title: Study of the mechanisms of a Japanese traditional fermented medicine in the improvement of constipation.
abstract: OBJECTIVE
  Gut Working Tablet (GWT) is a Japanese traditional fermented medicine based on Aspergillus oryzae NK-fermented grain germ. Although GWT has been used by patients with constipation, the mechanism has not been investigated. The aim of this study was to examine the possible mechanisms of the effect of GWT on constipation.
  
  
  METHODS
  The effect of GWT water extracts on gut contractility using ileum strips from guinea pig and on the growth of Bifidobacterium longum were examined in vitro. The 14 Sprague Dawley rats were administered loperamide at 10 mg/day per kg for 3 days. They were fed with and without 5% of GWT before and during administration of loperamide. Number of stools and weight of feces were measured before and during administration of loperamide. The concentrations of short-chain fatty acids (SCFAs) in the feces and cecal contents were measured by gas chromatography.
  
  
  RESULTS
  GWT water extracts dose-dependently induced ileal contractile responses, which were inhibited by atropine. The growth of B. longum was increased in the presence of GWT water extracts in a dose-dependent manner (P < 0.01 vs control). The decrease in both the number and weight of feces caused by loperamide was improved by GWT administration (P < 0.05 vs loperamide). The decrease in the butyric acid concentration in feces and cecal contents induced by the administration of loperamide was inhibited by GWT (P = 0.035 and 0.018).
  
  
  CONCLUSIONS
  GWT water extracts may induce cholinergic-like stimulation and promote the growth of probiotics. Furthermore, GWT water extract contributed to normalization of colonic SCFAs. These results may explain, at least in part, the beneficial effects of GWT on constipation.
authors.affiliation: Department of Gastroenterology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Shimoyama
authors.forename: Ryoki
authors.initials: R
authors.lastname: Takahashi
authors.forename: Moto
authors.initials: M
authors.lastname: Kimura
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Fukuda
mesh_terms: D000818:Animals; D001236:Aspergillus oryzae; D020148:Butyric Acid / Q000378:metabolism; D003248:Constipation / Q000628:therapy*; D004305:Dose-Response Relationship, Drug; D005227:Fatty Acids / Q000378:metabolism; D005243:Feces / Q000737:chemistry; D005285:Fermentation; D005766:Gastrointestinal Contents / Q000187:drug effects; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D007564:Japan; D008139:Loperamide / Q000037:antagonists & inhibitors; D008297:Male; D008519:Medicine, Traditional; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D056692:Prebiotics; D019936:Probiotics / Q000494:pharmacology* / Q000627:therapeutic use*; D017207:Rats, Sprague-Dawley; D013268:Stimulation, Chemical
chemical_list: D005227:Fatty Acids; D056692:Prebiotics; D020148:Butyric Acid; D008139:Loperamide
keywords: Gut Working Tablet; constipation; loperamide; short-chain fatty acids; traditional medicine