Study On The Preventive Effect Of Turmeric On Hyperlipidemia By Quantitative Proteomics

In recent years,with the change of people’s lifestyle and diet structure,the prevalence of hyperlipidaemia(HLP)has increased.It becomes an important risk factor that causes atherosclerosis,cardiovascular and cerebrovascular diseases,metabolic syndrome and other chronic diseases.Since medications represented by statins have serious adverse reactions such as elevated transaminase and myopathy that cannot be tolerated in the treatment of hyperlipidemia,the use of natural Chinese medicines for the prevention of hyperlipidemia has become the focus of research.Turmeric,as a natural herbal medicine and food,has shown the ability to effectively reduce the risk of atherosclerosis and cardiovascular disease.However,there are few reports about the effect study of turmeric in preventing hyperlipidemia by proteomics.In this study,TMT labeling technology coupled with LC-MS/MS technology were used to screen the differential proteins between normal diet and high-fat diet fed mice,also between mice fed with high-fat diet accompanied by turmeric and high-fat only diet.This study laied the foundation for understanding the mechanism of action for the prevention of hyperlipidemia.First,C57BL/6J male mouse was used as an animal model and the mice were randomly divided into three groups: normal diet group,high-fat diet group and high-fat diet with turmeric intervention group.After 8 weeks of feeding,the animal modeling was successful.The high-abundance proteins in plasma of three groups of mice were removed by using the Agilent Multi Affinity Removal Column(Mouse-3),then they were concentrated by ultrafiltration,followed by TMT labeling and LC-MS/MS analysis.The differential expression protein profiles in plasma were constructed between mice fed with high-fat diet accompanied by turmeric intervention and mice fed with high-fat diet only,also between high-fat diet fed mice and normal diet fed mice.All differentially expressed proteins were subjected to GO functional annotation classification enrichment,KEGG pathway annotation enrichment,andprotein-protein interaction analysis.The results showed that turmeric has obvious pharmacodynamic effects on hyperlipidemia mice induced by high-fat diets.By setting the screening criteria for differential proteins as ratio higher than 1.2(up-regulation)or ratio lower than 0.83(down-regulation)and p-value lower than0.05,24 differential proteins were found between the turmeric group and the high-fat diet fed group,among which 3 proteins were up-regulated and 21 proteins were down-regulated.Compared with the normal control group,36 differential proteins including 18 up-regulated proteins and 18 down-regulated proteins were identified.Bioinformatics analysis showed that the differentially expressed proteins related to lipid-lowering in turmeric are mainly Fga,Fgb,Fgg fibrinogen,Apo B and Apo C3 apolipoprotein,HL liver lipase,14-3-3η and 14-3-3ε protein.The signaling pathways involved in these differential proteins are the complement and coagulation cascades,cholesterol metabolism,fat digestion and absorption,glyceride metabolism,PI3K-Akt signaling pathway and PPAR signaling pathway.These pathways are involved in the synthesis,transportation,and metabolism of lipid components.Those results indicate that Fga,Fgb,Fgg fibrinogen,Apo B and Apo C3 apolipoprotein,and HL liver lipase are all promising targets for turmeric to prevent hyperlipidemia.In summary,these results laid the foundation for clarifying the mechanism of lipid-lowering for turmeric and finding potential drugs target.