Network pharmacology analysis and experimental validation of the antidepression mechanism of lactuside B

Background: Lactuside B (LB) is a novel active ingredient separated from Pterocypsela elata by our team. In our preliminary study, LB showed a therapeutic effect on depression. However, the underlying molecular mechanisms remain unclear. Objectives: This study was the first to study the pharmacological effects and mechanisms of LB on depression. Materials and Methods: Network pharmacology method was applied to screen the candidate targets and signaling pathways. Furthermore, molecular docking, cell test, and animal experiments were used to confirm the antidepression mechanisms. Results: The network pharmacology results showed 29 targets and 40 signaling pathways of LB on depression. Molecular docking showed that there was a strong binding effect between LB and each target (cAMP response element binding protein B [CREB], Ras, Raf, and ERK1/2). Cell tests indicated that the expressions of Ras and CREB in astrocyte cells (0.05-0.20 g/L of LB) exhibited significant differences (P < 0.05) compared with the model group, respectively. In animal tests, the expressions of Ras, ERK1/2, and Raf (12.5-50.0 μg/10 g of LB) showed a significant difference compared with mice in the model group (P < 0.05). Conclusion: These results indicated that the antidepression mechanism of LB was mainly associated with Ras signaling pathway, and the cAMP signaling pathway and PI3K-Akt signaling pathway may play an essential role.