RESUMO
OBJECTIVE To explore the mechanism of Cirsium japonicum extract in improving hypercholesterolemia based on metabolomics technology. METHODS The extract of C. japonicum was prepared by macroporous resin adsorption， and its main components were identified by liquid chromatography-tandem mass spectrometry. The experimental mice were randomly divided into control group （n＝6） and modeling group （n＝16）. The hypercholesterolemia model was induced by diet in modeling group； after modeling， the rats of modeling group were divided into model group （n＝8） and C. japonicum extract group （n＝8）. C. japonicum extract group was given C. japonicum extract 400 mg/（kg·d） by gavage （calculated by extract）， and other 2 groups were given constant volume of 0.3% sodium carboxymethyl cellulose solution， for 6 weeks. After medication， the intervention effect of C. japonicum extract was evaluated by the levels of serum total cholesterol （TC）， triglyceride （TG） and the histopathological changes of liver. The mechanism of C. japonicum extract in improving hypercholesterolemia model mice was investigated by metabolomics. RESULTS It was identified that C. japonicum extract contained 12 components， such as 030302005） chlorogenic acid， linarin and pectolinarin. After 6 weeks of intervention， compared with control group， serum level of TC was increased significantly while the level of TG was decreased significantly in model group （P＜0.05）， while a large number of lipid droplets， disorderly arrangement of liver cells and the damaged structure of liver cord were observed in liver tissue. Compared with model group， the serum level of TC was decreased significantly in C. japonicum extract group（P＜0.05）； the lipid droplets in liver tissue were significantly reduced， with liver cells arranged radially and tightly centered around the central vein， and liver cords arranged neatly. The metabolomics study showed that after the intervention of C. japonicum extract， the levels of metabolites were significantly adjusted back， such as ethanolamine， fumaric acid and cholesterol； finally， three metabolism pathways， such as alanine-aspartate-glutamic acid metabolism， arginine biosynthesis， citric acid cycle， were obtained. CONCLUSIONS The main components of C. japonicum extract are phenolic acids and flavonoids， such as chlorogenic acid， linarin， pectolinarin. C. japonicum extract can improve hypercholesterolemia by regulating the contents and distribution of differential metabolites， adjusting alanine-aspartate-glutamic acid metabolism， arginine biosynthesis and citric acid cycle， participating in oxidation-reduction reaction， improving liver lipid accumulation， and playing anti-inflammatory role.