Study on the Mechanism of Action of"Zang-Jiang-Zhi"Capsule in the Treatment of Hyperlipidemia Based on Serum Medicinal Chemistry and Network Pharmacology
Objective To analyse the blood entry components and metabolite products of"Zang-Jiang-Zhi"Capsule,and to investigate their mechanism of action in the treatment of hyperlipidemia.Methods The UHPLC-Q-Exactive Orbitrap MS technique was used for the determination of the blood-entry components of"Zang-Jiang-Zhi"Capsule,and the identification of the enrolled components and metabolites was carried out by comparing the mass spectral information of administered serum and blank serum,and by combining with the existing literature.Swiss Target Prediction and Super Pred databases were used to predict the targets of the entry components.Construct PPI network using STRING database.Cytoscape software was used to construct the"drug-component-target-disease"network.GO and KEGG enrichment analyses were performed on the targets using the DAVID database.The preliminary validation was carried out by molecular docking technique.Results A total of 13 components and 20 metabolites were detected in rat serum.The database was collected to obtain 556 targets corresponding to the blood entry components,of which 173 targets intersected with hyperlipidemic targets.PPI,GO,and KEGG analyses showed the main potential targets of HSP90AA1,PIK3CA,PIK3CB,AKT1,ESR1,RXRA,JAK1,JAK2.The main signaling pathways involved in the treatment of hyperlipidemia with"Zang-Jiang-Zhi"Capsule include th17 cell differentiation,endocrine resistance,lipid and atherosclerosis,AGE-RAGE signaling pathway in diabetic complications,sphingolipid signaling pathway,and insulin resistance.The molecular docking showed that there was a good affinity between the key targets and the blood-entry components.Conclusion The blood-entry components of"Zang-Jiang-Zhi"Capsule may be the main pharmacological material basis for its treatment of hyperlipidemia,and provide more molecular level evidence for its clinical application by treating hyperlipidemia through the mechanism of multi component-multi target-multi pathway.
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