Ba-Wei-Di-Huang-Wan through its active ingredient loganin counteracts substance P-enhanced NF-κB/ICAM-1 signaling in rats with bladder hyperactivity.
Overt bladder afferent activation may exacerbate endogenous substance P (SP) release to induce intercellular adhesion molecule-1 (ICAM-1)-mediated inflammation and reactive oxygen species (ROS) production leading to hyperactive bladder. Ba-Wei-Die-Huang-Wan (BWDHW), a traditional Chinese medicine, has been used to treat lower urinary tract symptoms in patients by undefined mechanisms. We explored the possible mechanisms and the active components of BWDHW on exogenous SP-induced bladder hyperactivity. BWDHW contained six major components: loganin, paeoniflorin, 5-hydroxymethylfurfural, cinnamic acid, cinnamaldehyde, and paeonol by high-performance liquid chromatography. In urethane-anesthetized female Wistar rats, we evaluated transcystometrogram, pelvic afferent nerve activity by electrophysiologic recording techniques, ICAM-1 expression by Western blot and immunohistochemistry, ROS amount by an ultrasensitive chemiluminescence method and possible ROS sources from the different leukocytes by specific stains in SP-treated bladder. BWDHW and its major component loganin dose-dependently inhibited H2 O2 and HOCl activity in vitro. Intragastrical BWDHW (250 mg/kg) and loganin (5 mg/kg) twice daily for 2 weeks did not affect the baseline micturition parameters. Intra-arterial SP (20 µg/rat) through neurokinin-1 receptor activation increased voiding frequency (shortened intercontraction intervals), pelvic afferent nerve activity, bladder NF-κB/ICAM-1 expression, bladder ROS amount, neutrophils adhesion to venous endothelium, CD68 (monocyte/macrophage), and mast cell infiltration in the inflamed bladder. BWDHW and loganin pretreatment significantly depressed SP-enhanced pelvic afferent nerve activity, bladder NF-κB/ICAM-1 expression, leukocyte infiltration, and ROS amount, and subsequently improved bladder hyperactivity. In conclusion, our results suggest that BWDHW and its active component loganin improves bladder hyperactivity via inhibiting SP/neurokinin-1 receptor signaling and depressing NF-κB/ICAM-1 mediated oxidative injury and inflammation. Neurourol. Urodynam. 35:771-779, 2016. © 2015 Wiley Periodicals, Inc.
Department of Life Science, National Taiwan Normal University, Taipei, Taiwan.|Department of Traditional Chinese Medicine, Taipei City Hospital Linsen (Chinese Medicine) Branch, Taipei, Taiwan.
Wen-Hsin
WH
Tsai
Department of Life Science, National Taiwan Normal University, Taipei, Taiwan.
Chung-Hsin
CH
Wu
Department of Traditional Chinese Medicine, Taipei City Hospital Linsen (Chinese Medicine) Branch, Taipei, Taiwan.
Chen-Hung
CH
Cheng
Department of Life Science, National Taiwan Normal University, Taipei, Taiwan.
Chiang-Ting
CT
Chien
D000818:Animals; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005260:Female; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D039823:Iridoids / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013373:Substance P / Q000494:pharmacology*; D053201:Urinary Bladder, Overactive / Q000378:metabolism*; D014554:Urination / Q000187:drug effects*
D004365:Drugs, Chinese Herbal; D039823:Iridoids; D016328:NF-kappa B; D017382:Reactive Oxygen Species; C054591:hachimijiogan; D018799:Intercellular Adhesion Molecule-1; D013373:Substance P; C059516:loganin
Ba-Wei-Die-Huang-Wan; inflammation; loganin; overactive bladder; substance P