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.
OBJECTIVE
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.
Imamura
Tetsuya
T
Department of Urology, Shinshu University School of Medicine, Matsumoto, Japan. imatetu@shinshu-u.ac.jp
Ishizuka
Osamu
O
Zhong
Chen
C
Ogawa
Teruyuki
T
Nakayama
Tsuyoshi
T
Kurizaki
Yoshiki
Y
Tanabe
Tomoaki
T
Nishizawa
Osamu
O
Andersson
Karl-Erik
KE
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000284:Administration, Oral; D000818:Animals; D004195:Disease Models, Animal; D015536:Down-Regulation; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D007150:Immunohistochemistry; D015288:Neurokinin A / Q000378:metabolism; D015287:Neurokinin B / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D018048:Receptors, Purinergic P2 / Q000235:genetics / Q000378:metabolism*; D058477:Receptors, Purinergic P2X3; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013373:Substance P / Q000378:metabolism; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism*; D015320:Tachykinins / Q000235:genetics / Q000378:metabolism*; D001743:Urinary Bladder / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D053201:Urinary Bladder, Overactive / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D014554:Urination / Q000187:drug effects
D004365:Drugs, Chinese Herbal; C544609:HARNCARE; C546410:P2rx3 protein, rat; D012333:RNA, Messenger; D018048:Receptors, Purinergic P2; D058477:Receptors, Purinergic P2X3; D050916:TRPV Cation Channels; D015320:Tachykinins; C493922:Trpv1 protein, rat; D013373:Substance P; D015288:Neurokinin A; D015287:Neurokinin B; D000255:Adenosine Triphosphate