【作者】 刘金；

【导师】 张立伟；

【作者基本信息】 山西大学 ， 无机化学， 2006， 硕士

【摘要】 自由基是生物体进行生化反应时普遍存在的中间介质。当人体内的自由基产生过多或清除过慢,就会攻击人体各种组织细胞、器官并使之受到损害,加速机体的衰老过程并诱发各种疾病。因此,适当补充抗氧化剂以清除多余的自由基是非常必要的。由于化学合成的抗氧化剂都稍有毒性,因此,人们要求开发和应用天然的抗氧化剂的愿望日益迫切。中草药连翘中有效成分连翘酯苷有抗活性氧的作用,因此,我们进一步研究了连翘酯苷的提取、分离方法及其对自由基的清除作用。本研究工作对拓宽连翘的药用范围和药用价值有一定的意义。 不少药物受热、光、空气和化学环境影响,容易挥发和升华,失去部分或全部疗效,将这些药物用β-CD包合能提高药物的稳定性。连翘为一常用中药,连翘酯苷是其有效成分之一,为咖啡酸的衍生物,分子结构中具有酯键和糖苷键,因而在加工、贮存过程中受外界环境影响而分解从而影响其疗效。因此,我们研究了连翘酯苷与β-CD的包合作用,旨在为研制有效的药物载体,开发连翘酯苷新剂型,用于药物分子设计提供一定的理论依据。 本论文研究了连翘有效成分连翘酯苷的提取分离、生物活性以及与β—CD包合作用。具体工作主要有以下几个方面: 1.对中草药连翘、天然抗氧化剂及β-CD包合药物的研究进展状况作了简要回顾总结。 2.利用大孔吸附树脂、真空液相色谱法和低压液相制备色谱对连翘酯苷进行了分离提取及鉴定研究。结果表明使用大孔吸附树脂富集连翘酯苷的同时,可除去大量杂质,所用溶剂仅为大量的水和少量乙醇,减少了有毒溶剂的使用,并使下一步纯化不需经反复柱层析即可得到较好产物。 3.采用分光光度分析法、TBA法在脱氧核糖水平上研究了肉桂酸衍生物对Phen-CuSO₄-Vc系统和H₂O₂系统引起的DNA损伤的防护效能,发现连翘酯苷能明显减轻上述系统对脱氧核糖和DNA的降解,能抑制脱氧核糖和DNA的损伤,且抑制作用随浓度增大而增强,这说明直接作用更多还原

【Abstract】 Free radicals are the general intermediates of biochemical reactions in organisms. When free radicals are produced excessively or removed extreme slowly, they will attack all kinds of histiocytes and organs which can be impaired by the free radicals, increase the fade process, and induce a lot of diseases. Therefore, the antioxidants are required to remove the extra free radicals. Although the antioxidants which are synthesized by the chemical methods can remove effectively the free radicals, they are little noxious. It is more and more urgent that the innoxiously natural antioxidants are required to exploit and use in practice. The effective ingredient (Forsythiaside) of the Chinese herb Forsythia has protection against free radical damages, so the studies on the extraction separation and clearance of free radicals of Forsythiaside are very interesting. This work help to extend the range and value of Forsythiaside, using as a medicine.Forsythiaside belonging to the derivatives of caffeinic acid is the effective ingredient of the Chinese herb Forsythia, included ester and glycosidic bonds in it’s structure. Therefore It’s effective ingredient can be easily decomposed in the process of the storage and preparation. And the interactions between Forsythiaside and cyclodextrin were investigated in this paper. All the work above mentioned aimed to the development of medicine carrier and new dosage form, which help to provide theory basis of design drug molecule.The dissertation consists of five chapters focusing on the study of extraction method and biological activities of forsythiaside, which is the effective ingredient of Forsythia suspense (Thunb) Vahl. The contents are as follows:1. The research developments of Forsythia suspense (Thunb) Vahl, natural antioxidants and application of β-cyclodextin inclusion compound to Chinese materia medica field were reviewed.2. Extraction and separation of Forsythiaside from Forsythia suspense (Thunb) Vahl were studied by using the Macroporous adsorptive resins D101 -. Vacuum liquid chromatography and low pressure liquid chromatography. The results shown that the Macroporous adsorptive resins D101 enriched the Forsythiaside, at the same time , could remove a lot of extraneous components , and obtained a higher content of Forsythiaside product .There are many advantages using this extraction technology : (1) the used solvents are safety and innoxious, and do not contaminate environment. (2) Macroporous adsorptive resins can be used many times and regenerated easily. (3) the method can save solves? time and have high performance n higher content products.3. The protection potency of Cinnamic acid derivatives to DNA damage by oxygen radical was studied in the systems containing Phen-CuSCVVc or H2O2, using both ultraviolet and fluorescence spectrumn the TBA reaction, with reference to the effects of Mannitol. The absorption in 532nm of DNA decreased. Deoxyribose damage was found in TBA reaction. DNA backbone-cleavage was observed in agrose gel electrophoresis. Trace metal ion such as Fe2+ and so on could accelerate the reactions of DNA damage by oxygen radical. In all case DNA damage was prevented by a series of -OH scarvages. The role of OH induced by the above two systems in the DNA damage including deoxyribose and backbone degradation was discussed. The result suggest that Cinnamic acid derivatives have the obvious protective function to the damage of DNA caused by. -OH.4. The inclusion interaction of Cyclodextrin with Forsythiaside was studied by ultraviolet and fluorescence spectral method > and thermodynamics. Fluorescence spectra indicated that complex had been formed. Inclusion equilibrium of Cyclodextrin with Forsythiaside in aqueous media had been studied using Fluorescence spectroscopy. Good linear relationships indicated that the structure of the inclusion complexes was 1:1. The steady constants(K) of the complexes had been obtained. The effect of temperature on K value and other parameters AG, AH and AS had also been discussed. It wassuggested that P-cyclodextrin can increase the stability of Forsythiaside.更多还原