红凉伞抗肿瘤转移化学成分研究
摘要
红凉伞[Ardisia Crenata Sims f hortensis (Migo)]为紫金牛科植物朱砂根(A. crenata Sims)的变种。分布于我国华东、中南、西南等地区。具有清热解毒、祛风除湿、活血散淤、消炎止痛的功效,临床上常用于咽喉肿痛、跌打损伤、风湿痹痛等症。现代药理研究表明,红凉伞具有抗HIV病毒、抗肿瘤、抗生育和防治心脑血管疾病的作用。
本文以发现新生物活性成分为目的,对红凉伞提取物进行抗肿瘤转移作用研究发现,95%乙醇提取物具有很强抗人乳腺癌细胞(MDA-MB-231)的趋化迁移作用,在浓度1.0μg/ml下对肿瘤细胞的趋化迁移抑制率达到92.5%。本课题开展了红凉伞抗肿瘤转移化学成分研究,采用溶剂萃取、常压硅胶柱色谱和凝胶柱色谱分离,制备高效液相色谱纯化,从红凉伞的乙酸乙酯和正丁醇层萃取物中共分得9个化合物,进一步利用Ms、1H-NMR、13C-NMR、1H-1H COSY、HMBC、HSQC等有机波谱方法,鉴定了各化合物的结构,分别为：车叶草酸(1),百两金皂苷B(2),岩白菜素(3),正丁基-a-D-呋喃果糖苷(4),正丁基-β-D-呋喃果糖苷(5),甲基-a-D-呋喃果糖苷(6),丁香酸(7),乙基-β-D-吡喃果糖苷(8),5-羟甲基糠醛(9)。化合物1、4-9首次从该植物中分离得到。
本文先以MTT法对红凉伞的提取物和分离的各单体化合物进行了非细胞毒剂量的测试,并在非细胞毒剂量下,以趋化小室法评价各化合物抑制肿瘤细胞迁移的作用。试验结果表明,化合物1-9均具有较强的抑制人乳腺癌细胞迁移的作用,其中化合物2,4和9的抗肿瘤细胞迁移作用较强,化合物4在浓度0.8μg/ml下对人乳腺癌细胞趋化抑制率达到93.8%,表明以上化合物具有潜在的抗肿瘤转移作用。
Ardisia Crenata Sins. f hortensis (Migo) is the variant of A. Crenata Sins. in family of Myrsinaceae, which is widely distributed in the east and southeast of China. As a Chinese folk medicine, it has been used in preventing sore throat, bruises in clinic. It also has the properties of anti-HIV, anti-tumor, anti-fertility and so on.
In order to search for new bioactive constituents from natural source, the 95% ethanol extract of Ardisia Crenata revealed significant anti-tumor metastasis effect in MDA-MB-231 cell lines. The metastatic inhibition ratio of value on MDA-MB-231 was 92.5% at the concentration of 1.0μg/ml. We started to study the anti-tumor metastatic chemical consitituents from Ardisia Crenata. By repeated column chromatography, including Silica gel, Toyopearl HW-40 and preparative HPLC, nine compounds were isolated from extract of A. Crenata. By analysis of MS,'H-NMR, 13C-NMR,1H-1H COSY, HMBC and HSQC spectra, the structures of nine compounds were identified as follows:Asperuloside acid (1), ardisiacrispins B (2), (+)-Bergenin (3), n-butyl-a-D-fructofuranoside (4), n-butyl-β-D-fructofuranoside (5), methyl-a-D-fructofuranoside (6), Syringic acid (7), ethyl-β-D-fructopyranoside (8),5-hydroxymethyl-2-furalclehyde (9). Compounds 1 and 4～9 were isolated from A. Crenata for the first time.
MTT was used to determine the non-cytotoxic concentrations for the extract and isolated compounds. Then transwell chemotaxis was used to evaluating the role of inhibition of tumor cell migration. Compounds 1-9 showed positive anti-tumor cell migration effects, and compounds 2,4, and 9 showed significant anti-tumor cell migration effects. The metastatic inhibition ratio of value on MDA-MB-231 was 93.8% at the concentration of 0.8μg/ml of compound 4. The above result indicated that the active compounds may be have potentical anti-tumor metastatic effect.
本文以发现新生物活性成分为目的,对红凉伞提取物进行抗肿瘤转移作用研究发现,95%乙醇提取物具有很强抗人乳腺癌细胞(MDA-MB-231)的趋化迁移作用,在浓度1.0μg/ml下对肿瘤细胞的趋化迁移抑制率达到92.5%。本课题开展了红凉伞抗肿瘤转移化学成分研究,采用溶剂萃取、常压硅胶柱色谱和凝胶柱色谱分离,制备高效液相色谱纯化,从红凉伞的乙酸乙酯和正丁醇层萃取物中共分得9个化合物,进一步利用Ms、1H-NMR、13C-NMR、1H-1H COSY、HMBC、HSQC等有机波谱方法,鉴定了各化合物的结构,分别为：车叶草酸(1),百两金皂苷B(2),岩白菜素(3),正丁基-a-D-呋喃果糖苷(4),正丁基-β-D-呋喃果糖苷(5),甲基-a-D-呋喃果糖苷(6),丁香酸(7),乙基-β-D-吡喃果糖苷(8),5-羟甲基糠醛(9)。化合物1、4-9首次从该植物中分离得到。
本文先以MTT法对红凉伞的提取物和分离的各单体化合物进行了非细胞毒剂量的测试,并在非细胞毒剂量下,以趋化小室法评价各化合物抑制肿瘤细胞迁移的作用。试验结果表明,化合物1-9均具有较强的抑制人乳腺癌细胞迁移的作用,其中化合物2,4和9的抗肿瘤细胞迁移作用较强,化合物4在浓度0.8μg/ml下对人乳腺癌细胞趋化抑制率达到93.8%,表明以上化合物具有潜在的抗肿瘤转移作用。
Ardisia Crenata Sins. f hortensis (Migo) is the variant of A. Crenata Sins. in family of Myrsinaceae, which is widely distributed in the east and southeast of China. As a Chinese folk medicine, it has been used in preventing sore throat, bruises in clinic. It also has the properties of anti-HIV, anti-tumor, anti-fertility and so on.
In order to search for new bioactive constituents from natural source, the 95% ethanol extract of Ardisia Crenata revealed significant anti-tumor metastasis effect in MDA-MB-231 cell lines. The metastatic inhibition ratio of value on MDA-MB-231 was 92.5% at the concentration of 1.0μg/ml. We started to study the anti-tumor metastatic chemical consitituents from Ardisia Crenata. By repeated column chromatography, including Silica gel, Toyopearl HW-40 and preparative HPLC, nine compounds were isolated from extract of A. Crenata. By analysis of MS,'H-NMR, 13C-NMR,1H-1H COSY, HMBC and HSQC spectra, the structures of nine compounds were identified as follows:Asperuloside acid (1), ardisiacrispins B (2), (+)-Bergenin (3), n-butyl-a-D-fructofuranoside (4), n-butyl-β-D-fructofuranoside (5), methyl-a-D-fructofuranoside (6), Syringic acid (7), ethyl-β-D-fructopyranoside (8),5-hydroxymethyl-2-furalclehyde (9). Compounds 1 and 4～9 were isolated from A. Crenata for the first time.
MTT was used to determine the non-cytotoxic concentrations for the extract and isolated compounds. Then transwell chemotaxis was used to evaluating the role of inhibition of tumor cell migration. Compounds 1-9 showed positive anti-tumor cell migration effects, and compounds 2,4, and 9 showed significant anti-tumor cell migration effects. The metastatic inhibition ratio of value on MDA-MB-231 was 93.8% at the concentration of 0.8μg/ml of compound 4. The above result indicated that the active compounds may be have potentical anti-tumor metastatic effect.
引文
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