Exploring the efficacious constituents and underlying mechanisms of sini decoction for sepsis treatment through network pharmacology and multi-omics

小桶 败血症 免疫系统 生物 旁分泌信号 药理学 计算生物学 基因表达 生物信息学 基因 免疫学 受体 转录组 遗传学
作者
Yang Gu,Ziying Li,Han Li,Xiaoling Yi,Xun Liu,Yan Zhang,Shu Gong,Changyuan Yu,Li Li
出处
期刊:Phytomedicine [Elsevier]
卷期号:123: 155212-155212 被引量:6
标识
DOI:10.1016/j.phymed.2023.155212
摘要

Traditional Chinese medicine prescription sini decoction (SND) can alleviate inflammation, improve microcirculation, and modulate immune status in sepsis patients. However, its underlying mechanisms remain unclear, and therapeutic effects may vary among individuals. Through a comprehensive and systematic network pharmacology analysis, the purpose of this study is to investigate the therapeutic mechanisms of SND in treating sepsis. An analysis of WGCNA identified CX3CR1 as a key gene influencing sepsis prognosis. A drug-active component-target network for SND was created using the traditional Chinese medicine systems pharmacology (TCMSP) database and Cytoscape software. Shared targets between SND and CX3CR1 high-expression gene modules were found through the GEO database. Gene module functionality was analyzed using GO, KEGG, GSEA, and GSVA. Unsupervised clustering of sepsis patients was performed based on the ferroptosis gene set, and immune cell interactions and mechanisms were explored using CIBERSORT, single-cell sequencing, and intercellular communication analysis. This study demonstrates that high expression of CX3CR1 improves survival rates in sepsis patients and is associated with immune cell signaling pathways. SND contains 116 active components involved in oxidative stress and lipid metabolism pathways. HMOX1, a co-expressed gene in SND and CX3CR1 high-expression gene module, plays a crucial role in sepsis survival. Unsupervised clustering analysis classified sepsis patients into three clusters based on the ferroptosis gene set, revealing differences in immune cell expression and involvement in heme metabolism pathways. Notably, intercellular interactions among immune cells primarily occur through paracrine and autocrine mechanisms in MIF, GALECTIN, and IL16 signaling pathways, modulating the immune-inflammatory microenvironment in sepsis. This study identifies CX3CR1 as a crucial molecule impacting sepsis prognosis through WGCNA analysis. It reveals that SND's active component, quercetin and kaempferol, target HMOX1 via related pathways to regulate heme metabolism, reduce inflammation, inhibit ferroptosis, and improve immune function, ultimately improving sepsis prognosis. These findings offer a solid pharmacological foundation and potential therapeutic targets for SND in treating sepsis.
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