Zhou Tong, Li Jianhua, Li Wei, Yu Jiamin, Deng Yongan, Duan Xiaodong, Lin Jiazi, Wang Xiao, Liang Yefang, Zhang Chongyang, Yu Miao, Shi Ruixiang, Chen Chengkai, Yang Simin, Zeng Shuting, Shen Xuejuan, Wang Yi, Sun Jing, Shu Zunpeng
Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, Department of Biology, Faculty of Arts and Sciences, Beijing Normal University, Zhuhai 519087, China; School of Chinese Materia Medica, Guangdong Pharmaceutical University, Guangzhou 510006, China.
School of Chinese Materia Medica, Guangdong Pharmaceutical University, Guangzhou 510006, China.
Int Immunopharmacol. 2025 Jan 10;144:113607. doi: 10.1016/j.intimp.2024.113607. Epub 2024 Nov 20.
The acute pulmonary infectious disease caused by influenza viruses is known as influenza virus pneumonia (IVP). In recent years, Gegen Qinlian Decoction (GQD) has been widely used to treat pulmonary inflammation; however, the underlying mechanism of action of GQD in IVP remains unclear. This study aimed to elucidate the molecular mechanism through which GQD improved IVP.
The efficacy of GQD was evaluated using classical pharmacodynamic indicators in a murine model of H1N1-induced IVP. Network pharmacology predicted the material basis of GQD in improving IVP, while metabonomics and 16 s rDNA sequencing assessed its regulation on small molecule metabolites and intestinal flora. Additionally, molecular biology techniques were used to investigate the molecular mechanism underlying the improvement of IVP by GQD.
The study results demonstrated that GQD exhibited a significant ameliorative effect on the inflammatory response in lung tissue of IVP mice. The potential pharmacological substances of GQD for improving IVP were identified by network pharmacology combined with ultra-high performance liquid chromatography/high-resolution time-of-flight mass spectrometry (UHPLC-HR-TOFMS) analysis, including puerarin, baicalin, berberine, and glycyrrhizin. Further analysis of biological processes and mechanisms of action predicted that GQD could improve IVP by inhibiting activation of inflammasomes, regulating the body's immune system, and intestinal microecology. Metabolomics and microbiomics findings revealed that GQD could bi-directionally regulate lipid and amino acid metabolites by increasing the abundance of beneficial bacteria like Akkermansia and Acetobacter, thereby maintaining host metabolic balance and immune homeostasis. RT-qPCR and immunohistochemistry results indicated that GQD improved IVP by inhibiting the complement C3/NLRP3 inflammasome pathway.
The findings of this study confirmed that GQD effectively inhibited IVP by modulating the "gut microbiota-metabolomics-immune/inflammation" axis in the host, thereby establishing a solid immunological foundation for the clinical application of GQD.
由流感病毒引起的急性肺部感染性疾病称为流感病毒肺炎（IVP）。近年来，葛根芩连汤（GQD）已被广泛用于治疗肺部炎症；然而，GQD治疗IVP的潜在作用机制仍不清楚。本研究旨在阐明GQD改善IVP的分子机制。
在甲型H1N1流感病毒诱导的IVP小鼠模型中，使用经典药效学指标评估GQD的疗效。网络药理学预测GQD改善IVP的物质基础，而代谢组学和16s rDNA测序评估其对小分子代谢物和肠道菌群的调节作用。此外，采用分子生物学技术研究GQD改善IVP的分子机制。
研究结果表明，GQD对IVP小鼠肺组织的炎症反应具有显著的改善作用。通过网络药理学结合超高效液相色谱/高分辨率飞行时间质谱（UHPLC-HR-TOFMS）分析，确定了GQD改善IVP的潜在药理物质，包括葛根素、黄芩苷、小檗碱和甘草酸。对生物学过程和作用机制的进一步分析预测，GQD可通过抑制炎性小体的激活、调节机体免疫系统和肠道微生态来改善IVP。代谢组学和微生物组学研究结果表明，GQD可通过增加阿克曼氏菌和醋杆菌等有益菌的丰度来双向调节脂质和氨基酸代谢物，从而维持宿主代谢平衡和免疫稳态。RT-qPCR和免疫组化结果表明，GQD通过抑制补体C3/NLRP三炎性小体途径改善IVP。
本研究结果证实，GQD通过调节宿主中的“肠道微生物群-代谢组学-免疫/炎症”轴有效抑制IVP，从而为GQD的临床应用奠定了坚实的免疫学基础。
