Rujin Jiedu decoction protects against influenza virus infection by modulating gut microbiota
Qilin Huang,
Guizhen Yang,
Chenchen Tang,
Biao Dou,
You Hu,
Hui Liu,
Xiao Wu,
Huan Zhang,
Haikun Wang,
Lirong Xu,
Xiao-Dong Yang,
Yanwu Xu,
Yuejuan Zheng
Affiliations
Qilin Huang
The Research Center for Traditional Chinese Medicine, Shanghai Institute of Infectious Diseases and Biosecurity, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; Center for Traditional Chinese Medicine and Immunology Research, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
Guizhen Yang
The Research Center for Traditional Chinese Medicine, Shanghai Institute of Infectious Diseases and Biosecurity, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; Center for Traditional Chinese Medicine and Immunology Research, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
Chenchen Tang
The Research Center for Traditional Chinese Medicine, Shanghai Institute of Infectious Diseases and Biosecurity, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; Center for Traditional Chinese Medicine and Immunology Research, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
Biao Dou
The Research Center for Traditional Chinese Medicine, Shanghai Institute of Infectious Diseases and Biosecurity, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; Center for Traditional Chinese Medicine and Immunology Research, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
You Hu
The Research Center for Traditional Chinese Medicine, Shanghai Institute of Infectious Diseases and Biosecurity, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; Center for Traditional Chinese Medicine and Immunology Research, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
Hui Liu
The Research Center for Traditional Chinese Medicine, Shanghai Institute of Infectious Diseases and Biosecurity, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; Center for Traditional Chinese Medicine and Immunology Research, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
Xiao Wu
The Research Center for Traditional Chinese Medicine, Shanghai Institute of Infectious Diseases and Biosecurity, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; Center for Traditional Chinese Medicine and Immunology Research, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
Huan Zhang
The Research Center for Traditional Chinese Medicine, Shanghai Institute of Infectious Diseases and Biosecurity, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; Center for Traditional Chinese Medicine and Immunology Research, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
Haikun Wang
CAS Key Laboratory of Molecular Virology and Immunology, Chinese Academy of Sciences, Shanghai, 200031, China
Lirong Xu
The Research Center for Traditional Chinese Medicine, Shanghai Institute of Infectious Diseases and Biosecurity, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; Center for Traditional Chinese Medicine and Immunology Research, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
Xiao-Dong Yang
The Research Center for Traditional Chinese Medicine, Shanghai Institute of Infectious Diseases and Biosecurity, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; Center for Traditional Chinese Medicine and Immunology Research, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; Corresponding author. The Research Center for Traditional Chinese Medicine, Shanghai Institute of Infectious Diseases and Biosecurity, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; Center for Traditional Chinese Medicine and Immunology Research, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
Yanwu Xu
The Research Center for Traditional Chinese Medicine, Shanghai Institute of Infectious Diseases and Biosecurity, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; Corresponding author.
Yuejuan Zheng
The Research Center for Traditional Chinese Medicine, Shanghai Institute of Infectious Diseases and Biosecurity, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; Center for Traditional Chinese Medicine and Immunology Research, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; Corresponding author. The Research Center for Traditional Chinese Medicine, Shanghai Institute of Infectious Diseases and Biosecurity, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
Background: Rujin Jiedu decoction (RJJDD) is a classical prescription of Traditional Chinese Medicine that has long been applied to treat pneumonia caused by external infection, but whether and how it benefits influenza virus therapy remains largely unclear. The aim of this study was to investigate the anti-inflammatory effect of RJJDD on the mouse model of influenza and to explore its potential mechanism. Methods: The mice were mock-infected with PBS or infected with PR8 virus followed by treatment with RJJDD or antiviral oseltamivir. The weight loss and morbidity of mice were monitored daily. Network pharmacology is used to explore the potential pathways that RJJDD may modulate. qRT-PCR and ELISA were performed to assess the expression of inflammatory cytokines in the lung tissue and macrophages. The intestinal feces were collected for 16S rDNA sequencing to assess the changes in gut microbiota. Results: We demonstrate that RJJDD protects against IAV-induced pneumonia. Comprehensive network pharmacology analyses of the Mass Spec-identified components of RJJDD suggest that RJJDD may act through down-regulating key signaling pathways producing inflammatory cytokines, which was experimentally confirmed by cytokine expression analysis in IAV-infected mouse lung tissues and IAV single-strand RNA mimic R837-induced macrophages. Furthermore, gut microbiota analysis indicates that RJJDD prevented IAV-induced dysbiosis of host intestinal flora, thereby offering a mechanistic explanation for RJJDD's efficacy in influenza pneumonia. Conclusion: This study defines a previously uncharacterized role for RJJDD in protecting against influenza likely by maintaining homeostasis of gut microbiota, and provides a new therapeutic option for severe influenza.
