title: Effects of Gegen (Puerariae lobatae Radix) water extract on improving detrusor overactivity in spontaneously hypertensive rats.
abstract: OBJECTIVE
  Ex vivo experiments showed that the water extract of Puerariae lobatae Radix (named Gegen in Chinese) induced detrusor relaxation. The aim of this study was to prove the in vivo efficacy of Gegen on improving detrusor overactivity and its possible synergism with darifenacin (a first-line muscarinic receptor-3 inhibitor) in spontaneously hypertensive rats (SHR), a rat model exhibiting symptoms of detrusor overactivity.
  
  
  METHODS
  After daily oral administration of Gegen 30 (Gegen, 30mg/kg); Gegen 300 (Gegen, 300mg/kg); Low_Dar (darifenacin, 3mg/kg); High_Dar (darifenacin, 30mg/kg) Low_Dar+Gegen 30 or High_Dar+Gegen 30 for 3 weeks, bladder detrusor strips of the rats were isolated and assessed with different stimulators for the measurement of tonic and phasic contractile activities (including phasic amplitude and frequency). Modes of stimulation included the use of carbachol, isoprenaline and electrical field stimulation (EFS).
  
  
  RESULTS
  All drug treatments significantly reduced carbachol-stimulated tonic contractile activities, but did not change the phasic amplitude. Meanwhile, the treatments with Gegen 300; Low_Dar; Low_Dar+Gegen 30; and High_Dar+Gegen 30 decreased carbachol-stimulated phasic frequency. Gegen 300 and Low_Dar+Gegen 30 showed stronger potency on lowering EFS-induced responses. Under isoprenaline-induced relaxation, only Gegen 300 significantly enhanced this relaxation by decreasing tonic contraction; Gegen 300; Low_Dar; Low_Dar+Gegen 30; and High_Dar+Gegen 30 increased the reduction of phasic frequency, but all treatment did not alter their phasic amplitude. Combination Index (CI) showed that the combination with Low_Dar and Gegen 30 had very strong synergism (CI <0.1) on inhibiting EFS-induced contractile response.
  
  
  CONCLUSIONS
  Gegen improved detrusor overactivity through neurogenic and anti-muscarinic mechanisms. Gegen and darifenacin together attained synergism for detrusor overactivity treatment via the neurogenic pathway.
authors.affiliation: Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China; State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China.
authors.forename: Xuelin
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China; State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China.
authors.forename: Wai Ping
authors.initials: WP
authors.lastname: Lam
authors.affiliation: Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China; State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China.
authors.forename: Hong Chai
authors.initials: HC
authors.lastname: Tang
authors.affiliation: Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China; State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China.
authors.forename: Chi-Man
authors.initials: CM
authors.lastname: Koon
authors.affiliation: Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China; State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Cheng
authors.affiliation: Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China; State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China.
authors.forename: Clara Bik-San
authors.initials: CB
authors.lastname: Lau
authors.affiliation: School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China. Electronic address: willmann@cuhk.edu.hk.
authors.forename: Willmann
authors.initials: W
authors.lastname: Liang
authors.affiliation: Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China; State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China. Electronic address: pingcleung@cuhk.edu.hk.
authors.forename: Ping-Chung
authors.initials: PC
authors.lastname: Leung
mesh_terms: D000818:Animals; D001572:Benzofurans / Q000494:pharmacology* / Q000627:therapeutic use; D002217:Carbachol / Q000009:adverse effects*; D002681:China; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D018517:Plant Roots / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry; D029908:Pueraria / Q000737:chemistry; D011759:Pyrrolidines / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D011918:Rats, Inbred SHR; D001743:Urinary Bladder / Q000187:drug effects*; D053201:Urinary Bladder, Overactive / Q000139:chemically induced* / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D001572:Benzofurans; D004365:Drugs, Chinese Herbal; D010936:Plant Extracts; D011759:Pyrrolidines; D002217:Carbachol; C101207:darifenacin
keywords: Darifenacin; Detrusor overactivity; Gegen; Puerariae lobatae Radix; Spontaneously hypertensive rat; Synergism