Geniposide improves depression by promoting the expression of synapse-related proteins through the Creb1/Six3os1 axis

The present study aims to investigate the mechanism of Geniposide in the treatment of depression. By screening the effective components and targets of Zhi-zi-chi decoction, 140 candidate targets related to depression were identified. Further transcriptome sequencing was conducted to screen differentially expressed mRNAs and lncRNAs; 7 candidate Geniposide treatment targets for depression were obtained. KEGG/GO enrichment analysis and molecular docking were performed to select the optimal drug target, revealing that Creb1 is an important target. Additionally, Six3os1 is the lncRNA with the smallest P-value among the differentially expressed lncRNAs, and the JASPAR database revealed a binding site between Creb1 and the Six3os1 promoter. The intersection of Synapse-related genes obtained from the GeneCards database and differentially expressed mRNAs produced 6 synaptic-related genes. RNA-protein interaction prediction revealed that Six3os1 interacts with the protein encoded by these genes. Geniposide upregulates the expression of Creb1 and Six3os1. Creb1 can transcriptionally activate Six3os1, thereby upregulating the expression of the synaptic-related proteins Htr3a and Htr2a, improving depression.