Research On The Mechanisms Of Xiaoai Jiedu Decoction Against Colon Cancer Based On Gut Microbiota And Metabonomics

Objective:1.To evaluate the anti-tumor effect of Xiaoai jiedu decoction from HCT116 cells tumor-bearing model.2.To explore the mechanism of inhibiting the development of colorectal cancer from serum metabolomics of colon cancer model mice.Methods:The HCT116 cells tumor-bearing model was established.The mice of"control" group were given normal saline by gavage.The mice of "Xiaoai jiedu decoction" group were given low and high concentration drug by gavage.During the experiment,the activity of mice was observed,the body weight and tumor volume of mice were measured.After intragastric administration,tumor tissues were taken to calculate the tumor inhibition rate.The liver,spleen and kidney tissues were weighed and organ coefficients were calculated.HE staining was performed to observe the effect of Xiaoai jiedu decoction to pathological tissue.Stool was taken for 16SrDNA sequencing.The pseudo germ free mice model of HCT116 cells tumor was established.The mice of "control" group were given normal saline by gavage.The mice of "Xiaoai jiedu decoction" group were given low and high concentration drug by gavage.The volume and weight of tumor were measured to verify whether Xiao ajiedu decoction still have anti-colon cancer effect.The HPLC-MS was used to analyze the serum metabolites of HCT116 cells tumor-bearing mice to screen out the differential metabolites and their action pathways.Results:1.Xiaoai Jiedu decoction has significant effect on anti-colon cancer,and the anti-tumor effect of low-dose group was better than that of high-dose group.Xiaoai Jiedu decoction had no significant effect on body weight,liver,spleen and kidney coefficients.2.Xiaoai jiedu decoction can improve the abundance of Bacteroidetes,Bacteroidaceae,Bacteroides,prevotellaceae,Parabacteroides_distasonis and reduce the abundance of Firmicutes,Actinobacteria,Desulfovibrio,Enterobacter,Deferr i bacteraceae.3.Lack of intestinal flora,Xiaoai jiedu decoction has no significant inhibitory effect on the growth of HCT116 transplanted tumor.4.Xiaoai jiedu decoction could increase Hypoxanthine,Xanthine,Glycine,Arginine,Citrulline,Alanine,Alpha-linolenic acid,Lysopc 18:2 and so on.The metabolites were down-regulated including:Linoleic acid,Bilirubin,Arachidonic acid,Ascorbic acid,Sinapinic acid,Cholic acid,Deoxycholic acid,5-Hydroxymethyluracil and so on.5.The process of anti-tumor of Xiaoai jiedu decoction was mainly involved in the following metabolic pathways:Biosynthesis of amino acids,Primary bile acid biosynthesis,Lipid metabolism,Lipopolysaccharide biosynthesis,HIF-1 signaling pathway,Glycine and arginine metabolism,Pentose phosphate pathway,alpha-Linolenic acid metabolism,Purine metabolism,Midine metabolism,Fatty acid metabolism,Secondary bile acid biosynthesis.Conclusion:Xiaoai Jiedu decoction relies on the intestinal flora to play a role in inhibiting colon cancer.Xiaoai jiedu decoction can improve the abundance of Bacteroidetes,Bacteroidaceae,Bacteroides,prevotellaceae,Parabacteroides_distasonis and reduce the abundance of Firmicutes,Actinobacteria,Desulfovibrio,Enterobacter,Deferribacteraceae.Xiaoai jiedu decoction could regulate the specific bacterias such as Actinobacteria,Proteobacteria,Tenericutes,Bacteroidetes,Prevotellaceae,and Alloprevotella to interfere with the energy metabolism and biosynthesis of amino acids,lipid metabolism,fatty acid metabolism,HIF-1 signaling pathway to enhance immunity,reduce inflammation,promote apoptosis and other ways to achieve anti-tumor effect.