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
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
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DOI：
10.1007/s000110050449
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发表时间：
1999-04-01
影响因子：
6.7
通讯作者：
Calixto, JB
中科院分区：
文献类型：
--
作者：
El Sayah, M;Cechinel, V;Calixto, JB
目的：研究cyparisensis水醇提取物和1,7-二羟基-2,3-二甲氧基山酮对正常豚鼠和主动致敏豚鼠气管激动剂和卵清蛋白诱导的收缩的体外作用。结果：cyparisias水醇提取物（0.125 ~ Img/ml）与豚鼠气管培养20 min，对制剂的静息张力无影响，但对乙酰胆碱、组胺、复方48/80、缓激肽、P物质、前列腺素E-2和稳定的血栓素a(2)类似物u46619诱导的收缩有浓度依赖性、可逆性和非竞争性的抑制作用。计算得到的平均IC50值分别为：0.37、0.51、0.06、0.32、0.48、0.3和0.17 mg/ml。此外，cyparisias提取物（0.125 ~ 0.5 mg/ml）对卵清蛋白诱导的豚鼠气管收缩具有分级拮抗作用（IC50为0.46 mg/ml）。经纯化的松酮（2.5 ~ 80 μ g/ml; 10.0 ~ 310.0 μ M）预育后，对乙酰胆碱、组胺、缓激肽、P物质、u46619和前列腺素E-2引起的收缩反应有明显的、浓度依赖性的、可逆的、非竞争性的抑制作用。这些效应的IC50平均值分别为：132.0、73.0、9.2、32.0、110.6和66.0 μ M。在极高浓度（155.0 ~ 620.0 μ M）下，山酮还能拮抗KCl诱导的豚鼠气管收缩（IC50为190.0 μ M）。结论：综合这些和我们之前的体内实验结果，我们的观点是一致的，即cyparisias中存在的活性原理，包括1,7-二羟基-2,3-二甲氧基山酮，在体外以非竞争性但可逆的方式拮抗化学炎症介质诱导的豚鼠气管收缩。因此，这些结果可能至少部分地解释了这种植物在治疗炎症、哮喘和过敏方面的药用价值。
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 Img/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 E-2 and the stable analogue of thromboxane A(2) 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 mu g/ml; 10.0 to 310.0 mu M) 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 E-2. The calculated mean IC50 values for these effects were: 132.0, 73.0, 9.2, 32.0, 110.6 and 66.0 mu M, respectively. At very high concentrations (155.0-620.0 mu M) the xanthone also antagonised contraction induced by KCl in guinea-pig trachea (IC50 of 190.0 mu M).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.