Study On Quality Assessment Of Zezhu Tablets Based On Quality Markers

Compound Chinese medicine is an important form of medicine used in the clinical treatment of traditional Chinese medicine.It embodies the essence of the whole formula of TCM,such as "bian-zheng-lun-zhi"and "qi-qing-he-he".Due to the complexity of the traditional Chinese medicine,the scientific connotation and significance of which is hard to be clarified,especially the quality control indicators of compound Chinese medicine are indeterminate.It has seriously impacted the modernization of traditional Chinese medicine.How to clarify the chemical basis and mechanism of compound Chinese medicine is an urgent problem to be solved in the modernization of Chinese medicine.Zexie decotion is a classical prescription in Jin-Kui-Yao-Lue and comprised of Zexie and Baizhu.It has shown significant effect on the therapy of hyperlipidemia in modern pharmacology and clinical studies.The lipid-lowering efficacy of Zexie decotion caused the wide attention of scholars currently,but the chemical basis and mechanism of which is not yet clear,in view of the lack of quality control model in the therapy of hyperlipidemia,the clinical application of which is under restrictions.It needs to adopt new ideas and technologies to further systematic research urgently.In this paper,several strategies were applied in the systematic research of Zexie decotion.A variety of analysis techniques such as the determination of the multi-components,the fingerprint analysis and the characterization of chemical group by UPLC-QTOF-MS were used,and the analysis of blood transitional components,network pharmacology,and metabolomics research were applied to systematically explore the chemical basis of pharmacodynamics and mechanism of Zexie decotion,and illuminate the quality markers.Quality control of zhe tablets originated from Alisma soup was studied on this basis.This study would provide reference for other traditional Chinese medicine research.In this paper,a stable,reliable and reproducible HPLC method was established to study the changes of different composition of Zexie decotion before and after compatibility.In the different compatibility of water decoction.Zexie significantly reduced the decocting amount of atractylenolide in the decoction,and Baizhu significantly reduced the decocting amount of alisol A and alisol F in the decoction,and the combined use of Zexie and Baizhu increased the decocting amount of alisol A 24-acetate and alisol B 23-acetate in the decoction.The difference of 7 characteristic components was significant in different compatible decoction when using different extraction methods and the stability of the drying process of Zexie decotion extract was better after compatibility.The HPLC-DAD-TOF-MS technique was used to identify the chemical components in the Zexie decotion,and the absorbed components in the rat plasma after the administration were identified.In combination with the database matching technology and methods,57 components were identified,including 34 components of Zexie and 23 components of Baizhu.17 serum active components were screened and identified in the serum of administration rats.This study laid a foundation for the study of metabolism and pharmacodynamics of Zexie decotion.LC-MS method was adopted to establish the rats hyperlipidemia serum metabolic fingerprint spectrum,and with exogenous high-fat diet induced hyperlipidemia model,the lipid-lowering effect of Zexie decotion was studied by serum metabolomics,and the effect of Zexie decotion in hyperlipidemia therapy was confirmed by the holistic metabolic regulation pattern.13 potential biomarkers in serum of hyperlipidemia was screened,which primarily involved hemolysis phosphatidyl choline metabolism,phospholipid metabolism,fatty acid transport and metabolism,arachidonic acid metabolism and so on,the study reveal that Zexie decotion by adjusting the metabolic pathway of these imbalances and play to the role in the therapy of hyperlipidemia,It provided a new idea for explaining the mechanism of reducing fat of Zexie decotion.The network pharmacology was applied in the explorative study of the pharmacodynamics mechanism of Zexie decotion.It was showed that the mechanism in therapy of hyperlipidemia involved a variety of lipid metabolic pathways,such as Insulin signaling pathway,PPAR signaling pathway and MAPK signaling pathway and fatty acid metabolism and so on.It was also closely related to cholesterol metabolism pathways such as biosynthesis of steroids and bile acid biosynthesis.Triterpenoids of Zexie and esters of Baizhu were the main lipid-lowering active components.The high efficient and rapid determination of multi-components for drug quality control and fingerprint control method was established on this basis,and the principal component analysis(PCA)was applied to study the quality of different batches of Zexie decotion,the key points of quality control of the product were the triterpenoids of Zexie and esters of Baizhu,and the quality control was established based on the qulaity marker.