{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:08:59Z","timestamp":1792789739735,"version":"4.5.0"},"reference-count":68,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Uppsala University","id":[{"id":"https:\/\/ror.org\/048a87296","id-type":"ROR","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/048a87296","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Aims: Morin is a flavonoid with potential neuroprotective and anti-inflammatory properties. This study evaluated the anticonvulsant and anxiolytic effects of morin-loaded PLGA-chitosan nanoparticles (Morin-PLGA-CS NPs) in male Wistar rats. Methods: Morin-PLGA-CS NPs were synthesized using a modified single emulsion-solvent evaporation method followed by CS coating. NPs were characterized by dynamic light scattering (DLS), scanning electron microscopy (SEM), and in vitro drug release analysis. Adult male Wistar rats received intraperitoneal injections of free morin (25 mg\/kg), Morin-PLGA-CS NPs, diazepam (1 mg\/kg), blank NPs, or vehicle. Behavioral assessments included the open-field test (OFT), elevated-plus maze (EPM), novel object recognition (NOR) test, and pentobarbital-induced sleep test. Anticonvulsant activity was evaluated using PTZ-induced seizure latency. Cytokine concentrations in cortical and hippocampal tissue lysates were quantified by ELISA at 12 h post-PTZ. Hippocampal relative mRNA expression of Nrf2, HO-1, GFAP, and Iba1 was quantified by quantitative real-time PCR (qRT-PCR). Results: Morin-PLGA-CS NPs demonstrated a hydrodynamic diameter of 221.6 nm, a zeta potential of +23.3 mV, and an encapsulation efficiency of 81%. FTIR spectroscopy showed spectral changes compatible with morin incorporation and possible hydrogen-bonding interactions. The NPs exhibited approximately 81.4% morin release over 72 h in vitro. Compared to free morin, Morin-PLGA-CS NPs increased center-zone exploration in the OFT and open-arm behavior in the EPM, but also reduced total distance traveled in the OFT, indicating that motor suppression or sedation may have contributed to the behavioral profile (p &lt; 0.001). It also improved the discrimination index (DI) in the NOR test and elevated sleep duration in the pentobarbital test (p &lt; 0.001). The NPs also prolonged seizure latency (137.2 s vs. 114.5 s for free morin; p &lt; 0.001) and markedly reduced IL-1\u03b2, IL-6, and TNF-\u03b1 levels in both the cortex and hippocampus. At the molecular level, Morin-PLGA-CS NPs were associated with significantly increased hippocampal Nrf2 and HO-1 mRNA transcript levels and decreased GFAP and Iba1 transcript levels relative to free morin and the PTZ-challenged vehicle control group. Conclusions: Morin-PLGA-CS NPs produced greater behavioral, anticonvulsant, inflammatory, and redox effects than free morin in male rats. Molecular data revealed changes in hippocampal mRNA expression, including increased Nrf2 and HO-1 transcripts and decreased GFAP and Iba1 transcripts. However, these transcript-level findings are preliminary and require protein-level validation.<\/jats:p>","DOI":"10.3390\/pharmaceutics18091170","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T16:07:29Z","timestamp":1789574849000},"page":"1170","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Morin-Loaded PLGA-Chitosan Nanoparticles Attenuate PTZ-Induced Seizure-Related Behavioral, Biochemical, and Transcriptional Changes in Male Rats"],"prefix":"10.3390","volume":"18","author":[{"given":"Ashraf","family":"Kakoo","sequence":"first","affiliation":[{"name":"Department of Biology, College of Science, Salahaddin University-Erbil, Erbil 44001, Iraq"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"software","vocabulary":"credit"}]},{"given":"Azad Hasan","family":"Kheder","sequence":"additional","affiliation":[{"name":"Physiotherapy Department, Erbil Health and Medical Technical College, Erbil Polytechnic University, Erbil 44001, Iraq"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"}]},{"given":"Ali A.","family":"Mohammedsaeed","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Science, College of Health Sciences, Lebanese French University, Erbil 44001, Iraq"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"visualization","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"}]},{"given":"Trefa Salih","family":"Mohamad","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science, Salahaddin University-Erbil, Erbil 44001, Iraq"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Mohammed Awat","family":"Ali","sequence":"additional","affiliation":[{"name":"Faculty of General Medicine, Koya University, Koya 46017, Iraq"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"}]},{"given":"Mohammad B.","family":"Ghayour","sequence":"additional","affiliation":[{"name":"Department of Biophysics, Faculty of Advanced Technologies, University of Mohaghegh Ardabili, Namin 56391-44991, Iran"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"visualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2858-4098","authenticated-orcid":false,"given":"Arash","family":"Abdolmaleki","sequence":"additional","affiliation":[{"name":"Department of Biophysics, Faculty of Advanced Technologies, University of Mohaghegh Ardabili, Namin 56391-44991, Iran"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"}]},{"given":"Dlzar B.","family":"Rahman","sequence":"additional","affiliation":[{"name":"Department of Genetics, Bio Diagnostic Center (BDC), Erbil 44001, Iraq"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]},{"given":"Shang Ziyad","family":"Abdulqadir","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science, Salahaddin University-Erbil, Erbil 44001, Iraq"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"conceptualization","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9586-7843","authenticated-orcid":false,"given":"Taban Kamal","family":"Rasheed","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science, Salahaddin University-Erbil, Erbil 44001, Iraq"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Mohammed Jarjees","family":"Hashm","sequence":"additional","affiliation":[{"name":"Department of Genetics, Bio Diagnostic Center (BDC), Erbil 44001, Iraq"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"}]},{"given":"Shukur Wasman","family":"Smail","sequence":"additional","affiliation":[{"name":"Department of Medical Science, Respiratory Medicine, and Allergology, Uppsala University and University Hospital, Uppsala 75185, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,16]]},"reference":[{"key":"ref_1","first-page":"99","article-title":"Prevalence of epilepsy in children and adolescents worldwide: A literature overview","volume":"4","author":"Eslamian","year":"2024","journal-title":"Health Prov."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1159\/000503831","article-title":"The Epidemiology of Epilepsy","volume":"54","author":"Beghi","year":"2020","journal-title":"Neuroepidemiology"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Giourou, E., Stavropoulou-Deli, A., Giannakopoulou, A., Kostopoulos, G.K., and Koutroumanidis, M. (2015). Introduction to epilepsy and related brain disorders. Cyberphysical Systems for Epilepsy and Related Brain Disorders: Multi-Parametric Monitoring and Analysis for Diagnosis and Optimal Disease Management, Springer.","DOI":"10.1007\/978-3-319-20049-1_2"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.phrs.2016.03.003","article-title":"Addressing the burden of epilepsy: Many unmet needs","volume":"107","author":"Beghi","year":"2016","journal-title":"Pharmacol. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1159\/000222775","article-title":"Refractory epilepsy: A clinically oriented review","volume":"62","author":"Beleza","year":"2009","journal-title":"Eur. Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1002\/epi4.12967","article-title":"Real-world anti-seizure treatment and adverse events among individuals living with drug-resistant focal epilepsy in the United States","volume":"9","author":"Mao","year":"2024","journal-title":"Epilepsia Open"},{"key":"ref_7","unstructured":"Sharma, A.K. (2025). Beyond the Label: A Literature Review on the Neurotoxic Effects of Everyday Medications. [Master\u2019s Thesis, Vilniaus Universitetas]."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Riva, A., Golda, A., Balagura, G., Amadori, E., Vari, M.S., Piccolo, G., Iacomino, M., Lattanzi, S., Salpietro, V., and Minetti, C. (2021). New Trends and Most Promising Therapeutic Strategies for Epilepsy Treatment. Front. Neurol., 12.","DOI":"10.3389\/fneur.2021.753753"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1007\/s11064-015-1771-2","article-title":"Neuroprotective Effect of Natural Products on Peripheral Nerve Degeneration: A Systematic Review","volume":"41","author":"Barreto","year":"2016","journal-title":"Neurochem. Res."},{"key":"ref_10","unstructured":"Chaudhari, S.K., Arshad, S., Amjad, M.S., and Akhtar, M.S. (2019). Natural compounds extracted from medicinal plants and their applications. Natural Bio-Active Compounds: Volume 1: Production and Applications, Springer."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Panche, A.N., Diwan, A.D., and Chandra, S.R. (2016). Flavonoids: An overview. J. Nutr. Sci., 5.","DOI":"10.1017\/jns.2016.41"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2651","DOI":"10.1002\/ptr.70274","article-title":"Morin: A Comprehensive Review of Its Sources, Nutraceutical Prospects, Chemistry, and Pharmacological Insights","volume":"40","author":"Kumar","year":"2026","journal-title":"Phytother. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"237","DOI":"10.22270\/jddt.v15i8.7269","article-title":"Morin: A powerful potential flavonoid for human","volume":"15","author":"Jain","year":"2025","journal-title":"J. Drug Deliv. Ther."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Lem, F.F., Jiunn Herng Lee, D., and Chee, F.T. (2023). Pharmacological insights into morin: Therapeutic applications and future perspectives. Handbook of Dietary Flavonoids, Springer.","DOI":"10.1007\/978-3-030-94753-8_21-1"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1080\/1028415X.2025.2544605","article-title":"Morin hydrate: A comprehensive review on therapeutic potential in treating neurological diseases","volume":"29","author":"Noor","year":"2026","journal-title":"Nutr. Neurosci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"175213","DOI":"10.1016\/j.ejphar.2022.175213","article-title":"Morin offsets PTZ-induced neuronal degeneration and cognitive decrements in rats: The modulation of TNF-\u03b1\/TNFR-1\/RIPK1, 3\/MLKL\/PGAM5\/Drp-1, IL-6\/JAK2\/STAT3\/GFAP and Keap-1\/Nrf-2\/HO-1 trajectories","volume":"931","author":"Sarah","year":"2022","journal-title":"Eur. J. Pharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Rabidas, S.S., Prakash, C., Tyagi, J., Suryavanshi, J., Kumar, P., Bhattacharya, J., and Sharma, D. (2023). A Comprehensive Review on Anti-Inflammatory Response of Flavonoids in Experimentally-Induced Epileptic Seizures. Brain Sci., 13.","DOI":"10.3390\/brainsci13010102"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1038\/s41583-024-00805-1","article-title":"mTOR and neuroinflammation in epilepsy: Implications for disease progression and treatment","volume":"25","author":"Ravizza","year":"2024","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"226","DOI":"10.5607\/en.2018.27.3.226","article-title":"Morin Prevents Granule Cell Dispersion and Neurotoxicity via Suppression of mTORC1 in a Kainic Acid-induced Seizure Model","volume":"27","author":"Lee","year":"2018","journal-title":"Exp. Neurobiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"601","DOI":"10.26599\/NBE.2024.929016","article-title":"Design and Development of Self-nanoemulsifying Drug Delivery System (SNEDDS) with Morin Hydrate to Enhance Nimodipine\u2019s oral Bioavailability and Pharmacokinetics","volume":"16","author":"Patel","year":"2024","journal-title":"Nano Biomed. Eng."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1620","DOI":"10.1080\/21691401.2016.1276919","article-title":"Development and characterization of morin hydrate loaded microemulsion for the management of Alzheimer\u2019s disease","volume":"45","author":"Sharma","year":"2017","journal-title":"Artif. Cells Nanomed. Biotechnol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"5233","DOI":"10.1039\/D2NA00524G","article-title":"Polymeric nanoparticles for dopamine and levodopa replacement in Parkinson\u2019s disease","volume":"4","author":"Alabrahim","year":"2022","journal-title":"Nanoscale Adv."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1080\/17425247.2016.1178237","article-title":"Solid lipid nanoparticles as a drug delivery system for the treatment of neurodegenerative diseases","volume":"13","author":"Cacciatore","year":"2016","journal-title":"Expert. Opin. Drug Deliv."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2212","DOI":"10.2174\/0929867311320170006","article-title":"Potential use of polymeric nanoparticles for drug delivery across the blood-brain barrier","volume":"20","author":"Tosi","year":"2013","journal-title":"Curr. Med. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"101658","DOI":"10.1016\/j.arr.2022.101658","article-title":"Brain drug delivery and neurodegenerative diseases: Polymeric PLGA-based nanoparticles as a forefront platform","volume":"79","author":"Pinto","year":"2022","journal-title":"Ageing Res. Rev."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Abbas, H., Sayed, N.S.E., Youssef, N.A.H.A., Gaafar, P.M.E., Mousa, M.R., Fayez, A.M., and Elsheikh, M.A. (2022). Novel Luteolin-Loaded Chitosan Decorated Nanoparticles for Brain-Targeting Delivery in a Sporadic Alzheimer\u2019s Disease Mouse Model: Focus on Antioxidant, Anti-Inflammatory, and Amyloidogenic Pathways. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14051003"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"7440","DOI":"10.1039\/D3RA08738G","article-title":"Surface modification strategies for improved hemocompatibility of polymeric materials: A comprehensive review","volume":"14","author":"Bhattacharjee","year":"2024","journal-title":"RSC Adv."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"74254","DOI":"10.1039\/C6RA15408E","article-title":"Resveratrol loaded PLGA: D-\u03b1-tocopheryl polyethylene glycol 1000 succinate blend nanoparticles for brain cancer therapy","volume":"6","author":"Vijayakumar","year":"2016","journal-title":"RSC Adv."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1007\/s00289-020-03506-8","article-title":"Designing chitosan nanoparticles embedded into graphene oxide as a drug delivery system","volume":"79","author":"Hosseini","year":"2022","journal-title":"Polym. Bull."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1023\/B:PHAM.0000012150.60180.e3","article-title":"Effect of chitosan on epithelial cell tight junctions","volume":"21","author":"Smith","year":"2004","journal-title":"Pharm. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"18348","DOI":"10.3390\/ijms160818348","article-title":"Overview of Nrf2 as Therapeutic Target in Epilepsy","volume":"16","author":"Sampieri","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Sandouka, S., and Shekh-Ahmad, T. (2021). Induction of the Nrf2 Pathway by Sulforaphane Is Neuroprotective in a Rat Temporal Lobe Epilepsy Model. Antioxidants, 10.","DOI":"10.3390\/antiox10111702"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s13578-022-00951-y","article-title":"Nrf2 is predominantly expressed in hippocampal neurons in a rat model of temporal lobe epilepsy","volume":"13","author":"Sandouka","year":"2023","journal-title":"Cell Biosci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1111\/j.1528-1167.2008.01491.x","article-title":"Rapid astrocyte and microglial activation following pilocarpine-induced seizures in rats","volume":"49","author":"Shapiro","year":"2008","journal-title":"Epilepsia"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Zakharova, M.V., Kovalenko, A.A., Zubareva, O.E., Schwarz, A.P., Postnikova, T.Y., Trofimova, A.M., and Zaitsev, A.V. (2024). Pentylenetetrazole-Induced Seizures Cause Short-Term Changes in the Phenotype of Microglial and Astroglial Cells in the Hippocampus and Temporal Cortex of Young Male Wistar Rats. J. Neurosci. Res., 102.","DOI":"10.1002\/jnr.25385"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1021\/acs.jafc.6b05147","article-title":"Suppression of Lipopolysaccharide-Induced Neuroinflammation by Morin via MAPK, PI3K\/Akt, and PKA\/HO-1 Signaling Pathway Modulation","volume":"65","author":"Jung","year":"2017","journal-title":"J. Agric. Food Chem."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Yang, F., Cabe, M., Nowak, H.A., and Langert, K.A. (2022). Chitosan\/poly(lactic-co-glycolic)acid Nanoparticle Formulations with Finely-Tuned Size Distributions for Enhanced Mucoadhesion. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14010095"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Gould, T.D., Dao, D.T., and Kovacsics, C.E. (2009). The open field test. Mood and Anxiety Related Phenotypes in Mice: Characterization Using Behavioral Tests, Humana Press.","DOI":"10.1007\/978-1-60761-303-9"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1016\/S0149-7634(96)00058-9","article-title":"Anxiety, defence and the elevated plus-maze","volume":"21","author":"Rodgers","year":"1997","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.ejphar.2016.07.048","article-title":"Evaluation of neuroprotective, anticonvulsant, sedative and anxiolytic activity of citicoline in rats","volume":"789","author":"Abdolmaleki","year":"2016","journal-title":"Eur. J. Pharmacol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1016\/j.physbeh.2009.09.005","article-title":"A revised Racine\u2019s scale for PTZ-induced seizures in rats","volume":"98","author":"Luttjohann","year":"2009","journal-title":"Physiol. Behav."},{"key":"ref_42","first-page":"55718","article-title":"Novel Object Recognition Test for the Investigation of Learning and Memory in Mice","volume":"126","author":"Lueptow","year":"2017","journal-title":"J. Vis. Exp."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1458","DOI":"10.1111\/epi.17564","article-title":"Failure to use new breakthrough treatments for epilepsy","volume":"64","author":"Klein","year":"2023","journal-title":"Epilepsia"},{"key":"ref_44","unstructured":"Olsen, R.W. (2020). Convulsant and anticonvulsant drug receptor binding. Receptor Binding in Drug Research, CRC Press."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"352","DOI":"10.4103\/2221-1691.237078","article-title":"Anti-epileptic effect of morin against experimental pentylenetetrazol-induced seizures via modulating brain monoamines and oxidative stress","volume":"8","author":"Kandhare","year":"2018","journal-title":"Asian Pac. J. Trop. Biomed."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/j.brainresbull.2018.03.006","article-title":"Involvement of GABAergic, BDNF and Nox-2 mechanisms in the prevention and reversal of ketamine-induced schizophrenia-like behavior by morin in mice","volume":"139","author":"Aderibigbe","year":"2018","journal-title":"Brain Res. Bull."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"106343","DOI":"10.1016\/j.archoralbio.2025.106343","article-title":"Anti-inflammatory, antioxidant, and antimicrobial evaluation of morin","volume":"178","author":"Sales","year":"2025","journal-title":"Arch. Oral Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1192\/bjp.133.3.239","article-title":"Molecular mechanisms mediating the action of diazepam on GABA receptors","volume":"133","author":"Costa","year":"1978","journal-title":"Br. J. Psychiatry"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Alonso, M., Barcia, E., Gonzalez, J.F., Montejo, C., Garcia-Garcia, L., Villa-Hermosilla, M.C., Negro, S., Fraguas-Sanchez, A.I., and Fernandez-Carballido, A. (2022). Functionalization of Morin-Loaded PLGA Nanoparticles with Phenylalanine Dipeptide Targeting the Brain. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14112348"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"147881","DOI":"10.1016\/j.brainres.2022.147881","article-title":"Anti-inflammatory and neuroprotective effects of insulin-like growth factor-1 overexpression in pentylenetetrazole (PTZ)-induced mouse model of chronic epilepsy","volume":"1785","author":"Wu","year":"2022","journal-title":"Brain Res."},{"key":"ref_51","first-page":"147","article-title":"Possible Role of Oxidative Stress and Nrf2\/HO-1 Pathway in Pentylenetetrazole-induced Epilepsy in Aged Rats","volume":"12","author":"Obydah","year":"2023","journal-title":"Rep. Biochem. Mol. Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"114304","DOI":"10.1016\/j.intimp.2025.114304","article-title":"The Keap1\/Nrf2\/ARE\/HO-1 axis in epilepsy: Crosstalk between oxidative stress and neuroinflammation","volume":"153","author":"Manavi","year":"2025","journal-title":"Int. Immunopharmacol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"S86","DOI":"10.1111\/j.1528-1157.2000.tb01563.x","article-title":"Hippocampal neurons express GABAA receptor insensitive to diazepam in hyperexcitable conditions","volume":"41","author":"Kapur","year":"2000","journal-title":"Epilepsia"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Noebels, J.L., Avoli, M., Rogawski, M.A., Vezzani, A., and Delgado-Escueta, A.V. (2024). GABAA receptors, seizures, and epilepsy. Jasper\u2019s Basic Mechanisms of the Epilepsies, Oxford University Press. [5th ed.].","DOI":"10.1093\/med\/9780197549469.001.0001"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Elsayed, H.R.H., Rabei, M.R., Elshaer, M.M.A., El Nashar, E.M., Alghamdi, M.A., Al-Qahtani, Z., and Nabawy, A. (2023). Suppression of neuronal apoptosis and glial activation with modulation of Nrf2\/HO-1 and NF-kB signaling by curcumin in streptozotocin-induced diabetic spinal cord central neuropathy. Front. Neuroanat., 17.","DOI":"10.3389\/fnana.2023.1094301"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Winiarska-Mieczan, A., Baranowska-Wojcik, E., Kwiecien, M., Grela, E.R., Szwajgier, D., Kwiatkowska, K., and Kiczorowska, B. (2020). The Role of Dietary Antioxidants in the Pathogenesis of Neurodegenerative Diseases and Their Impact on Cerebral Oxidoreductive Balance. Nutrients, 12.","DOI":"10.3390\/nu12020435"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/S0166-2236(99)01543-X","article-title":"Ascorbate regulation and its neuroprotective role in the brain","volume":"23","author":"Rice","year":"2000","journal-title":"Trends Neurosci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.neulet.2013.03.038","article-title":"Activation of Nrf2-ARE signal pathway in hippocampus of amygdala kindling rats","volume":"543","author":"Wang","year":"2013","journal-title":"Neurosci. Lett."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1016\/j.freeradbiomed.2003.11.029","article-title":"Mitochondrial oxidative stress and increased seizure susceptibility in Sod2(\u2212\/+) mice","volume":"36","author":"Liang","year":"2004","journal-title":"Free Radic. Biol. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"105470","DOI":"10.1016\/j.nbd.2021.105470","article-title":"Neuron-specific mitochondrial oxidative stress results in epilepsy, glucose dysregulation and a striking astrocyte response","volume":"158","author":"Fulton","year":"2021","journal-title":"Neurobiol. Dis."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"113247","DOI":"10.1016\/j.expneurol.2020.113247","article-title":"Transcriptional activation of antioxidant gene expression by Nrf2 protects against mitochondrial dysfunction and neuronal death associated with acute and chronic neurodegeneration","volume":"328","author":"Goodfellow","year":"2020","journal-title":"Exp. Neurol."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Parsons, A.L.M., Bucknor, E.M.V., Castroflorio, E., Soares, T.R., Oliver, P.L., and Rial, D. (2022). The Interconnected Mechanisms of Oxidative Stress and Neuroinflammation in Epilepsy. Antioxidants, 11.","DOI":"10.3390\/antiox11010157"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"10","DOI":"10.19026\/bjpt.4.5382","article-title":"Morin a flavonoid exerts antioxidant potential in streptozotocin-induced hepatotoxicity","volume":"4","author":"Alkhamees","year":"2013","journal-title":"Br. J. Pharmacol. Toxicol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1007\/s11010-009-0053-1","article-title":"Morin a flavonoid exerts antioxidant potential in chronic hyperammonemic rats: A biochemical and histopathological study","volume":"327","author":"Subash","year":"2009","journal-title":"Mol. Cell Biochem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1002\/jnr.24205","article-title":"Glial source of nitric oxide in epileptogenesis: A target for disease modification in epilepsy","volume":"97","author":"Sharma","year":"2019","journal-title":"J. Neurosci. Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"808","DOI":"10.2174\/187152711798072347","article-title":"Nitric oxide, epileptic seizures, and action of antiepileptic drugs","volume":"10","author":"Banach","year":"2011","journal-title":"CNS Neurol. Disord. Drug Targets"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"111114","DOI":"10.1016\/j.cbi.2024.111114","article-title":"Withaferin A alleviates inflammation in animal models of arthritis by inhibiting the NF-kappaB pathway and cytokine release","volume":"398","author":"Alenazi","year":"2024","journal-title":"Chem. Biol. Interact."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2703","DOI":"10.1039\/D0FO03353G","article-title":"Cardamonin protects nucleus pulposus cells against IL-1beta-induced inflammation and catabolism via Nrf2\/NF-kappaB axis","volume":"12","author":"Xie","year":"2021","journal-title":"Food Funct."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/18\/9\/1170\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T04:13:20Z","timestamp":1789704800000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/18\/9\/1170"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,16]]},"references-count":68,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["pharmaceutics18091170"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics18091170","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,16]]}}}