{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T18:45:44Z","timestamp":1790707544540,"version":"4.1.0"},"reference-count":119,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:00:00Z","timestamp":1782691200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Funda\u00e7\u00e3o de Apoio \u00e0 Pesquisa do Estado da Paraiba","award":["No. 03\/2026"],"award-info":[{"award-number":["No. 03\/2026"]}]},{"award":["No. 03\/2026"],"award-info":[{"award-number":["No. 03\/2026"]}],"id":[{"id":"https:\/\/ror.org\/021y4b202","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"CAPES","doi-asserted-by":"crossref","award":["001"],"award-info":[{"award-number":["001"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"crossref"}]},{"award":["001"],"award-info":[{"award-number":["001"]}],"id":[{"id":"https:\/\/ror.org\/00x0ma614","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"CNPq","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Epilepsy is a chronic neurological disorder prevalent worldwide, characterized by recurrent episodes of epileptic seizures. The primary current treatment approach is pharmacological, aimed at reducing the intensity and frequency of seizures, though it does not provide a cure. Neuroinflammation plays a central role in epilepsy by activating glial cells and stimulating the release of inflammatory mediators, further disrupting the balance between excitation and inhibition, thereby promoting the onset and recurrence of seizures. Furthermore, persistent inflammatory processes induce synaptic remodeling and the formation of dysfunctional neural circuits, establishing a pathological cycle in which inflammation and epileptic activity feed into each other. In this regard, natural products represent an important avenue for the discovery of new treatments. Thus, this review aimed to relate the role of the main inflammatory targets (Inflammasome\/NLRP3, NF-\u03baB, MAPK, mTOR, COX-2\/PGE2, and TLR4\/HMGB1) to epilepsy and to investigate in the literature natural products acting through these pathways in the treatment of epileptic seizures. Consequently, inflammatory pathways have emerged as critical targets in epilepsy, highlighting the importance of strategies capable of modulating neuroinflammatory processes. In this context, natural products stand out as promising therapeutic alternatives, given their multitarget mechanisms of action, potential to attenuate neuroinflammation and neuronal hyperexcitability.<\/jats:p>","DOI":"10.3390\/ijms27135857","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:55:11Z","timestamp":1782780911000},"page":"5857","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Neuroinflammation in Epilepsy: Biochemical and Molecular Mechanisms and Implications for Natural Product-Driven Drug Discovery"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4278-7596","authenticated-orcid":false,"given":"Arthur Lins","family":"Dias","sequence":"first","affiliation":[{"name":"Institute of Drugs and Medicines Research, Federal University of Para\u00edba, Jo\u00e3o Pessoa 58051-900, Brazil"},{"name":"Postgraduate Program in Cognitive and Behavior Neuroscience, Federal University of Para\u00edba, Jo\u00e3o Pessoa 58051-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8354-3198","authenticated-orcid":false,"given":"Pablo R.","family":"da Silva","sequence":"additional","affiliation":[{"name":"Institute of Drugs and Medicines Research, Federal University of Para\u00edba, Jo\u00e3o Pessoa 58051-900, Brazil"},{"name":"Postgraduate Program in Cognitive and Behavior Neuroscience, Federal University of Para\u00edba, Jo\u00e3o Pessoa 58051-900, Brazil"},{"name":"Postgraduate Program in Natural and Synthetic Bioactive Compounds, Federal University of Para\u00edba, Jo\u00e3o Pessoa 58051-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Livia R. P.","family":"Souza","sequence":"additional","affiliation":[{"name":"Institute of Drugs and Medicines Research, Federal University of Para\u00edba, Jo\u00e3o Pessoa 58051-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugo F. O.","family":"Pires","sequence":"additional","affiliation":[{"name":"Institute of Drugs and Medicines Research, Federal University of Para\u00edba, Jo\u00e3o Pessoa 58051-900, Brazil"},{"name":"Postgraduate Program in Cognitive and Behavior Neuroscience, Federal University of Para\u00edba, Jo\u00e3o Pessoa 58051-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria C. F.","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Institute of Drugs and Medicines Research, Federal University of Para\u00edba, Jo\u00e3o Pessoa 58051-900, Brazil"},{"name":"Postgraduate Program in Natural and Synthetic Bioactive Compounds, Federal University of Para\u00edba, Jo\u00e3o Pessoa 58051-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luiza C. D.","family":"Neri","sequence":"additional","affiliation":[{"name":"Institute of Drugs and Medicines Research, Federal University of Para\u00edba, Jo\u00e3o Pessoa 58051-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-4822-4616","authenticated-orcid":false,"given":"Nayana M. M. V.","family":"Barbosa","sequence":"additional","affiliation":[{"name":"Institute of Drugs and Medicines Research, Federal University of Para\u00edba, Jo\u00e3o Pessoa 58051-900, Brazil"},{"name":"Postgraduate Program in Natural and Synthetic Bioactive Compounds, Federal University of Para\u00edba, Jo\u00e3o Pessoa 58051-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9 Luiz Leoc\u00e1dio","family":"de Souza Matos","sequence":"additional","affiliation":[{"name":"Institute of Drugs and Medicines Research, Federal University of Para\u00edba, Jo\u00e3o Pessoa 58051-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2567-9630","authenticated-orcid":false,"given":"Anuraj","family":"Nayarisseri","sequence":"additional","affiliation":[{"name":"In Silico Research Laboratory, Eminent Biosciences, Indore 452010, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4863-8057","authenticated-orcid":false,"given":"Marcus T.","family":"Scotti","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Natural and Synthetic Bioactive Compounds, Federal University of Para\u00edba, Jo\u00e3o Pessoa 58051-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana M. 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