Effects Of Eucommia Ulmoides Oliv And Gardenia Extract On Lipid Metabolism And Intestinal Flora In Obese HFD Rats

Objective:Observe the effects of Eucommia ulmoides leaves extract and Gardenia extract on blood glucose and lipids,body weight and histopathology of obese rats with High Fat Diet(HFD).The present study aimed to examine the effects of Eucommia ulmoides leaves extract and Gardenia extract on bile flow and lipid metabolism in HFD obese rats,and study the effects of Eucommia ulmoide leaves extract and Gardenia extract on intestinal flora of eight species of obese rats with HFD.Methods:The SD rats were fed HFD rat diet,The N control group was fed with the basic rat diet,and after 8 weeks the successful M rats were selected and divided into 8 groups:blank control group(N),M group(M),Gardenia extract group(GE)500mg/kg,Eucommia ulmoides leaves extract group(EE)500mg/kg,combination of low-dose group(EEL+GEL)200mg/kg+200mg/kg,combined high-dose group(EEH+GEH)500mg/kg+500mg/kg,resveratrol group(RES)500mg/kg,and ursodeoxycholic acid group(UC)500mg/kg.Ten rats in each group were orally administered for 8 weeks.N group and M group were orally administered with an equal volume of 0.5%Carboxymethylcellulose Sodium(CMC-Na)vehicle,and the other groups were orally administered at the same dose once a day.Body weight,blood lipid level,blood glucose level,body length,glucose tolerance and insulin tolerance of each test group were measured at the end of the 8th week.HE staining,oil red O staining method were used to observe changes on liver,skeletal muscle,ileum,white fat,brown fat morphological changes;immunohistochemical was adopted to observe to observe Uncoupling Protein 1(UCP-1)expression in white fat(WAT)and brown fat(WAT);And Bile flow in 6 hours were monitored.Western Blot was used to determine adipokine in the white fat,bile acid-related transporter receptors in the ileum and liver and inflammatory factor in the liver;16sRNA fluorescence quantitative method was used to detect the changes of eight species on intestinal flora in rats.Results:1.8 weeks administration,compared with the N group,the M group rats of weight,WAT wet weight,Lee's index were increased in varying degrees,serum Glutamic Oxalacetic Transaminase(AST),Glutamic Pyruvic Transaminase(ALT),Triglycerid(TG),Total Cholesterol(TC),Low-density Lipoprotein Cholesterol(LDL-C)also were increased in varying degrees,High-density Lipoprotein Cholesterol(HDL-C)was reduced,glucose level and insulin level were increased,the difference was statistically significant(P<0.05).And a certain amount of glucose tolerance and insulin resistance occur.Compared with the M group,the indicators above were improved in varying degrees in each test group(P<0.05).HE staining results showed that compared with the M group,each test group improved inflammation in the liver,reduced fat vacuoles,and the liver cells were arranged neatly.Intestinal glands were lined up and inflammation was reduced.Fat cells in white fat and brown fat were arranged orderly,and the number of WAT cells and BAT cells were increased in the same field.Skeletal muscle cells damage were reduced.The results of oil red O staining showed that compared with the M group,the aggregation of lipid droplets were reduced in each group in the liver and WAT,the accumulation of BAT lipid droplets was increased,and the droplets and the heterotopic fat deposition were decreased in skeletal muscle.The immunohistochemical results showed that compared with the M group,the average optical density of UCP-1 in WAT and BAT in each trial group increased significantly(P<0.05).2.The results of bile flow showed that,compared with the M group,total bile flow was increased within 6 hours in varying degrees in each group,among which the differences of RES group,EE group,EEH+GEH group and UC group were statistically significant(P<0.05).Western Blot results showed that compared with the M group,the expression of Cholesterol 7?-hydroxyl(CYP7A1),Multidrug resistance-associated proteins 2(MRP2),Multidrug resistance-associated proteins 3(MRP3),G protein-coupled receptor for bile acid(TGR5),Peroxisome proliferator-activated receptor?(PPAR?),Fibroblast growth factor 19(FGF19),Na~+-taurocholate cotransporting polypeptide(NTCP),Bile salt export pump(BSEP),Transmembrane G Protein Coupled Receptor(TGR5),ATP-binding cassette(ABC)transporters G5(ABCG5)and ABC transporters G8(ABCG8)in liver tissues were up-regulated in each groups,and the expression of Peroxisome proliferator-activated receptor?(PPAR?)in WAT was up-regulated in each groups(P<0.05).The expressions of Fibroblast growth factor 15(FGF15),Apical sodium-dependent bile acid transporter(ASBT),ABCG5 and ABCG8 in the ileum were down-regulated in each groups(P<0.05).The differences of Pregnane X Receptor(PXR)and Kelch-like ECH-associated protein-1(KEAP-1)in liver tissue were down-regulated in each drug-administered group(P<0.05).The expression levels of Interleukin-6(IL-6),Tumor necrosis factor alpha(TNF-?),Nuclear factor-?B(NF-?B),inducible nitric oxide synthase(iNOS)in liver tissues were down-regulated in each groups(P<0.05),the expression levels of P65 and Nuclear factor erythroid-2-related factor(NRF2)in liver tissues were up-regulated in each groups(P<0.05).3.16sRNA fluorescence quantification showed that compared with the M group,the relative abundance of Bacteroides,Lachnospiraceae,Bifidobacterium,Lactobacillus and Rikenellaceae in each group were increased at different degrees,the relative abundance of Colibacillus,Clostridium and Firmicutes in each group were reduced at different degrees.Conclusion:In summary,The single-dose and combined doses of Eucommia ulmoides leaves extract and Gardenia extract can function as follows:(1)The body weight,liver function and histopathology of HFD obese rats were improved to different degree.(2)Increase bile flow,reduce inflammation in the liver,regulate lipid metabolism.(3)Regulate the eight kinds of intestinal flora and contribute to the stability of the intestinal environment.