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基于网络药理学探讨地黄治疗脓毒症的潜在作用机制。

Exploring the potential mechanisms of Rehmannia glutinosa in treating sepsis based on network pharmacology.

机构信息

Department of Clinical Medicine, Southwest Medical University, Luzhou, People's Republic of China.

Department of Emergency Medicine, Affiliated Hospital of Southwest Medical University, Luzhou, People's Republic of China.

出版信息

BMC Infect Dis. 2024 Aug 31;24(1):893. doi: 10.1186/s12879-024-09796-x.

Abstract

The present study utilized network pharmacology to identify therapeutic targets and mechanisms of Rehmannia glutinosa in sepsis treatment. RNA-sequencing was conducted on peripheral blood samples collected from 23 sepsis patients and 10 healthy individuals. Subsequently, the RNA sequence data were analyzed for differential expression. Identification of active components and their putative targets was achieved through the HERB and SwissTarget Prediction databases, respectively. Functional enrichment analysis was performed using GO and KEGG pathways. Additionally, protein-protein interaction networks were constructed and survival analysis of key targets was conducted. Single-cell RNA sequencing provided cellular localization data, while molecular docking explored interactions with central targets. Results indicated significant involvement of identified targets in inflammation and Th17 cell differentiation. Survival analysis linked several targets with mortality rates, while molecular docking highlighted potential interactions between active components and specific targets, such as rehmaionoside a with ADAM17 and rehmapicrogenin with CD81. Molecular dynamics simulations confirmed the stability of these interactions, suggesting Rehmannia glutinosa's role in modulating immune functions in sepsis.

摘要

本研究利用网络药理学来确定地黄治疗脓毒症的治疗靶点和机制。对 23 名脓毒症患者和 10 名健康个体的外周血样本进行了 RNA 测序。随后,对 RNA 序列数据进行了差异表达分析。通过 HERB 和 SwissTarget Prediction 数据库分别鉴定了活性成分及其潜在的靶标。使用 GO 和 KEGG 通路进行了功能富集分析。此外,构建了蛋白质-蛋白质相互作用网络,并对关键靶标进行了生存分析。单细胞 RNA 测序提供了细胞定位数据,而分子对接则探索了与中央靶标的相互作用。结果表明,鉴定出的靶标在炎症和 Th17 细胞分化中起重要作用。生存分析将几个靶标与死亡率联系起来,而分子对接则突出了活性成分与特定靶标之间的潜在相互作用,例如 rehmaionoside a 与 ADAM17 和 rehmapicrogenin 与 CD81。分子动力学模拟证实了这些相互作用的稳定性,表明地黄在调节脓毒症中的免疫功能方面发挥作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/320b/11366132/5e06498f0dc7/12879_2024_9796_Fig1_HTML.jpg

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