Therapeutic Potential of Traditional Chinese Medicine on Overactive Bladder

Substance P (SP) through its neurokinin-1 receptor (NK1R) may increase oxidative stress and inflammation. Upregulation of SP and NK1R activation induces proinflammatory bladder hyperactivity through the PKC/ ERK/NF-κB/ICAM-1/IL-33 signaling pathways to increase the leukocyte infiltration and adhesion leading to reactive oxygen species (ROS) production, autophagy and apoptosis. According to Jin Kui Yao Lue (Prescriptions from the Golden Cabinet), a classic traditional Chinese medicine (TCM) clinical book, Shen Qi Wan could be used to treat people suffering had recorded that Shen Qi Wan could be used to treat people suffering from abnormal diabetes-like thirst, urinary frequency, and polyuria because of excessive water intake, and large amount of urine output. Ba-Wei-Di-Huang-Wan (BWDHW), known as Shen Qi Wan, is composed of eight herbal extracts. L-theanine is a unique non-protein-forming amino acid present in tea [Camellia sinensis (L.) O. Kuntze] and known for its antioxidant, anti-inflammatory and relaxation effects to improve cognition, mood, gastric ulcer injury, and cerebral ischemia/reperfusion injury, and posttraumatic stress disorder. We discussed the protective effects of BWDHW or L-theanine on SP-induced bladder hyperactivity. In urethane-anesthetized female Wistar rats, we explored the transcystometrogram, pelvic nerve activity, proinflammatory PKC/ERK/NF-κB/ICAM-1/IL-33 signaling, apoptosis-related Caspase 3/ poly-(ADP-ribose)- polymerase (PARP) and autophagy-mediated LC3 II expression by western blot, electrophoretic-mobility 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-evoked hyperactive bladder. BWDHW or L-Theanine dose-dependently depressed H_2O_2 and HOCl activity in vitro. In urethane-anesthetized female Wistar rats, intraarterial SP through NK1R activation increased voiding frequency (shortened intercontraction intervals) associated with the increase in bladder nerve activity, proinflammatory PKC/ERK/NF-κB/ICAM-1/IL-33 signaling, Caspase 3/ PARP-mediated apoptosis, LC3 II-mediated autophagy, ROS amount, neutrophils adhesion, CD68 (monocyte/ macrophage) infiltration and mast cells degranulation in the hyperactive bladder. Intragastrical BWDHW or Ltheanine twice daily for two weeks efficiently improved all the enhanced parameters in the SP-treated hyperactive bladder. In conclusion, BWDHW or L-theanine through antioxidant and anti-inflammatory actions improves SP-induced bladder hyperactivity via the inhibition of proinflammatory PKC/ERK/NF-κB/ICAM-1/IL-33 signaling, oxidative stress, bladder nerve hyperactivity, apoptosis and autophagy.

並列關鍵字

traditional Chinese medicine ； Ba-Wei-Di- Huang-Wan ； L-theanine ； overactive bladder ； inflammation ； reactive oxygen species ； autophagy ； apoptosis

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