An integrative metabolomics and network pharmacology method for exploring the effect and mechanism of Radix Bupleuri and Radix Paeoniae Alba on anti-depression.

Depression is a common mental illness, which is caused by 'liver qi stagnationin in traditional Chinese medicine (TCM) theory. Thus, relieving "liver qi stagnation" is considered to be effective at treating depression. The Radix Bupleuri and Radix Paeoniae Alba drug pair is the most classic compatible drug pair for mitigating a great variety of depression symptoms. However, its mechanisms remain largely unclear. In this study, metabolomics and network pharmacology methods were used to explore the potential mechanism of antidepressant-like effects of the Radix Bupleuri and Radix Paeoniae Alba drug pair. Analysis of metabolomics results showed that the drug pair can significantly improve CUMS-induced depression. The underlying mechanism of its antidepressant effect involves regulating the expression of brain-derived neurotrophic factors, inhibiting neurotoxicity, and regulating the HPA axis. Network pharmacology showed that drug pairs screened a total of 23 active ingredients and 63 targets, participated in the regulation of protein metabolism, Metabolism, Energy pathways, Cell growth and / or maintenance and other biological processes (BP), and mainly involved multiple signaling pathways and metabolic pathways to jointly exert antidepressant effects. Four related metabolic pathways regulated by the Radix Bupleuri and Radix Paeoniae Alba drug pair were input into the KEGG database to obtain the key genes of the related metabolic pathways. The predicted target of the network pharmacology was compared with the key genes of the metabolic pathway, and the common genes were screened: CYP1A1, CYP1A2; Western blot results showed that the drug pair up-regulated the protein expression of CYP1A1, CYP1A2. The medicine has an antidepressant effect by regulating the action of key enzymes. Metabolomics combined with network pharmacology research strategy revealed that antidepressant-like effects of the Radix Bupleuri and Radix Paeoniae Alba drug pair are characterized by multi-component, multi-target and multi-path mechanism of action.