Study on Protective Effect and Mechanism of Apigenin on Liver of Mice with Hyperlipidemia Based on Metabolomics Methods
Objective To investigate the protective effect and mechanism of apigenin on the liver of hyperlipidemic mice based on metabolomics methods.Methods C57BL/6 mice were randomly divided into four groups including blank,model,fenofibrate(26.0 mg·kg-1),and apigenin(12.5 mg·kg-1)groups,with six mice in each group.Each group was treated with corresponding drug by gavage once a day for five days.On the third day of administration,the mouse model of acute hyperlipidemia was induced by a single intramuscular injection of Triton WR-1339(5 mL·kg-1)at a concentration of 0.12 g·mL-1.Biochemical indexes such as TC and TG in mice serum were measured by using a fully automatic microplate reader.HE staining was used to observe pathological changes in liver tissue.UPLC-Q-TOF-MS/MS technology was applied to analyze liver tissue samples.Differential metabolites were screened by using multivariate statistical analysis methods such as PCA,PLS-DA,and OPLS-DA.Then we ran the mass spectrometry information of these metabolites through online databases including HMDB,METLIN and KEGG,as well as combined with relevant literature to obtain the potential differential metabolites.The identified potential differential compounds were imported into the MetaboAnalyst platform for metabolic pathway analysis.Results Compared with the blank group,TC and TG levels in mice serum of model group increased obviously(P＜0.01).Irregular arrangement of liver cells,fat vacuoles and infiltration of inflammatory cells were found.Compared with the model group,TC and TG levels in mice serum of apigenin group decreased(P＞0.05).Fatty lesions in liver tissue were significantly improved,and fat vacuoles and inflammatory cell infiltration were significantly reduced.A total of 35 differential metabolites were screened.Twenty-six differential metabolites showed callback trend after apigenin treatment.Eight metabolic pathways were obviously affected,among which pantothenate and CoA biosynthesis,as well as arachidonic acid metabolism are two main metabolic pathways(P＜0.05).Conclusion Apigenin exhibits a certain protective effect on liver of hyperlipidemic mice,and its mechanism may be related to regulating liver inflammatory response and lipid metabolism-related pathways.
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