Study On The Mechanism Of Antidepressant Components Of Radix Bupleurum And Radix Glycyrrhiza Based On Melatonin Receptor

Depression involves complex etiology and factors,and the formulation of multiple hypotheses provides us with new ideas and theoretical foundations for further understanding of the pathogenesis of depression and the development of drugs.Although numerous studies have shown that Sinisan and Radix Bupleuri and Radix Glycyrrhizae in the compound can exert antidepressant effects through various pathways and mechanisms,the first target of action of the drug has not been elaborated.MTR has great potential in the treatment of depression,and the different structural characteristics of MT1 R and MT2 R also provide different mechanisms and pathways for antidepressants.Therefore,it is of great significance to find the basis of the antidepressant efficacy of Radix Bupleuri and Radix Glycyrrhizae in Sinisan,as well as the first target of action and explain the mechanism of action.In this study,based on the process of drug metabolism in vivo,the identification of blood entry components was proposed.Firstly,part of blood entry components of Radix Bupleuri and Radix Glycyrrhizae were screened out through literature mining and GPCR related to depression.Then use the molecular structure to filter out the drug target,then detect the accumulation level of the protein in the southern MAPK/ERK receiver and the organic solder to identify the drug’s first shared target.In addition,the anti-inflammatory activity of the effective antidepressant components in Radix Bupleuri and Radix Glycyrrhizae was tested to explore the mechanism of anti-depression action.Through these research methods,we can further understand the pharmacodynamic components of Sinisan as well as its action sites and mechanisms,and provide scientific basis for the clinical application of traditional Chinese medicine.The main results and conclusions of this study are as follows:1.In this study,according to serum pharmaceutical chemistry and molecular docking,compounds of saikosaponin A,saikosaponin B2,saikosaponin C,saikosaponin D,glycyrrhiza,isoglycyrrhiza,formononetin,glycyrrhetinic acid,and daidzein in Radix Bupleuri and Radix Glycyrrhizae were selected to study their effects on MT1 R and MT2 R.2.(1)Saikosaponin A,isoglycyrrhiza and glycyrrhetinic acid can significantly activate MT2 R and mediate MAPK/ERK pathway(p < 0.05),indicating that MT2 R may play an antidepressant role.(2)Daidzein can significantly activate MT1 R and mediate MAPK/ERK pathway(p < 0.05),indicating that MT1 R may play an antidepressant role.(3)Saikosaponin B2 and saikosaponin D could significantly activate MT1 R and MT2 R and mediate MAPK/ERK pathway(p < 0.05),suggesting that they may act on MT1 R and MT2 R to play an antidepressant role.(4)Saikosaponin C,glycyrrhizin,isoglycyrrhizin and formononetin could not induce MAPK/ERK pathway downstream of MT1 R and MT2R(p > 0.05),suggesting that MTR may not play an antidepressant role through mediating MTR.