摘要
功效互不相同的桑类中药,其原植物古今均不只《中国药典》所采用的Morusalba L。一种。本论文提出了研究中药中普遍存在的“多基原、多味中药”现象的品质评价思路,以中药桑枝和桑白皮为研究对象,在深入研究品种的基础上,开展了品质评价研究和药效比较研究。
一、品种研究。(1)在系统考证中国桑树分类的基础上,深入探讨了桑类中药的原植物,证实了历史上桑类中药原植物的多样性。(2)针对当今桑类中药的药材不少来源于栽培桑树的事实,核证了中国现有主要桑树种质的原植物,以利于生药的鉴定。(3)全面考察了四川地区的桑资源现状,为进一步开发利用提供了基本信息。(4)首次运用分形理论研究了桑枝药材的纹理特征,给出了表征形念复杂程度的参数分形维数。
二、品质研究。(1)对桑类药材石油醚部位进行了GC-MS分析,根据对质谱图的解析及检索质谱库,鉴定出56个成分,并对桑类药材两两间的共有成分进行了归纳;(2)提出了桑类中药生物碱类成分的分析方法和提取方法;(3)首次提出了基于FFT变换和支持向量机的UV光谱指纹特征分析方法并应用于桑枝和桑白皮的品质评价;(4)首次提出了基于图像分析技术(连续光强扫描)和支持向量机的数字化薄层色谱指纹特征分析方法并应用于桑枝和桑白皮的品质评价;(5)首次运用支持向量机方法研究了桑枝、桑白皮的HPLC指纹特征。
三、药效研究部分。(1)在系统总结桑枝、桑白皮功效和药理作用的基础上,根据桑类中药的功能与主治,开展了镇咳祛痰、对免疫功能的影响、体外抗氧化、对基于STAT5b靶控报告基因的胰岛素受体细胞模型的影响等实验研究;(2)首次提出了基于虚拟筛选的中药药效研究方法,将桑类中药的化学成分分别与胰岛素受体、a-葡萄糖苷酶、β2肾上腺素受体、磷酸二酯酶4B、PSGL-1蛋白、血管紧张素转化酶、谷胱甘肽S-转移酶、HIV-1、COX-Ⅱ、碳酸酐酶Ⅻ、盐皮质激素受体等靶点进行了对接,分别发现了一些潜在的活性成分,有助于阐明桑类中药的物质基础。
根据研究结果,提出了“模式化中药”的概念,可用于解决多基原、多部位药用所致的中药品质不稳定性这一重要问题。
The Chinese herbs Sang mainly include the leaves, fruits, twigs and root barks of mulberry. In Chinese Pharmacopoeia, they are different drugs and all originated from Morus alba L. But in fact, several plants from Morus L. are involved in their original plants. Strategies for quality evaluation of this kind of circumstance in TCM were proposed and Ramulus Mori and Cortex Mori were investigated as examples in this dissertation.
1. About herbal species. (1) The textual research results of taxonomy of ancient China mulberry and original plants of Sang in Bencao indicated Sang's diversity. (2) Considering the facts that the medicinal materials of Sang in the market are mainly from the cultivated mulberry tree, the original plants of mulberry germplasm in most regions of China were investigated. (3) The mulberry resources in Sichuan were all-round analyzed. (4) The texture feature in transverse section of Ramulus Mori was measured using fractal dimension for the first time.
2. About quality evaluation. (1) The result of GC-MS analysis of petroleum fraction of Folium, Fructus, Ramulus and Cortex Mori confirmed 56 compounds and their structure were identified by analyzing the given mass spectra and searching in Mass Spectral Library (NIST05.LIB), and the same compounds between each other were summarized. (2) The methods for extracting and detecting alkaloids in Sang were studied. (3) For the first time, a method for finding UV spectra fingerprint features based on fast fourier transform (FFT) and support vector machine (SVM) was proposed and used in quality evaluation of Ramulus Mori and Cortex Mori. (4) For the first time, a method for finding TLC fingerprint features based on image analysis technique (continuous image optical intensity scanning) and SVM was proposed and used in quality evaluation of Ramulus Mori and Cortex Mori. (5) For the first time, Analysis of HPLC fingerprint features of Ramulus Mori and Cortex Mori using SVM method was performed.
3. About efficacy. (1) The efficacy of Sang in Bencao and the reported pharmacological action of Ramulus Mori and Cortex Mori were comprehensively summarized. (2) Experiments for evaluating antitussive activity, expectorant effect, immune effect, antioxidant activity and effect on STAT5b-INSULIN-RECEPTOR cell model were implemented. (3) For the first time, a method for studying the efficacy of TCM based virtual screening was established. A molecular library composed of the reported chemical constituents of Sang was docked to the three dimensional structure of insulin receptor, a-glucosidase,β2 adrenoceptor, PDE-4B, PSGL-1, angiotensin converting enzyme, glutathione S-transferase, HIV-1,COX-Ⅱ, carbonic anhydraseⅫand mineralocorticoid receptor respectively, and many potential active constituents were found.
In the end, a scheme included a new conception for the quality evaluation of Sang was proposed, this new conception is named "modeled TCM".
引文
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