| Traditional Chinese medicine and pharmacy is the crystallization of the wisdom of the Chinese nation, and still plays an important role in treatment and health care of people in China. Good doctor with good quality of Chinese materia medica is the guarantee of good curative effect of Chinese materia medica, however, with the differentiation of the modern discipline, traditional Chinese medicine (TCM) and Chinese materia medica also gradually differentiation in order to adapt to the development of traditional Chinese medicine and pharmacy modernization. This discipline differentiation brought out some problems as well. The quality of Chinese materia medica was influenced with multiple factors from producing area to the clinical use, and the quality of Cheese materia medica was often uneven. However, on clinic, the clinical dosage was always fixed. This is one of the important factors that affect Chinese materia medica curative effect consistency. Nevertheless, the quality control system which could set connection between the quality of Chinese materia medica and clinical dosage, and furthermore guide the doctor adjust dosage reasonably was lack of.Aiming at the problems existing in the quality evaluation and control of Chinese materia medica, our research team has been committed to the establishment of quality control and evaluation method correlated to clinic. This thesis chose Coptidis Rhizoma as model drug to put forward the concept of effective constituent equivalence, as its quality is of volatility, however, its material basis is relatively clear, frequency of clinical use is high, and our team has been successfully established biological activity detection method associated with clinic for it. This method measured the quality and consistency of TCM from the end of decoction, and was used to guide the investigation of consistency of Coptidis Rhizoma decoction pieces dispensing. The main research results are as follows:1 Chemical composition analysis of Coptidis Rhizoma from different origin by UHPLC-MS16 chemical compounds were preliminary identified from extract of Coptidis Rhizoma. including 11 alkaloids and 5 acidic components, and multivariate statistical analysis results showed that the chemical composition of different origin of rhizoma coptidis existed obvious difference, of which genuine producing area and the ordinary-region was especially of significant difference. Furthermore, berberine. coptisine. epiberberine, jateorhizine and palmatine were.chosen as important distinguish compounds between them.2 The establishment of effective constituent equivalence and application for evaluation of consistency of Coptidis Rhizoma decoction pieces dispensing.This method measured the quality and consistency of TCM from the end of decoction, and the formula for it was the sum of Coptidis Rhizoma composition content revised with biological activity multiplied by the dosage. The result of effective constituent equivalence applied for evaluation of consistency of Coptidis Rhizoma decoction pieces dispensing showed as follow. Effective constituent equivalence could effectively characterize the influence of specifications, weighing and decoction on medicinal slices dispensing consistency. Effective constituent equivalence high, the quality of medicinal materials good. Consistency of effective constituent equivalence of different batches of medicinal materials good, as well as the consistency of dispensing.3 The component differences of coptidis chinensis rhizome and fibrousPlant metabolomics research showed that chemical composition of coptidis chinensis rhizome and fibrous was similar, the difference between them was mainly reflected on the content of some alkaloids, of which berberine, coptisine, epiberberine, jateorhizine and palmatine were chosen as important distinguish compounds between them, and our quantitative analysis results of HPLC also showed that in fibrous the content of these five alkaloids was obvious lower than that in rhizome.4 The effective constituent equivalence was verified based on the ulcerative colitis model in mice induced by dextran sodium sulfate.Coptidis Rhizoma has therapeutic effect on dextran sodium sulfate (DSS) induced ulcerative colitis mice, and at the same dose, there was obvious treatment effect difference between mice oral administration with aqueous extract of Coptidis Rhizoma with different effective constituent equivalence. The higher effective constituent equivalence, treatment effect was better. This result from one side verified the correlation of effective constituent equivalence to clinical curative effect.5 Metabolomics research on the therapeutical effect of Coptidis Rhizoma for ulcerative colitis induced by DSSBased on serum metabolomics research, we found 4 potential treatment biomarkers of Coptidis Rhizoma for ulcerative colitis, including leukotriene A4.3-oxo-octadecanoic acid, L-Histidine, phytosphingosine. Through pathway analysis, treatment related pathways including arachidonic acid metabolism, histidine metabolism and sphingolipid metabolism were hited. According to the literature, the three metabolism were closely associated with the inflammatory response. So in our later research, we can study the mechanism of treatment of Coptidis Rhizoma for ulcerative colitis based on these three metabolic pathways, which will also promote the development and utilization of Coptidis Rhizoma. Based on potential markers, principal component analysis was applied for groups administrated with different effective constituent equivalence of Coptidis Rhizoma, the result showed good discrimination, which further verified the correlation of effective constituent equivalence to curative effect.This study focused on the insufficient of current quality control method, which quality control method was not connected with clinical dosage, and could not guide the clinical dosage adjust reasonably, put forward the concept of effective constituent equivalence with exploratory purpose. Through chemical analysis and in vivo experiments, the curative effect dependence and biomarker dependence of effective constituent equivalence was verified. It was expected to be used to guide the evaluation between the quality and dosage of Chinese materia medica, and furthermore provide reference to guide clinical consistency evaluation of Chinese materia medica. |
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