Nobiletin And Ferulic Acid Through Anti-inflammatory And Oxidative Stress And Ghrelin Exerts Antidepressant And Prokinetic Effects Similar To Zhiqiaodanggui

Objective:To compare the efficacy of ZG and its absorbed component nobiletin and ferulic acid on gastrointestinal motility and depression,study on their anti-depressive mechanism,especially nobiletin and ferulic acid.Methods:First,we compare the efficacy of ZG and its absorbed component nobiletin and ferulic acid on gastrointestinal motility and depression:forced swimming rats:FST,in vivo measurements of GI motility;chronic antidepressant,weight change,sugar preference,food consumption,open field test and forced swimming test;Second,the anti-depressive and prokinetic mechanism of ZG:monoamine neurotransmitter,hormone level testing;Third,the anti-depressive mechanism of nobiletin:detection of oxidation index;Fourth,the anti-depressive mechanism of ferulic acid:detection of cytokines;Fifth,cell experiments:using hydrogen peroxide to establish the model of oxidative damage in PC 12 cells,to observe the effect of nobiletin.Using LPS to establish BV2 cell inflammation model,observe the effect of ferulic acid.Results:First,ZG have antidepressant effect which is similar to fluoxetine,but contrary to fluoxetine on prokinetic.Nobiletin and ferulic acid are similar to ZG on anti-depressive and prokinetic;Second,ZG can improve the content of 5-HT,NE,ghrelin and gastrina.Third,nobiletin can reduce ROS,COX,MDA,thereby affecting the content of p-mTOR and BDNF in the hippocampus.Fourth,ferulic acid can reduce the contents of inflammatory factors,which leads to changes of IDO,5-HT.Fifth,nobiletin has protective effect on PC 12 cell injury induced by hydrogen peroxide oxidation,ferulic acid has inhibitory effect on BV2 cell proliferation induced by LPS.Conclusion:Nobiletin and ferulic acid are similar to ZG on the antidepressive and prokinetic,the content change of antioxidase and inflammatory factors is the key to ferulic acid and nobiletin.