Research On Hypocholesterolemic Effects And Mechanism Of Mulberry Leaves Water Extract On Cholesterol Metabolism In High Fat Diet Female Mice

With the continuous improvement of people's living standards and changes in eating habits,the incidence of hyperlipidemia increased year by year.Dyslipidemia is a metabolic disorder that is one or more of total cholesterol(TC),triglyceride(TG),low density lipoprotein cholesterol(LDL-C)and high density lipoprotein cholesterol(HDL-C)occur abnormalities,it is a major risk factor for cardiovascular morbidity and mortality.By controlling the serum total cholesterol(TC)to control the atherosclerosis,which can reduce the cardiovascular morbidity.Research have shown that mulberry leaves have antibacterial,antiviral,anti-inflammatory,hypoglycemic and hypolipidemic effects.However,there is little research on the reduction of cholesterol in mulberry leaves,and the mechanism of action is unclear.In this study,we investigated the hypolipidemic effects of water extract of mulberry leaves from the aspects of synthesis and metabolism of cholesterol in female mice with high fat diet.The main contents and results of this study are as follows:(1)The effect of mulberry leaves water extract(MWE)on the basic growth index was studied.Daily administration of 8 mg kg-1·bw MWE(in terms of DNJ content)can be significantly reduced weight gain rate,liver coefficient,fat coefficient,and liver fat content.Compared with the high fat control group,after 16 weeks,the female mice could decreased the weight gain rate by 24.22%(P<0.05);reduced the liver coefficient was 16.22%(P<0.05);reduced the fat coefficient was 54.05%(P<0.05);reduced the liver fat coefficient was 38.29%(P<0.05).were administered with mulberry leaf water for 16 weeks,most of the liver tissue structure has been restored,the arrangement of liver cell cord was radial,hepatic lobular boundaries clear,hepatic sinus was clearly visible,the normal size of the nucleus,the center,the portal area without inflammatory cell infiltration.Indicating mulberry leaf water extract can reduce the weight gain,liver and fat coefficient,and can reduce liver fat content and improve liver cell morphology,reduce liver cell steatosis.(2)The effect of MWE on the serum lipids and liver cholesterol metabolism related enzyme activity was studied.Daily administration of 8 mg kg-1·bw MWE(in terms of DNJ content)can be significantly reduced the levels of TC?TG?LDL-C?ApoB in serum and Atherosclerosis index(AI).Compared with the high fat control group,after 16 weeks,the female female mice could decreased the TC level 39.97%(P<0.05);reduced the TG level 52.08%;reduced the LDL-C level 28.93%(P<0.05);significantly reduce the Apo B level 48.58(P<0.05);reduced the AI 44.05%(P<0.05);increased the ApoA1 56.88%(P<0.05).Daily administration of 8 mg kg-1·bw MWE(in terms of DNJ content)can be significantly increased the activity of LCAT,and CYP7A1,and the activity of HMG-COA reductase was decreased(P<0.05).Compared with the high fat control group,after 16 weeks,the male and female mice could increased the LCAT 23.03%(P<0.05);increased the CYP7A1 27.43%(P<0.05).The results showed that the aqueous extract of mulberry leaves could promote the transport of cholesterol,decrease the levels of TC,TG,LDL-C and ApoB and decrease the atherosclerosis index by increasing the serum HDL-C and ApoA1 levels,increase liver LCAT activity,Liver HMG-COA reductase activity,increased CYP7A1 activity,to achieve the purpose of lowering blood lipid.(3)The effect of mulberry leaves water extract on the liver cholesterol metabolism related factor mRNA expression was studied.Daily administration of 8 mg kg-1·bw MWE(in terms of DNJ content)can be significantly increased LDL-R?LCAT?SREBP2?CYP7A1?FXR and LXR mRNA expression,decreased CETP mRNA expression.Compared with the high fat control group(P<0.05),after 16 weeks,the male and female mice could increased the LDL-R mRNA expression 56.99%(P<0.05);increased the LCAT mRNA expression 56.99%(P<0.05);increased the SREBP2 mRNA expression 115.96%(P<0.05);increased the CYP7A1 mRNA expression 41.39%(P<0.05);increased the FXR mRNA expression 60.86%(P<0.05);decreased the LXR mRNA expression 44.35%(P<0.05);increased the CETP mRNA expression 50.63%(P <0.05).Compared with the high fat control group,the liver HMG-COA reductase mRNA expression was not significantly affected(P <0.05).The results showed that the MWE could up-regulate the expression of LDL-R and up-regulate the expression of LDL-R in combination with blood LDL,decrease the content of plasma cholesterol,increase the expression of LCAT and decrease the expression of LCAT CETP,promote free cholesterol binding to HDL,Into the HDL-C;mallow leaf water extract LXR,FXR and CYP7A1 between the front feedback and negative feedback regulation,promote cholesterol into bile acid into the enterohepatic circulation and excreted,so as to achieve the effect of hypolipidemic.(4)The effect of mulberry leaves water extract on fecal metabolites was studied.Daily administration of 8 mg kg-1·bw MWE(in terms of DNJ content)can be significantly increased the levels of stercorin TBA and SCFAs in facal.Compared with the high fat control group,the male and female rats were increased stercorin level 18.35%(P<0.05);increased TBA level 18.35%(P<0.05);increased SCFAs level 40.70%(P<0.05);increased acetic acid level 33.41%(P<0.05);increased propionic acid level 106.44%(P<0.05);increased butyric acid level 49.20%(P<0.05);significantly increased isobutyric acid level 106.54%(P<0.05);increased valeric acid level 79.20%(P<0.05);increased isovalic acid level 36.53%(P <0.05).The results showed that the water extract of mulberry leaves could improve the intestinal environment of micefemale mice,regulate intestinal microenvironment,promote intestinal microbial fermentation to produce short-chain fatty acids,promote the excretion of fecal and bile acids,and then achieve the effect of hypolipidemic.