A study on the compatibility mechanism based on network pharmacology and experimental validation of Zhi-zi-chi Decoction in the treatment of depression
Objective Based on network pharmacology and in vivo and in vitro experimental validation to explore the action mechanism of Zhi-zi-chi Decoction(ZZCD)in the treatment of depression.Methods The UPLC-QE-MS technique was used to analyze the components in Gardeniae Fructus(Zhizi in Chinese,ZZ in brief),Sojae Semen Praeparatum(Dandouchi in Chinese,DDC in brief)and ZZCD,combined with bioinformatics to predict the relevant targets and signalling pathways of ZZ,DDC and ZZCD for depression treatment.The predictions were validated by in vivo and in vitro experiments.The pseudo germ-free rats were established using antibiotic cocktail(Abx)pretreatment to find the differences in blood entry components and their metabolites under the influence of intestinal flora in vivo for ZZ,DDC and ZZCD.The antidepressant effects of ZZ,DDC and ZZCD-containing serum based on neuroprotection were also evaluated using the glutamate-induced PC12 cell model.Results In ZZ,DDC and ZZCD,37,7 and 43 components were identified respectively,187,146 and 196 potential targets were identified for the treatment of depression,respectively.And 9 common core targets were further screened.The results of enrichment analysis showed that ZZ and ZZCD exerted antidepressant effects through multiple signaling pathways such as neuroactive ligand-receptor pathway,MAPK signaling pathway and IL-17 signaling pathway.In the analysis of ZZ and ZZCD blood components,18 blood components and their metabolites were identified in ZZCD-administered normal rats,whereas 9,3 and 12 blood components and their metabolites were identified in ZZ,DDC-administered normal rats and ZZCD-administered pseudo germ-free rats.The above results suggested that ZZ in vivo metabolism was altered in the absence of DDC compatibility or in the absence of in vivo intestinal flora modulation.Celluar experiments showed that both ZZ and ZZCD had neuroprotective effects,with the most significant neuroprotective effect of ZZCD-containing serum.The levels of pro-inflammatory cytokines IL-1β,TNF-α and IL-6 in the supernatant of glutamate-induced PC12 cells decreased after administration of drug-containing serum in all goups.Conclusion DDC has certain neuroprotective effects,and when paired with ZZ can regulate the intestinal flora in vivo and affect the in vivo metabolism of ZZ,and the antidepressant effect of ZZCD may be related to its inhibition of inflammatory response.
NETL
NSTL
万方数据
维普
