Network-based analysis and experimental validation explored Bu-Yang-Huan-Wu-Tang protects endothelial cells after hypoxia-reoxygenation injury by inhibiting the PI3K/AKT/FOXO1 pathway

Shi Yan; Zhou Yue; Guan Qing; Wen Qingsi; Sun Yu; Yan Zewen; Li Yuye; Zhu Qingnan; Lin Hongli; Wang Dapeng

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Network-based analysis and experimental validation explored Bu-Yang-Huan-Wu-Tang protects endothelial cells after hypoxia-reoxygenation injury by inhibiting the PI3K/AKT/FOXO1 pathway

Shi Yan 1,Zhou Yue 2,Guan Qing 2,Wen Qingsi 2,Sun Yu 2,Yan Zewen 2,Li Yuye 2,Zhu Qingnan 2,Lin Hongli 2,Wang Dapeng 2 *

1.College of Integrative Medicine, Dalian Medical University, Dalian 116041; Department of Nephrology, The First Affiliated Hospital of Dalian Medical University, Dalian 116011; Department of Nephrology, The First Affiliated Hospital of Dalian Medical University, Dalian 116011;College of Integrative Medicine, Dalian Medical University, Dalian 116041; Department of Nephrology, The First Affiliated Hospital of Dalian Medical University, Dalian 116011;College of Integrative Medicine, Dalian Medical University, Dalian 116041; Department of Nephrology, The First Affiliated Hospital of Dalian Medical University, Dalian 116011;College of Integrative Medicine, Dalian Medical University, Dalian 116041; Department of Nephrology, The First Affiliated Hospital of Dalian Medical University, Dalian 116011;Department of Nephrology, The First Affiliated Hospital of Dalian Medical University, Dalian 116011;Department of Nephrology, The First Affiliated Hospital of Dalian Medical University, Dalian 116011;Department of Nephrology, The First Affiliated Hospital of Dalian Medical University, Dalian 116011;Department of Nephrology, The First Affiliated Hospital of Dalian Medical University, Dalian 116011;Department of Nephrology, The First Affiliated Hospital of Dalian Medical University, Dalian 116011

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Funding: none

Opened online: 6 March 2024

Accepted by: none

Citation: Shi Yan,Zhou Yue,Guan Qing.Network-based analysis and experimental validation explored Bu-Yang-Huan-Wu-Tang protects endothelial cells after hypoxia-reoxygenation injury by inhibiting the PI3K/AKT/FOXO1 pathway[OL]. [ 6 March 2024] http://en.paper.edu.cn/en_releasepaper/content/4762351

Purpose: To explore the drug targets and potential mechanisms of Bu-Yang-Huan-Wu-Tang (BYHWT) in the treatment of acute kidney injury (AKI) through network pharmacology and experimental validation. Methods: A network-based analysis research approach was used to predict the main active ingredients, targets of action and potential signaling pathways of BYHWT for AKI treatment. The protective effect of BYHWT on human umbilical vein endothelial cells (HUVEC) was verified by detecting the PI3K/AKT/FOXO1 signaling pathway and related factors through in vitro experiments. Results：A total of 124 active components of BYHWT were screened, with 444 action targets, 1,708 AKI disease-related target genes, and 210 targets at the intersection of components and diseases were obtained. Through GO and KEGG enrichment analysis, we obtained 219 signaling pathways of BYHWT for the treatment of AKI, and screened the top 10 pathways with the highest degree of enrichment, which involved the PI3K-AKT signaling pathway, and the experimental validation results showed that BYHWT-containing serum increased the expression of p-PI3K, p-AKT, and p-FOXO1, and increased the phosphorylation of FOXO1, and decreased the expression of FOXO1 expression. Conclusion: BYHWT may play a role in ameliorating endothelial cell apoptosis and protecting injured endothelial cells by regulating the PI3K/AKT/FOXO1 pathway.

Keywords:AKI; Network-based analysis; BYHWT; hypoxia-reoxygenation; HUVEC; network analysis

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