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 1mg/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 0.46mg/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 μg/ml; 10.0 to 310.0 μM) caused significant and concentration-dependent, reversible and non-competitive 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 μM, respectively. At very high concentrations (155.0-620.0 μM) the xanthone also antagonised contraction induced by KCl in guinea-pig trachea (IC₅₀ of 190.0 μM).¶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.