{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T14:38:27Z","timestamp":1783953507051,"version":"3.55.0"},"reference-count":50,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2021,11,9]],"date-time":"2021-11-09T00:00:00Z","timestamp":1636416000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"King Saud University, Riyadh, Saudi Arabia.","award":["Researchers Supporting Project number (RSP-2021\/96)"],"award-info":[{"award-number":["Researchers Supporting Project number (RSP-2021\/96)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Chondroitin sulfate is a proteoglycan component of the extracellular matrix (ECM) that supports neuronal and non-neuronal cell activity, provides a negative domain to the extracellular matrix, regulates the intracellular positive ion concentration, and maintains the hypersynchronous epileptiform activity. Therefore, the present study hypothesized an antiepileptic potential of chondroitin sulfate (CS) in pentylenetetrazole-induced kindled epilepsy and pilocarpine-induced status epilepticus in mice. Levels of various oxidative stress markers and inflammatory mediators were estimated in the brain tissue homogenate of mice, and histopathological changes were evaluated. Treatment with valproate (110 mg\/kg; i.p.) as a standard drug and chondroitin sulfate (100 &amp; 200 mg\/kg, p.o.) significantly (p &lt; 0.01) and dose-dependently prevented the severity of kindled and spontaneous recurrent seizures in mice. Additionally, chondroitin sulfate showed its antioxidant potential by restoring the various biochemical levels and anti-inflammatory properties by reducing NF-kB levels and pro-inflammatory mediators like TNF-alpha, IL-1\u03b2, and IL-6, indicating the neuroprotective effect as well as the suppressed levels of caspase-3, which indicated a neuroprotective treatment strategy in epilepsy. The proteoglycan chondroitin sulfate restores the normal physiology and configuration of the neuronal tissue. Further, the molecular docking of chondroitin sulfate at the active pockets of TNF-alpha, IL-1\u03b2, and IL-6 showed excellent interactions with critical amino acid residues. In conclusion, the present work provides preclinical evidence of chondroitin sulfate as a new therapeutic approach in attenuating and preventing seizures with a better understanding of the mechanism of alteration in ECM changes influencing abnormal neuronal activities.<\/jats:p>","DOI":"10.3390\/molecules26226773","type":"journal-article","created":{"date-parts":[[2021,11,9]],"date-time":"2021-11-09T21:39:07Z","timestamp":1636493947000},"page":"6773","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Anticonvulsive Effects of Chondroitin Sulfate on Pilocarpine and Pentylenetetrazole Induced Epileptogenesis in Mice"],"prefix":"10.3390","volume":"26","author":[{"given":"Shareen","family":"Singh","sequence":"first","affiliation":[{"name":"Chitkara College of Pharmacy, Chitkara University, Changdigarh 140401, Punjab, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2979-1590","authenticated-orcid":false,"given":"Thakur Gurjeet","family":"Singh","sequence":"additional","affiliation":[{"name":"Chitkara College of Pharmacy, Chitkara University, Changdigarh 140401, Punjab, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manjinder","family":"Singh","sequence":"additional","affiliation":[{"name":"Chitkara College of Pharmacy, Chitkara University, Changdigarh 140401, Punjab, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1185-8884","authenticated-orcid":false,"given":"Agnieszka","family":"Najda","sequence":"additional","affiliation":[{"name":"Department of Vegetable Crops and Medicinal Plants, University of Life Sciences in Lublin, 50A Do\u015bwiadczalna Street, 20-280 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renata","family":"Nurzy\u0144ska-Wierdak","sequence":"additional","affiliation":[{"name":"Department of Vegetable Crops and Medicinal Plants, University of Life Sciences in Lublin, 50A Do\u015bwiadczalna Street, 20-280 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafa","family":"Almeer","sequence":"additional","affiliation":[{"name":"Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Kamel","sequence":"additional","affiliation":[{"name":"Department of Medicine and Infectious Diseases, Faculty of Veterinary Medicine, Cairo University, Giza 12211, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4341-2713","authenticated-orcid":false,"given":"Mohamed M.","family":"Abdel-Daim","sequence":"additional","affiliation":[{"name":"Pharmacology Department, Faculty of Veterinary Medicine, Suez Canal University, Ismailia 41522, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"469","DOI":"10.4103\/1673-5374.320966","article-title":"Therapeutic potential of glial cell line-derived neurotrophic factor and cell reprogramming for hippocampal-related neurological disorders","volume":"17","author":"Chiavellini","year":"2022","journal-title":"Neural Regen. 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