Study On The Constituents Of Kunlun Chrysanthemum And Its Mechanism To Improve Lipid Metabolism

Hyperlipidemia is a common lipid disorder characterized by elevated total cholesterol and/or triglyceride levels.Hyperlipidemia threatens human health and its incidence is increasing gradually worldwide.However,there is no ideal procedure for the treatment of lipid-lowering.Kunlun Chrysanthemum(KLCS)has been reported to exert antihyperlipidemic effects.However,the material basis responsible for lipid-lowering and its underlying mechanism remain unclear.This experiment was designed to illustrate the material basis of KLCS improving lipid metabolism and explore its mechanism of action from metabolism and intestinal flora combination point of view.The main research were as follows:(1)The research on the effective material basis of KLCS.The fingerprint profile of KLCS aqueous extract was established by UPLC-PDA.Based on accurate molecular weight and multi-level fragmentation information acquired from ESI-Q/TOF MS,the chemical structures of 80 components in KLCS aqueous extract were confirmed by Peak View software and HMDB database.In addition,GC-MS was used to separate and determine chemical components of volatile oil from KLCS by steam distillation,and 48 components were identified based on NIST11.L database.(2)Pharmacodynamic study on KLCS in the treatment of hyperlipidemia model mice.Male C57BL/6 mice were fed on a high-fat diet to establish a hyperlipidemia model.The Hyperlipidemia mice received intragastric administration of KLCS.The hypolipidemic efficacy was assessed by body weight,serum lipid indexes,fasting blood glucose level,insulin resistance and hepatic steatosis.The results revealed that KLCS had a significant lipid-lowering effect.(3)The study on mechanism of action of KLCS improving lipid metabolism from network pharmacology,metabolomics and microbiomics.Based on the integrated analysis of network pharmacology,metabolomics and microbiomics,the hypothesis of mechanism of KLCS improving lipid metabolism have been put forward.Network pharmacology: network pharmacology was utilized to reveal the potential pharmacological mechanisms of KLCS on hyperlipidemia.The networks of KLCS key bioactive component and hyperlipidemia-related targets were constructed through Genecards database and Cytoscape software.Network analysis was performed to identify 60 key ingredients and 40 targets of KLCS treatment of hyperlipidemia.KEGG pathway analysis identified signaling pathways involved in KLCS regulation including PPAR signaling pathway,insulin resistance and fat digestion and absorption.Metabolomics: UPLC-ESI-Q/TOF MS based metabolomics was used to characterize the metabolic profiles of normal,model and administration mice.This analysis yielded 35 differentially expressed metabolites between model and administration groups with fold change >|2| and P <0.05.Metabolic pathways analysis revealed that a crucial role of glycerophospholipid metabolism,GPI-anchored synthesis and linoleic acid metabolism pathway in regulating lipid-lowering effect of KLCS.Microbiomics: Microbiomics was performed on feces samples from normal,model and administration groups.Analysis of 16 S r DNA sequencing results revealed 7 differential bacteria between model and administration groups with P <0.05.Moreover,the correlation analysis illustrated that Enterobacteriaceae,Enterococciaceae,Peptostreptococcaceae and Verrucobacteriaceae had a close relationship with 3-oxododecanoic acid and 9E,11E-octadecadienoic acid.The main conclusions of this study are as follows:(1)The effective material basis of KLCS has been clarified.This work found that medicinal ingredients of KLCS mainly include flavonoids,phenolic acids,saponins,phytosterols,nucleosides,and amino acids.The chemical structures of 80 chemical components in KLCS aqueous extract and 48 chemical components in KLCS volatile oil were identified.(2)The lipid-lowering effect of KLCS on hyperlipidemia mice has been confirmed.This study showed that KLCS administration resulted in significant decrease in TC,TG and LDL levels and increase in HDL.As well as,KLCS improved glucose metabolism and ameliorated hepatic steatosis.(3)The mechanism of KLCS improving lipid metabolism was delineated.The lipid-lowering effect of KLCS was involved amelioration of intestinal flora and metabolism.On one hand,KLCS regulated the growth and metabolism of Enterobacter,gut＿metagenome.On the other hand,faradiol,isoliquiritigenin and cynarin in KLCS acted on ESR,MMP and NR1H3 to mediate PPAR and estrogen signaling pathway.Both of them modulated glycerophospholipid metabolism,GPI-anchored synthesis and linoleic acid metabolism pathway to achieve the effect of improving lipid metabolism.This study revealed the material basis and mechanism of KLCS improving lipid metabolism,which provided a research foundation and scientific basis for the development and application of KLCS.Furthermore,this project offered new perspective for the development of therapeutic drugs on hyperlipidemia.