{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T13:42:44Z","timestamp":1792676564069,"version":"4.5.0"},"reference-count":61,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T00:00:00Z","timestamp":1765584000000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Archiv der Pharmazie"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Cystitis, characterized by bladder inflammation, represents a significant clinical challenge in cancer chemotherapy, particularly with cyclophosphamide administration. Drug repurposing, which involves applying existing pharmaceuticals to new therapeutic areas, offers increased efficiency, reduced costs, and lower risks. This study investigated the molecular mechanisms underlying the uro\u2010protective application of lacosamide, an FDA\u2010approved antiepileptic drug, against cyclophosphamide\u2010induced cystitis via suppression of the Notch\u20101\/NICD\/NF\u2010\n                    <jats:italic>\u03ba<\/jats:italic>\n                    B inflammatory pathway. Network pharmacology analysis identified key molecular targets and pathways involved in lacosamide's protective mechanisms, followed by molecular docking studies that validated the binding interactions between lacosamide and target proteins. In vivo validation was performed using adult male Wistar rats with cyclophosphamide\u2010induced cystitis. Network analysis revealed Notch\u20101 as a primary target for lacosamide's uroprotective action. Experimental validation demonstrated that lacosamide pretreatment significantly attenuated oxidative bladder injury by decreasing malondialdehyde levels while enhancing superoxide dismutase activity and reduced glutathione content. Lacosamide substantially downregulated pro\u2010inflammatory mediators including TNF\u2010\u03b1, IL\u20101\u03b2, and IL\u20106 via NF\u2010\n                    <jats:italic>\u03ba<\/jats:italic>\n                    B suppression. Additionally, lacosamide suppressed the Notch\u20101\/NICD\/NF\u2010\n                    <jats:italic>\u03ba<\/jats:italic>\n                    B pathway, elevated Bcl\u20102 expression, and reduced Bax protein and caspase\u20103 levels. Histopathological examination corroborated biochemical findings. Lacosamide demonstrates significant uro\u2010protective efficacy through coordinated anti\u2010inflammatory, antioxidant, and anti\u2010apoptotic mechanisms through modulation of Notch\u20101\/NICD\/NF\u2010\n                    <jats:italic>\u03ba<\/jats:italic>\n                    B pathway.\n                  <\/jats:p>","DOI":"10.1002\/ardp.70171","type":"journal-article","created":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T14:08:47Z","timestamp":1765634927000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Uro\u2010Protective Role of Lacosamide Against Cyclophosphamide\u2010Induced Cystitis via Notch1\/NICD\/NF\u2010\n                    <i>\u03ba<\/i>\n                    B Pathway: Network Pharmacology, Molecular Docking, and Rat Model Validation"],"prefix":"10.1002","volume":"358","author":[{"given":"Ahmed S.","family":"Abdel\u2010Samea","sequence":"first","affiliation":[{"name":"Department of Pharmacology &amp; Toxicology, Faculty of Pharmacy Deraya University New Minia City Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0778-304X","authenticated-orcid":false,"given":"Mohammed R. A.","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Pharmacology &amp; Toxicology, Faculty of Pharmacy Beni\u2010Suef University Beni\u2010Suef Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reham H.","family":"Mohyeldin","sequence":"additional","affiliation":[{"name":"Department of Pharmacology &amp; Toxicology, Faculty of Pharmacy Deraya University New Minia City Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mina Ezzat","family":"Attya","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Medicine Minia University Minia Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Basim A. S.","family":"Messiha","sequence":"additional","affiliation":[{"name":"Department of Pharmacology &amp; Toxicology, Faculty of Pharmacy Beni\u2010Suef University Beni\u2010Suef Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,13]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2006.09.032"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0090-4295(99)80327-6"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1177\/1078155220920690"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jfma.2013.06.004"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrclinonc.2009.146"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-128-12_Part_1-199806150-00012"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.27280"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-016-3152-1"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfu233"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bmt.1701355"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(79)90222-3"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2006.04.011"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/sigtrans.2017.23"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-410X.2007.06773.x"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.668207"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.133232"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/1791222"},{"key":"e_1_2_8_19_1","first-page":"1","article-title":"Anti\u2010Inflammatory Effects of Resveratrol in Treating Interstitial Cystitis\/Bladder Pain Syndrome: A Multi\u2010Faceted Approach Integrating Network Pharmacology, Molecular Docking, and Experimental Validation","volume":"1","author":"Li W.","year":"2024","journal-title":"Molecular Diversity"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/scrt190"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600902"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nurt.2006.10.002"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1586\/14737175.9.1.33"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/ane.12920"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1517\/17425255.2014.883378"},{"key":"e_1_2_8_26_1","article-title":"Lacosamide Add\u2010On Therapy for Partial Epilepsy","volume":"6","author":"Weston J.","year":"2015","journal-title":"Cochrane Database of Systematic Reviews"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2016.09.033"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2017.05.031"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc09-1578"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1136\/spcare-2024-005212"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-031-67648-2_37"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.12788\/jcso.0136"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-015-0276-0"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00404-019-05262-1"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.2515\/therapie\/2012012"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2018.08.007"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2012.01.009"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cotox.2017.11.002"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19880201)61:3<451::AID-CNCR2820610308>3.0.CO;2-G"},{"issue":"6","key":"e_1_2_8_40_1","first-page":"45","article-title":"The Pathological Features of Cyclophosphamide Induced Multi\u2010Organs Toxicity in Male Wister Rats","volume":"11","author":"Al\u2010Salih H. 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