两种土家族药用植物化学成分及其生物活性研究
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摘要
金粉蕨属野雉尾金粉蕨为湖北省鄂西地区土家族常用民间药物,具有清热,利湿,解毒,止血的功效,用于黄疸,咳血,便血,尿血,疔疮及无名肿毒。大旋鸡尾为中国蕨科金粉蕨属(Onychium)野雉尾金粉蕨Onychium japonicum (Thunb.) Kze的全草,又名野鸡尾。多分布于日本、韩国以及其它一些亚洲国家。在中国主要分布秦岭以南,广东以北,及山西、台湾等地。具有清热,利湿,解毒,止血的功效。用于治疗风热感冒,急性胃肠炎,痢疾,黄疸,咳血,吐血,便血,尿血,疔疮及外伤肿痛。其化学成分研究很少,近十几年来国内外未见化学成分和药理活性研究报道。
     白马骨为白马骨属(Serissa)白马骨Serissa serissoides (DC.) Druce的全草,别名六月雪、路边荆、路边金等,主要分布在我国的长江以南地区。具有祛风、利湿、清热、解毒等功效。用于治疗偏正头痛,牙痛,喉痛,目赤肿痛,湿热黄疽等。白马骨属植物的药理学研究主要包括抗乙肝病毒和护肝,抑制细菌生长,抗肿瘤,抑制酪氨酸酶活性,致突变性和急性毒性。
     本文在对湖北省土家族民间药物调查的基础上,选用湖北省鄂西地区土家族常用的,临床应用疗效确切的野雉尾金粉蕨和白马骨为研究对象,以阐明其药效作用物质基础为研究目标,开展了土家族民间药物野雉尾金粉蕨和白马骨的化学成分及其生物活性的研究。
     本文以天然药物化学研究手段,对野雉尾金粉蕨和白马骨进行了提取分离,实验采用多种分离技术,包括大孔吸附树脂、聚酰胺、正相柱色谱、LH-20、 Toyopear HW-40、制备型高效液相色谱技术,对野雉尾金粉蕨和白马骨的乙酸乙酯和正丁醇提取部位进行分离,以多种有机波谱手段,包括IR、UV、MS、1H-NMR、13C-NMR、1H-1HCOSY、HSQC、HMBC、NOESY和旋光光谱等波谱技术结合化学反应,从野雉尾金粉蕨的乙酸乙酯和正丁醇提取部位中共分离得到28个化合物,并鉴定了其中16个化合物的结构,另外12个正在鉴定中。其中6个为文献未见报道新化合物。从白马骨的乙酸乙酯和正丁醇提取部位中共分离得到10个已知化合物。
     对分离野雉尾金粉蕨得到的八个新化合物进行了逆转肿瘤多药耐药的活性测定。研究结果显示化合物6,7,8,4,10和12有逆转MCF-7/ADR和BEL-7402/5-FU肿瘤细胞的多药耐药作用,其中化合物6,7,8的逆转作用较强。
Da-Xuan-Ji-Wei is the whole herb of Onychium japonicum (Thunb.) Kze of Onychium genus, which is distributed mainly in Japan, Korea and other Asiatic countries. In China it is distributed mainly in the south of Qinling Mountains, the north of Guangdong, Shanxi and Taiwan province. Onychium japonicum has the effects of clearing heat, removing damplaw, arresting bleeding, hemostasis, and is used for treatment of wind-heat type common cold, acute gastroenteritis, dysentery, jaundice, hemoptysis, hematemesis, hemafecia, hematuria, furunculosis, injury and pain in traditional Chinese medicine.
     Serissa serissoides (DC.) Druce is the whole herb of Serissa genus, which is distributed mainly in south of the Yangtze River in china. Serissa serissoides has the effects of the wind, dampness, clearing heat and detoxification. For the treatment of headache, toothache, sore throat, swollen red eyes and damp-heat jaundice.
     The material(Onychium japonicum and Serissa serissoides) in this study is the folk medicine of Tujia Nationality in Western Hubei, which has common use and remarkable effects in traditional Tujia Nationality medicine. We began to study on the bioactive constituents from O. japonicum and S. serissoides in order to develop modern drug from this traditional Chinese medicine.
     By using repeated column chromatography, including Silica gel, Sephadex LH-20, Toyopearl HW-40and preparative HPLC,28compounds were isolated from the P.E. and EtoAc extracts of the Onychium japonicum. By the means of IR, UV, MS,1H-NMR,13C-NMR,1H-1H COSY, HSQC, HMBC, NOESY spectra, optical rotation and chemical reaction. The structures of6new compounds and10known compounds were identified from the EtoAc and BuOH extracts of O. japonicum. Ten known compounds were identified from the EtoAc and BuOH extracts of S. serissoides.
     In a screen for reversal agents of cancer multidrug resistance from eight compounds of O. japonicum, we investigated the reversal effect of sesquiterpene compound6,7,8,4,10and12on BEL-7402/5-FU and MCF-7/ADR cells by MTT assay. Compound6.7and8revealed partially reverse effect on the multidrug resistance of MCF-7/ADR cells.
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