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

作　　者：Kunyu Li Leiming You Jianhua Zhen Guangrui Huang Ting Wang Yanan Cai Yunan Zhang Anlong Xu 

机构地区：[1]School of Life Sciences,Bejing University of Chinese Medicine,Beijing 102488,China [2]School of Life Sciences,Sun Yat-Sen University,Guangzhou 510006,Chin

出　　处：《Journal of Traditional Chinese Medical Sciences》2024年第1期3-20,共18页中医科学杂志（英文）

基　　金：supported by the National Key Research and Development Program of China(SQ2019YFC170218).

摘　　要：Objective:To investigate the molecular mechanism and identify potential drugs for subthreshold depression(SD),and elucidate the detalied mechanism of Danzhi Xiaoyao powder(DZXY)in SD.Methods:Using RNA-sequencing,we identified differentially expressed genes(DEGs)in leukocytes of SD compared to healthy controls,deciphered their functions and pathways,and identified the hub genes of SD.We also assessed changes in leukocyte transcription factor activity in patients with SD using the TELis platform.The Connectivity Map database was retrieved to screen candidate drugs for SD.Based on network pharmacology,we elucidated the"multi-component,multi-target,and multi-pathway"mechanism of DZXY in the treatment of SD.Results:We identified 1080 DEGs(padj<0.05 and|log2(fold change)l≥1&protein coding)in the leukocytes of patients with SD.These DEGs,including hub genes,were primarily involved in immune and inflammatory response-related processes.Transcription factor activity analysis revealed similarities between the leukocyte transcriptome profile in SD and the conserved transcriptional response to adversities in immune cells.Connectivity Map analysis identified 28 potential drugs for SD treatment,particularly SB-202190 and TWS-119.Constructing the"Direct Compounds-Direct Targets-Pathways"network for DZXY and SD revealed the curative mechanisms of DZXY in SD,primarily including inflammatory response,lipid metabolism,immune response,and other processes.Conclusion:These results provide new insights into the characteristics and functional changes of leukocytes in SD,partially illustrate the pathogenesis of SD,and suggest potential drugs for SD.The curative mechanisms of DZXY in SD are also partially elucidated.

关 键 词：Subthreshold depression LEUKOCYTE mRNAbiomarker CTRA Transcription factor activity CMAP Danzhi Xiaoyaopowder Networkpharmacology 

分 类 号：R285[医药卫生—中药学]