Background:Traumatic cerebral edema(TCE)is a life-threatening condition caused by excessive fluid accumulation in the brain,leading to elevated intracranial pressure and potential brain damage.Current treatments,inclu...Background:Traumatic cerebral edema(TCE)is a life-threatening condition caused by excessive fluid accumulation in the brain,leading to elevated intracranial pressure and potential brain damage.Current treatments,including osmotic diuretics and antihypertensive medications,have limitations.Zhenwu Decoction,a traditional Chinese medicine formulation,has shown promise due to its multi-target pharmacological effects,including modulation of inflammation and regulation of aquaporins.Methods:Active components and targets of Zhenwu Decoction were identified using databases such as SymMap and TCMID.Protein-protein interaction networks and gene expression data related to toxic chemical exposure were analyzed through the GEO database and gene set enrichment analysis.Weighted gene co-expression network analysis(WGCNA)was used to identify TCE-associated gene modules.Molecular docking and in vivo validation using a traumatic brain injury model were conducted.Results:A total of 880 active components and 235 potential targets of Zhenwu Decoction were identified.Protein-protein interaction network analysis and WGCNA revealed key gene modules and inflammatory response-related DEGs.Molecular docking suggested lactiflorin and poricoic acid A as potential drug candidates targeting ATP2A2 and ATP2C1.Experimental results confirmed that Zhenwu Decoction improved TCE outcomes by upregulating these proteins.Conclusion:This study provides molecular evidence for the efficacy of Zhenwu Decoction in treating TCE,highlighting its mechanisms.The integration of WGCNA and molecular docking offers new insights into drug development and precision medicine for TCE.展开更多
基金the financial support provided by the Discipline Construction Project of Shanghai Pudong New Area Health Commission(Grant Number:PWZzb2022-21)the Shanghai Pudong New Area Health System Discipline Leader Training Project(Grant Number:PWRd2022-14)+1 种基金the Health Science and Technology Project of Shanghai Pudong New Area Health Committee(Grant Number:PW2023A-51)the Shanghai Pudong New Area Gongli Hospital Youth Fund Project(Grant Number:2020YQNJJ-16).
文摘Background:Traumatic cerebral edema(TCE)is a life-threatening condition caused by excessive fluid accumulation in the brain,leading to elevated intracranial pressure and potential brain damage.Current treatments,including osmotic diuretics and antihypertensive medications,have limitations.Zhenwu Decoction,a traditional Chinese medicine formulation,has shown promise due to its multi-target pharmacological effects,including modulation of inflammation and regulation of aquaporins.Methods:Active components and targets of Zhenwu Decoction were identified using databases such as SymMap and TCMID.Protein-protein interaction networks and gene expression data related to toxic chemical exposure were analyzed through the GEO database and gene set enrichment analysis.Weighted gene co-expression network analysis(WGCNA)was used to identify TCE-associated gene modules.Molecular docking and in vivo validation using a traumatic brain injury model were conducted.Results:A total of 880 active components and 235 potential targets of Zhenwu Decoction were identified.Protein-protein interaction network analysis and WGCNA revealed key gene modules and inflammatory response-related DEGs.Molecular docking suggested lactiflorin and poricoic acid A as potential drug candidates targeting ATP2A2 and ATP2C1.Experimental results confirmed that Zhenwu Decoction improved TCE outcomes by upregulating these proteins.Conclusion:This study provides molecular evidence for the efficacy of Zhenwu Decoction in treating TCE,highlighting its mechanisms.The integration of WGCNA and molecular docking offers new insights into drug development and precision medicine for TCE.