Regulatory Mechanism Of Liquiritin Apioside On DSS-induced Ulcerative Colitis And Depression-like Behavior In Mice

Ulcerative colitis(UC)is a chronic idiopathic autoimmune disease characterized by diffuse inflammation,mucosal damage and fibrosis.The prevalence of UC has steadily increased in recent years,but its cure rate is still unsatisfactory.Clinical studies have shown that patients with UC have a higher incidence of anxiety and depression,and psychiatric disorders can prolong the course of the disease and even induce disease relapse.Liquiritin apioside(LA)is a natural,non-toxic flavonoid derived from licorice.It has immunomodulatory,highly antioxidant and anti-inflammatory biological activities and plays an essential role in intestinal protection.This study explored the alleviating effect of Liquiritin apioside on ulcerative colitis and its accompanying depression-like behaviors in mice induced by dextran sulfate sodium(DSS),and preliminarily explored its mechanism,so as to provide a theoretical basis and direction for the development of new safe and effective prebiotics suitable for UC patients.The research contents of this paper are as follows:1.Firstly,the protective effect of LA administration on UC was preliminarily explored by constructing a mouse UC model.The results showed that LA significantly alleviated weight loss,increased DAI,shortened colonic length and colonic injury in mice with colitis,and prolonged survival.2.Secondly,the mechanism of LA intervention on UC was explored from the aspects of inflammatory response,immune balance,changes of intestinal flora and SCFAs content.The results showed that the expression levels of inflammatory cytokines(IL-1β,TNF-α,IL-6 and IL-17A)in colon of mice were decreased after LA administration,while the level of IL-10 was significantly increased.LA treatment decreased the relative proportion and absolute number of Th17 cells in Lamina propria(LP),while increased the proportion and number of Treg cells and IL-10~+Foxp3~+cells in LP.16S r RNA sequencing analysis of mouse fecal bacterial DNA showed that LA administration significantly increased the abundance and diversity of gut bacterial species in mice,increased the abundance of SCFAs-producing probiotics and inhibited the growth of pathogenic bacteria.GC-MS analysis of SCFAs content in feces showed that LA significantly increased the contents of acetate,butyrate and isobutyrate.3.Finally,intestinal bacterial depletion and FMT experiments provide further strong evidence that these mechanisms could be attributed to the alteration of the gut microbiome by LA.In conclusion,LA administration has a significant relief effect on DSS-induced colitis in mice.The mechanism of action is to significantly increase the diversity of intestinal microbiota in mice and change the distribution and composition of microbiota,especially by increasing the abundance of SCFAs-producing bacteria to reverse the imbalance of Treg/Th17 cells and eventually rebuild tissue homeostasis.At the same time,LA also significantly alleviated depression-like behavior in UC model mice.