Lampronti I, Khan M T H, Bianchi N, Ather A, Borgatti M, Vizziello L, Fabbri E, Gambari R
ER-GenTech, Department of Biochemistry and Molecular Biology, Ferrara University, Via L. Borsari, 46, 44100 Ferrara, Italy.
Med Chem. 2005 Jul;1(4):327-33. doi: 10.2174/1573406054368684.
Several medicinal plants can be employed to produce extracts exhibiting biological effects. The aim of this work was to verify the ability of extracts derived from different medicinal plants of Bangladesh in interfering with specific DNA-protein interactions. The rationale for this study is based on the observation that alteration of gene transcription represents a very promising approach to control the expression of selected genes and could be obtained using different molecules acting on the interactions between DNA and transcription factors (TFs). We have analysed the antiproliferative activity of extracts from the medicinal plants Hemidesmus indicus, Polyalthia longifolia, Aphanamixis polystachya, Moringa oleifera, Lagerstroemia speciosa, Paederia foetida, Cassia sophera, Hygrophila auriculata and Ocimum sanctum. Antiproliferative activity was assayed on different human cell lines, including erythroleukemia K562, B-lymphoid Raji, T-lymphoid Jurkat and erythroleukemia HEL cell lines. We employed the electrophoretic mobility shift assay (EMSA) as a suitable technique for the identification of plant extracts altering the binding between transcription factors and the specific DNA elements. We found that low concentrations of Hemidesmus indicus, Polyalthia longifolia, Moringa oleifera and Lagerstroemia speciosa, and very low concentrations of Aphanamixis polystachya extracts inhibit the interactions between nuclear factors and target DNA elements mimicking sequences recognized by the nuclear factor kappaB (NF-kappaB). On the contrary, high amount of extracts from Paederia foetida, Cassia sophera, Hygrophila auriculata or Ocimum sanctum were unable to inhibit NF-kappaB/DNA interactions. Extracts inhibiting both NF-kappaB binding activity and tumor cell growth might be a source for anti-tumor compounds, while extracts inhibiting NF-kappaB/DNA interactions with lower effects on cell growth, could be of interest in the search of compounds active in inflammatory diseases, for which inhibition of NF-kappaB binding activity without toxic effects should be obtained.
几种药用植物可用于制备具有生物学效应的提取物。本研究的目的是验证源自孟加拉国不同药用植物的提取物干扰特定DNA-蛋白质相互作用的能力。本研究的理论依据基于以下观察结果:基因转录的改变是控制选定基因表达的一种非常有前景的方法,并且可以使用作用于DNA和转录因子(TFs)之间相互作用的不同分子来实现。我们分析了药用植物印度牛弭、长叶暗罗、多穗阿芳榄仁、辣木、紫薇、臭鸡矢藤、决明、耳叶水蓑衣和圣罗勒提取物的抗增殖活性。在不同的人类细胞系上测定抗增殖活性,包括红白血病K562、B淋巴细胞Raji、T淋巴细胞Jurkat和红白血病HEL细胞系。我们采用电泳迁移率变动分析(EMSA)作为一种合适的技术,用于鉴定改变转录因子与特定DNA元件之间结合的植物提取物。我们发现,低浓度的印度牛弭、长叶暗罗、辣木和紫薇提取物,以及极低浓度的多穗阿芳榄仁提取物可抑制核因子与模拟核因子κB(NF-κB)识别序列的靶DNA元件之间的相互作用。相反,大量的臭鸡矢藤、决明、耳叶水蓑衣或圣罗勒提取物不能抑制NF-κB/DNA相互作用。抑制NF-κB结合活性和肿瘤细胞生长的提取物可能是抗肿瘤化合物的来源,而抑制NF-κB/DNA相互作用但对细胞生长影响较小的提取物,可能在寻找对炎症性疾病有活性的化合物方面具有意义,对于炎症性疾病,应在不产生毒性作用的情况下抑制NF-κB结合活性。