl acetone and 4-dimethylamino-2-hydroxybenzaldehyde, the product was then reacted with some aldehydes in the presence of ethanol and a little hydrochloric acid as a catalyst, after which the product was reacted with some aldehydes to prepare chalcone. The prepared derivatives were characterized by FT-IR, ¹H-NMR, and ¹³C-NMR spectra, the melting point was measured, and the biological activity of the prepared compounds as antibacterials was studied. Molecular docking also determined the anti-breast cancer potential of these derivatives by docking the prepared derivatives with PDB:3eqm protein using the MOE 2015.10 program. The prepared compounds showed good efficacy as antibacterial agents against Gram-negative bacteria at diluted concentrations. Additionally, molecular docking studies demonstrated good efficacy of some derivatives as breast cancer inhibitors, along with a study of the toxic effects of the prepared compounds using the ProTox 3.0 program prediction of toxicity of chemicals. Full article

Cannabidiol (CBD) is a chemical produced by the cannabis plant that acts as an allosteric modulator of cannabinoid receptors resulting in non-competitive receptor antagonism in the central nervous system. This mechanism of action leads to anti-convulsant, anti-anxiety, and analgesic properties with minimal psycho-activity, which has led to significant interest in the use of CBD as a medication. Legislation around cannabis has changed in recent years, with many states permitting the use of CBD-based products as “medication” without approval from the Federal Drug Administration. This has led to a proliferation of products with associated marketing claims that are often unsubstantiated. This review summarizes the evidence for cannabidiol as a medical treatment, focusing on epilepsy, mental health, behavioral and substance use disorders occurring in pediatric and adolescent populations for which information is available. CBD preparations have been approved by the FDA to treat epilepsy in childhood; no other indications currently exist, and the literature remains inconclusive. Few adverse effects related to CBD use have been reported. However, endogenous cannabinoids play an important role in guiding brain development, and the long-term impact of modulating the endocannabinoid system during periods of brain growth during childhood and adolescence is unknown. While there is excitement about the potential for the development of CBD medications, currently, there is very limited information about the long-term safety of CBD, especially in children and adolescents, and caution is recommended regarding the use of unregulated, unapproved CBD preparations that are currently available over the counter. Full article

Background: Epilepsy is a high-burden neurological disorder worldwide, and several sedative drugs are used as therapy. Topiramate is among the more recent drugs shown to be effective in some patients, although its benefits are limited. Two carbohydrate derivatives, FB1 (from D-fructose) and AB1 (from D-arabinose), as well as phenylboronic acid, were recently reported as sedative and safe agents in mice. Their sedative properties and structural similarity to topiramate suggest potential antiseizure activity. Objective: The objective of this study was to evaluate the antiseizure potential of FB1 and AB1. Methods: Boron-containing compounds were administered to mice with seizures induced by pentylenetetrazol (a GABA-A receptor antagonist), 4-aminopyridine (a non-selective K⁺ channel blocker), or pilocarpine (a muscarinic agonist) to assess efficacy across models and explore potential mechanisms of action. Neuronal and glial toxicity was evaluated both in vitro and in vivo. Results: AB1 reduced seizure activity after intraperitoneal administration, whereas FB1 did not exhibit anticonvulsant effects, although it modified motor performance and limited neuronal loss. The effect of AB1 was comparable to that of topiramate across all three seizure models. Docking studies suggested that these compounds can interact with GABA-A (chloride), NMDA (glutamate), calcium, and potassium channels. Toxicity assays indicated that the concentrations required to affect neurons or glial cells were ≥300 µM, supporting the safety of these compounds. Conclusions: This preliminary evaluation demonstrates the antiseizure potential of AB1. Further experimental studies are needed to clearly establish its mechanism(s) of action. Full article

This review of thiazolidinedione or glitazone, which have a five-membered heterocyclic ring C₃NS, shows their versatile properties in terms of pharmacological actions such as antimicrobial, antifungal, insecticidal, pesticidal, antidiabetic, anti-inflammatory, anti-proliferative, anti-neurotoxicity, anticonvulsant, anti-thyroidal, and anti-tubercular uses. While having a wide range of biological activities, the TZDs mainly act via binding to the peroxisome proliferator-activated receptor (PPAR) members. PPAR-γ are ligand-activated transcription factors, which are members of the nuclear hormone receptors group. Activations of PPAR-γ regulate cell proliferation and differentiation, glucose homeostasis, apoptosis, lipid metabolism, and inflammatory responses. This review explores the synthesis of a thiazolidinedione and its derivatives, focusing on their pharmacological profiles and antidiabetic activity. It highlights the benefits of synthesis, reaction profiles, and catalyst recovery, which may encourage further investigation into these scaffolds by researchers. Based on synthesized derivatives, some glimpses of the structure–activity relationships of some compounds have been compiled. All the synthesized derivatives have been reviewed concerning their standard drugs already available and concluded with the highly or moderately active synthesized derivatives of thiazolidinedione. The data for this review was collected by an extensive review of current scientific literature, including on the synthesis, biological evaluation, SAR, and patents (2015–25). Full article