{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T02:51:00Z","timestamp":1790736660572,"version":"4.1.0"},"reference-count":50,"publisher":"American Chemical Society (ACS)","issue":"43","license":[{"start":{"date-parts":[[2022,10,20]],"date-time":"2022-10-20T00:00:00Z","timestamp":1666224000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001411","name":"Indian Council of Medical Research","doi-asserted-by":"publisher","award":["36\/9\/2020-TOXI\/BMS"],"award-info":[{"award-number":["36\/9\/2020-TOXI\/BMS"]}],"id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001411","name":"Indian Council of Medical Research","doi-asserted-by":"publisher","award":["45\/14\/2020\/PHA\/BMS"],"award-info":[{"award-number":["45\/14\/2020\/PHA\/BMS"]}],"id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001411","name":"Indian Council of Medical Research","doi-asserted-by":"publisher","award":["45\/47\/2013-PHA\/BMS"],"award-info":[{"award-number":["45\/47\/2013-PHA\/BMS"]}],"id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001409","name":"Department of Science and Technology, Ministry of Science and Technology","doi-asserted-by":"publisher","award":["SR\/FST\/LS- 1\/2017\/05[C]"],"award-info":[{"award-number":["SR\/FST\/LS- 1\/2017\/05[C]"]}],"id":[{"id":"10.13039\/501100001409","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001409","name":"Department of Science and Technology, Ministry of Science and Technology","doi-asserted-by":"publisher","award":["SR\/PURSE Phase 2\/39[C]"],"award-info":[{"award-number":["SR\/PURSE Phase 2\/39[C]"]}],"id":[{"id":"10.13039\/501100001409","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Valproic acid (VPA) is short branched-chain fatty acid (BCFA) derived from valeric acids which are naturally produced by Valeriana officinalis (flowering plant). Neurotoxicity caused by BCFA-like VPA may be mediated by oxidative stress, according to research involving the cerebral cortex and cerebellum. In the present study, we explored the possible protective effect of different antioxidants such as melatonin, quercetin, and piperine on VPA exposure by using a supernatant preparation of the cerebral cortex and cerebellum regions of the rat brain. The present study revealed that melatonin, quercetin, and piperine significantly prevented VPA-induced oxidative stress in the cerebral cortex and cerebellum regions. VPA was also observed to lower the level of reduced glutathione, and this effect was significantly mitigated by these antioxidants. Melatonin, quercetin, and piperine also ameliorated and altered the activities of AChE, Na+, K+ATPase, and MAO in the cerebral cortex and cerebellum. Results of this study also suggest that prior treatment of antioxidants like melatonin, quercetin, and piperine helps in combating the oxidative stress induced by VPA in the cerebral cortex and cerebellum region of the rat brain. Thus, sufficient dietary intake of these antioxidants by individuals at high risk of VPA exposure could prove beneficial in combating the adverse effect of VPA.<\/jats:p>","DOI":"10.1021\/acsomega.2c00163","type":"journal-article","created":{"date-parts":[[2022,10,20]],"date-time":"2022-10-20T13:36:36Z","timestamp":1666272996000},"page":"38269-38276","source":"Crossref","is-referenced-by-count":5,"title":["Neuroprotective\nEffects of Natural Antioxidants Against\nBranched-Chain Fatty Acid-Induced Oxidative Stress in Cerebral Cortex\nand Cerebellum Regions of the Rat Brain"],"prefix":"10.1021","volume":"7","author":[{"given":"Shaista","family":"Chaudhary","sequence":"first","affiliation":[{"name":"Jamia Hamdard , , ,","place":["New Delhi, India, 110062"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Pinky","sequence":"additional","affiliation":[{"name":"Jamia Hamdard , , ,","place":["New Delhi, India, 110062"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6318-6506","authenticated-orcid":true,"given":"Suhel","family":"Parvez","sequence":"additional","affiliation":[{"name":"Jamia Hamdard , , ,","place":["New Delhi, India, 110062"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2022,10,20]]},"reference":[{"key":"2026081709205393600_cit1","doi-asserted-by":"publisher","first-page":"479364","DOI":"10.1155\/2010\/479364","article-title":"Molecular\nand therapeutic potential and toxicity of valproic acid","volume":"2010","author":"Chateauvieux","year":"2010","journal-title":"J. Biomed. Biotechnol."},{"key":"2026081709205393600_cit2","first-page":"416","article-title":"Ellagic acid modulates sodium valproate\ninduced reproductive\ntoxicity in male Wistar rats","volume":"58","author":"Girish","year":"2014","journal-title":"Indian J. Physiol.\nPharmacol."},{"key":"2026081709205393600_cit3","doi-asserted-by":"publisher","first-page":"454","DOI":"10.3109\/15563650.2015.1035441","article-title":"Extracorporeal treatment for valproic\nacid poisoning: systematic review and recommendations from the EXTRIP\nworkgroup","volume":"53","author":"Ghannoum","year":"2015","journal-title":"Clin. Toxicol."},{"key":"2026081709205393600_cit4","doi-asserted-by":"publisher","first-page":"390","DOI":"10.1016\/j.ntt.2008.03.060","article-title":"Hydroxamic acid and\nfluorinated derivatives\nof valproic acid: anticonvulsant activity, neurotoxicity and teratogenicity","volume":"30","author":"Gravemann","year":"2008","journal-title":"Neurotoxicol. Teratol."},{"key":"2026081709205393600_cit5","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1016\/j.tiv.2012.01.020","article-title":"A new approach\non valproic acid induced hepatotoxicity:\nInvolvement of lysosomal membrane leakiness and cellular proteolysis","volume":"26","author":"Pourahmad","year":"2012","journal-title":"Toxicol. Vitro"},{"key":"2026081709205393600_cit6","doi-asserted-by":"publisher","first-page":"979","DOI":"10.1124\/mol.111.072314","article-title":"Valproic acid increases\nformation of reactive oxygen\nspecies and induces apoptosis in postimplantation embryos: A role\nfor oxidative stress in valproic acid-induced neural tube","volume":"80","author":"Tung","year":"2011","journal-title":"Mol. Pharmacol."},{"key":"2026081709205393600_cit7","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1016\/j.neulet.2011.04.044","article-title":"Valproic acid induces\napoptosis in differentiating hippocampal neurons\nby the release of tumor necrosis factor-\u03b1 from activated astrocytes","volume":"497","author":"Wang","year":"2011","journal-title":"Neurosci. Lett."},{"key":"2026081709205393600_cit8","doi-asserted-by":"publisher","first-page":"1762","DOI":"10.1093\/hmg\/ddn085","article-title":"Early oxidative damage underlying\nneurodegeneration in X-adrenoleukodystrophy","volume":"17","author":"Fourcade","year":"2008","journal-title":"Hum. Mol. Genet."},{"key":"2026081709205393600_cit9","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1080\/03602530600959433","article-title":"Oxidative stress\nas a mechanism of valproic acid-associated\nhepatotoxicity","volume":"38","author":"Chang","year":"2006","journal-title":"Drug Metab. Rev."},{"key":"2026081709205393600_cit10","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1093\/toxsci\/kfi185","article-title":"Valproic\nacid II:\neffects on oxidative stress, mitochondrial membrane potential, and\ncytotoxicity in glutathione-depleted rat hepatocytes","volume":"86","author":"Tong","year":"2005","journal-title":"Toxicol. Sci."},{"key":"2026081709205393600_cit11","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1016\/j.neulet.2011.06.037","article-title":"Valproic acid inhibits\nneurosphere formation by adult subventricular cells by a lithium-sensitive\nmechanism","volume":"500","author":"Zhou","year":"2011","journal-title":"Neurosci. Lett."},{"key":"2026081709205393600_cit12","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1016\/j.ijdevneu.2007.04.002","article-title":"N-acetylaspartic acid promotes oxidative\nstress in cerebral cortex of rats","volume":"25","author":"Pederzolli","year":"2007","journal-title":"Int. J. 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Res."},{"key":"2026081709205393600_cit18","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1007\/s12011-009-8490-y","article-title":"Protective\nRole of Melatonin on Oxidative Stress Status\nand RNA Expression in Cerebral Cortex and Cerebellum of A\u03b2PP\nTransgenic Mice After Chronic Exposure to Aluminum","volume":"135","author":"Garci\u0301a","year":"2010","journal-title":"Biol. Trace Elem. Res."},{"key":"2026081709205393600_cit19","doi-asserted-by":"publisher","first-page":"1169","DOI":"10.1007\/s10571-009-9411-5","article-title":"Protective\nEffects of Resveratrol\nand Quercetin Against MPP+ -Induced Oxidative Stress Act by Modulating\nMarkers of Apoptotic Death in Dopaminergic Neurons","volume":"29","author":"Bournival","year":"2009","journal-title":"Cell. Mol. 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Bull."},{"key":"2026081709205393600_cit24","article-title":"Suppression\nof neuroinflammatory\nand apoptotic signaling cascade by curcumin alone and in combination\nwith piperine in rat model of olfactory bulbectomy induced depression","volume":"8","author":"Rinwa","year":"2010","journal-title":"PLoS One"},{"key":"2026081709205393600_cit25","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1016\/j.lfs.2010.06.015","article-title":"Neurochemical\nevidence that phytanic acid induces oxidative damage and reduces the\nantioxidant defenses in cerebellum and cerebral cortex of rats","volume":"87","author":"Leipnitz","year":"2010","journal-title":"Life Sci."},{"key":"2026081709205393600_cit26","doi-asserted-by":"publisher","first-page":"3901","DOI":"10.3390\/ijms14023901","article-title":"Comparison of B16 Melanoma\nCells\nand 3T3 Fibroblasts Concerning Cell Viability and ROS Production in\nthe Presence of Melatonin, Tested Over a Wide Range of Concentrations","volume":"14","author":"Bonmati-Carrion","year":"2013","journal-title":"Int. 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Res."},{"key":"2026081709205393600_cit29","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1093\/toxsci\/kfi184","article-title":"Valproic acid I:\ntime course of lipid peroxidation biomarkers, liver toxicity, and\nvalproic acid metabolite levels in rats","volume":"86","author":"Tong","year":"2005","journal-title":"Toxicol.\nSci."},{"key":"2026081709205393600_cit30","doi-asserted-by":"publisher","first-page":"1973","DOI":"10.1016\/j.fct.2010.04.047","article-title":"Protective\neffect of lipoic acid against methotrexate-induced oxidative stress\nin liver mitochondria","volume":"48","author":"Tabassum","year":"2010","journal-title":"Food Chem. 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Brain Res."},{"key":"2026081709205393600_cit39","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1515\/jbcpp-2014-0065","article-title":"Protective effects of blackberry\nand quercetin on sodium fluoride-induced oxidative stress and histological\nchanges in the hepatic, renal, testis and brain tissue of male rat","volume":"26","author":"Hamza","year":"2015","journal-title":"J. Basic Clin. Physiol. Pharmacol."},{"key":"2026081709205393600_cit40","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1016\/j.etp.2009.06.006","article-title":"Quercetin protects against oxidative stress-related\nrenal dysfunction by cadmium in rats","volume":"62","author":"Renugadevi","year":"2010","journal-title":"Exp. 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Arch.\nPharmacol."},{"key":"2026081709205393600_cit49","doi-asserted-by":"publisher","first-page":"2835","DOI":"10.1007\/s00221-014-3946-5","article-title":"Protective\neffects of melatonin against\nmitochondrial injury in a mouse model of multiple sclerosis","volume":"232","author":"Kashani","year":"2014","journal-title":"Exp. Brain Res."},{"key":"2026081709205393600_cit50","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1016\/j.ijdevneu.2007.04.002","article-title":"N-acetylaspartic acid promotes oxidative\nstress in cerebral cortex of rats","volume":"25","author":"Pederzolli","year":"2007","journal-title":"Int. J. Dev.\nNeurosci."}],"container-title":["ACS Omega"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acsomega.2c00163","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/7\/43\/38269\/4182281\/ao2c00163.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/7\/43\/38269\/4182281\/ao2c00163.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T13:30:03Z","timestamp":1786973403000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/acsodf\/article\/7\/43\/38269\/414024\/Neuroprotective-Effects-of-Natural-Antioxidants"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,20]]},"references-count":50,"journal-issue":{"issue":"43","published-online":{"date-parts":[[2022,10,20]]},"published-print":{"date-parts":[[2022,11,1]]}},"URL":"https:\/\/doi.org\/10.1021\/acsomega.2c00163","relation":{},"ISSN":["2470-1343"],"issn-type":[{"value":"2470-1343","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,20]]}}}