| Depression is a chronic mood disorder disease which seriously endangers the physical and mental health of human beings.It has high incidence,high disability rate and high suicide rate.Depression seriously plagues the work and life of the patient,and brings a heavy burden to the family and the society.A joint study by the WHO,the world bank and the Harvard University has shown that depression has become the second major disease in China's disease burden.About the pathogenesis of depression,there are generally accepted cytokine theory,monoamine neurotransmitter theory,hypothalamus pituitary adrenal axis theory and neuronal plasticity.In recent years,the abnormal metabolic pathway of tryptophan has gradually become a breakthrough point in the study of the pathogenesis of depression.Monoamine neurotransmitter theory is mainly related to the decrease of 5-HT,norepinephrine(NA)and Dobaamine(DA)in the central nervous system.The antidepressants also play an antidepressant role by increasing the concentration of these transmitters."Dampness obstructing qi stagnation" is a type of depressive syndromes in TCM theory.Magnolia officinalis,as a traditional Chinese medicine for drying dampness,dispersing phlegm and degassing,has been attracted much attention at the application and research in depression in recent years.Modern studies have shown that Pinellia Magnolia soup and Gardenia Hou Putang have antidepressant effects.The main components of magnolia officinalis,magnolol and honokiol,can produce anti-depressant effects.However,the antidepressant effects of magnolia officinalis need to be comprehensively evaluated and in-depth studied based on its related components.In this study,taking honokiol as the carrier,multiple depression models were used to evaluate the antidepressant pharmacodynamics and mechanism.1.Antidepressant effects of honokiol on the model of drug depressive mouseObjective:To study the antidepressant effects of honokiol on the model of drug depressive mouse.Methods:Adopt the mouse depression model of reserpine antagonism and 5-hydroxytryptophan(5-HTP)enhancement.Observe the protective effects of honokiol low,medium and high dose group(2.5,5,10mg/kg)on hypothermia,ptosis,akinesia in mice caused by reserpine;and the effects of head twitches in mice induced by 5-HTP.Results:1.Reserpine antagonistic model:compared with the blank group,the temperature of the model group mice decreased significantly(P<0.01),the number of blepharoptosis and movement cannot were significantly increased(P<0.01);compared with the model group,the honokiol low,middle and high dose group could reverse the hypothermia.caused by reserpine(P<0.01),the honokiol middle and high dose group could decrease the number of ptosis(P<0.05),the number of movements can not of the honokiol middle dose group is decreased(P<0.05).2.Model of head twitches induced by 5-HTP:compared with the model group,the honokiol low,middle and high dose group could significantly enhance the head twitches of mice induced by 5-HTP(P<0.05).Conclusion:Honokiol can relieve the depression behavior of the reserpine antagonistic model and 5-HTP induced head twitches model in mouse and has certain antidepressant effect,its mechanism may be associated with increased synaptic monoamine neurotransmitter.2.Antidepressant effect and mechanism of honokiol on forced swimming mouseObjective:To study the antidepressant effect and the mechanism of honokiol on cute stress mouse.Methods:Forced swimming model of forced swimming mouse(FST)was used,75 mice were randomly divided into model group,fluoxetine group,honokiol group(2.5,5,10 mg/kg).After 7 days of intragastric administration,observe the immobility time of forced swimming and test the norepinephrine(NA),5-hydroxytryptamine(5-HT)and 2,3-indole dioxygenase(IDO)contents in mouse brain tissue by Elisa Kits.Results:Compared with control group,the fluoxetine group and the honokiol low,medium and high dose group mice immobility time of forced swimming was significantly shortened(P<0.05);and magnolol in the high dose group of brain NA content increased significantly(P<0.05);fluoxetine group and honokiol in high dose group,cerebral 5-HT content significantly increased(P<0.05,P<0.01).Conclusion:honokiol can improve the depressive behavior of mice with acute stress and depression,and has a certain antidepressant effect.Its main mechanism is related to the increase of NA and 5-HT levels in the brain.3.Antidepressant effect and mechanism of honokiol on chronic stress miceObjective:To study the antidepressant effect and the mechanism of magnolol on chronic stress mice.Methods:Adopting the chronic stress mice model,60 mice were randomly divided into control group,model group,fluoxetine group,honokiol low medium and high dose group(2.5,5,10 mg/kg).Except the blank group,two weeks of chronic stress stimulation with noise and shackles were given for the other groups of mouse.At the same time,the mouse in each treatment group was given the corresponding medicine.Then,observe the immobility time of forced swimming,test 5-HT and IDO contents in mouse brain tissue and serum corticosterone content by Elisa Kit and detect the expression of IDO mRNA in brain tissue used Quantitative real-time PCR.Results:Compared with the blank group,the immobility time of the model group was significantly increased(P<0.01),cerebral 5-HT content was decreased(P<0.01),cerebral IDO content and IDO mRNA expression level were significantly increased(P<0.01),serum corticosterone content was increased significantly(P<0.01).Compared with the model group,the immobility time of honokiol low,medium and high dose group,brain tissue IDO content and IDO mRNA expression level were significantly decreased,5-HT content in brain tissue increased significantly,serum corticosterone content decreased significantly,the difference was statistically significant(P<0.01,P<0.05).Conclusion:Honokiol can relieve the depression behavior of mouse and has certain antidepressant effect.Its main mechanism is related to decreasing tryptophan pathway restriction enzyme IDO content and gene expression level,promoting the transformation of tryptophan to 5-HT and increasing 5-HT level in brain.4.Antidepressant effect of honokiol in chronic stress depression ratsObjective:To study the effect of honokiol on the plasticity of hippocampal neurons in chronic stress depression rats.Methods:Using chronic stress rats depression model,60 rats were randomly divided into control group,model group,fluoxetine group,honokiol group(1.75,3.5,7mg/kg).Except the blank group,the other rats were given the unpredictable mild stimulation for 6 weeks.At the same time,the rats in each treatment group was given the corresponding medicine.Then,observe whether the model is established or not through the behavioral indexes,such as the open field experiment,the sugar water consumption experiment.Detecte the contents of 5-HT1A,GR2 and NMDAR1 receptors in hippocampus by immunohistochemistry,and the labeling of Ki67/GFAP and Ki67/NeuN by double labeling immunefluorescence.Results:Compared with the blank group,in model group,the activity scores of open field test and sucrose consumption were significantly reduced(P<0.01),GR2 receptor in hippocampus decreased significantly(P<0.01),NMDAR1 receptor in hippocampus increased significantly(P<0.01).Compared with the model group,the activity scores of open field test and sucrose consumption in honokiol low medium and high dose group were significantly increased(P<0.05),the hippocampal GR2 of honokiol middle dose group was significantly increased(P<0.01),and the hippocampal NMDARl of honokiol each dose group was significantly decreased(P<0.05).In the model group and treatment group of chronic stress rats,no new astrocytes and new neurons were observed in hippocampus.Conclusion:Honokiol can relieve the depression behavior of chronic stress rats and has certain antidepressant effect.Its main mechanism is related to repairing the abnormal changes of hippocampal GR2,reducing the content of NMDAR1 receptor,restraining the persistent excitatory state of NMD A receptor and reducing neurotoxicity.5.Effects of honokiol on the content of inflammatory factors and free calcium ions in the compound depression model of miceObjective:To study the effect of honokiol on the content of inflammatory factors and free calcium ions in the compound depression model of mice.Methods:using a compound model of chronic stress and lipopolysaccharide injection,90 mice were randomly divided into control group,model group,fluoxetine group and honokiol groups(5,10 mg/kg).Except the blank group,ten days chronic stress stimulation with noise and shackles were given for the other groups of mouse and inject lipopolysaccharide at 11th days.At the same time,the mouse in each treatment group was given the corresponding medicine.Then,observe the immobility time of forced swimming,test IFN-? content in mouse brain tissue by Elisa Kit and serum TNF-?,IL-1?,IFN-ycontents by radioimmunoassay.Flow cytometry was used to detect the concentration of free calcium ions in the brain tissue of mice.Results:Compared with the blank group,in model group,the immobility time,IFN-y content in brain tissue,serum TNF-?,IL-1?,IFN-ycontent were significantly increased(P<0.05,P<0.01).Compared with the model group,the immobility time of honokiol medium and high dose group was significantly reduced,the IFN-ycontent of honokiol high dose group and the serum TNF-?,IL-1?,IFN-?content of honokiol medium and high dose group were significantly reduced(P<0.05,P<0.01).The content of free calcium in brain tissue of honokiol high dose group was significantly decreased(P<0.05).Conclusion:Honokiol showed a certain antidepressant effect on compound depressive mice.Its mechanism was related to the reduction of inflammatory factors such as TNF-?,IL-1?,IFN-?,inhibiting inflammatory reaction and inhibiting calcium overload in central nervous system. 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