PMID- 38476533 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20240314 IS - 1920-8642 (Print) IS - 1920-8642 (Linking) VI - 15 IP - 2 DP - 2024 TI - Protective mechanism of quercetin in alleviating sepsis-related acute respiratory distress syndrome based on network pharmacology and in vitro experiments. PG - 111-120 LID - 10.5847/wjem.j.1920-8642.2024.030 [doi] AB - BACKGROUND: Sepsis-related acute respiratory distress syndrome (ARDS) has a high mortality rate, and no effective treatment is available currently. Quercetin is a natural plant product with many pharmacological activities, such as antioxidative, anti-apoptotic, and anti-inflammatory effects. This study aimed to elucidate the protective mechanism of quercetin against sepsis-related ARDS. METHODS: In this study, network pharmacology and in vitro experiments were used to investigate the underlying mechanisms of quercetin against sepsis-related ARDS. Core targets and signaling pathways of quercetin against sepsis-related ARDS were screened and were verified by in vitro experiments. RESULTS: A total of 4,230 targets of quercetin, 360 disease targets of sepsis-related ARDS, and 211 intersection targets were obtained via database screening. Among the 211 intersection targets, interleukin-6 (IL-6), tumor necrosis factor (TNF), albumin (ALB), AKT serine/threonine kinase 1 (AKT1), and interleukin-1beta (IL-1beta) were identified as the core targets. A Gene Ontology (GO) enrichment analysis revealed 894 genes involved in the inflammatory response, apoptosis regulation, and response to hypoxia. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis identified 106 pathways. After eliminating and generalizing, the hypoxia-inducible factor-1 (HIF-1), TNF, nuclear factor-kappaB (NF-kappaB), and nucleotide-binding and oligomerization domain (NOD)-like receptor signaling pathways were identified. Molecular docking revealed that quercetin had good binding activity with the core targets. Moreover, quercetin blocked the HIF-1, TNF, NF-kappaB, and NOD-like receptor signaling pathways in lipopolysaccharide (LPS)-induced murine alveolar macrophage (MH-S) cells. It also suppressed the inflammatory response, oxidative reactions, and cell apoptosis. CONCLUSION: Quercetin ameliorates sepsis-related ARDS by binding to its core targets and blocking the HIF-1, TNF, NF-kappaB, and NOD-like receptor signaling pathways to reduce inflammation, cell apoptosis, and oxidative stress. CI - Copyright: (c) World Journal of Emergency Medicine. FAU - Ding, Weichao AU - Ding W AD - Department of Emergency Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210002, China. AD - Department of Emergency Medicine, Jinling Clinical Medical College of Nanjing University of Chinese Medicine, Nanjing 210002, China. AD - Department of Emergency Medicine, the Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, China. FAU - Zhang, Wei AU - Zhang W AD - Department of Emergency Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210002, China. FAU - Chen, Juan AU - Chen J AD - Department of Emergency Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210002, China. AD - Department of Emergency Medicine, Jinling Clinical Medical College of Nanjing University of Chinese Medicine, Nanjing 210002, China. AD - Department of Emergency Medicine, Xuzhou Municipal Hospital Affiliated to Xuzhou Medical University, Xuzhou 221000, China. FAU - Wang, Mengmeng AU - Wang M AD - Department of Emergency Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210002, China. FAU - Ren, Yi AU - Ren Y AD - Department of Emergency Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210002, China. FAU - Feng, Jing AU - Feng J AD - Department of Emergency Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210002, China. FAU - Han, Xiaoqin AU - Han X AD - Department of Emergency Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210002, China. FAU - Ji, Xiaohang AU - Ji X AD - Department of Emergency Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210002, China. FAU - Nie, Shinan AU - Nie S AD - Department of Emergency Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210002, China. AD - Department of Emergency Medicine, Jinling Clinical Medical College of Nanjing University of Chinese Medicine, Nanjing 210002, China. FAU - Sun, Zhaorui AU - Sun Z AD - Department of Emergency Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210002, China. AD - Department of Emergency Medicine, Jinling Clinical Medical College of Nanjing University of Chinese Medicine, Nanjing 210002, China. LA - eng PT - Journal Article PL - China TA - World J Emerg Med JT - World journal of emergency medicine JID - 101549691 PMC - PMC10925531 OTO - NOTNLM OT - Network pharmacology OT - Quercetin OT - Sepsis-related acute respiratory distress syndrome COIS- Conflicts of interest: All authors declared no competing interests. EDAT- 2024/03/13 06:47 MHDA- 2024/03/13 06:48 PMCR- 2024/01/01 CRDT- 2024/03/13 03:53 PHST- 2023/11/29 00:00 [received] PHST- 2024/02/08 00:00 [accepted] PHST- 2024/03/13 06:48 [medline] PHST- 2024/03/13 06:47 [pubmed] PHST- 2024/03/13 03:53 [entrez] PHST- 2024/01/01 00:00 [pmc-release] AID - WJEM-15-111 [pii] AID - 10.5847/wjem.j.1920-8642.2024.030 [doi] PST - ppublish SO - World J Emerg Med. 2024;15(2):111-120. doi: 10.5847/wjem.j.1920-8642.2024.030.