title: In vitro effect of the extract and the 1,7-dihydroxy-2,3-dimethoxy xanthone from Polygala cyparissias on the contractions induced by inflammatory mediators and ovalbumin in normal and actively sensitised trachea from guinea pig.
abstract: OBJECTIVE
  This study describes the in vitro action of the hydroalcoholic extract and the 1,7-dihydroxy-2,3-dimethoxy xanthone isolated from P. cyparissias on agonist and ovalbumin induced contractions in trachea, from normal and actively sensitised guinea pigs.
  
  
  RESULTS
  The hydroalcoholic extract of P. cyparissias (0.125 to 1 mg/ml), incubated with the guinea-pig trachea for 20 min, had no effect on the resting tone of the preparations, but caused a concentration-dependent, reversible and non competitive inhibition of contractions induced by acetylcholine, histamine, compound 48/80, bradykinin, substance P, prostaglandin E2 and the stable analogue of thromboxane A2 mimetic U 46619. The calculated mean IC50 values for the hydroalcoholic extract were: 0.37, 0.51, 0.06, 0.32, 0.48, 0.3 and 0.17 mg/ml, respectively. Also, the extract of P. cyparissias (0.125 to 0.5 mg/ml) antagonised, in a graded manner (IC50 of 0.46 mg/ml) ovalbumin-induced contractions in guinea-pig trachea obtained from animals which had been actively sensitised to this antigen. Pre-incubation of the preparations with the purifed xanthone isolated from P. cyparssias (2.5 to 80 microg/ml; 10.0 to 310.0 microM) caused significant and concentration-dependent, reversible and noncompetitive inhibition of the contractile responses elicited by acetylcholine, histamine, bradykinin, substance P, U 46619 and prostaglandin E2. The calculated mean IC50 values for these effects were: 132.0, 73.0, 9.2, 32.0, 110.6 and 66.0 microM, respectively. At very high concentrations (I55.0-620.0 microM) the xanthone also antagonised contraction induced by KCl in guinea-pig trachea (IC50 of 190.0 microM).
  
  
  CONCLUSIONS
  Taken together these and our previous in vivo results are consistent with the view that the active principles present in P. cyparissias, including the 1,7-dihydroxy-2,3-dimethoxy xanthone, antagonise, in a non competitive but, reversible manner the contractions induced by chemical inflammatory mediators in the guinea pig trachea in vitro. Thus, these results might explain at least in part, the medicinal use of this plant in the management of inflammation, asthma and allergy.
authors.affiliation: Department of Pharmacology, Universidade Federal de Santa Catarina, Florianópolis, Brazil.
authors.forename: M
authors.initials: M
authors.lastname: El Sayah
authors.forename: V
authors.initials: V
authors.lastname: Cechinel-Filho
authors.forename: T R
authors.initials: TR
authors.lastname: Pinheiro
authors.forename: R A
authors.initials: RA
authors.lastname: Yunes
authors.forename: J B
authors.initials: JB
authors.lastname: Calixto
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D018836:Inflammation Mediators / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D010047:Ovalbumin / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology; D019685:Rosales / Q000737:chemistry*; D013997:Time Factors; D014132:Trachea / Q000187:drug effects* / Q000502:physiology; D014966:Xanthenes / Q000302:isolation & purification / Q000494:pharmacology*; D044004:Xanthones
chemical_list: C120436:1,7-dihydroxy-2,3-dimethoxyxanthone; D018836:Inflammation Mediators; D010936:Plant Extracts; D014966:Xanthenes; D044004:Xanthones; D010047:Ovalbumin