Jing-Yin-Gu-Biao formula protects mice from postinfluenza Staphylococcus aureus infection by ameliorating acute lung injury and improving hypercoagulable state via inhibiting NETosis
BackgroundJing-Yin-Gu-Biao formula (JYGBF) is a Chinese medicine derived from Yupingfeng power, Huoxiangzhengqi powder and Yinqiao powder, and has been widely used to treat acute respiratory infections. This study aims to observe the effects of JYGBF against postinfluenza Staphylococcus aureus (S. a...
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Frontiers Media S.A.
2025-03-01
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| author | Biao Lei Biao Lei Jingwen Mu Jingwen Mu Guihua Xu Xiaodong Yang Xiaodong Yang Wenbo Huang Liang Hu Dan Liu Dan Liu Ting Cheng Ting Cheng Yuhe Ma Yuhe Ma Lirong Xu Lirong Xu Qiankun Liang Qiankun Liang Yuan Lin Linqiong Zhou Linqiong Zhou Linqiong Zhou Chunxian Zhou Chunxian Zhou Wei Zhang Wei Zhang Wei Zhang Yuejuan Zheng Yuejuan Zheng |
| author_facet | Biao Lei Biao Lei Jingwen Mu Jingwen Mu Guihua Xu Xiaodong Yang Xiaodong Yang Wenbo Huang Liang Hu Dan Liu Dan Liu Ting Cheng Ting Cheng Yuhe Ma Yuhe Ma Lirong Xu Lirong Xu Qiankun Liang Qiankun Liang Yuan Lin Linqiong Zhou Linqiong Zhou Linqiong Zhou Chunxian Zhou Chunxian Zhou Wei Zhang Wei Zhang Wei Zhang Yuejuan Zheng Yuejuan Zheng |
| author_sort | Biao Lei |
| collection | DOAJ |
| description | BackgroundJing-Yin-Gu-Biao formula (JYGBF) is a Chinese medicine derived from Yupingfeng power, Huoxiangzhengqi powder and Yinqiao powder, and has been widely used to treat acute respiratory infections. This study aims to observe the effects of JYGBF against postinfluenza Staphylococcus aureus (S. aureus) infection.Purpose and study designA mouse model of secondary S. aureus infection following PR8 infection was established to evaluate the protective effects of JYGBF against postinfluenza Staphylococcus aureus (S. aureus) infection and related mechanisms were validated in vivo and in vitro.ResultsThe administration of JYGBF significantly ameliorated acute lung injury (ALI) and inhibited overactivated inflammatory response (MIP-2, IL-6, etc.) in mice with postinfluenza S. aureus infection. Single cell RNA-sequencing (scRNA-seq) data indicated that neutrophils had the highest cytokine score in lungs and JYGBF inhibited neutrophil chemotaxis, reactive oxygen species (ROS) biosynthesis and ERK1/2 cascades in neutrophils. Meanwhile, JYGBF inhibited the formation of neutrophil extracellular traps (NETs) in lungs, which is characterized by the production of ROS, peptidyl arginine deiminase 4 (PAD4), citrullinated histone H3 (CitH3), myeloperoxidase (MPO), neutrophil elastase (NE), S100A8/A9 and MPO-CitH3 colocalization. Moreover, JYGBF decreased platelet counts and the expression of its activated markers (CD62P and αIIbβ3) accompanied by the drop of fibrinogen (FIB) and fibrin degradation product (FDP), accounting for alleviating hypercoagulable state. JYGBF inhibited ERK1/2 phosphorylation in neutrophils and in lungs of infected mice. Acacetin, a critical compound from JYGBF, inhibited NET formation via downregulating ERK/ROS axis.ConclusionsThese results indicated that JYGBF inhibited NET formation and overactivated inflammatory response by suppressing ERK/ROS axis in neutrophils, thereby mitigating ALI and improving the hypercoagulable state during postinfluenza S. aureus infection. JYGBF could be considered a potent therapeutic agent for the prevention and treatment of postinfluenza bacterial infection. |
| format | Article |
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| institution | OA Journals |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-5ae3a8de24034b57bbbb89c4a5f929df2025-08-20T01:58:04ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-03-011610.3389/fimmu.2025.15675221567522Jing-Yin-Gu-Biao formula protects mice from postinfluenza Staphylococcus aureus infection by ameliorating acute lung injury and improving hypercoagulable state via inhibiting NETosisBiao Lei0Biao Lei1Jingwen Mu2Jingwen Mu3Guihua Xu4Xiaodong Yang5Xiaodong Yang6Wenbo Huang7Liang Hu8Dan Liu9Dan Liu10Ting Cheng11Ting Cheng12Yuhe Ma13Yuhe Ma14Lirong Xu15Lirong Xu16Qiankun Liang17Qiankun Liang18Yuan Lin19Linqiong Zhou20Linqiong Zhou21Linqiong Zhou22Chunxian Zhou23Chunxian Zhou24Wei Zhang25Wei Zhang26Wei Zhang27Yuejuan Zheng28Yuejuan Zheng29The Research Center for Traditional Chinese Medicine, Shanghai Institute of Infectious Diseases and Biosecurity, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaCenter for Traditional Chinese Medicine and Immunology Research, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaThe Research Center for Traditional Chinese Medicine, Shanghai Institute of Infectious Diseases and Biosecurity, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaCenter for Traditional Chinese Medicine and Immunology Research, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Pulmonary Diseases, ShuGuang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaThe Research Center for Traditional Chinese Medicine, Shanghai Institute of Infectious Diseases and Biosecurity, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaCenter for Traditional Chinese Medicine and Immunology Research, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, ChinaThe Research Center for Traditional Chinese Medicine, Shanghai Institute of Infectious Diseases and Biosecurity, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaThe Research Center for Traditional Chinese Medicine, Shanghai Institute of Infectious Diseases and Biosecurity, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaCenter for Traditional Chinese Medicine and Immunology Research, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaThe Research Center for Traditional Chinese Medicine, Shanghai Institute of Infectious Diseases and Biosecurity, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaCenter for Traditional Chinese Medicine and Immunology Research, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaThe Research Center for Traditional Chinese Medicine, Shanghai Institute of Infectious Diseases and Biosecurity, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaCenter for Traditional Chinese Medicine and Immunology Research, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaThe Research Center for Traditional Chinese Medicine, Shanghai Institute of Infectious Diseases and Biosecurity, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaCenter for Traditional Chinese Medicine and Immunology Research, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaThe Research Center for Traditional Chinese Medicine, Shanghai Institute of Infectious Diseases and Biosecurity, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaCenter for Traditional Chinese Medicine and Immunology Research, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaThe Research Center for Traditional Chinese Medicine, Shanghai Institute of Infectious Diseases and Biosecurity, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaShuguang Hospital, Shanghai Institute of Infectious Diseases and Biosecurity, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaShanghai University of Traditional Chinese Medicine Epidemic Research Center, Shanghai, ChinaShanghai Baoshan Hospital of Integrated Traditional Chinese and Western Medicine, Respiratory and Critical Care Medicine, Shanghai, ChinaThe Research Center for Traditional Chinese Medicine, Shanghai Institute of Infectious Diseases and Biosecurity, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaCenter for Traditional Chinese Medicine and Immunology Research, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaShuguang Hospital, Shanghai Institute of Infectious Diseases and Biosecurity, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaShanghai University of Traditional Chinese Medicine Epidemic Research Center, Shanghai, ChinaShanghai Baoshan Hospital of Integrated Traditional Chinese and Western Medicine, Respiratory and Critical Care Medicine, Shanghai, ChinaThe Research Center for Traditional Chinese Medicine, Shanghai Institute of Infectious Diseases and Biosecurity, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaCenter for Traditional Chinese Medicine and Immunology Research, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaBackgroundJing-Yin-Gu-Biao formula (JYGBF) is a Chinese medicine derived from Yupingfeng power, Huoxiangzhengqi powder and Yinqiao powder, and has been widely used to treat acute respiratory infections. This study aims to observe the effects of JYGBF against postinfluenza Staphylococcus aureus (S. aureus) infection.Purpose and study designA mouse model of secondary S. aureus infection following PR8 infection was established to evaluate the protective effects of JYGBF against postinfluenza Staphylococcus aureus (S. aureus) infection and related mechanisms were validated in vivo and in vitro.ResultsThe administration of JYGBF significantly ameliorated acute lung injury (ALI) and inhibited overactivated inflammatory response (MIP-2, IL-6, etc.) in mice with postinfluenza S. aureus infection. Single cell RNA-sequencing (scRNA-seq) data indicated that neutrophils had the highest cytokine score in lungs and JYGBF inhibited neutrophil chemotaxis, reactive oxygen species (ROS) biosynthesis and ERK1/2 cascades in neutrophils. Meanwhile, JYGBF inhibited the formation of neutrophil extracellular traps (NETs) in lungs, which is characterized by the production of ROS, peptidyl arginine deiminase 4 (PAD4), citrullinated histone H3 (CitH3), myeloperoxidase (MPO), neutrophil elastase (NE), S100A8/A9 and MPO-CitH3 colocalization. Moreover, JYGBF decreased platelet counts and the expression of its activated markers (CD62P and αIIbβ3) accompanied by the drop of fibrinogen (FIB) and fibrin degradation product (FDP), accounting for alleviating hypercoagulable state. JYGBF inhibited ERK1/2 phosphorylation in neutrophils and in lungs of infected mice. Acacetin, a critical compound from JYGBF, inhibited NET formation via downregulating ERK/ROS axis.ConclusionsThese results indicated that JYGBF inhibited NET formation and overactivated inflammatory response by suppressing ERK/ROS axis in neutrophils, thereby mitigating ALI and improving the hypercoagulable state during postinfluenza S. aureus infection. JYGBF could be considered a potent therapeutic agent for the prevention and treatment of postinfluenza bacterial infection.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1567522/fullJing-Yin-Gu-Biao formulapostinfluenza Staphylococcus aureus infectionneutrophil extracellular trapplatelet activationERK/ROS axis |
| spellingShingle | Biao Lei Biao Lei Jingwen Mu Jingwen Mu Guihua Xu Xiaodong Yang Xiaodong Yang Wenbo Huang Liang Hu Dan Liu Dan Liu Ting Cheng Ting Cheng Yuhe Ma Yuhe Ma Lirong Xu Lirong Xu Qiankun Liang Qiankun Liang Yuan Lin Linqiong Zhou Linqiong Zhou Linqiong Zhou Chunxian Zhou Chunxian Zhou Wei Zhang Wei Zhang Wei Zhang Yuejuan Zheng Yuejuan Zheng Jing-Yin-Gu-Biao formula protects mice from postinfluenza Staphylococcus aureus infection by ameliorating acute lung injury and improving hypercoagulable state via inhibiting NETosis Frontiers in Immunology Jing-Yin-Gu-Biao formula postinfluenza Staphylococcus aureus infection neutrophil extracellular trap platelet activation ERK/ROS axis |
| title | Jing-Yin-Gu-Biao formula protects mice from postinfluenza Staphylococcus aureus infection by ameliorating acute lung injury and improving hypercoagulable state via inhibiting NETosis |
| title_full | Jing-Yin-Gu-Biao formula protects mice from postinfluenza Staphylococcus aureus infection by ameliorating acute lung injury and improving hypercoagulable state via inhibiting NETosis |
| title_fullStr | Jing-Yin-Gu-Biao formula protects mice from postinfluenza Staphylococcus aureus infection by ameliorating acute lung injury and improving hypercoagulable state via inhibiting NETosis |
| title_full_unstemmed | Jing-Yin-Gu-Biao formula protects mice from postinfluenza Staphylococcus aureus infection by ameliorating acute lung injury and improving hypercoagulable state via inhibiting NETosis |
| title_short | Jing-Yin-Gu-Biao formula protects mice from postinfluenza Staphylococcus aureus infection by ameliorating acute lung injury and improving hypercoagulable state via inhibiting NETosis |
| title_sort | jing yin gu biao formula protects mice from postinfluenza staphylococcus aureus infection by ameliorating acute lung injury and improving hypercoagulable state via inhibiting netosis |
| topic | Jing-Yin-Gu-Biao formula postinfluenza Staphylococcus aureus infection neutrophil extracellular trap platelet activation ERK/ROS axis |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1567522/full |
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