Network Pharmacology and Transcriptomics to Explore the Pharmacological Mechanisms of 20(S)-Protopanaxatriol in the Treatment of Depression

Autor: Xiangjuan Guo, Lili Su, Meiling Shi, Li Sun, Weijia Chen, Jianan Geng, Jianming Li, Ying Zong, Zhongmei He, Rui Du
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: International Journal of Molecular Sciences, Vol 25, Iss 14, p 7574 (2024)
Druh dokumentu: article
ISSN: 1422-0067
1661-6596
DOI: 10.3390/ijms25147574
Popis: Depression is one of the most common psychological disorders nowadays. Studies have shown that 20(S)-protopanaxatriol (PPT) can effectively improve depressive symptoms in mice. However, its mechanism needs to be further explored. In this study, we used an integrated approach combining network pharmacology and transcriptomics to explore the potential mechanisms of PPT for depression. First, the potential targets and pathways of PPT treatment of depression were screened through network pharmacology. Secondly, the BMKCloud platform was used to obtain brain tissue transcription data of chronic unpredictable mild stress (CUMS) model mice and screen PPT-altered differential expression genes (DEGs). Gene ontology (GO) analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed using network pharmacology and transcriptomics. Finally, the above results were verified by molecular docking, Western blotting, and quantitative real-time polymerase chain reaction (qRT-PCR). In this study, we demonstrated that PPT improved depression-like behavior and brain histopathological changes in CUMS mice, downregulated nitric oxide (NO) and interleukin-6 (IL-6) levels, and elevated serum levels of 5-hydroxytryptamine (5-HT) and brain-derived neurotrophic factor (BDNF) after PPT treatment compared to the CUMS group. Eighty-seven potential targets and 350 DEGs were identified by network pharmacology and transcriptomics. Comprehensive analysis showed that transthyretin (TTR), klotho (KL), FOS, and the phosphatidylinositol 3-kinase–protein kinase B (PI3K-AKT) signaling pathway were closely associated with the therapeutic effects of PPT. Molecular docking results showed that PPT had a high affinity for PI3K, AKT, TTR, KL, and FOS targets. Gene and protein level results showed that PPT could increase the expression of PI3K, phosphorylation of PI3K (p-PI3K), AKT, phosphorylation of AKT (p-AKT), TTR, and KL and inhibit the expression level of FOS in the brain tissue of depressed mice. Our data suggest that PPT may achieve the treatment of depression by inhibiting the expression of FOS, enhancing the expression of TTR and KL, and modulating the PI3K-AKT signaling pathway.
Databáze: Directory of Open Access Journals
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