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

• Published in: Neurourology and urodynamics Vol. 28; no. 6; pp. 529 - 534
• Main Authors: Imamura, Tetsuya, Ishizuka, Osamu, Zhong, Chen, Ogawa, Teruyuki, Nakayama, Tsuyoshi, Kurizaki, Yoshiki, Tanabe, Tomoaki, Nishizawa, Osamu, Andersson, Karl-Erik
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01-01-2009
• Subjects: Adenosine Triphosphate - metabolism; Administration, Oral; Animals; detrusor overactivity; Disease Models, Animal; Down-Regulation; Drugs, Chinese Herbal - administration & dosage; Drugs, Chinese Herbal - pharmacology; Female; Hypertension - complications; Hypertension - drug therapy; Hypertension - metabolism; Hypertension - physiopathology; Immunohistochemistry; Neurokinin A - metabolism; Neurokinin B - metabolism; P2X3 receptor; Rats; Rats, Inbred SHR; Receptors, Purinergic P2 - genetics; Receptors, Purinergic P2 - metabolism; Receptors, Purinergic P2X3; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - metabolism; SHR; Substance P - metabolism; tachykinins; Tachykinins - genetics; Tachykinins - metabolism; THC-002; TRPV Cation Channels - genetics; TRPV Cation Channels - metabolism; TRPV1 receptor; urinary bladder; Urinary Bladder - drug effects; Urinary Bladder - metabolism; Urinary Bladder - physiopathology; Urinary Bladder, Overactive - etiology; Urinary Bladder, Overactive - metabolism; Urinary Bladder, Overactive - physiopathology; Urinary Bladder, Overactive - prevention & control; Urination - drug effects
• ISSN: 0733-2467; 1520-6777
• DOI: 10.1002/nau.20702

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. Neurourol. Urodyn. 28:529–534, 2009. © 2009 Wiley‐Liss, Inc.