Deng Mingtao, Chen Siqi, Wu Jian, Su Liling, Xu Zijin, Jiang Changrun, Sheng Lei, Yang Xinyi, Zeng Long, Wang Jingwei, Dai Wei
Shangrao Key Laboratory of Health Hazards and Bioprevention of Heavy Metals, Jiangxi Medical College, No. 399 Zhimin Avenue, Xinzhou District, Shangrao, Jiangxi Province, 334000, People's Republic of China; Department of Medical Technology, Jiangxi Medical College, No. 399 Zhimin Avenue, Xinzhou District, Shangrao, Jiangxi Province, 334000, People's Republic of China.
Department of Medical Technology, Jiangxi Medical College, No. 399 Zhimin Avenue, Xinzhou District, Shangrao, Jiangxi Province, 334000, People's Republic of China.
J Ethnopharmacol. 2024 Oct 28;333:118404. doi: 10.1016/j.jep.2024.118404. Epub 2024 May 31.
Sepsis presents complex pathophysiological challenges. Taohe Chengqi Decoction (THCQ), a traditional Chinese medicine, offers potential in managing sepsis-related complications, though its exact mechanisms are not fully understood.
This research aimed to assess the therapeutic efficacy and underlying mechanisms of THCQ on sepsis-induced lung injury.
The study began with validating THCQ's anti-inflammatory effects through in vitro and in vivo experiments. Network pharmacology was employed for mechanistic exploration, incorporating GO, KEGG, and PPI analyses of targets. Hub gene-immune cell correlations were assessed using CIBERSORT, with further scrutiny at clinical and single-cell levels. Molecular docking explored THCQ's drug-gene interactions, culminating in qPCR and WB validations of hub gene expressions in sepsis and post-THCQ treatment scenarios.
THCQ demonstrated efficacy in modulating inflammatory responses in sepsis, identified through network pharmacology. Key genes like MAPK14, MAPK3, MMP9, STAT3, LYN, AKT1, PTPN11, and HSP90AA1 emerged as central targets. Molecular docking revealed interactions between these genes and THCQ components. qPCR results showed significant modulation of these genes, indicating THCQ's potential in reducing inflammation and regulating immune responses in sepsis.
This study sheds light on THCQ's anti-inflammatory and immune regulatory mechanisms in sepsis, providing a foundation for further research and potential clinical application.
脓毒症呈现出复杂的病理生理挑战。桃核承气汤（THCQ）作为一种中药，在管理脓毒症相关并发症方面具有潜力，但其确切机制尚未完全明确。
本研究旨在评估桃核承气汤对脓毒症诱导的肺损伤的治疗效果及潜在机制。
该研究首先通过体外和体内实验验证桃核承气汤的抗炎作用。采用网络药理学进行机制探索，纳入对靶点的基因本体（GO）、京都基因与基因组百科全书（KEGG）和蛋白质-蛋白质相互作用（PPI）分析。使用CIBERSORT评估枢纽基因与免疫细胞的相关性，并在临床和单细胞水平进行进一步审查。分子对接探索桃核承气汤的药物-基因相互作用，最终通过定量聚合酶链反应（qPCR）和蛋白质免疫印迹（WB）验证脓毒症及桃核承气汤治疗后枢纽基因的表达情况。
通过网络药理学确定，桃核承气汤在调节脓毒症炎症反应方面具有疗效。丝裂原活化蛋白激酶14（MAPK14）、丝裂原活化蛋白激酶3（MAPK3）、基质金属蛋白酶9（MMP9）、信号转导和转录激活因子3（STAT3）、淋巴细胞特异性蛋白酪氨酸激酶（LYN）、蛋白激酶B（AKT1）、蛋白酪氨酸磷酸酶非受体型11（PTPN11）和热休克蛋白90α家族成员1（HSP90AA1）等关键基因成为核心靶点。分子对接揭示了这些基因与桃核承气汤成分之间的相互作用。qPCR结果显示这些基因有显著调节，表明桃核承气汤在减轻脓毒症炎症和调节免疫反应方面具有潜力。
本研究揭示了桃核承气汤在脓毒症中的抗炎和免疫调节机制，为进一步研究和潜在的临床应用奠定了基础。
