~1H-NMR based metabolomics approach to evaluate effect of Cydonia oblanga Miller total flavonoid on atherosclerosis apoE-/- mice

OBJECTIVE ~1H-NMR-based metabolomics approach was conducted to holistically explore the effect and mechanisms of Cydonia oblanga Mill flavonoids(COMF) on high-fat diet induced Atherosclerosis(AS) apoE-/-mice.METHODS AS model was established on the apolipoprotein e knockout mice by high-fat diet.The ApoE-/-mice were split into 6 groups including control group,AS model group,COMF High dose(COMF-H) group,COMF medium dose(COMF-M) group,COMF Low dose(COMF-L) group and Simvastatin group as the positive control group.Serum samples from all groups were analyzed by ~1H-NMR technology and the OPLS-DA was conducted to distinguish the metabolic phenotypes.RESULTS Compared to the control group,serum levels of cholesterol,VLDL,leucine,isoleucine,valine,blood lipid,citrulline,methylamine,glucose,glycine,glycerol,myo-inositol,fructose,phenylalanine,unsaturated lipid,urea and other metabolites content significantly increased,while HDL,lactate,alanine,glutamate,glutamine,pyruvate,carnitine,citrate,choline content signifi.cantly decreased and the difference was statistically significant(P<0.05).The trend of metabolites in serum samples of COMF low,medium and high group was opposite to that of atherosclerosis model group and the difference was statistically significant(P<0.05).CONCLUSION Through functional analysis of these biomakers,amino acid metabolism,lipid metabolism,cholesterol metabolism,energy metabolism and inflammation reaction were considered as the most relevant pathological biomakers in the serum of AS mice.This study also demonstrates that COMF had the therapeutic effectiveness on AS through partly reversing the lipid,cholesterol,amino acid,energy metabolism and Inflammation reaction.