摘要
本文通过S180荷瘤小鼠体内实验研究了中药龙葵(Solanum nigrum)全草乙醇提取物中的总皂苷部分的抗癌活性,初步试验表明龙葵总皂苷有抗癌作用,且表现出一定的量效关系。
通过综合运用D-101大孔吸附树脂、硅胶柱色谱、ODS柱色谱、Sephadex LH-20柱色谱以及制备型反相HPLC等多种色谱学分离手段,对龙葵乙醇提取物的总皂苷部分的化学成分进行了系统研究,从中分离得到43个化合物。利用理化性质、现代光谱学(IR、MS、~1H-NMR、~(13)C-NMR和2D-NMR)以及化学沟通(酸水解,Mosher法)等手段鉴定了它们的结构,分别为:solasonine (1),β_1-solasonine (2),β_2-solasonine (3), solamargine (4),β_2-solamargine (5),solanigroside P (6)~*, solanigroside Q (7)~*, (3β, 12β, 22α, 25R)-3,12-dihydroxy-spirosol-5-en-27-oic acid(8), hypoglaucin H(9), dumoside(10), degalactotigonin(11), tigogenin 3-O-β-D-glucopyranosyl-(1→2)-O-[β-D-glucopyranosyl-(1→3)]-O-β-D-glucopyranosyl-(1→4)-O-β-D-galactopyranoside(12), nigrumninⅠ(13), solanigroside C (14)~*,solanigroside D (15)~*, solanigroside E (16)~*, solanigroside F (17)~*, solanigroside G (18)~*,solanigroside H (19)~*, uttroside B (20), uttroside A (21), (22α, 25R)-26-O-(β-D-glucopyranosyl)-22-methoxy-furost-△~5-3β, 26-diol-3-O-β-D-glucopyranosyl-(1→2)-O-[β-D-xylopyranosyl-(1→3)]-O-β-D-glucopyranosyl-(1→4)-O-β-D-galactopyranoside (22), (22α,25R)-26-O-(β-D-glucopyranosyl)-22-hydroxy-furost-△~5-3β, 26-diol-3-O-β-D-glucopyranosyl-(1→2)-O-[β-D-xylopyranosyl-(1→3)]-O-β-D-glucopyranosyl-(1→4).-O-β-D-galac-topyranoside (23), (5α, 22α, 25R)-26-O-(β-D-glucopyranosyl)-22-methoxy-furostan-3β,26-diol-3-O-β-D-glucopyranosyl-(1→2)-O-[β-D-glucopyranosyl-(1→3)]-O-β-D-glucopyranosyl-(1→4).-O-β-D-galactopyranoside (24), (5α, 22α, 25R)-26-O-(β-D-glucopyranosyl)-22-hydroxy-furost-3β, 26-diol-3-O-β-D-glucopyranosyl-(1→2)-O-[β-D-glucopyranosyl-(1→3)]-O-β-D-glucopyranosyl-(1→4)-O-β-D-galactopyranoside (25), solanigrosideⅠ(26)~*, solanigrosideJ (27)~*, solanigroside K (28)~*, solanigroside L (29)~*, solanigroside M (30)~*, solanigroside N(31)~*, solanigroside O (32)~*, solanigroside R (33)~*, solanigroside S (34)~*, solanigroside T (35)~*,5α-pregn-16-en-3β-ol-20-one lycotetraoside (36), solanigroside A (37)~*, solanigroside B (38)~*,(5α, 20S)-3β, 16β-dihydroxy pregn-22-carboxylic acid (22, 16)-lactone-3-(O-β-D-glucopyranosyl-(1→2)-O-[β-D-xylpyranosyl-(1→3)]-O-β-D-glucopyranosyl-(1→4)-O-β-D-galactopyranoside (39), solanigroside U (40)~*, solanigroside V (41)~*, solanigroside W (42)~*,solanigroside X(43)~*。43个化合物中包括42个甾体皂苷类化合物和一个甾体皂苷元。其中,8个化合物分子中含有N原子,为生物碱型甾体皂苷类化合物,35个化合物分子中不含有N原子,为非生物碱型甾体皂苷类化合物。另外,有24个化合物(6、7、14-19、26-35、37、38、40-43)为新化合物,8个化合物(9、10、22-25、36、39)为首次从该属中分离得到,2个化合物(2、3)为首次从该种中分离得到。这些化合物中还包含了9种未见文献报道的全新苷元的糖苷(28-35,42)。
采用HPLC-ELSD方法建立了龙葵总皂苷标准提取物(活性部位)的指纹图谱,并用分离得到的11个化合物(30、25、20、31、17、36、15、4、12、13)为对照品,对标准提取物中峰面积占85%以上的峰进行了指认,测定了2个主要皂苷(11,20)的含量。
采用MTT法对分离得到的40个化合物进行了体外细胞毒活性考察。结果表明生物碱型甾体皂苷(1、3、4),螺甾皂苷(11)和孕甾皂苷(36、38)等三种类型共6个化合物显示了不同程度的体外细胞毒活性。在综合分析测试结果的基础上,对体外细胞毒活性的构效关系进行了初步探讨。
本研究工作在化学和生物活性研究的基础上,证实了传统中药龙葵抗癌活性的作用物质基础为其中所含的甾体皂苷类化合物(包括生物碱型及非生物碱型)。化合物体外细胞毒活性和总皂苷体内活性表明中药龙葵有抗肿瘤作用。本文的实验结果将为今后对龙葵的研究与开发提供详实的理论和实验依据。
The total saponins extract from Solarium nigrum L. exhibited inhibitory activity on S180, and the anti-tumor effect demonstrated a positive effect relationship on the basis of amount.In our systematical study on the chemical constituents of Solarium nigrum L., 43 compounds were obtained from the ethanolic extract of the whole herb of this plant through various chromatographic techniques. Their structures were elucidated on the basis of physic-chemical property, spectroscopic analysis and chemical correlation (acidic hydrolysis, Mosher method). The 43 compounds from Solarium nigrum are solasonine (1),β_1-solasonine (2),β_2-solasonine (3), solamargine (4),β_2-solamargine (5), solanigroside P (6)*, solanigroside Q (7)*, (3β, 12β, 22α, 25R)-3, 12-dihydroxy-spirosol-5-en-27-oic acid (8), hypoglaucin H (9), dumoside (10), degalactotigonin (11), tigogenin 3-O-β-D-glucopyranosyl-(1→2)-O-[β-D-glucopyranosyl-(1→3)]-O-β-D-glucopyranosyl-(1→4)-O-β-D-galactopyranoside (12), nigrumnin I (13), solanigroside C(14)*, solanigroside D (15)*, solanigroside E (16)*, solanigroside F (17)*, solanigroside G(18)*, solanigroside H (19)*, uttroside B (20), uttroside A (21), (22α, 25R)-26-O-(β-D-glucopyranosyl)-22-methoxy-furost-Δ~5-3β26-diol-3-O-β-D-glucopyranosyl-(1→2)-O-[β-D-xylopyranosyl-(1→3)]-O-β-D-glucopyranosyl-(1→4)-O-β-D-galactopyranoside (22), (22α, 25β)-26-O-(β-D-glucopyranosyl)-22-hydroxy-furost-Δ~5-3β, 26-diol-3-O-β-D-glucopyranosyl-(1→2)-O-[β-D-xylopyranosyl-(1→3)]-O-β-D-glucopyranosyl-(1→4)-C)-β-D-galac-topyranoside (23), (5α, 22α, 25R)-26-O-(β-D-glucopyranosyl)-22-methoxy-furostan-3β, 26-diol-3-O-β-D-glucopyranosyl-(1→2)-O-[β-D-glucopyranosyl-(1→3)]-O-β-D-glucopyranosyl-(1→4)-O-β-D-galactopyranoside (24), (5α, 22α, 25R)-26-O-(β-D-glucopyranosyl)-22-hydroxy-furost-3β, 26-diol-3-O-β-D-glucopyranosyl-(1→2)-O-[β-D-glucopyranosyl-(1→3)]-O-β-D-glucopyranosyl-(1→4)-O-β-D-galactopyranoside (25), solanigroside I (26)*, solanigroside J (27)*, solanigroside K (28)*, solanigroside L (29)*, solanigroside M (30)*, solanigroside N (31)*, solanigroside O (32)*, solanigroside R (33)*, solanigroside S (34)*, solanigroside T (35)*, 5α-pregn-16-en-3β-ol-20-one lycotetraoside (36), solanigroside A (37)*, solanigroside B (38)*, (5α, 20S)-3β,16β-dihydroxy pregn-22-carboxylic acid (22, 16)-lactone-3-(O-β-D-glucopyranosyl-(1→2)-O-[β-D-xylopyranosyl-(1→3)]-O-β-D-glucopyranosyl-(1→4)-O-β-D-galactopyranoside (39), solanigroside U (40)*, solanigroside V (41)*, solanigroside W (42)*, solanigroside X (43)*. These compounds are comprised of 1 sapogenin and 42 saponins, including 8 steroidal alkaloids and 35 other steroidal saponins. Compounds 6, 7, 14-19, 26-35, 37, 38, 40-43 are new compounds. Compounds 9, 10, 22-25, 36, 39 were isolated for the first time from the solanum genus, and compounds 2, 3 were isolated from this plant for the first time. Compounds 28-35 and 42 are steroidal glycosides with new sapogenin.
Simultaneously, the fingerprint chromatomap of the total saponins extract from Solanum nigrum has been established using HPLC-ELSD. Above 85%of the peak areas in the chromatography have been identified by comparing with 11 compounds (4, 12, 13, 15, 17, 20, 25, 30, 31, 36) separated from the plant. The contents of two main steroidal saponins (11, 20) in the total glycosidic extract have been determined.
MTT method was used to test the cytotoxic activity of 40 compounds against four human tumor cell lines. Alkaloidal steroidal saponins (1, 3 and 4), spirostane saponin (11) and pregane saponins (36 and 38) showed cytotoxic activity. On the basis of results of cytotoxic activity assay, the structure-activity relationship for the compounds with similar aglycone structures from Solanum nigrum was discussed.
On the basis of chemical and bioactive studies in this academic dissertation, it was confirmed that the plant Solanum nigrum possess anti-tumor activities, and illustrated that the steroidal saponins from Solanum nigrum are responsible for its antitumor activity as a folk medicine.
引文
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