Gegen Qinlian Decoction improves H1N1-induced viral pneumonia by modulating the “gut microbiota-metabolomics-immune/inflammation” axis

[Display omitted] •GQD regulates the "gut microbiota-metabolomics-immune/inflammation" axis, thereby inhibiting the immune/inflammatory response in the body and improving IVP.•GQD can protect against IVP by inhibiting the complement C3/NLRP3 inflammasome pathway in lung tissue.•This study provides novel strategies for secondary development and clinical application of the traditional prescription GQD for enhancing IVP. 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 immunologica