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银线草抗肿瘤有效部位化学成分及指纹图谱研究
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摘要
银线草为金粟兰科植物银线草(Chloranthus japonicus Sieb)的植物名。银线草药用历史悠久,生理活性较强,民间应用十分广泛。祛湿散寒、活血止痛、散瘀解毒,主治风寒咳嗽、风湿痛、闭经,跌打损伤、瘀血肿痛、核咳血、肺结淋巴腺炎、神经衰弱、毒蛇咬伤、疟疾、疮痈等。银线草分布于我国黑龙江、吉林、河北、山西、山东、峡西、甘肃等省。植物资源极为丰富。但长期以来,对该植物几乎没有进行有效的开发和利用。文献报道银线草有抗肿瘤作用,为找到其抗肿瘤有效成分并对药材质量加以控制,本文对银线草抗肿瘤有效部位进行化学成分和指纹图的研究。
     本文对银线草抗肿瘤的有效部位进行了系统的提取分离和结构鉴定研究。通过硅胶、ODS、Sephadex LH-20等柱色谱和HPLC等现代提取分离方法和技术,分离出10个化合物,采用~1H-NMR、~(13)C-NMR、~1H-~1HCOSY、~1H-~(13)CCOSY、HMBC和NOESY等1D及2D-NMR波谱学测试技术,并结合ESI-MS,HR-ESI-MS等质谱,鉴定了其中6个化合物,结构分别为1个木脂素类化合物(cleomiscosin C-4-O-β-glucopyraNoside),2个倍半萜类化合物(pisumioNoside and 1α-hydroxyeudesman-4(15),7(11)-dien-8α-12-olide-1-O-glucopyraNoside),2个皂苷类化合物(CaulosideD and LenticinD)和1个香豆素类化合物(kimmin-7-O-glucopyrano-side)。
     通过对银线草指纹图谱的研究,确立了适宜的色谱测定条件,通过对精密度、稳定性、重现性等方法学考察,表明所建立的银线草指纹图谱测定方法符合中药指纹图谱的技术要求,可用于银线草指纹图谱的测定。对不同产地和来源的银线草药材进行了指纹图谱测定,确定了20个共有峰,对银草药材指纹图谱进行了相似度比较,对相似度评价指标夹角余弦和相关系数进行了测算,结果显示不同产地和来源的银线草药材相似度良好。
     本文通过对银线草抗肿瘤有效部位进行系统深入的化学成分和指纹图谱的研究,为今后深入研制临床急需的抗肿瘤新药提供了坚实的研究基础和科学依据。本研究填补国内外对银线草的抗肿瘤化学成分和指纹图谱研究领域的空白,不仅具有重要的理论和学术价值,也具有非常广阔的应用前景。
Chloranthus japonicus Sieb is a kind of perennial herbaceous plant, which belongs to the family of Chloranthaceae.Chloranthus japonicus Sied has been widely used to treat cold rheum,injuries from falls,fracture, rheumatism ache,pulmonary tuberculosis,neurasthenic,impaludism,etc.in the civilian society of China.It mainly grows in shady places,including hillside,valley,tussock,etc.Chloranthus japonicus Sieb has comprehensively distributed in many places in China,including Heilongjiang,Jilin,Hebei, Shanxi,Shandong,Shanxi,Gansu,etc.Chloranthus japonicus Sieb is very rich in the plant resources in China.However,for the long time,this plant has Not been exploited and utilized availably by people.
     For better illumination medical substance basis on treating cancer,we have studies on chemical constituents of 50%ethaNol elution section of macroporous absorption resin for Chloranthus japonicus Sieb by silica gel, ODS,Sephadex LH-20 column chromatography and HPLC preparation chromatography.As a result,chemical structures of 6 compounds were fully determined by 1D and 2D NMR such as ~1H-NMR,~(13)C-NMR,DEPT, ~1H-~1HCOSY,HSQC and HMBC,etc,combined with ESI-MS and HR-ESI-MS, UV,IR and chemical methods.The compounds are one lignans (cleomiscosin C-4-O-β-glucopyraNoside),two sesquiterpences(pisumio No side and 1α-hydroxyeudesman-4(15),7(11)-dien-8α-12-olide-l-O- glucopyra Noside),two saponin compounds(CaulosideD,LenticinD)and one coumarins (kimmin-7-O-glucopyra Noside).
     Proper method for the determination of HPLC fingerprint spectrum of Chloranthus japonicus Sieb was established and up to the technical demands for TCM fingerprint spectrums.HPLC fingerprint spectrums of different places and sources of Chloranthus japonicus Sieb were determined and 20 common fingerprint peaks were asertained.Similarities of the fingerprint spectrums were compared and showed that their compenents were similar.
     This dissertation elucidated the anti-tumor material basis of Chloranthus japonicus Sieb by chemical and Fingerprint Spectrums research. It will provide important scientific foundation for further research and the development of new drugs and promote the exploitation of this abundant natural medicinal resource.
引文
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