| The particularity of traditional Chinese medicine preparations is to study the processing technology and its scientificity of“from Chinese medicinal decoction pieces to pharmaceutical materials”.Therefore,the material properties before forming is an important factor restricting the development of traditional Chinese medicine preparations,and the in-depth research on the material basic of traditional Chinese medicine is the fundamental way to solve it.In the early stage,our team puts forward the“component structure theory”based on the integrity and complexity of the traditional Chinese medicine composition system.It also proposed that the“component”as the basic unit for the development of traditional Chinese medicine preparations in the future.And it provide a new idea for the research and development of traditional Chinese medicine preparations.In the early stage,our team participated in“the research on the design technology of the effective component group of Chinese medicine related to blood stasis and chest obstruction”in National Key Project of Scientific and Technical Supporting Programs,and carried out an in-depth study around“Shen Shao Shu Xiong prescription”（prescription including Salviae miltiorrhiza,Radix Paeoniae Rubra,Panax notoginseng,Ligusticum Chuanxiong and so on）.Modern studies have shown that Ligusticum chuanxiong has a good anti-myocardial ischemic effect,it is widely used in the treatment and prevention of cardiovascular diseases such as coronary heart disease,angina pectoris and atherosclerosis.However,The material basis of Ligusticum chuanxiong against myocardial ischemia injury is not clear,and the biopharmaceutical properties of the active components are also unknown,so the research and development process of traditional Chinese medicine preparations is seriously restricted.In view of the time factors and complexity of“Shen Shao Shu Xiong prescription”,this project selected Ligusticum chuanxiong of prescription to further research,in order to provide a theoretical basis for the final study of“Shen Shao Shu Xiong prescription”,and to provide reference for the development of innovative structural components of Chinese medicine preparations.This project is based on“components structure theory”,to evaluate anti-myocardial ischemic effect of Ligusticum chuanxiong,identification of basic components of Ligusticum chuanxiong against myocardial ischemia,optimize the structure of components,explore the potential mechanism of Chuanxiong lactone components,and integrate the biological pharmaceutical properties of Chuanxiong lactone components,the main contents are as follows:1.Evaluation of Ligusticum chuanxiong in preventing myocardial ischemia and confirmation of material base componentsIn this part,the rats were subcutaneously injected with isoproterenol（ISO）to induce myocardial ischemia injury.Then,the effects alcohol extract and water extract of Ligusticum chuanxiong on myocardial index,CK,LDH and AST level,SOD and T-AOC activity,morphology and structure of myocardial tissue in rats with myocardial ischemia injury were investigated respectively.The results showed that Ligusticum chuanxiong had good effect in preventing and treating myocardial ischemia.In addition,the main components of Ligusticum chuanxiong were enriched and purified by modern separation and analysis techniques:Chuanxiong phenolic acid components,Chuanxiong lactone components and Chuanxiong polysaccharide components.The structural characteristics of Chuanxiong phenolic acid components andChuanxiong lactone components were analyzed by HPLC.The yield of Chuanxiong phenolic acid components was 1.41%and the content was 43.49%.The yield of Chuanxiong lactone components was 3.43%,and the content was 71.56%.And the yield of Chuanxiong polysaccharide components was 5.79%and the content was51%by phenol sulfuric acid method.Then we constructed H2O2 induced HUVECs oxidative damage model and oxygen-glucose deprivation damage model in H9c2 cells to evaluated different components of Ligusticum chuanxiong against myocardial ischemia by various pharmacodynamic evaluation methods.The results showed that the Chuanxiong phenolic acid components,Chuanxiong lactone components and Chuanxiong polysaccharide components have good cardiovascular protective effect,such as antioxidant,anti-inflammatory,anti apoptotic,improving energy metabolism and other biological activities.Thus,the material components of Ligusticum chuanxiong were identified as Chuanxiong phenolic acid components,Chuanxiong lactone components and Chuanxiong polysaccharide components.2.Composition optimization of Ligusticum chuanxiong for prevention and treatment of myocardial ischemiaIn this part,we optimized the best components structure of Chuanxiong phenolic acid components,Chuanxiong lactone components and Chuanxiong polysaccharide components by uniform design.We used ISO induced myocardial ischemia model and comprehensive evaluation of multiple index.The results were analyzed by DPS7.05software to obtain the best component structure of Ligusticum chuanxiong.The best components structure of Ligusticum chuanxiong against myocardial ischemia was Chuanxiong phenolic acid components was divided into 23.94 mg·kg-1,Chuanxiong lactone components was 43.87 mg·kg-1,Chuanxiong polysaccharide components was65.45 mg·kg-1,namely Chuanxiong phenolic acid components:Chuanxiong lactone components:Chuanxiong polysaccharide components=2.39:4.39:6.55.3.Study on the potential mechanism of Chuanxiong lactone components against myocardial ischemia injuryFrom the perspective of autophagy,this study explored the effects of Chuanxiong lactone components on autophagy induced by myocardial ischemia in vitro and in vivo,and then studied the potential mechanism by oxygen-glucose deprivation damage model in H9c2 cells.The results showed that Chuanxiong lactone components could play an important role in inhibiting autophagy of cardiomyocytes to alleviate myocardial ischemia by activating PI3K/Akt/mTOR pathway.4.Demonstrative study on biopharmaceutical properties of Chuanxiong lactone componentsThis part mainly focuses on equilibrium solubility and the oil-water partition coefficient of each representative compound of Chuanxiong lactone components.The similarity analysis of biopharmaceutical properties of each compound in the components was carried out by the angle cosine method,and the overall biopharmaceutical properties of Chuanxiong lactone components were characterized by mass weight coefficient.The results showed that subunit a of Chuanxiong lactone components was class III component,that is,it has high solubility and low permeability,and subunit b of Chuanxiong lactone components was class II component,that is,it has low solubility and high permeability.To sum up,under the guidance of the“component structure theory”,we quickly identified the basic material components of Ligusticum chuanxiong against myocardial ischemia,and analyzed the structure characteristics of Ligusticum chuanxiong,and further optimized the best component structure of Ligusticum chuanxiong.The mechanism of Chuanxiong lactone components against myocardial ischemia injury was elucidated and its overall biopharmaceutical properties were characterized.This study has created the precondition for the construction of the multi-release drug system with components as the basic unit,and also provided a new model for the research of the component of traditional Chinese medicine. |
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