title: Activation of M3 muscarinic receptor and Ca²⁺ influx by crude fraction from Crotonis Fructus in isolated rabbit jejunum.
abstract: BACKGROUND
  Crotonis Fructus is the mature fruit of Croton tiglium L. (Euphorbiaceae), which has been used in traditional Chinese medicine for the treatment of gastrointestinal (GI) diseases, such as constipation, abdominal pain, peptic ulcer, and intestinal inflammation for thousands of years. The aim of this study was to investigate the pharmacological effect of extracts and fractions from Crotonis Fructus on GI tract.
  
  
  METHODS
  The activities of methanol extract and fractions from Crotonis Fructus on the smooth muscle contractions were evaluated using isolated rabbit jejunum model.
  
  
  RESULTS
  The results suggest that the n-BuOH and H(2)O fractions showed spasmolytic activity, while the MeOH extract, PE and EtOAc fractions exerted spasmogenic effect. Moreover, bioassay-guided fractionation verified that the EtOAc fraction was more potent than others, followed by PE fraction and methanol extract. Additionally, atropine (10μM), 4-DAMP (10μM) and verapamil (0.1μM) produced a significant inhibition of contractions caused by EtOAc fraction, while either hexamethonium (10μM) or methoctramine (10μM) was inactive. Additionally, a HPLC fingerprint of EtOAc fraction was appraised to ensure its chemical consistency and the main component has been identified as phorbol 12-acetate-13-tiglate.
  
  
  CONCLUSIONS
  These data indicate that the regulatory effect of EtOAc fraction on GI motility are medicated via the activation of M3 muscarinic receptor and Ca(2+) influx through L-type Ca(2+) channel. These provide a scientific basis for the traditional use of Crotonis Fructus in GI disorders.
authors: Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China.
authors: Jing
authors: J
authors: Hu
authors: Wen-Yuan
authors: WY
authors: Gao
authors: Lin
authors: L
authors: Ma
authors: Shu-Li
authors: SL
authors: Man
authors: Lu-Qi
authors: LQ
authors: Huang
authors: Chang-Xiao
authors: CX
authors: Liu
mesh_terms: D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D029802:Croton / Q000737:chemistry; D005260:Female; D005638:Fruit / Q000737:chemistry; D066298:In Vitro Techniques; D007583:Jejunum / Q000187:drug effects* / Q000502:physiology; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D010880:Piperidines / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology*; D011817:Rabbits; D043587:Receptor, Muscarinic M3 / Q000037:antagonists & inhibitors / Q000502:physiology*; D012997:Solvents / Q000737:chemistry; D014700:Verapamil / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D018727:Muscarinic Antagonists; D010880:Piperidines; D010936:Plant Extracts; D043587:Receptor, Muscarinic M3; D012997:Solvents; D001285:Atropine; C042375:4-diphenylacetoxy-1,1-dimethylpiperidinium; D014700:Verapamil; D002118:Calcium