A Study On The Efficacy Mechanism Of Banxia Xiexin Decoction Based On The "Gut Microbiome-Lipid Metabolism Axis" In The Treatment Of Mice With Atherosclerosis Co-Depression Model

Objective:The pathogenesis of atherosclerosis（AS）co-depression disorders is unknown,and the current clinical treatment for these disorders is ineffective,and there is an urgent need to develop new and effective treatment strategies.Banxia Xiexin decoction（BXD）is a classical traditional Chinese medicine formula recorded in the Treatise on Exogenous Febrile Diseases,which has the therapeutic effects of dispersing lumps and knots,harmonizing the liver and spleen,tonifying the spleen and stomach,and resolving phlegm and promoting transportation,and modern clinical studies have shown that BXD has good therapeutic effects on depression and lipid lowering.It has been found that gut microbiome can regulate lipid metabolism in the host and thus participate in the development of AS co-depression disorders.Therefore,this study investigates whether BXD exerts its effect on the treatment of AS co-depression disorders by regulating the gut microbiome-lipid metabolic axis.Methods:To determine the primary constituents of BXD,UPLC-Q/TOF-MS analysis was carried out.Sixteen C56BL/6 mice were fed normal chow as a control group;64 ApoE^-/-mice were randomized into four groups（model group and three treatment groups）and fed high-fat chow combined with daily bind stimulation for sixteen weeks to develop the AS co-depression mouse model and were administered saline or low,medium or high concentrations of BXD during the experimental modeling period.The antidepressant efficacy of BXD was examined by weighing,a sucrose preference test,an open field test,and a tail suspension experiment.The effectiveness of BXD as an anti-AS treatment was evaluated through biochemical indices,the HE staining method,and the Oil red O staining method.The impacts of BXD on the gut microbiome structure and brain（hippocampus and prefrontal cortex tissue）lipids in mice with the AS co-depression model were examined by 16S rDNA sequencing combined with lipidomics analysis.Results:The main components of BXD include baicalin,berberine,ginsenoside Rb1,and 18 other substances.BXD could improve depression-like behavioral characteristics and AS-related indices in AS co-depression mice;BXD could regulate the abundance of some flora（phylum level:a reduced abundance of Proteobacteria and Deferribacteres;genus level:a reduced abundance of Clostridium＿IV,Helicobacter,and Pseudoflavonifractor,Acetatifactor,Oscillibacter）.The lipidomics analysis showed that the differential lipids between the model and gavaged high-dose BXD（BXH）groups were enriched in glycerophospholipid metabolism,and lysophosphatidylcholine（LPC）（20:3）（rep）（rep）)in the hippocampus and LPC（20:4）（rep）in the prefrontal cortex both showed downregulation in BXH.The correlation analysis illustrated that the screened differential lipids were mainly linked to Deferribacteres and Actinobacteria.Conclusion:BXD may exert an anti-AS co-depression therapeutic effect by modulating the abundance of some flora and thus intervening in peripheral lipid and brain lipid metabolism（via downregulation of LPC levels）.