title: Gastrointestinal effect of methanol extract of Radix Aucklandiae and selected active substances on the transit activity of rat isolated intestinal strips.
abstract: BACKGROUND
  Radix Aucklandiae, the dry rhizome of Aucklandia lappa Decne (Asteraceae), enjoyed traditional popularity for its antidiarrheal effects. Although there are many investigations on its chemical constituents and pharmacologic actions, few studies explaining its activity and mechanism in gastrointestinal disorders are available.
  
  
  OBJECTIVE
  In this paper, we focused on the effects of the methanol extract of R. Aucklandiae (RA ext) on gastrointestinal tract, so as to assess some of the possible mechanisms involved in the clinical treatment.
  
  
  METHODS
  In vivo, in neostigmine-induced mice and normal mice, after intragastric administration, RA ext (100, 200, 300, and 400 mg/kg) was studied on gastrointestinal transit including gastric emptying and small intestinal motility. Meanwhile, in vitro, the effect of it (0.1, 0.2, 0.3, and 0.4 mg/mL) on the isolated tissue preparations of rat jejunum was also investigated, as well as costunolide and dehydrocostuslactone which were the main constituents.
  
  
  RESULTS
  In vivo, the gastric emptying increased and intestinal transit decreased after the administration of RA ext in normal mice. However, RA ext inhibited the gastric emptying and the intestinal transit throughout the concentrations in neostigmine-induced mice. In vitro, RA ext caused inhibitory effect on the spontaneous contraction of rat-isolated jejunum in a dose-dependent manner ranging from 0.1 to 0.4 mg/mL, and it also relaxed the acetylcholine chloride (Ach, 10(-5) M), 5-hydroxytryptamine (5-HT, 200 μM)-induced, and K(+) (60 mM)-induced contractions. RA ext shifted the Ca(2+) concentration-response curves to right, similar to that caused by verapamil (0.025 mM). The Ca(2+) concentration-response curves were shifted by costunolide (CO) (5.4, 8.1, and 10.8 μg/mL), dehydrocostuslactone (DE) (4.6, 6.9, and 9.2 μg/mL), costunolide-dehydrocostuslactone (CO-DE) (5.4-4.6, 8.1-6.9, and 10.8-9.2 μg/mL) to the right, similar to that caused by verapamil (0.01 mM).
  
  
  CONCLUSIONS
  These results indicate that RA ext played a spasmolytic role in gastrointestinal motility, which is probably mediated through the inhibition of muscarinic receptors, 5-HT receptors, and calcium influx. The presence of cholinergic and calcium antagonist constituents may be the compatibility of CO and DE. All these results provide a pharmacological basis for its clinical use in the gastrointestinal tract.
authors.affiliation: Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University , Tianjin , China .
authors.forename: Huimin
authors.initials: H
authors.lastname: Guo
authors.forename: Jingze
authors.initials: J
authors.lastname: Zhang
authors.forename: Wenyuan
authors.initials: W
authors.lastname: Gao
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Qu
authors.forename: Changxiao
authors.initials: C
authors.lastname: Liu
mesh_terms: D000818:Animals; D019659:Asteraceae / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005746:Gastric Emptying / Q000187:drug effects*; D005769:Gastrointestinal Motility / Q000187:drug effects; D005772:Gastrointestinal Transit / Q000187:drug effects*; D007583:Jejunum / Q000187:drug effects; D007783:Lactones / Q000302:isolation & purification / Q000494:pharmacology; D008297:Male; D000432:Methanol / Q000737:chemistry; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D010276:Parasympatholytics / Q000494:pharmacology; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D027343:Rhizome; D012717:Sesquiterpenes / Q000302:isolation & purification / Q000494:pharmacology
chemical_list: D007783:Lactones; D010276:Parasympatholytics; D010936:Plant Extracts; D012717:Sesquiterpenes; C083030:dehydrocostus lactone; C002602:costunolide; D000432:Methanol
keywords: Cholinergic and calcium antagonist; gastric emptying; intestinal smooth muscle; small intestinal motility