{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T05:16:51Z","timestamp":1777526211851,"version":"3.51.4"},"reference-count":74,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2025,7,8]],"date-time":"2025-07-08T00:00:00Z","timestamp":1751932800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["ASSAY and Drug Development Technologies"],"published-print":{"date-parts":[[2026,1,1]]},"abstract":"<jats:p>Stroke is an intricate oxidative and inflammatory response resulting from cerebral ischemia followed by reperfusion injury. Complex pathophysiology of stroke poses challenges for treatment. Peroxisome proliferator-activated receptor (PPAR) expression in the rat hippocampus is markedly elevated post cerebral ischemia\/reperfusion (I\/R) injury. Hence, saroglitazar, a dual PPAR-\u03b1\/\u03b3 agonist, was investigated against cerebral I\/R injury in rats. Male Sprague\u2013Dawley rats were subjected to bilateral common carotid artery occlusion for 30 min and reperfusion for 3 days. During the reperfusion, animals were treated with vehicle or saroglitazar once a day for 3 days. The behavioral parameters were assessed, and animals were sacrificed to measure oxidative markers (malondialdehyde, superoxide dismutase, catalase, and reduced glutathione), inflammatory markers (interleukin-6, tumor necrosis factor-\u03b1, nuclear factor kappa-light chain enhancer of activated B cells (NF-\u03baB), and high mobility group box 1 (HMGB-1) protein, infarction, and histopathology changes. Following I\/R injury, antioxidant enzymes were reduced, while nitric oxide and inflammatory markers were increased in the disease group. In the rat hippocampus, these changes led to neurobehavioral impairment and cerebral infarction. Saroglitazar improved the levels of antioxidants and reduced inflammation; 2,3,5-triphenyltetrazolium chloride stain and histopathological analysis revealed the neuroprotective effect of saroglitazar in the hippocampus region. The neuroprotective effects of saroglitazar were attributed to its activation of both PPAR-\u03b1 and PPAR-\u03b3. It improved antioxidant levels and inhibited proinflammatory cytokines by suppressing the HMGB-1\/NF-\u03baB signaling pathway. These findings underscore the potential of saroglitazar in mitigating cerebral I\/R injury.<\/jats:p>","DOI":"10.1089\/adt.2025.057","type":"journal-article","created":{"date-parts":[[2025,7,8]],"date-time":"2025-07-08T09:38:44Z","timestamp":1751967524000},"page":"65-80","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Neuroprotective Potential of Saroglitazar Against Cerebral Ischemia\/Reperfusion Injury in Sprague\u2013Dawley Rats: Targeting HMGB-1\/NF-\u03baB Pathway"],"prefix":"10.1177","volume":"24","author":[{"given":"Prachi","family":"Mistry","sequence":"first","affiliation":[{"name":"L.J. Institute of Pharmacy, L J University, Ahmedabad, India."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sanjiv","family":"Prajapati","sequence":"additional","affiliation":[{"name":"L.J. Institute of Pharmacy, L J University, Ahmedabad, India."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paridhi","family":"Vadher","sequence":"additional","affiliation":[{"name":"L.J. Institute of Pharmacy, L J University, Ahmedabad, India."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jhanvi","family":"Soni","sequence":"additional","affiliation":[{"name":"L.J. Institute of Pharmacy, L J University, Ahmedabad, India."},{"name":"Department of Pharmacology, Parul Institute of Pharmacy, Parul University, Waghodia, India."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5959-024X","authenticated-orcid":false,"given":"Vijay","family":"Kevlani","sequence":"additional","affiliation":[{"name":"L.J. Institute of Pharmacy, L J University, Ahmedabad, India."},{"name":"School of Pharmacy, National Forensic Sciences University, Gandhinagar, India."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2025,7,8]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/00004647-200404000-00001"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000001123"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2008.01.005"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11739-023-03312-w"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2024.12.042"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2015.6397"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2020.600280"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.600618"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.4103\/2231-4040.90879"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/596394"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-014-8882-7"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/541394"},{"issue":"6","key":"e_1_3_4_14_2","first-page":"541","article-title":"Rosiglitazone protect PC12 cells against oxygen-glucose deprivation\/reoxygenation through HMGB1 reduction and DUSP8 upregulation","volume":"36","author":"Li W","year":"2019","unstructured":"Li W, , Meijie Z, , Wenjing LI, et al. Rosiglitazone protect PC12 cells against oxygen-glucose deprivation\/reoxygenation through HMGB1 reduction and DUSP8 upregulation. Journal of Apoplexy and Nervous Diseases, 2019; 36(6):541\u2013545.","journal-title":"Journal of Apoplexy and Nervous Diseases"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1186\/1744-9081-10-21"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1111\/cbdd.14306"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2023.e22051"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2020.117729"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.13005\/bpj\/1830"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1111\/liv.13634"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuro.2024.09.004"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1021\/acschemneuro.3c00320"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2014.01.005"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.5115\/acb.2014.47.2.111"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxrep.2024.02.001"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.3109\/19390211.2015.1036186"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsps.2012.05.002"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1006\/niox.2000.0319"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.2174\/1871524921666210625112356"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)52451-6"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2006.205"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.hest.2020.09.001"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2012.185"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2021.667511"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2023.1140769"},{"issue":"10","key":"e_1_3_4_36_2","first-page":"607","article-title":"Neurological tests for functional outcome assessment in rodent models of ischaemic stroke","volume":"53","author":"Zarruk J","year":"2011","unstructured":"Zarruk J, , Garcia-Yebenes I, , Romera VG, et al. Neurological tests for functional outcome assessment in rodent models of ischaemic stroke. Rev Neurol, 2011; 53(10):607\u2013618.","journal-title":"Rev Neurol"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12915-022-01434-9"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresprot.2003.12.001"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/s1474-4422(23)00277-6"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-017-1667-0"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1364\/boe.432688"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1042\/BST0341341"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1002\/brb3.2642"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.reprotox.2008.10.001"},{"issue":"4","key":"e_1_3_4_45_2","article-title":"Amelioration of oxidative stress and Neuroinflammation by Saroglitazar, a dual PPAR\u03b1\/\u03b3 agonist in MES induced epileptic rats","volume":"12","author":"Panigrahy SR","year":"2019","unstructured":"Panigrahy SR, , Pradhan S, , Maharana CS. Amelioration of oxidative stress and Neuroinflammation by Saroglitazar, a dual PPAR\u03b1\/\u03b3 agonist in MES induced epileptic rats. Biomed Pharmacol J, 2019; 12(4).","journal-title":"Biomed Pharmacol J"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.107.507939"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0039-3402675"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2013.233"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12933-019-0884-3"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000152271.21943.a2"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1177\/039463201102400320"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21097"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejvs.2004.06.004"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2004.10.021"},{"key":"e_1_3_4_55_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2005.03.012"},{"key":"e_1_3_4_56_2","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.53.4.1052"},{"key":"e_1_3_4_57_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M208132200"},{"key":"e_1_3_4_58_2","doi-asserted-by":"publisher","DOI":"10.1038\/aps.2012.82"},{"key":"e_1_3_4_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2006.04.030"},{"key":"e_1_3_4_60_2","doi-asserted-by":"publisher","DOI":"10.1523\/jneurosci.23-15-06264.2003"},{"key":"e_1_3_4_61_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.2769-2795.2019.tb00039.x"},{"key":"e_1_3_4_62_2","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2015.2363"},{"key":"e_1_3_4_63_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gendis.2019.05.002"},{"key":"e_1_3_4_64_2","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-8-87"},{"key":"e_1_3_4_65_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-47057-z"},{"key":"e_1_3_4_66_2","doi-asserted-by":"publisher","DOI":"10.1155\/2008\/512196"},{"key":"e_1_3_4_67_2","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.21555"},{"key":"e_1_3_4_68_2","doi-asserted-by":"publisher","DOI":"10.1159\/000488183"},{"key":"e_1_3_4_69_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2010.05735.x"},{"key":"e_1_3_4_70_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.28.5.1073"},{"key":"e_1_3_4_71_2","article-title":"Effects of ischemic postconditioning on TLR4 signaling pathway during focal cerebral ischemla\/reperfusion in rats","author":"Peng W","year":"2012","unstructured":"Peng W, , Ren-liangA Z, , Jing-Lei L, et al. Effects of ischemic postconditioning on TLR4 signaling pathway during focal cerebral ischemla\/reperfusion in rats. Exp Ther Med, 2012.","journal-title":"Exp Ther Med"},{"key":"e_1_3_4_72_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.120.315189"},{"key":"e_1_3_4_73_2","doi-asserted-by":"publisher","DOI":"10.3390\/bs12080287"},{"issue":"6","key":"e_1_3_4_74_2","first-page":"1597","article-title":"Chrysin alleviates cerebral ischemia-reperfusion injury by inhibiting ferroptosis in rats","volume":"48","author":"Shang J-F","year":"2023","unstructured":"Shang J-F, , Jiao J-K, , Li Q-N, et al. Chrysin alleviates cerebral ischemia-reperfusion injury by inhibiting ferroptosis in rats. Zhongguo Zhong Yao Za Zhi, 2023; 48(6):1597\u20131605.","journal-title":"Zhongguo Zhong Yao Za Zhi"},{"key":"e_1_3_4_75_2","first-page":"68","article-title":"Study on effect of simvastatin on regeneration of hippocampal dentate gyrus nerve after cerebral ischemia in rats","volume":"83","author":"Ma Z","year":"2021","unstructured":"Ma Z, , Guo N, , Ma H, et al. Study on effect of simvastatin on regeneration of hippocampal dentate gyrus nerve after cerebral ischemia in rats. Ijps, 2021; 83:68\u201371.","journal-title":"Ijps"}],"container-title":["ASSAY and Drug Development Technologies"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1089\/adt.2025.057","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/adt.2025.057","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/adt.2025.057","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T16:28:58Z","timestamp":1777393738000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1089\/adt.2025.057"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,8]]},"references-count":74,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1,1]]}},"alternative-id":["10.1089\/adt.2025.057"],"URL":"https:\/\/doi.org\/10.1089\/adt.2025.057","relation":{},"ISSN":["1540-658X","1557-8127"],"issn-type":[{"value":"1540-658X","type":"print"},{"value":"1557-8127","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,8]]}}}