PMID- 37382018 OWN - NLM STAT- MEDLINE DCOM- 20230630 LR - 20230630 IS - 1001-5302 (Print) IS - 1001-5302 (Linking) VI - 48 IP - 12 DP - 2023 Jun TI - [Mechanism of Xuebijing Injection in treatment of sepsis-associated ARDS based on network pharmacology and in vitro experiment]. PG - 3345-3359 LID - 10.19540/j.cnki.cjcmm.20230202.703 [doi] AB - The aim of this study was to investigate the effect and molecular mechanism of Xuebijing Injection in the treatment of sepsis-associated acute respiratory distress syndrome(ARDS) based on network pharmacology and in vitro experiment. The active components of Xuebijing Injection were screened and the targets were predicted by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). The targets of sepsis-associated ARDS were searched against GeneCards, DisGeNet, OMIM, and TTD. Weishengxin platform was used to map the targets of the main active components in Xuebijing Injection and the targets of sepsis-associated ARDS, and Venn diagram was established to identify the common targets. Cytoscape 3.9.1 was used to build the "drug-active components-common targets-disease" network. The common targets were imported into STRING for the building of the protein-protein interaction(PPI) network, which was then imported into Cytoscape 3.9.1 for visualization. DAVID 6.8 was used for Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment of the common targets, and then Weishe-ngxin platform was used for visualization of the enrichment results. The top 20 KEGG signaling pathways were selected and imported into Cytoscape 3.9.1 to establish the KEGG network. Finally, molecular docking and in vitro cell experiment were performed to verify the prediction results. A total of 115 active components and 217 targets of Xuebijing Injection and 360 targets of sepsis-associated ARDS were obtained, among which 63 common targets were shared by Xuebijing Injection and the disease. The core targets included interleukin-1 beta(IL-1beta), IL-6, albumin(ALB), serine/threonine-protein kinase(AKT1), and vascular endothelial growth factor A(VEGFA). A total of 453 GO terms were annotated, including 361 terms of biological processes(BP), 33 terms of cellular components(CC), and 59 terms of molecular functions(MF). The terms mainly involved cellular response to lipopolysaccharide, negative regulation of apoptotic process, lipopolysaccharide-mediated signaling pathway, positive regulation of transcription from RNA polyme-rase Ⅱ promoter, response to hypoxia, and inflammatory response. The KEGG enrichment revealed 85 pathways. After diseases and generalized pathways were eliminated, hypoxia-inducible factor-1(HIF-1), tumor necrosis factor(TNF), nuclear factor-kappa B(NF-kappaB), Toll-like receptor, and NOD-like receptor signaling pathways were screened out. Molecular docking showed that the main active components of Xuebijing Injection had good binding activity with the core targets. The in vitro experiment confirmed that Xuebijing Injection suppressed the HIF-1, TNF, NF-kappaB, Toll-like receptor, and NOD-like receptor signaling pathways, inhibited cell apoptosis and reactive oxygen species generation, and down-regulated the expression of TNF-alpha, IL-1beta, and IL-6 in cells. In conclusion, Xuebijing Injection can regulate apoptosis and response to inflammation and oxidative stress by acting on HIF-1, TNF, NF-kappaB, Toll-like receptor, and NOD-like receptor signaling pathways to treat sepsis-associated ARDS. FAU - Ding, Wei-Chao AU - Ding WC AD - Nanjing University of Chinese Medicine Nanjing 210023, China Department of Emergency Medicine, Jinling Hospital(General Hospital of Eastern Theater Command), Medical School of Nanjing University Nanjing 210002, China Department of Emergency Medicine, the Affiliated Hospital of Xuzhou Medical University Xuzhou 221002, China. FAU - Chen, Juan AU - Chen J AD - Nanjing University of Chinese Medicine Nanjing 210023, China Department of Emergency Medicine, Jinling Hospital(General Hospital of Eastern Theater Command), Medical School of Nanjing University Nanjing 210002, China. FAU - Liao, Hao-Yu AU - Liao HY AD - Department of Emergency Medicine, Jinling Hospital(General Hospital of Eastern Theater Command), Medical School of Nanjing University Nanjing 210002, China. FAU - Feng, Jing AU - Feng J AD - Department of Emergency Medicine, Jinling Hospital(General Hospital of Eastern Theater Command), Medical School of Nanjing University Nanjing 210002, China. FAU - Wang, Jing AU - Wang J AD - Department of Emergency Medicine, Jinling Hospital(General Hospital of Eastern Theater Command), Medical School of Nanjing University Nanjing 210002, China. FAU - Zhang, Yu-Hao AU - Zhang YH AD - Department of Emergency Medicine, Jinling Hospital(General Hospital of Eastern Theater Command), Medical School of Nanjing University Nanjing 210002, China. FAU - Ji, Xiao-Hang AU - Ji XH AD - Department of Emergency Medicine, Jinling Hospital(General Hospital of Eastern Theater Command), Medical School of Nanjing University Nanjing 210002, China. FAU - Chen, Qian AU - Chen Q AD - Department of Emergency Medicine, Jinling Hospital(General Hospital of Eastern Theater Command), Medical School of Nanjing University Nanjing 210002, China. FAU - Wu, Xin-Yao AU - Wu XY AD - Nanjing University of Chinese Medicine Nanjing 210023, China Department of Emergency Medicine, Jinling Hospital(General Hospital of Eastern Theater Command), Medical School of Nanjing University Nanjing 210002, China. FAU - Sun, Zhao-Rui AU - Sun ZR AD - Nanjing University of Chinese Medicine Nanjing 210023, China Department of Emergency Medicine, Jinling Hospital(General Hospital of Eastern Theater Command), Medical School of Nanjing University Nanjing 210002, China. FAU - Nie, Shi-Nan AU - Nie SN AD - Nanjing University of Chinese Medicine Nanjing 210023, China Department of Emergency Medicine, Jinling Hospital(General Hospital of Eastern Theater Command), Medical School of Nanjing University Nanjing 210002, China. LA - chi PT - English Abstract PT - Journal Article PL - China TA - Zhongguo Zhong Yao Za Zhi JT - Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica JID - 8913656 RN - 0 (Xuebijing) RN - 0 (Vascular Endothelial Growth Factor A) RN - 0 (NF-kappa B) RN - 0 (Interleukin-6) RN - 0 (Lipopolysaccharides) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (NLR Proteins) SB - IM MH - Humans MH - Network Pharmacology MH - Vascular Endothelial Growth Factor A MH - NF-kappa B MH - Interleukin-6 MH - Lipopolysaccharides MH - Molecular Docking Simulation MH - *Respiratory Distress Syndrome MH - Tumor Necrosis Factor-alpha MH - *Sepsis/complications/drug therapy/genetics MH - NLR Proteins OTO - NOTNLM OT - Xuebijing Injection OT - acute respiratory distress syndrome(ARDS) OT - in vitro experiment OT - network pharmacology OT - sepsis EDAT- 2023/06/29 06:43 MHDA- 2023/06/30 06:42 CRDT- 2023/06/29 05:34 PHST- 2023/06/30 06:42 [medline] PHST- 2023/06/29 06:43 [pubmed] PHST- 2023/06/29 05:34 [entrez] AID - 10.19540/j.cnki.cjcmm.20230202.703 [doi] PST - ppublish SO - Zhongguo Zhong Yao Za Zhi. 2023 Jun;48(12):3345-3359. doi: 10.19540/j.cnki.cjcmm.20230202.703.