Deciphering the therapeutic effects of Xiyanping injection: insights into pulmonary and gut microbiome modulation, SerpinB2/PAI-2 targeting, and alleviation of influenza a virus-induced lung injury
Abstract Infection with Influenza A virus (IAV) induces severe inflammatory responses and lung injury, contributing significantly to mortality and morbidity rates. Alterations in the microbial composition of the lungs and intestinal tract resulting from infection could influence disease progression...
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2025-01-01
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| Series: | Virology Journal |
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| Online Access: | https://doi.org/10.1186/s12985-025-02636-7 |
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| author | Tengwen Liu Shuping Li Xuerui Wang Mingjiang Liu Yuchen Wang Jie Ying Shuwen Zhang Yan Lin Ning Wang Yungjing Bai Lan Xie Tengfei Chen Quansheng Feng Xiaolong Xu |
| author_facet | Tengwen Liu Shuping Li Xuerui Wang Mingjiang Liu Yuchen Wang Jie Ying Shuwen Zhang Yan Lin Ning Wang Yungjing Bai Lan Xie Tengfei Chen Quansheng Feng Xiaolong Xu |
| author_sort | Tengwen Liu |
| collection | DOAJ |
| description | Abstract Infection with Influenza A virus (IAV) induces severe inflammatory responses and lung injury, contributing significantly to mortality and morbidity rates. Alterations in the microbial composition of the lungs and intestinal tract resulting from infection could influence disease progression and treatment outcomes. Xiyanping (XYP) injection has demonstrated efficacy in clinical treatment across various viral infections. However, its specific effects and mechanisms against IAV remain unclear. In this study, we established an IAV infection mice model, and utilized 16 S rRNA sequencing, RNA sequencing, protein chips, and molecular docking, to investigate the mechanisms of XYP injection on altering pulmonary and gut microbiota, and identifying its target sites. We revealed that XYP injection significantly reduced mortality, weight loss, lung viral titers, and lung pathology in IAV-infected mice. XYP injection down-regulated the activity of malondialdehyde, and the levels of interleukin (IL)-1β, IL-5, IL-6, tumor necrosis factor-α, IL-18, IL-15, granulocyte colony-stimulating factor, IL-9, chemokine (C-C motif) ligand-5, and C-X-C motif chemokine ligand 5, while up-regulated the activities of glutathione peroxidase reactive and superoxide dismutase, and the level of interferon-γ. The diversity of the pulmonary and gut microbiota was altered slightly after XYP injection. The linear discriminant analysis of the gut microbes revealed a higher proportion of potentially beneficial bacteria, including Akkermansia, Parabacteroides goldsteinii, Defluviitaleaceae, Oscillospirales, and Eubacterium_coprostanoligenes_group characterized the XYP group. Peritoneal macrophage RNA sequencing highlighted Serpinb2 as the most significantly regulated gene by XYP injection, along with consistent changes in multiple downstream Th2 structure genes. KEGG pathway analysis indicated significant modifications in genes associated with influenza A, mitogen-activated protein kinase signaling, nuclear factor kappa-B signaling, and apoptosis following XYP injection. Finally, human protein chips and molecular docking were carried out to confirm the binding of the main component of XYP injection, andrographolide, with SERPINB2/PAI-2 protein. Overall, our study provides valuable insights into the therapeutic potential of XYP injection in treating influenza, highlighting its multifaceted effects on host microbiota and immune responses, and pinpointing SerpinB2/PAI-2 as the target for XYP injection in exerting anti-inflammatory and antiviral therapeutic mechanisms. |
| format | Article |
| id | doaj-art-781736bb218a442da8e3fd821302c070 |
| institution | Kabale University |
| issn | 1743-422X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Virology Journal |
| spelling | doaj-art-781736bb218a442da8e3fd821302c0702025-02-02T12:08:37ZengBMCVirology Journal1743-422X2025-01-0122111810.1186/s12985-025-02636-7Deciphering the therapeutic effects of Xiyanping injection: insights into pulmonary and gut microbiome modulation, SerpinB2/PAI-2 targeting, and alleviation of influenza a virus-induced lung injuryTengwen Liu0Shuping Li1Xuerui Wang2Mingjiang Liu3Yuchen Wang4Jie Ying5Shuwen Zhang6Yan Lin7Ning Wang8Yungjing Bai9Lan Xie10Tengfei Chen11Quansheng Feng12Xiaolong Xu13School of Basic Medical Sciences, Chengdu University of Traditional Chinese MedicineBeijing Hospital of Traditional Chinese Medicine, Capital Medical UniversityBeijing Hospital of Traditional Chinese Medicine, Capital Medical UniversityCollege of Veterinary Medicine, Yangzhou UniversityBeijing University of Chinese MedicineBeijing Hospital of Traditional Chinese Medicine, Capital Medical UniversityBeijing Hospital of Traditional Chinese Medicine, Capital Medical UniversityBeijing Hospital of Traditional Chinese Medicine, Capital Medical UniversityBeijing Hospital of Traditional Chinese Medicine, Capital Medical UniversityBeijing Hospital of Traditional Chinese Medicine, Capital Medical UniversityMedical Systems Biology Research Center, Tsinghua UniversityBeijing Hospital of Traditional Chinese Medicine, Capital Medical UniversitySchool of Basic Medical Sciences, Chengdu University of Traditional Chinese MedicineBeijing Hospital of Traditional Chinese Medicine, Capital Medical UniversityAbstract Infection with Influenza A virus (IAV) induces severe inflammatory responses and lung injury, contributing significantly to mortality and morbidity rates. Alterations in the microbial composition of the lungs and intestinal tract resulting from infection could influence disease progression and treatment outcomes. Xiyanping (XYP) injection has demonstrated efficacy in clinical treatment across various viral infections. However, its specific effects and mechanisms against IAV remain unclear. In this study, we established an IAV infection mice model, and utilized 16 S rRNA sequencing, RNA sequencing, protein chips, and molecular docking, to investigate the mechanisms of XYP injection on altering pulmonary and gut microbiota, and identifying its target sites. We revealed that XYP injection significantly reduced mortality, weight loss, lung viral titers, and lung pathology in IAV-infected mice. XYP injection down-regulated the activity of malondialdehyde, and the levels of interleukin (IL)-1β, IL-5, IL-6, tumor necrosis factor-α, IL-18, IL-15, granulocyte colony-stimulating factor, IL-9, chemokine (C-C motif) ligand-5, and C-X-C motif chemokine ligand 5, while up-regulated the activities of glutathione peroxidase reactive and superoxide dismutase, and the level of interferon-γ. The diversity of the pulmonary and gut microbiota was altered slightly after XYP injection. The linear discriminant analysis of the gut microbes revealed a higher proportion of potentially beneficial bacteria, including Akkermansia, Parabacteroides goldsteinii, Defluviitaleaceae, Oscillospirales, and Eubacterium_coprostanoligenes_group characterized the XYP group. Peritoneal macrophage RNA sequencing highlighted Serpinb2 as the most significantly regulated gene by XYP injection, along with consistent changes in multiple downstream Th2 structure genes. KEGG pathway analysis indicated significant modifications in genes associated with influenza A, mitogen-activated protein kinase signaling, nuclear factor kappa-B signaling, and apoptosis following XYP injection. Finally, human protein chips and molecular docking were carried out to confirm the binding of the main component of XYP injection, andrographolide, with SERPINB2/PAI-2 protein. Overall, our study provides valuable insights into the therapeutic potential of XYP injection in treating influenza, highlighting its multifaceted effects on host microbiota and immune responses, and pinpointing SerpinB2/PAI-2 as the target for XYP injection in exerting anti-inflammatory and antiviral therapeutic mechanisms.https://doi.org/10.1186/s12985-025-02636-7Influenza A virusXiyanpingSerpinB2PAI-2AndrographolideTraditional Chinese medicine |
| spellingShingle | Tengwen Liu Shuping Li Xuerui Wang Mingjiang Liu Yuchen Wang Jie Ying Shuwen Zhang Yan Lin Ning Wang Yungjing Bai Lan Xie Tengfei Chen Quansheng Feng Xiaolong Xu Deciphering the therapeutic effects of Xiyanping injection: insights into pulmonary and gut microbiome modulation, SerpinB2/PAI-2 targeting, and alleviation of influenza a virus-induced lung injury Virology Journal Influenza A virus Xiyanping SerpinB2 PAI-2 Andrographolide Traditional Chinese medicine |
| title | Deciphering the therapeutic effects of Xiyanping injection: insights into pulmonary and gut microbiome modulation, SerpinB2/PAI-2 targeting, and alleviation of influenza a virus-induced lung injury |
| title_full | Deciphering the therapeutic effects of Xiyanping injection: insights into pulmonary and gut microbiome modulation, SerpinB2/PAI-2 targeting, and alleviation of influenza a virus-induced lung injury |
| title_fullStr | Deciphering the therapeutic effects of Xiyanping injection: insights into pulmonary and gut microbiome modulation, SerpinB2/PAI-2 targeting, and alleviation of influenza a virus-induced lung injury |
| title_full_unstemmed | Deciphering the therapeutic effects of Xiyanping injection: insights into pulmonary and gut microbiome modulation, SerpinB2/PAI-2 targeting, and alleviation of influenza a virus-induced lung injury |
| title_short | Deciphering the therapeutic effects of Xiyanping injection: insights into pulmonary and gut microbiome modulation, SerpinB2/PAI-2 targeting, and alleviation of influenza a virus-induced lung injury |
| title_sort | deciphering the therapeutic effects of xiyanping injection insights into pulmonary and gut microbiome modulation serpinb2 pai 2 targeting and alleviation of influenza a virus induced lung injury |
| topic | Influenza A virus Xiyanping SerpinB2 PAI-2 Andrographolide Traditional Chinese medicine |
| url | https://doi.org/10.1186/s12985-025-02636-7 |
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