Exploration of the Mechanism of Anti-atherosclerosis Effect of Optimized Tanyu Tongzhi Decoction Based on Intestinal Flora and Bile Acid Metabolism

LI Yingying; LI Ruoqi; WU Haonan; LI Xiang; TANG Danli

Abstract：Objective To explore the efficacy and mechanism of optimized Tanyu Tongzhi decoction(TYTZD)in atherosclerosis(AS)mice based on the regulation of intestinal flora and bile acid metabolism.Methods ApoE-/-mice were fed a high-fat diet for 12 weeks to establish an AS model,while the mice were randomly divided into the model group,TYTZD-L group(6.5 g·kg-1·d-1)and TYTZD-H group(13 g·kg-1·d-1).Mice of control group were fed a standard diet.Biochemical assay kits were used to detect serum lipid levels.HE and oil red O staining were used to evaluate the degree of atherosclerotic plaque lesions in the aorta.ELISA was used to detect serum inflammatory factor levels.16S rRNA was used to detect gut microbiota composition,and targeted metabolomics was used to analyze serum bile acid content.Results Compared with the control group,the levels of serum TG,TC,and LDL-C in the model group significantly increased(P<0.05),while the level of HDL-C significantly decreased(P<0.01).The plaque area at the aortic root significantly increased.The levels of serum IL-1β and TNF-α significantly increased(P<0.01).In addition,the ratio of intestinal Firmicutes/Bacteroidota significantly increased(P<0.01).There were a total of 96 different bacterial genera,among them,the abundance of Escherichia-Shigella,etc.significantly increased(P<0.05),while the abundance of Muribaculaceae,etc.significantly decreased(P<0.01).Notably,the levels of serum β-MCA,CDCA,and LCA significantly increased(P<0.01).Compared with the model group,the TYTZD-L group and TYTZD-H group showed significantly reduced levels of TG and TC(P<0.05),decreased area of aortic AS plaques,and significantly lower serum levels of IL-1β and TNF-α(P<0.01).In the TYTZD-H group,the LDL-C level was significantly reduced(P<0.01),the Firmicutes/Bacteroidota ratio in the gut was significantly decreased(P<0.01),the abundance of Escherichia-Shigella,etc.was significantly reduced(P<0.05),the abundance of Muribaculaceae,etc.was significantly increased(P<0.05),and the serum levels of CDCA and LCA were significantly lowered(P<0.01).Conclusion The optimized TYTZD can alleviate high-fat diet induced AS,whose mechanism of action is closely related to regulating gut microbiota composition and bile acid metabolism.