Effects Of Curcumin Nicotinate On Lipid Metabolism And Inflammation In Apolipoprotein E-deficient Mice

ObjectiveTo investigate the effects and mechanisms of Curcumin Nicotinate (CN) on thehigh-fat/cholesterol diet induced atherosclerosis in apoE-/-mice.Methods:ApoE-/-mice were fed the chow diet for1week to adapt to the new environment,and then the forty ApoE-/-mice were randomly divided into five groups:controlgroup(0.5%CMCNa(0.2mL/10g/d)), atherosclerotic model group (0.5%CMCNa(0.2mL/10g/d)), simvastatin group(5mg/kg/d), low doses of Curcumin Nicotinate(33mg/kg/d) and high doses of Curcumin Nicotinate (99mg/kg/d), gavaged every day.All the mice fed up with high-fat, high-cholesterol diet that contained5.0%fat(wt/wt)and1.0%cholesterol except for control group. The statues of the mice,such as foodintake and water intake, as well as weight of mice were observed. After six week oftreatment, tissue specimens from liver, aorta and blood were collected. And then theserum lipid(TC、TG、LDL-C、HDL-C) was detected by the Automatic biochemicalanalyzer; Assessment the atherosclerosis in aortic trees and aortic sinus was carriedout by staining with oil red O; The atherosclerosis plaque in aortic atches wasobserved by HE staining;The expression of TNF-αand IL-6were measured by Elisakit; And the expression of Caveolin-1、SREBP-2in liver were detected by IHC andWestern blotting.Results:After ApoE-/-mice fed high-fat six weeks, compared with the control group,serum total cholesterol (TC), low-density lipoprotein (LDL-C) were increased,high-density lipoprotein (HDL-C) was decreased, and aortic sinus plates wassignificantly increased, staining of the whole aorta and HE staining of the aortic arch were both observed increase plaque, which suggested: high-fat accelerate the processof atherosclerosis in ApoE-/-mice, and model was established successfully. After sixweeks of treatment, Curcumin Nicotinate (CN) could reduced significantly the levelof TC and LDL-C in mouse serum, and the high dose of CN had a more significanteffect, which suggested that Curcumin Nicotinate could reduce high blood cholesterol.Oil Red O staining of aortic sinus, aortic overall and HE staining of the aorticarchsuggested Curcumin Nicotinate could reduce the area of atherosclerotic plaquesin high-fat fed ApoE-/-mouse. Immunohistochemical and Western blotting resultsshowed that Curcumin Nicotinate reduced the expression of Cav-1and SPEBP-2levels in mice liver. Immunohistochemical and serum ELISA results in mice livershowed that Curcumin Nicotinate could reduce the level of TNF-α, had someregulatory role in IL-6.Conclusion:Curcumin Nicotinate could inhibit the atherosclerotic plaque formation inhigh-fat/cholesterol diet fed apoE-/-mice. And the effects of Curcumin Nicotinate maybe related to its regulation on lipid metabolism and inflammation of apoE-/-mice liver.