Traditional Chinese Medicine Zhike-Houpu Herb Pair Regulated Gut Microbiota And Ameliorated Inflammation In Chronic Unpredictable Mild Stress Induced Depressive Rats

Objective: To explore the effects of Zhike-Houpu herb pair intestinal on gut microbiota and inflammation level in chronic unpredictable mild stress(CUMS)induced depressive rats,and preliminarily analyze the correlation between gut microbiota and inflammation.Methods: The antidepressant effect of Zhike-Houpu herb pair on CUMS rats was evaluated by multiple behavioral tests.16 s r DNA sequencing technology was used to explore the effects of Zhike-Houpu herb pair on gut microbiota of CUMS rats.Hematoxylin-Eosin(HE)staining,immunofluorescence and Western Blots(WB)were used to observe the effects of drugs on inflammation levels in colon,prefrontal cortex and hippocampus of CUMS rats.Pearson’s correlation analysis was used to preliminarily explore the correlation between gut microbiota and the inflammation levels in colon,prefrontal cortex and hippocampus.Results: Zhike-Houpu herb pair increased the body weight and sucrose preference percentage of depression-like rats induced by CUMS procedure,and shortened the immobile time in forced swimming test and escape latency in water maze.In addition,Zhike-Houpu herb pair regulated gut microbiota composition of CUMS rats,upregulated the relative abundance of Lactobacillus,Bifidobacterium and Akkermansia,and downregulated the relative abundance of Ruminococcus and Romboutsia.The expression levels of pro-inflammatory factors(TNF-α,IL-1β,IL-6)and Iba-1 in hippocampus,pro-inflammatory factors(TNF-α,IL-1β)in prefrontal cortex,and pro-inflammatory factors(TNF-α,IL-6,IL-1β)in colon were reduced.In addition,the expression level of IL-10 in hippocampus and colon were increased.The expression of tight junction protein(zo-1)in prefrontal cortex and tight junction protein(Occludin and claudin-5)in colon were increased.In Pearson’s correlation analysis,the relative abundance of Lactobacillus was found to be negatively correlated with the expression level of proinflammatory factors(TNF-α,IL-1β,IL-6)and Iba-1 in hippocampus,proinflammatory factors(TNF-α,IL-6,IL-1β)in prefrontal cortex and proinflammatory factor(IL-6)in colon and be positively correlated with the expression level of anti-inflammatory factor(IL-10)in hippocampus and colon,junction protein(zo-1,occludin)in prefrontal cortex.The relative abundance of Romboutsia was positively correlated with the expression level of proinflammatory factors(IL-1β,IL-6)and Iba-1 in hippocampus,proinflammatory factors(TNF-α,IL-6,IL-1β)in prefrontal cortex and proinflammatory factors(IL-1β,IL-6)in colon.It was negatively correlated with anti-inflammatory factor(IL-10)in the hippocampus and colon,and tight junction protein occludin in the colon.Conclusion: There was no significant difference between the 10g/kg and 20g/kg Zhike-Houpu herb pair,both doses have antidepressant effects.Zhike-Houpu herb pair reverse the changes of gut microbiota caused by CUMS procedure and effectively reduce the inflammatory levels of colon,prefrontal cortex and hippocampus.The reverse effect of Zhike-Houpu herb pair on the up-regulation of Romboutsia and down-regulation of Lactobacillus induced by CUMS procedure are closely related to the antiinflammatory and repair barrier functions in colon,hippocampus and forehead of CUMS rats.