麻风树中抑制小胶质细胞活化物质基础研究

Basic study on pharmacodynamic compositions inhibiting microglia activation in Jatropha curcas L.

目的对麻风树(Jatropha curcas L.)叶活性部位进行化学成分研究,并评价其对脂多糖(lipopolysaccharide,LPS)激活的BV-2小胶质细胞的抑制作用。方法前期活性导向筛选表明,麻风树叶的体积分数95%乙醇提取物的乙酸乙酯萃取物为活性部位。采用大孔吸附树脂、硅胶、ODS、Sephadex LH-20柱色谱和高效制备液相等多种色谱方法进行分离纯化,运用多种波谱手段对化合物进行结构鉴定,并研究其对LPS激活的BV-2小胶质细胞释放一氧化氮(NO)的抑制作用。结果从麻风树叶提取物的乙酸乙酯萃取物中鉴定出25个化合物,其中化合物3、8~10、12、15~17、19和25为首次从麻风树属中分离得到。化合物1、19和25表现出显著的抑制活性,优于阳性药(米诺环素,IC_(50)值为39.36μmol·L^(-1)),同时在活性浓度下均未表现出细胞毒性。结论麻风树叶中分离得到的活性化合物能够抑制LPS诱导的小胶质细胞活化,其可能具有减轻小胶质细胞活化介导的神经系统疾病(如神经退行性疾病)的潜在作用。

Objective To study the chemical constituents from the leaves of Jatropha curcas L.and evaluate their inhibition on lipopolysaccharide(LPS)-activated BV-2 microglia.Methods The previous bioactivity-guided results showed that the ethyl acetate extract of the 95%ethanol extract of the leaves of Jatropha curcas L.was the active part.Macroporous adsorption resin, silica gel, ODS,Sephadex LH-20 column chromatography and HPLC were used to separate and purify the compounds.The structures of the compounds were identified using a variety of spectral methods, and their inhibition on the release of nitric oxide(NO)by LPS-activated BV-2 microglia was evaluated.Results Twenty-five compounds were identified from the ethyl acetate extract of Jatropha curcas,of which 10 compounds were isolated from genus Jatropha for the first time.Besides, compounds 1,19 and 25 showed significant inhibitory activity over the positive control(minocycline, IC_(50)=39.36 μmol·L^(-1))and showed no cytotoxicity at the active concentration.Conclusion The active compounds isolated from the leaves of Jatropha curcas can inhibit the activation of microglia induced by LPS,which may have a potential role in alleviating nervous system diseases(such as neurodegenerative diseases)mediated by microglia activation.