Ameliorative effects and molecular mechanisms of Shuangxia Decoction on depression based on network pharmacology and experimental validation
Objective To investigate the ameliorative effect and molecular mechanism of Shuangxia Decoction on the behaviour of chronic unpredictable mild stress stimulation(CUMS)-like depressed rats based on network pharmacology and animal experiments.Methods A network pharmacology approach was used to collect the active ingredients and potential targets of Shuangxia Decoction for the treatment of depression and to screen the core network targets.The network pharmacology results were experimentally verified through animal experiments,as follows:depression-like modeling in rats by CUMS for 3 consecutive weeks,Shuangxia Decoction and fluoxetine were given to intervene for 2 weeks,and behavioral tests were conducted at the end of drug administration to assess the depressive behaviors through the absent-field experiment and forced-swimming experiment,the serum IL-6 level of the rats was detected by the ELISA method,and the Western blotting was used to detect the protein expression levels of HIF-1α and CREB,as well as the expression levels of p-Akt and p-GSK3B proteins in the hippocampal tissues of rats in each group.Results Network pharmacological analysis obtained 245 potential targets of Shuangxia Decoction for antidepression.PPI network analysis revealed that Shuangxia Decoction might exert antidepressant effects by regulating target proteins such as GSK3B,Akt1 and PIK3CA.It involves neuroactive ligand-receptor interaction,HIF-1 and other signaling pathways.The experimental results showed that compared with the model group,the body mass of rats in the Shuangxia Decoction group were increased significantly,and immobility time of rats in the forced swimming test and open field test was shortened significantly(P<0.05,0.001),serum IL-6 was significantly were decreased(P<0.01).And the protein expression of HIF-1α,CREB,p-Akt,and p-GSK3B was significantly reduced,and that of GSK3B was significantly elevated.Conclusion Shuangxia Decoction can improve the depression-like behavior of CUMS rats,and its mechanism may be to improve the plasticity of hippocampal neurons through the regulation of circadian rhythm and glucose homeostasis in hippocampal tissues through AKT/GSK3B and HIF-1α/CREB signaling pathways.
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