Study On The Mechanism Of Zhibai Dihuang Decoction In Improving The Phenotype Of Obese Mice By Regulating Intestinal Flora

Background: At present,the number of obese people is increasing,and a series of diseases caused by obesity is a burden to both society and individuals.Existing treatments for obesity are discouraged due to their divergent side effects.The traditional Chinese medicine prescriptions,featuring with multi-directional,multi-target,as well as minor side effect,was therefore applied in our study.Objective: To observe the metabolic in obese mice and explore how to influence carbolipid metabolism esp.by improving intestinal functionMethods: Male C57BL/6J mice about 4 weeks old were fed in groups.C57 mice were divided into five groups,namely,the high-dose(26g·kg-1·day-1)group(HHF),the middledose(13g·kg-1·day-1)group(MHF),the low-dose(6.5g·kg-1·day-1)group(LHF),the highfat control group(HF)and the blank control group(Con).The detailed information was in the results.a)The weight changes of mice were recorded every day during the administration,so as to observe the drug efficacy of different dose groups.b)By real-time fluorescent quantitative PCR(QRT-PCR)experimental detection of mouse small intestine and colon tissue of IL-10,IL-6,SOD,GLP-1,5-HT2 c Tph1.Tph2,Ghrelin.Occludin and ZO-1 gene expression.c)P-akt and ZO-1 and Occludin genes in mouse small intestine and colon tissues were detected by Western blot.d)The spontaneous peristalsis of the small intestine of mice in each group was detected by the Power Lab polysomnography.e)Protein expression levels of GLP-1,5-HT,IL-10,IL-6 and ZO-1 in serum of mice were detected by Elisa kit.f)16S sequencing of feces of mice was performed to detect the difference of intestinal flora between the mice in the administration group and the control group.Research results:a)TCM formula treatment improved the phenotype of obese mice.Three doses of drugs were used for oral gavage,and it was found that the weight loss of mice in the high-dose group and the middle-dose group was not significant,while the weight loss of mice in the low-dose group was similar and both significant compared to controls.Considering the toxic and side effects,we chose the middledose group for the follow-up experiment.After two weeks of gavage administration,it was obvious that the weight of mice in the HF Med group was significantly lower than that in the HF group(P<0.05);The expression of p-Akt protein in muscle and fat was also increased compared with that in the HF group(P<0.05).b)The prescription of Traditional Chinese medicine can reduce fat by affecting the secretion of gastrointestinal endocrine peptide.The expressions of GLP-1,CCK and PYY in the small intestine and colon of MICE in THE HF Med group were increased compared with those in the HF group(P<0.05).The expression of GLP-1 in serum of MICE in THE HF Med group was consistent with the expression of m RNA in small intestine and colon tissues of mice,both of which were higher in the HF Med group than in the HF group(P<0.05).c)The expression of IL-6 m RNA in small intestine and colon tissues of MICE in THE HF Med group was lower than that in the HF group(P<0.05);The m RNA expression levels of IL-10 and SOD were higher than those of the HF group(P<0.05),the expression levels of ZO-1 and occlusive protein in the small intestine and colon of mice in the HF Med group were all higher than those in the HF group(P<0.05).The serum levels of IL-10,IL-6 and ZO-1 in the HF Med group were consistent with the mRNA results of the small intestine and colon tissues of the mice.d)m RNA expression of Tph1 in small intestine and colon tissues of mice in the HF Med group was lower than that in the HF group(P<0.05);The expressions of Tph2 and 5-HT2 C m RNA were higher than those of the HF group(P<0.05),the serological expression level of 5-HT in the HF Med group was higher than that of the HF group(P<0.05).The contractility and dilation of small intestine of mice in HF Med group were higher than those in HF group(P<0.05).e)16S results showed that,compared with mice in the HF Med group,the beneficial probiotics in the HF Med group was increased compared with that of the control group(P<0.05),the number of desulfurized vibrio decreased compared with the control group(P<0.05).Conclusion:a)The TCM formula can alleviate the phenotype of fat-induced obese mice,make the mice lose weight,reduce the lipid droplets in the liver,and increase the secretion of appetite-related endocrine peptide in mice to achieve the effect of appetite suppression.b)The TCM formula can reduce the inflammatory factors in the small intestine and colon of mice,improve their anti-inflammatory ability,and enhance the intestinal barrier function and intestinal motor function of mice.c)The herbal formula can change the intestinal flora of high-fat mice,increase the proportion of beneficial bacteria,and increase the secretion of GLP-1 and Occludin in small intestine and colon to varying degrees after the recovery of flora.