{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T15:25:28Z","timestamp":1773069928579,"version":"3.50.1"},"reference-count":33,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2019,9,20]],"date-time":"2019-09-20T00:00:00Z","timestamp":1568937600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Chang Gung Medical Fundation","award":["CMRPG8F0053"],"award-info":[{"award-number":["CMRPG8F0053"]}]},{"name":"Chang Gung Medical Fundation","award":["CMRPG8F1211"],"award-info":[{"award-number":["CMRPG8F1211"]}]},{"name":"Chang Gung Medical Fundation","award":["CMRPG8G1461"],"award-info":[{"award-number":["CMRPG8G1461"]}]},{"name":"Chang Gung Medical Fundation","award":["CMRPG8J0451"],"award-info":[{"award-number":["CMRPG8J0451"]}]},{"name":"The Ministry of Science and Technology of the Republic of China","award":["MOST104-2314-B-182A-081"],"award-info":[{"award-number":["MOST104-2314-B-182A-081"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neurourology and Urodynamics"],"published-print":{"date-parts":[[2019,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>We investigated the effects of Ba\u2010Wei\u2010Die\u2010Huang\u2010Wan (BWDHW) on ketamine\u2010induced cystitis (KIC) in a rat model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Female Sprague\u2010Dawley rats were distributed into three groups: control (saline), ketamine (25\u2009mg\/kg\/day for 28 days), or ketamine (25\u2009mg\/kg\/day for 28 days) plus BWDHW (90\u2009mg\/kg\/day, started from day 14). Functional magnetic resonance imaging (fMRI), metabolic cage study, and cystometry were evaluated. Bladder histology was evaluated. Western blots of the bladder proteins were carried out.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared with controls, ketamine\u2010treated rats showed stronger fMRI intensity in the periaqueductal gray area and bladder overactivity in the bladder functional study, but the ketamine\/BWDHW\u2010treated rats did not. Furthermore, ketamine breached the uroplakin III membrane at the apical surface of the urothelium, enhanced substance P spread over the urothelium, induced suburothelial hemorrhage and monocyte\/macrophage infiltration, and caused interstitial fibrosis deposition. By contrast, the BWDHW\u2010treated rats exhibited less substance P spread, lower suburothelial monocyte\/macrophage infiltration, and lower interstitial fibrosis deposition. The ketamine group showed significant overexpression of neuroreceptors in the bladder mucosa (the transient receptor potential vanilloid 1 and M<jats:sub>2<\/jats:sub>\u2010 and M<jats:sub>3<\/jats:sub>\u2010muscarinic receptors) and detrusor (M<jats:sub>2<\/jats:sub>\u2010 and M<jats:sub>3<\/jats:sub>\u2010muscarinic receptors); inflammatory mediators in the detrusor (interleukin\u20101\u03b2 [IL\u20101\u03b2], IL\u20106, tumor necrosis factor\u2010\u03b1, nuclear factor\u2010\u03baB, cyclooxygenase\u20102, and intercellular adhesion molecule\u20101); and fibrogenesis molecules in the detrusor (transforming growth factor\u2010\u03b21, collagen I, collagen III, and fibronectin). However, no significant changes were noted between the ketamine\/BWDHW and control groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>BWDHW could exert therapeutic effects by inhibiting the upregulation of neuroreceptors, modulating inflammatory mediators, suppressing fibrogenesis, and ameliorating bladder overactivity in rats with KIC.<\/jats:p><\/jats:sec>","DOI":"10.1002\/nau.24165","type":"journal-article","created":{"date-parts":[[2019,9,21]],"date-time":"2019-09-21T05:06:06Z","timestamp":1569042366000},"page":"2159-2169","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Ba\u2010Wei\u2010Die\u2010Huang\u2010Wan (Hachimi\u2010jio\u2010gan) can ameliorate ketamine\u2010induced cystitis by modulating neuroreceptors, inflammatory mediators, and fibrogenesis in a rat 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