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The present study aimed to investigate the potential of aqueous ethanol extract of <jats:italic>Cuminum cyminum<\/jats:italic> (AEECC) on oxidative stress, inflammation and overactivity of urinary bladder induced by cyclophosphamide (CYP). Female Sprague\u2010Dawley rats received intraperitoneal administration of cyclophosphamide (150\u2005mg\/kg, <jats:italic>i.\u2009p<\/jats:italic>. 1<jats:sup>st<\/jats:sup>, 4<jats:sup>th<\/jats:sup>, and 7<jats:sup>th<\/jats:sup> days). To investigate the urothelial damage, the bladder weight, nociception behavior, and Evans blue dye extravasation method was used. The antioxidants CAT, GPX and NO were measured. ELISA determined the IL\u20106 and TNF\u2010\u03b1 levels. The spasmolytic effect of AEECC was investigated on isolated bladder strips and its mechanisms were determined. The enhanced nociception behavior, bladder weight, vascular permeability, edema, hemorrhage, nitric oxide, IL\u20106 and TNF\u2010\u03b1 levels by CYP administration were significantly reduced by AEECC (250 and 500\u2005mg\/kg). A significant increase in serum antioxidant system such as CAT and GPx was also observed in AEECC\u2010treated rats. The AEECC (3\u2005mg\/ml) significantly reduced urinary bladder tone in the strips pre\u2010contracted with carbachol in both control and CYP\u2010treated rats. This relaxation was demolished by atropine, nifedipine, glibenclamide, and indomethacin but not with propranolol. The plant extract showed the presence of antioxidant and anti\u2010inflammatory phytochemicals. These results suggest that <jats:italic>Cuminum cyminum<\/jats:italic> offers uroprotective activity and can ameliorate CYP\u2010induced bladder toxicity by modulating antioxidant parameters, pro\u2010inflammatory cytokine levels and bladder smooth muscle overactivity. The <jats:italic>in silico<\/jats:italic> binding interactions of antioxidant 2I3Y and anti\u2010inflammatory protein 1TNF with various ligands from <jats:italic>Cuminum cyminum<\/jats:italic> seeds revealed potential bioactive compounds with promising antioxidant and anti\u2010inflammatory properties, providing valuable insights for drug development and nutraceutical research.<\/jats:p>","DOI":"10.1002\/cbdv.202301268","type":"journal-article","created":{"date-parts":[[2023,10,16]],"date-time":"2023-10-16T12:28:25Z","timestamp":1697459305000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["<i>Cuminum cyminum<\/i> Ameliorates Urotoxic Effects of Cyclophosphamide by Modulating Antioxidant, Inflammatory Cytokines, and Urinary Bladder Overactivity: <i>In vivo<\/i> and <i>in Silico<\/i> Investigations"],"prefix":"10.1002","volume":"20","author":[{"given":"Irfan","family":"Anjum","sequence":"first","affiliation":[{"name":"Department of Basic Medical Sciences, Shifa College of Pharmaceutical Sciences Shifa Tameer-e-Millat University  Islamabad 44000 Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daanyaal","family":"Ali","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy The University of Lahore  Lahore 54590 Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3707-8461","authenticated-orcid":false,"given":"Mohammed","family":"Bourhia","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Faculty of Medicine and Pharmacy Ibn Zohr University  Laayoune 70000 Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mueen Ahmad","family":"Chaudhry","sequence":"additional","affiliation":[{"name":"Allied College of Health Sciences  Multan 60000 Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farhan","family":"Siddique","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Science and Technology Tianjin University  Tianjin 300072 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehvish","family":"Bibi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy Bahauddin Zakariya University  Multan 60800 Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdel\u2010Rhman Z.","family":"Gaafar","sequence":"additional","affiliation":[{"name":"Department of Botany and Microbiology, College of Science King Saud University, P.O. 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