An extract (THC-002) of Ba-Wei-Die-Huang-Wan inhibits expression of tachykinins, and P2X3 and TRPV1 receptors, and inhibits ATP-induced detrusor overactivity in spontaneously hypertensive rats.

AIMS: To investigate possible mechanisms of action of THC-002 (HARNCARE), a galenical produced from the traditional Chinese herbal mixture Ba-Wei-Die-Huang-Wan, which has been reported to improve lower urinary tract symptoms (LUTS) in patients. METHODS: Forty-five female SHRs were randomly separated into three groups. Two groups were given 20 ml physiological saline solution (PSS) per kg-body weight orally daily for 1 week. An hour after the administration of PSS, one of the groups received 20 mg THC-002 per kg body weight, and the other a similar volume of THC-002-free saline. The third group received no treatments. The bladders were analyzed by real time RT-PCR (n = 6) and immunohistochemistry (n = 3) for the expression of tachykinins and P2X3 and TRPV1 receptors. Cystometric investigation (n = 6) was conducted after intravesical instillation of saline followed by 5 mg/ml ATP solution. RESULTS: Treatment with PSS caused and upregulation of tachykinins and P2X3 and TRPV1 receptors, which was prevented in the group treated with THC-002. In the normal (non-treated) and non-THC-002-treated SHRs, instillation of the ATP solution decreased voiding interval, micturition volume, and bladder capacity compared to the instillation of saline. However, in the THC-002-treated SHRs, ATP instillation had no effect. CONCLUSIONS: In SHRs, THC-002 reduced the bladder expression of tachykinins and P2X3 and TRPV1 receptors, and inhibited ATP-induced detrusor overactivity. These effects may explain part of its beneficial effects on LUTS.

Gosha-jinki-gan reduces transmitter proteins and sensory receptors associated with C fiber activation induced by acetic acid in rat urinary bladder.

AIM: We determined if Gosha-jinki-gan, a traditional Chinese herbal mixture, reduced the presence of the tachykinins neurokinin A, neurokinin B, and substance P, as well as the transient receptor potential vanilloid 1 (TRPV1) and P2X3 purine receptors that are functionally associated with C fibers in the urinary bladder. METHODS: Thirty-six female rats were fed with either a standard diet or one supplemented with 1.08% Gosha-jinki-gan. After 4 weeks, the urinary bladders were instilled with either saline or 0.1% acetic acid. After 30 min, the bladders were removed and expression of the tachykinins and the TRPV1 and P2X3 receptors was determined by immunohistochemistry and mRNA expression. RESULTS: In rats fed with the standard diet, the tachykinins and the TRPV1 and P2X3 receptors expressed nearby or within urothelium of the acetic acid-treated rats increased compared with the saline-instilled rats. In rats pretreated with Gosha-jinki-gan, the tachykinins and the TRPV1 and P2X3 receptors in the acetic acid-treated rats also increased compared with the saline-instilled rats. However, with the instillation of acetic acid, the tachykinins and the TRPV1 and P2X3 receptors of Gosha-jinki-gan pretreated rats decreased compared with standard diet fed rats. The mRNA expression levels of neurokinin A, substance P, and the TRPV1 receptor in acetic acid-treated Gosha-jinki-gan pretreated rats were lower than that in acetic acid-treated standard diet fed rats. Gosha-jinki-gan did not destroy nerve fibers within the bladders. CONCLUSIONS: Gosha-jinki-gan partially reduced the tachykinins and TRPV1 and P2X3 purine receptors without destroying the nerve fibers.

Effects of goshajinkigan (niu-che-sen-qi-wan) for resiniferatoxin-sensitive afferents on detrusor overactivity induced by acetic acid in conscious rats.

This study was performed to investigate the effects of goshajinkigan, a traditional Chinese herbal mixture, in conscious rats undergoing continuous cystometry. Systemic resiniferatoxin (RTX) pretreatment can block resiniferatoxin-sensitive (C-fiber) nerve-mediated bladder overactivity, such as that induced by intravesical administration of acetic acid. The effects of pretreatment with goshajinkigan and RTX alone or in combination on acetic acid-induced bladder overactivity in conscious rats were also compared. Female SD rats were divided into four groups. Groups 1 and 3 received normal food for 4 weeks, while groups 2 and 4 received goshajinkigan (0.09 g/kg/day) during the same period. Two days after bladder catheterization, groups 3 and 4 received RTX (0.3 mg/kg) injection, while groups 1 and 2 received vehicle alone. Cystometric investigations were performed on all animals 24 hours after RTX or vehicle injection. The effects of intravesical instillation of acetic acid (pH = 4.0) were compared with those of intravesical saline. Goshajinkigan significantly increased threshold pressure, voiding interval, micturition volume, and bladder capacity. Intravesical instillation of acetic acid induced bladder overactivity in both normal rats and in those pretreated with goshajinkigan. However, the effects of acetic acid on voiding interval and micturition volume were significantly different between rats given normal diet and those pretreated with goshajinkigan. The effect of acetic acid was not different between goshajinkigan- and RTX-pretreated rats. The results of the present study indicated that goshajinkigan increases voiding interval, micturition volume, and bladder capacity, and pretreatment with goshajinkigan partially blocks the bladder overactivity induced by intravesical administration of acetic acid in rats.