title: Ba-Wei-Die-Huang-Wan (Hachimi-jio-gan) can ameliorate cyclophosphamide-induced ongoing bladder overactivity and acidic adenosine triphosphate solution-induced hyperactivity on rats prestimulated bladder.
abstract: BACKGROUND
  Ba-Wei-Die-Huang-Wan (BWDHW) is the traditional Chinese medicine formula containing eight ingredients, namely Rehmannia glutinosa (Gaetn.) DC., root, steamed & dried; Cornus officinalis Siebold & Zucc., fructus, dried; Dioscorea oppositifolia L., root, dried; Alisma plantago-aquatica, subsp. orientale (Sam.) Sam., tuber, dried; Poria cocos (Fr.) Wolf., sclerotium, dried; Paeonia×suffruticosa Andrews, bark, dried; Cinnamomum cassia (Nees & T.Nees) J. Presl, bark, dried; Aconitum carmichaeli Debeaux, lateral root, dried & processed. It has been used for diabetes and urinary frequency treatments.
  
  
  OBJECTIVE
  We investigate effects of BWDHW on cyclophosphamide (CYP)-induced ongoing bladder overactivity and acidic adenosine triphosphate (ATP) solution-induced hyperactivity on rat's prestimulated bladder.
  
  
  METHODS
  Female Wistar rats were injected with intraperitoneal CYP (100mg/kg) or saline respectively. Rats were treated with BWDHW (90mg/kg/day) or vehicle for the next five days. After treatments animals were evaluated both in metabolic cage model and then by cystometry. Acidic ATP solution (5mM, pH 3.3) was instilled to provoke bladder hyperactivity. Bladder mucosa and muscle proteins were assessed by Western blotting.
  
  
  RESULTS
  As compared to the controls, the CYP group showed significantly decreased mean cystometric intercontractile interval and increased micturition frequency, whereas the CYP/BWDWH group did not. The CYP group had significant protein overexpression in mucosal M2, M3, P2X2, and P2X3 receptors as well as detrusor M2 and M3 receptors. However, the CYP/BWDWH group had insignificant changes from controls. In the provoking test, the control/BWDHW and CYP/BWDHW groups were less affected by acidic ATP stimulation of intercontractile interval changes than the control group. Compared to the control group, the control/BWDHW group showed significantly lower mucosal P2X3 protein expression and the CYP group showed significant mucosal TRPV1 protein upregulation after the provoking test.
  
  
  CONCLUSIONS
  BWDHW treatment can ameliorate CYP-induced ongoing bladder overactivity and suppress mucosal P2X2, P2X3, M2, and M3 receptor protein overexpression, as well as detrusor M2 and M3 receptor protein overexpression. BWDHW pretreatment can reduce acidic ATP solution-provoked hyperactivity by preventing TRPV1 receptor overexpression in CYP-treated bladder mucosa and inhibiting P2X3 receptor overexpression in naïve bladder mucosa.
authors.affiliation: Division of Urology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. Electronic address: dinor666@ms32.hinet.net.
authors.forename: Wei-Chia
authors.initials: WC
authors.lastname: Lee
authors.affiliation: Department of International Business, College of Commerce and Management, Cheng Shiu University, Kaohsiung, Taiwan. Electronic address: angelawu1974@yahoo.com.tw.
authors.forename: Chia-Ching
authors.initials: CC
authors.lastname: Wu
authors.affiliation: Division of Urology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. Electronic address: chuang82@ms26.hinet.net.
authors.forename: Yao-Chi
authors.initials: YC
authors.lastname: Chuang
authors.affiliation: Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. Electronic address: tainyl@hotmail.com.
authors.forename: You-Lin
authors.initials: YL
authors.lastname: Tain
authors.affiliation: Division of Urology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. Electronic address: cphtem@yahoo.com.tw.
authors.forename: Po-Hui
authors.initials: PH
authors.lastname: Chiang
mesh_terms: D000255:Adenosine Triphosphate; D000818:Animals; D003520:Cyclophosphamide; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006863:Hydrogen-Ion Concentration; D008516:Medicine, Chinese Traditional; D009092:Mucous Membrane / Q000187:drug effects / Q000378:metabolism; D008517:Phytotherapy; D017208:Rats, Wistar; D043585:Receptor, Muscarinic M2 / Q000378:metabolism; D043587:Receptor, Muscarinic M3 / Q000378:metabolism; D058476:Receptors, Purinergic P2X2 / Q000378:metabolism; D058477:Receptors, Purinergic P2X3 / Q000378:metabolism; D012996:Solutions; D050916:TRPV Cation Channels / Q000378:metabolism; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D053201:Urinary Bladder, Overactive / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology
chemical_list: D004365:Drugs, Chinese Herbal; D043585:Receptor, Muscarinic M2; D043587:Receptor, Muscarinic M3; D058476:Receptors, Purinergic P2X2; D058477:Receptors, Purinergic P2X3; D012996:Solutions; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; C054591:hachimijiogan; D000255:Adenosine Triphosphate; D003520:Cyclophosphamide
keywords: 5-Hydroxymethylfurfural (PubChem CID: 237332); Ba-Wei-Die-Huang-Wan; Cinnamaldehyde (PubChem CID: 637511); Cinnamic acid (PubChem CID: 444539); Hachimi-jio-gan; Loganin (PubChem CID: 87691); Muscarinic receptors; Overactive bladder; P2X receptor; Paeoniflorin (PubChem CID: 442534); Paeonol (PubChem CID: 11092); TRPV1 receptor