Study On Effective Substances Of Cyclocarya Paliurus And Souliea Vaginata

The systematic research on the effective substances of medicinal plants is the basis for the discussion of the mechanism of action,and the innovation of drug research and development.This paper revolves two aspects of anti-diabetes and anti-inflammation,taking Cyclocarya paliurus and Souliea vaginata as the research objects,using a combination of research models and modern analytical tools,and the pharmacodynamic substances of anti-diabetic and anti-inflammatory effects from C.paliurus and S.vaginata and the related mechanisms of action are discussed.On this basis,further research is carried out on the metabolism of active ingredients and the preparation process of high-purity active ingredients,in order to provide scientific basis for the development of new drugs based on active natural products.The main researches and results are as follows:1.Study on the effective substances and mechanism of anti-diabetic effects from Cyclocarya paliurusFour undescribed compounds,including three rarely occurring seco-dammarane triterpenoid glycosides(1?3)possessing 20,24-epoxy linkages,and a pentacyclic triterpenic acid(4),were systematically isolated,along with eleven known triterpenoids(5?15).Their structures were elucidated on the basis of chemical and spectroscopic approaches,including 2D NMR and HRESIMS techniques.Finally,the effects of the isolates in insulin-stimulated glucose uptake in 3T3-L1 adipocytes and C2C12 myotubes were further evaluated.These results indicated that several triterpenoids were found to enhance insulin-stimulated glucose uptake in both C2C12 myobutes and 3T3-L1 adipocytes.Compound 1 further enhanced the phosphorylation of IRS-1,Akt,and GSK-3?,and activate AMPK and p38 MAPK,to enhance insulin-stimulated glucose uptake in adipocytes.Collectively,triterpenoids from C.paliurus could be developed as insulin sensitizers,which might have therapeutic potential for insulin resistance and hyperglycemia.Furthermore,the study on the hypoglycemic activity of triterpenoids will help to reveal the material basis of anti-diabetic effects from C.paliurus.2.Study on the metabolism of arjunolic acid in ratsArjunolic acid is one of the main anti-diabetic triterpenoids from C.paliurus.This study was based on UPLC-Q-TOF-MS/MS method for the first time,combined with multiple data post-processing methods,to screen and identify the metabolites in plasma,urine and feces samples of rats after intragastric administration of arjunolic acid.59 metabolites were detected,and the metabolic pathways and types of metabolic reactions of arjunolic acid in rats were speculated.The results suggested that arjunolic acid is mainly involved in phase ? metabolism in rats.Deoxygenation,demethylation,oxidation,reduction,hydrolysis,and glucuronide conjugation are the main metabolic pathways that may occur in rats.The results of this experiment will provide a basis for the chemical structure modification and evaluation of druggability of arjunolic acid,and it is helpful to correctly understand the material basis in vivo of the efficacy of this ingredient.3.Study on simultaneous preparation of high purity total triterpenoids and total flavonoids from Cyclocarya paliurusThe simultaneous preparation process of high-purity total triterpenoids and total flavonoids was established using resin combined technology.By optimizing the process parameters and process verification,the total triterpenoids obtained can be more than 90% pure and total flavonoids can be more than 80% pure.Besides,it improved the comprehensive utilization of leaves of C.paliurus in a simple,strong practical,renewable and reusable way.Also,this study will provide important reference for the later pilot trial and industrial production,and help to the in-depth development of anti-diabetes drugs and health food from C.paliurus.4.Study on the effective substances and mechanism of anti-inflammatory effects from Souliea vaginataTwo unprecedented cycloartane trinor-triterpenoids(1,2),together with other four undescribed(3-6)and thirteen known(7-19)ones,were discovered from the traditional Tibetan medicine Souliea vaginata.A reduced density gradient calculation for intramolecular noncovalent interactions allowed the determination of relative configuration of C-24 secondary hydroxyl group on the rotatable side chain of compound 3.The anti-inflammatory effects of all compounds(1?19)were evaluated by an LPS-stimulated NO production model on RAW264.7 macrophage cells.As one of the most potent compounds in an LPS-stimulated NO production assay,compound 3 dose-dependently suppressed LPS-induced NO production and pro-inflammatory cytokines secretion,prevented degradation of I?B?,and decreased the expression of iNOS,through inhibiting NF-?B activity.The study will help to reveal the anti-inflammatory mechanism of Tibetan medicine S.vaginata.5.Chemical composition analysis of Souliea vaginata by HPLC-Q-TOF-MS/MSBased on HPLC-Q-TOF-MS/MS technology,a comprehensive and systematic analysis of the chemical constituents in Souliea vaginata was conducted,and 47 major compounds were identified.Furthermore,the structure was classified and the law of mass spectrometry was summarized.The 47 compounds are divided into four major groups: phenylpropanoids,alkaloids,terpenoids and steroids.And phenylpropanoids and cycloartane triterpenoids were the main component types of S.vaginata.This study provides data support for the rapid identification of cycloartane triterpenoids in medicinal plants,the study of the chemical substance basis and mechanism of action of S.vaginata.