Chaabi M, Freund-Michel V, Frossard N, Randriantsoa A, Andriantsitohaina R, Lobstein A
UMR/CNRS 7175 Pharmacognosie et Molécules Naturelles Bioactives, Faculté de Pharmacie, Université Louis Pasteur, Strasbourg I, Illkirch, France.
J Ethnopharmacol. 2007 Jan 3;109(1):134-9. doi: 10.1016/j.jep.2006.07.016. Epub 2006 Jul 21.
The ethanolic extract of a Malagasy species Euphorbia stenoclada (ES) (Euphorbiaceae), traditionally used as a herbal remedy against asthma and acute bronchitis, was tested to evaluate possible anti-proliferative activity on human airway smooth muscle cells (HASMC). The ES ethanolic extract totally abolished the interleukin-1beta (IL-1beta) induced proliferation of HASMC (IC(50)=0.73+/-0.08 microg/mL). No cytotoxic effect was observed up to 20 microg/mL. A bioassay-guided fractionation of the ethanolic extract was performed by reversed-phase (RP) flash chromatography, giving five fractions (FA to FE) where fraction FE was the only active one (IC(50)=0.38+/-0.02 microg/mL). The purification of this bioactive fraction FE was carried out by RP-HPLC affording six sub-fractions 1-6, and only sub-fraction 5 kept the anti-proliferative activity. Its major constituent was identified as quercetin (IC(50)=0.49+/-0.12 microg/mL) by means of HPLC/UV/MS and co-elution with the authentic standard. Quercitrin was also identified in the fraction FE but was inactive. A structure-activity relationship with flavonols determined that methylation reduced the anti-proliferative activity whereas glycosylation abolished it. The present study shows that the anti-proliferative properties of Euphorbia stenoclada are mediated through the presence of quercetin that may explain the traditional use of this plant as a remedy against asthma.
马达加斯加的一种植物窄叶大戟（ES）（大戟科）的乙醇提取物，传统上被用作治疗哮喘和急性支气管炎的草药，对其在人气道平滑肌细胞（HASMC）上的抗增殖活性进行了测试。ES乙醇提取物完全抑制了白细胞介素-1β（IL-1β）诱导的HASMC增殖（IC50 = 0.73±0.08微克/毫升）。在高达20微克/毫升时未观察到细胞毒性作用。通过反相（RP）快速色谱法对乙醇提取物进行生物测定导向的分级分离，得到五个级分（FA至FE），其中级分FE是唯一具有活性的级分（IC50 = 0.38±0.02微克/毫升）。通过RP-HPLC对该生物活性级分FE进行纯化，得到六个亚级分1-6，只有亚级分5保持抗增殖活性。通过HPLC/UV/MS并与标准品共洗脱，确定其主要成分是槲皮素（IC50 = 0.49±0.12微克/毫升）。在级分FE中也鉴定出了槲皮苷，但它没有活性。与黄酮醇的构效关系表明，甲基化降低了抗增殖活性，而糖基化则消除了该活性。本研究表明，窄叶大戟的抗增殖特性是由槲皮素介导的，这可能解释了这种植物作为哮喘治疗药物的传统用途。
