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Integrated analyses of transcriptomics and network pharmacology reveal leukocyte characteristics and functional changes in subthreshold depression, elucidating the curative mechanism of Danzhi Xiaoyao powder

Author: Kunyu Liu a, 1, Leiming quia, 1, Jianhua a, Huang a, Ting a, Cai a, Yunan a, Anlong Xaqu

Doi: https://ctm.2023.v7.i1.pp01-21


Purpose: to learn more about the molecular basis of subthreshold depression (SD), find medications that might help with it, and understand how Danzhi Xiaoyao powder (DZXY) works in SD. Methods: We used RNA-sequencing to find the hub genes of SD, roles and pathways of differentially expressed genes (DEGs) in SD leukocytes compared to healthy controls, and to identify these genes. Using the TELiS technology, we also evaluated alterations in leukocyte transcription factor activity in SD patients. Potential SD medications were screened by retrieving the Connectivity Map information. We used network pharmacology to explain how DZXY works to treat SD by identifying its "multi-component, multi-target, and multi-pathway" mechanism. Found 1080 differentially expressed genes (DEGs) in the white blood cells of SD patients (p < 0.05, |log2 (fold change)| ≥ 1, and protein coding). Immune and inflammatory response-related activities were the primary domains of activity for these DEGs, which included hub genes. A comparison of the SD leukocyte transcriptome profile with the conserved immune cell transcriptional response to adversities was shown by transcription factor activity analysis. Among the 28 medications that might be useful in treating SD, the Connectivity Map analysis highlighted SB-202190 and TWS-119. The therapeutic mechanisms of DZXY in SD, mainly encompassing in-flammatory response, lipid metabolism, immunological response, and other processes, were discovered by constructing the "Direct Compounds-Direct Targets-Pathways" network for both DZXY and SD.

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