{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T02:13:25Z","timestamp":1790129605405,"version":"4.0.1"},"reference-count":49,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,5,30]],"date-time":"2023-05-30T00:00:00Z","timestamp":1685404800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"King Saud University, Riyadh, Saudi Arabia","award":["RSP2023R457"],"award-info":[{"award-number":["RSP2023R457"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Apigenin is a phytochemical obtained from Chamomilla recutita. Its role in interstitial cystitis is not yet known. The present study is aimed at understanding the uroprotective and spasmolytic effects of apigenin in cyclophosphamide-induced interstitial cystitis. The uroprotective role of apigenin was analyzed by qRT-PCR, macroscopic analysis, Evans blue dye leakage, histological evaluation, and molecular docking. The spasmolytic response was measured by adding cumulative concentrations of apigenin to isolated bladder tissue pre-contracted with KCl (80 mM) and carbachol (10\u22129\u201310\u22124) on non-incubated and pre-incubated tissues with atropine, 4DAMP, methoctramine, glibenclamide, barium chloride, nifedipine, indomethacin, and propranolol. Apigenin inhibited pro-inflammatory cytokines (IL-6, TNF-\u03b1 and TGF 1-\u03b2) and oxidant enzymes (iNOS) while increasing antioxidant enzymes (SOD, CAT, and GSH) in CYP-treated groups compared to the control. Apigenin restored normal tissue of the bladder by decreasing pain, edema, and hemorrhage. Molecular docking further confirmed the antioxidant and anti-inflammatory properties of apigenin. Apigenin produced relaxation against carbachol-mediated contractions, probably via blockade of M3 receptors, KATP channels, L-type calcium channels, and prostaglandin inhibition. While the blockade of M2 receptors, KIR channels, and \u03b2-adrenergic receptors did not contribute to an apigenin-induced spasmolytic effect, apigenin presented as a possible spasmolytic and uroprotective agent with anti-inflammatory, antioxidant effects by attenuating TGF-\u03b2\/iNOS-related tissue damage and bladder muscle overactivity. Thus, it is a potential agent likely to be used in treatment of interstitial cystitis.<\/jats:p>","DOI":"10.3390\/ph16060811","type":"journal-article","created":{"date-parts":[[2023,5,31]],"date-time":"2023-05-31T04:40:51Z","timestamp":1685508051000},"page":"811","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Spasmolytic and Uroprotective Effects of Apigenin by Downregulation of TGF-\u03b2 and iNOS Pathways and Upregulation of Antioxidant Mechanisms: In Vitro and In Silico Analysis"],"prefix":"10.3390","volume":"16","author":[{"given":"Saima","family":"Saima","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy, The University of Lahore, Lahore 54000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5884-8950","authenticated-orcid":false,"given":"Irfan","family":"Anjum","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy, The University of Lahore, Lahore 54000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aisha","family":"Mobashar","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy, The University of Lahore, Lahore 54000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1730-5025","authenticated-orcid":false,"given":"Shah","family":"Jahan","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Health Sciences Lahore, Lahore 54600, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2588-7037","authenticated-orcid":false,"given":"Saima","family":"Najm","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Lahore College of Pharmaceutical Sciences, Lahore 54000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiba-Allah","family":"Nafidi","sequence":"additional","affiliation":[{"name":"Department of Food Science, Faculty of Agricultural and Food Sciences, Laval University, Quebec City, QC G1V 0A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3302-4036","authenticated-orcid":false,"given":"Yousef A.","family":"Bin Jardan","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11481, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3707-8461","authenticated-orcid":false,"given":"Mohammed","family":"Bourhia","sequence":"additional","affiliation":[{"name":"Laboratory of Chemistry and Biochemistry, Faculty of Medicine and Pharmacy, Ibn Zohr University, Laayoune 70000, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.urology.2008.07.031","article-title":"Multiplex analysis of urinary cytokine levels in rat model of cyclophosphamide-induced cystitis","volume":"73","author":"Smaldone","year":"2009","journal-title":"Urology"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Chung, J.W., Chun, S.Y., Lee, E.H., Ha, Y.S., Lee, J.N., Song, P.H., Yoo, E.S., Kwon, T.G., Chung, S.K., and Kim, B.S. 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