The Analysis And Application Of The Mechanism Of The Triplet Codon Based On The Bio-network Based On The Taste Of The Drug

Background:Herb property is a summary of the clinical function and mechanism of herbs. And it is the main basis of clinic prescription. Research on the pharmacological and molecular biological characterization of herb properties, leads the development of Chinese Medicine Theory,contributes to the spread and popularization of Chinese medical knowledge,promote safe and rational use of herbs in clinic,and helps to give TCM features to drug research and development process.In recent years,by induction of a large number of studies about single herb property,we were gradually aware that there is no one-to-one correspondence between the herb property and efficacy, but the different elements of herb properties as a whole are related to the herb function.Because the studies about single property cannot fully reflect the property-function correspondence,my lab members previously proposed the concept of herb property combination, including triple main elements of nature, flavor and meridian distribution. Herb property combination (HPC) is the basic unit which reflects the efficacy of traditional Chinese medicine. Model of multi-HPCs (is also called model of multi-combination) is a compatibility mode of multiple herb property combinations repeated occurring in herbs, herb pairs or formulas. Model of multi-HPCs can reflect drug compatibility law on the level of herb property.The triple combination of herb properties in form is similar to the three base codons in molecular biology and is the basic unit composed of property information of herbs, herb pairs and formulas. Functionally, the triple combination of herb properties cannot only reflect the specific function of herbs, but is also easier to focus on herb functions than single properties.Meanwhile, the model of multi-combination can reflect the compatibility laws of herb pairs and formulas,is a core set of herb property compatibility. Its function is just like biological genotype,which determines essential characteristics and inherent laws of the clinical phenotypes as an herb pair or a formula. Therefore,the triple combination of herb properties are called three-property codons.Objective:To truly depict the outline of three-property codon from molecular level and integrate life science knowledge into modern Chinese herbal nature theories, this thesis tightly around the key issue of how to formulate recipes with the theory of Chinese herbal nature,researches the functional law of the codons composed of triple herb properties and their usage in prescription's formation.Methods:Mechanism of Chinese herbal medicine is difficult to be attributed to the effect of acting on a specific target,but the multi-targets,multi-links,which integrated a regulatory network.Therefore, the thesis raised the concept of "building the biological networks of three-property codons ": 1) Use the pharmacological effects as a bridge to link the three-property codons to corresponding target proteins. 2) Anchor the HPC-related targets to the specific reactions in the context of cell signaling pathways network, which is composed of biochemical reactions step by step. Then use the entity grammar systems as the modeling tool to deduce the biological networks of three-property codons, eventually forming relation-based network conduction technology for three-property codons.Results:1) Using the method of association rules in data mining,81 three-property codons found their related pharmacological effects. By chi-square test, we explicated single pharmacological effects were associated with three-property codons. Two results were consolidated and eventually gain 25 three-property codons associated with multiple pharmacological effects.2) Using network qualitative simulation method, according to herb property-pharmacology-targets associations, we built the biological networks of three-property codons respectively on the background of the protein interaction network and the cellular reaction network.The results revealed that the cellular reaction network is more suitable to resolve the biological mechanism of three-property codons, because chemical reactions in cells is capable of expressing the role of molecules and their react direction. Therefore, we use the cellular reaction network as background to construct 25 three-property codons' biological networks.3) Taking Han-Ku-Lung biological network for example, we analyzed the mechanism of Han-ku-lung medicine for pneumonia treatment. And Han-Ku-Lung biological network were screened for key targets,which can influent the lung pneumonia targets by network delivery. In this part, a key target identification technology was proposed for the disease treatment in three-property codons networks.4) Based on the key targets of Han-Ku-Lung, taking skullcap and forsythia for example,we carried out the active ingredients identification of Chinese medicine based on three-property codons' biological networks. Partial active ingredients were proved in vivo or in vitro from literature, which can prove the reliability and practicality of the method.Conclusions:Parsing mechanism of three-property codon is an important part of Chinese herbal medicine theory study. It is one of the key tasks reflecting the characteristics of Chinese medicine research and development of new drugs, and also an important part of traditional Chinese medicine knowledge dissemination and popularization. This thesis, using the relation-based network conduction technology, built 25 biological networks and systematically explained the mechanism of three-property codons.On the other hand, using network qualitative simulation method, we screened biological networks of three-property codons and identified key targets, which can influent the disease targets by network delivery. A key target identification technology was formed from three-property codons networks for the disease treatment. Under the premise that targets of herb components were clear, the active ingredients of an herb can be screened according to the key targets of three-property codons. The active ingredients identified can provide a guidance for the secondary development of Chinese medicine and a design method of active ingredients drug for the disease treatment.