Systematic Pharmacological Study Of The Mechanism Of Action Of Qi Prescription On Depression

Background:Depression is the most prevalent mood disorders and has the main features of the clinical syndrome with prominent and persistent low mood and impaired cognitive function,and has characteristic clinical manifestations including long-term depressed mood,anhedonia,slow thought,mental activity decline,decreased speech and motions,low self-evaluation,pessimism for the future,diminished interests for the life and work,taking the initiative with people and so on.The notable characteristics of depression have high morbidity,high recurrence rate,high disability rate and high suicide rate.It is a kind of complex disease,its causes,pathogenesis,complex factors,which are a long-standing problem in the use of drug and the design of drug.Development of many antidepressants for a long time,and some antidepressants have been first-line drugs for the treatment of depression,but they has some disadvantages of the effect to be slow,adverse effects and intolerance for some patients,causing that the treatment is not satisfactory at present.However,Traditional Chinese Medicine(TCM)has applied the prescription of the functions of operating Qi to treat depression based the principle of promoting the circulation of Qi,getting certain satisfactory effects.Chaihu-Shugan-San(CSS),Yueju-Pill(YJW),Banxia-Houpo-Tang(BHT)are the common and famous formulas of regulating Qi in the clinic.But the Qi of TCM is still abstract and its potential biologic mechanisms are still clear,and the affects of it in depression are also not clearly elucidated.Objective:Systematically unveiling the effect of regulating Qi to further analyse and deciphering the biological mechanisms of Qi of TCM,and comparing the anti-depression mechanisms between the TCM formulas and antidepressants to probe into the potential novel therapeutic strategies for the diseases,and providing scientific basis for development of the drug.Method:Through pharmacology approach we conducted the networks about the targets of the ingredients in CSS,YJW and BHT,respectively;and conducted the networks about the targets of antidepressants.Finally,we use the entity grammar system as a guide to conduct the biological network related disease of the above three formulas;in the same method,conducting the biological network related disease of antidepressants.First,ingredients in CSS,YJW and BHT were retrieved from TCMD and TCMID database;the genes targeted by these ingredients were chosen from STITCH database;antidepressants and drug targets were retrieved from DrugBank database;the proteins related disease were collected from GeneCard database;and the background database about biology were retrieved from hiPathDB database.Conducting corresponding network model by system pharmacology approach and the entity grammar system,we also further analyzing the network and deciphering functionally grouped gene ontology and pathway annotation networks by Clue GO.Results:The common mechanisms of CSS,YJW and BHT mainly belonged to metabolism,nervous system,signal transduction,endocrine system,immune system,digestive system,cellular processes,sensory system,excretory system,and transport and so on.Those biological processes are consistent with the actions of Qi of TCM,and these results explained underlying the molecular mechanisms of Qi.The mechanisms of targets of single drug among thirty-eight antidepressants are nervous system,but the general mechanism of combating thirty-eight antidepressants in the treatment of depression are mainly involved in nervous system,signal transduction,endocrine system,immune system,digestive system,cellular processes and so on,but the intermediate processes are not complex than TCM formulas.The common molecular mechanisms of three formulas acting on depression mainly included nervous system,signal transduction,endocrine system,immune system,digestive system,cellular processes and so on,but their pathways are wider and more than antidepressants.Conclusions:This study preliminary deciphering the underlying mechanisms of Qi of TCM,and its mechanisms are closely related to the treatment of depression.It will help to improve the treatment of disease through the in-depth study in the further.On the other hand,comparing between TCM formulas and antidepressants whose molecular mechanisms,we found that the functions of TCM are wider and more systematic,this showed that they not only acted on disease targets but also affect the middle course of disease,getting better treatment of disease,while most of the targets of antidepressants are the targets of nervous system,but they have little effect on other systems of the organism,so they can not overall adjustment of the disease.Above all,we believed that the systemic treatment of depression may be the best treatment strategy from the aspects of metabolism,signal transduction,immune system,nervous system,endocrine system,digestive system,cell process and so on.