{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T23:56:09Z","timestamp":1790034969036,"version":"4.0.1"},"reference-count":43,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2016,2,1]],"date-time":"2016-02-01T00:00:00Z","timestamp":1454284800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"National Science Council of the Republic of China","award":["NSC98-2320-B002-043-MY3"],"award-info":[{"award-number":["NSC98-2320-B002-043-MY3"]}]},{"name":"National Science Council of the Republic of China","award":["NSC98-2314-B-214-001-MY3"],"award-info":[{"award-number":["NSC98-2314-B-214-001-MY3"]}]},{"name":"Taipei City Hospital","award":["TCH103-66"],"award-info":[{"award-number":["TCH103-66"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neurourology and Urodynamics"],"published-print":{"date-parts":[[2017,2]]},"abstract":"<jats:sec><jats:label\/><jats:p><jats:bold>Aims:<\/jats:bold> Upregulation of substance P (SP) and neurokinin\u20101 receptor (NK1R) activation induces pro\u2010inflammatory bladder hyperactivity through the PKC\/ERK\/NF\u2010\u03baB\/ICAM\u20101\/IL\u201033 signaling pathways to increase the leukocyte infiltration and adhesion leading to reactive oxygen species (ROS) production, autophagy, and apoptosis. <jats:sc>l<\/jats:sc>\u2010Theanine is a unique non\u2010protein\u2010forming amino acid present in tea (<jats:italic>Camellia sinensis<\/jats:italic> [L.] O. Kuntze) with its antioxidant, anti\u2010inflammatory, and relaxation effects to improve cognition, mood, gastric ulcer injury, and cerebral ischemia\/reperfusion injury, and posttraumatic stress disorder. We explored the protective effect of <jats:sc>l<\/jats:sc>\u2010theanine on SP\u2010induced bladder hyperactivity.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> In urethane\u2010anesthetized female Wistar rats, we explored the transcystometrogram, pelvic nerve activity, proinflammatory PKC\/ERK\/NF\u2010\u03baB\/ICAM\u20101\/IL\u201033 signaling, apoptosis\u2010related Caspase 3\/poly\u2010(ADP\u2010ribose)\u2010polymerase (PARP), and autophagy\u2010mediated LC3 II expression by Western blot, electrophoretic\u2010mobility shift assay and immunohistochemistry, bladder ROS amount by a ultrasensitive chemiluminescence method, and possible ROS sources from the different leukocytes by specific stains in SP\u2010evoked hyperactive bladder.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> <jats:sc>l<\/jats:sc>\u2010Theanine dose\u2010dependently depressed H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> and HOCl activity in vitro. In urethane\u2010anesthetized female Wistar rats, intra\u2010arterial SP through NK1R activation increased voiding frequency (shortened intercontraction intervals) associated with the increase in bladder nerve activity, proinflammatory PKC\/ERK\/NF\u2010\u03baB\/ICAM\u20101\/IL\u201033 signaling, Caspase 3\/PARP\u2010mediated apoptosis, LC3 II\u2010mediated autophagy, ROS amount, neutrophils adhesion, CD68 (monocyte\/macrophage) infiltration, and mast cells degranulation in the hyperactive bladder. Intragastrical <jats:sc>l<\/jats:sc>\u2010theanine (15\u2009mg\/kg) twice daily for 2 weeks efficiently ameliorated all the enhanced parameters in the SP\u2010treated hyperactive bladder.<\/jats:p><jats:p><jats:bold>Conclusions:<\/jats:bold> In conclusion, <jats:sc>l<\/jats:sc>\u2010theanine through antioxidant and anti\u2010inflammatory actions ameliorates SP\u2010induced bladder hyperactivity via the inhibition of proinflammatory PKC\/ERK\/NF\u2010\u03baB\/ICAM\u20101\/IL\u201033 signaling, oxidative stress, bladder nerve hyperactivity, apoptosis, and autophagy. <jats:italic>Neurourol. Urodynam. 36:297\u2013307, 2017<\/jats:italic>. \u00a9 2016 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/nau.22965","type":"journal-article","created":{"date-parts":[[2016,2,1]],"date-time":"2016-02-01T17:32:00Z","timestamp":1454347920000},"page":"297-307","source":"Crossref","is-referenced-by-count":28,"title":["<scp>l<\/scp>\u2010Theanine inhibits proinflammatory PKC\/ERK\/ICAM\u20101\/IL\u201033 signaling, apoptosis, and autophagy formation in substance P\u2010induced hyperactive bladder in rats"],"prefix":"10.1002","volume":"36","author":[{"given":"Wen\u2010Hsin","family":"Tsai","sequence":"first","affiliation":[{"name":"Department of Life Science National Taiwan Normal University Taipei Taiwan"},{"name":"Department of Traditional Chinese Medicine Taipei City Hospital Linsen (Chinese Medicine) Branch Taipei 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