Cistanche deserticola Stem Extract Attenuates Depression Through NF-κB Pathway Modulation: Insights from Network Pharmacology and Experimental Validation

Purpose: This study aims to elucidate the effects of Cistanche deserticola Y. C. Ma on depression and its mechanisms through a comprehensive approach involving network pharmacology evaluation, molecular docking, and animal experiments. Methods: By integrating network pharmacology, molecular docking, and animal testing, we systematically revealed the molecular mechanisms of the antidepressant effects of Cistanche deserticola . The main active components of Cistanche deserticola were selected from the TCMSP database, and depression-related targets were cross-verified using the OMIM/DisGeNET databases. Subsequently, a protein-protein interaction network was constructed using STRING, and the relationships between drug, target, and pathway were visualized using Cytoscape. GO function and KEGG pathway enrichment analyses were performed using DAVID and Metascape, molecular docking of core components with target proteins was completed using AutoDock Vina. The antidepressant effects and neuroprotective effects of Cistanche deserticola were further evaluated in a chronic unpredictable mild stress (CUMS) mouse model through behavioral tests and immunofluorescence, Nissl, and HE staining in the hippocampus. Results: Network pharmacology identified 6 key active components and 74 potential targets, focusing on 25 core targets. Molecular docking demonstrated that key components exhibited high affinity with core targets, with binding energies less than − 5 kcal·mol − 1 . KEGG enrichment analysis indicated that the NF-κB signaling pathway serves as a core regulatory axis ( FDR < 0.001). Animal experiments confirmed that Cistanche deserticola significantly inhibited the activation of M1 microglia in the hippocampus of CUMS mice, reducing the expression of IL-1β, VCAM1, and NF-κB ( P < 0.0001), while alleviating neuronal morphological damage and significantly improving depressive-like behaviors and cognitive impairments. Conclusion: Cistanche deserticola exerts antidepressant effects by regulating the NF-κB signaling pathway and inhibiting neuroinflammation. This study provides preliminary theoretical and experimental evidence supporting the potential of Cistanche deserticola stem as a safe and tolerable plant-derived antidepressant. Keywords: depression, Cistanche deserticola , network pharmacology, molecular docking, molecular mechanisms, targets