摘要
目的:分离和鉴定虎杖乙酸乙酯提取物中能显著抑制H1N1流感病毒神经氨酸酶(neuraminidase,NA)的活性成分。方法:基于药理活性导向法,综合利用硅胶,葡聚糖凝胶和制备液相等色谱分离虎杖提取物活性成分,采用MS和NMR等波谱数据及其理化性质鉴定分子结构。结果:从虎杖乙酸乙酯活性部位分离出7个化合物,分别鉴定为:2-methoxystypandrone(1),大黄素(2),白藜芦醇(3),虎杖苷(4),大黄素-8-O-β-D-吡喃葡萄糖苷(5),(E)-3,5,12-trihydroxystilbene-3-O-β-D-glucopy-ranoside-2'-(3″,4″,5″-trihydroxybenzoate)(6)和儿茶素-3-O-没食子酸酯(7);NA测试表明化合物3,6和7显著抑制NA活性,IC50分别为129.8,44.8,21.3μmol·L-1,进一步CPE测试表明化合物6和7具有显著抗H1N1流感病毒效果(EC50分别为5.9,0.9μmol·L-1),对宿主MDCK细胞表现出非常低的细胞毒性,选择性指数分别为56和269。结论:基于药理活性导向从虎杖提取物中分离鉴定出能显著抗H1N1流感病毒的神经氨酸酶抑制剂,对阐明其药效物质基础和抗流感药物研发具有指导意义。
Objective： To isolate and identify active neuraminidase constituents of Polygonum cuspidatum against influenza a （H1N1） influenza virus. Method： On the basis of the bioassay-guided fractionation, such chromatographic methods as silica gel, sephadex LH-20 and HPLC were adopted to isolate active constituents of extracts from Polygonum cuspidatum, and their molecular structures were identifiied on the basis of their spectral data such as NMR and MS and physico-chemical properties. Result： Seven compounds were isolated from the ethyl acetate extract of P. cuspidatum and identified as 2-methoxystypandrone （1）, emodin （2）, res- veratrol （ 3 ） , polydatin （ 4 ） , emodin-8-O-β-D-glucopyranoside （ 5 ） , （E） -3, 5, 12-trihydroxystilbene-3 -O-β-D-glucopyranoside-2＇ - （ 3 ″, 4″, 5″-trihydroxybenzoate） （6） and catechin-3-O-gallate（7） , respectively. Among them, the NA test showed that compounds 3, 6 and 7 had inhibitory effect against NAs activity, with IC50 values of 129.8, 44. 8 and 21.3 μmol · L -1 , respectively. Moreover, the further CPE test showed compounds 6 and 7 had significant inhibitory effect against H1N influenza virus（ EC50 = 5.9,0. 9 ·mol · L-1 , respec- tively）, with very low cytotoxicity to the host cells, their therapeutic selective index（SI） in MDCK cells ranged from 56 to 269. Conclusion： The neuraminidase inhibitors against H1N1 anti-influenza virus isolated from extracts of P. cuspidatum on the basis of the bio- assay-guided fractionation are significant in specifying their therapeutic material basis and drug R＆D against influenza.
出处
《中国中药杂志》
CAS
CSCD
北大核心
2012年第20期3068-3073,共6页
China Journal of Chinese Materia Medica
基金
国家“重大新药创制”科技重大专项(2008ZX09401-004,2009ZX09302-00)
北京市自然基金项目(7103172)
广州中医药大学《南药的现代研究与综合开发利用》“211工程”重点学科建设项目
