Antidepressant Effects And Mechanisms Of Sulforaphane （SFN） And Its Derivatives Based On The Microbiota-gut-brain Axis

Depression is featured by mental abnormal,severe mental disorders and high suicidal tendencies,which make it a heavy burden on society and individuals.Although some antidepressants can effectively relieve depression symptoms in clinical treatment,they still have limitations such as delayed onset,low sensitivity in some patients and obvious side effects.Therefore,it is necessary to find more effective antidepressants for the treatment and prevention of depression.SFN is a pot ent ial drug fo r t he t reat ment o f depressio n,so we est ablished a mo use mo d el o f depressio n by CUMS co mbined wit h so lit ar y r ear ing,t o exp lo re t he ro le and mechanis m o f SFN and it s derivat ive s SLL-Ⅲ-9 and SLL-Ⅲ-120 in relieving depressive based o n micro bio me-gut brain axis.The resu lt s were as fo llo ws:1.SFN and its derivatives SLL-Ⅲ-9 and SLL-Ⅲ-120 relieve depressive behavior in model miceIn the depression model mice,the sucrose preference of SFN,SLL-Ⅲ-9 and SLL-Ⅲ-120 groups increased significantly,indicating that these three compounds can reverse the pleasure deficiency caused by depression.In tail suspension and forced swimming experiments,SFN and SLL-Ⅲ-120 could significantly shorten the immobility time of depressed mice,suggesting that SFN and SLL-Ⅲ-120 could alleviate the degree of despair in mice.Although SLL-Ⅲ-9 could alleviate the loss of pleasure caused by CUMS,there was no significant reduction in behavioral despair.2.SFN and its derivatives SLL-Ⅲ-9 and SLL-Ⅲ-120 change the composition of gut microflora in depression model miceThe gut contents of mice in each group were collected for macrogenomic sequencing.The results showed that the composition of gut flora of mice in each group changed after SFN and its derivatives SLL-Ⅲ-9 and SLL-Ⅲ-120 were given intragastric administration.At genus level,compared with the model group,the relative abundance of Candidatus Amulumruptor in the intestines of the three groups decreased significantly;and the relative abundance of Oscillibacter was significantly increased after intragastric administration of SLL-Ⅲ-120 and SLL-Ⅲ-9,but there was no significant change in the SFN group;and the relative abundance of Lactobacilli increased significantly,while the relative abundance of Trichomonas decreased after intragastric administration of SLL-Ⅲ-120.Oscillibacter 、 Tritrichomonas and Lactobacilli are closely related to gut diseases in mice,and also play an important role in nervous system diseases such as depression.These results suggest that SFN,SLL-Ⅲ-9 and SLL-Ⅲ-120 may restore gut microflora homeostasis by regulating the composition of gut microflora,and then affect the degree of depression in mice.3.Effects of SFN and its derivatives SLL-Ⅲ-9 and SLL-Ⅲ-120 on the levels of inflammatory factors and neurotransmitters in depression model miceThe results of HE staining showed that SFN and SLL-Ⅲ-120 group showed lighter staining,indicating that SFN and SLL-Ⅲ-120 could alleviate hippocampal injury and neuroinflammation in mice.ELISA results showed that SFN,SLL-Ⅲ-9 and SLL-Ⅲ-120 significantly decreased the concentration of inflammatory factor TNF-αin serum,hippocampus and colon of mice,and significantly increased the concentration of anti-inflammatory factor IL-10,monoamine neurotransmitter DA and5-HT.It is suggested that SFN and its derivatives SLL-Ⅲ-9 and SLL-Ⅲ-120 may affect the levels of inflammatory factors and neurotransmitters in depressed mice.In conclusion,SFN and its derivatives SLL-Ⅲ-9 and SLL-Ⅲ-120 may improve the disorder of intestinal flora in depressed mice by regulating microflora closely related to intestinal diseases,such as Oscillibacter,Trichomonas,Lactobacillus,etc.,thus reducing the inflammatory response of colon tissue and acting on the brain through bi-directional regulation of the "intestinal-brain" axis,resulting in a significant increase in the content of neurotransmitters in the hippocampus.And then improve the depression-like symptoms of mice.The results of this study can provide more theoretical basis for the targeted microbiota-gut-brain axis study of depression and provide new drugs for the treatment of depression.