Dissecting Scientific Connotation Of Compatibility Law In Si-Ni Decoction Analogous Formulae Using Network Formulaology Approach

Traditional Chinese medicine(TCM),is great treasure for China,which has been practiced for thousands of years and proven to be especially effective to treat chronic and complex diseases.Traditional Chinese medicine formulae(TCM formulae),embodying the essence of original philosophy in TCM and the dialectical TCM theory,is the main application form to treat diseases in clinic.As the connecting bridge between cultural inheritance and modern TCM drugs development,scientific interpretations of compatibility law of TCM formula have become one of the most important scientific problems in modern research of TCM.However,current research progress is strongly hampered by the complexity of chemical composition of TCM formulae and biological system.In this thesis,five Si-Ni Decoction Analogous Formulae(SNs)including Si-Ni decoction(SIN),Ginseng Si-Ni decoction(RSIN),Fuling Si-Ni decoction(FSIN),Tongmai Si-Ni decoction(TSIN)and Tongmai Si-Ni with Suis fellis pulvis decoction(ZSIN)were taken as research subjects.Their relationships between compounds and bio molecular network were systemically investigated using network formulaology approach.This successful application in Si-Ni Decoction Analogous Formulae suggests network formulaology could be a useful tool for TCM formulae research and provides a new way to dissect scientific connotation of compatibility law of TCM Formulae.The main contents and results of current work are listed below:1.Systematic chemical profiling of five Si-Ni decoctions in vitro and in vivo was performed by multistage MS and high-resolution MS(HR-MS)experiments.A total number of 83 compounds have been separated and identified by reference compounds comparison through several sources,including mo lecular formulae matching,characteristic fragmentation information,UV spectra as well as the relevant literature.Analysis on SNs-treated rats detected 55 prototype compounds and 39 metabolites in the systemic circulation in vivo,which may contribute directly to their observed clinical efficacies.2.Pharmacological effects and molecular mechanisms of SNs against coronary heart disease were investigated experimentally.Using coronary heart disease related experimental models,we confirmed the efficacy of SNs treatment of coronary heart disease at the cellular level and overall animal level.Furthermore,based on the gene expression profiling from DNA microarray experiments on dysregulation of biomolecular network caused by acute myocardial infarction,the pharmacological mechanism of SNs were studied by means of network modeling,network visualization and network analysis.Our results indicated that SNs exert their pharmacological effects by regulating multitarget and multiprocess.3.Based on the system integration of chemical profiling and pharmacological mechanisms of the SNs,we further proposed a FRE algorithm for quantitative evaluation of regulation of biological network by five Si-Ni Decoction Analogous Formulae.This algorithm takes the docking scores of compound-target interactions and the relative content of prototype compounds into account.Our results demonstrate that SNs have good regulatory effect in Net.Calcium.RSIN and FSIN have better regulatory effect in Net.Angiogenesis than the other three formulae.ZSIN has better regulatory effect in Net.EnergyMetabolism,Net.Steroid and Net.VSMContraction than others.This association analysis between the chemical profiling and the biological function provided important scientific evidence for dissecting scientific connotation of compatibility law of SNs.