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Network pharmacology showed that XYS exhibited anti-depression effects through paeoniflorin, quercetin, licochalcone a, naringenin, β-sitosterol, formononetin and kaempferol acting on interleukin-6 (IL6), mitogen-activated protein kinase 1 (MAPK1), signal transducer and activator of transcription 3 (STAT3) and transcription factor AP-1 (JUN). Based on hippocampal metabolomics and network pharmacology, this study proved that the actions of XYS in treating depression depend on multi-components, multi-targets and multi-pathways, the unique