Da-Yuan-Yin decoction suppresses NETs formation, inhibits the IL-23/JAK2/STAT3 signalling pathway, and modulates metabolic profiles and gut microbiota composition in damp-heat syndrome

Background Da-Yuan-Yin Decoction (DYY), used since the early Qing Dynasty in China for damp-heat syndrome, was evaluated for its comprehensive protective effects.Materials and methods Rats received a high-fat/high-sugar diet for 14 days, then daily exposure to high temperature/humidity (31.0 ± 0.5°C...

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Main Authors: Yun Yang, Lengqiu Guo, Jinghua Yu, Wei Peng, Qi Wang, Lan Wei, Xihua Chen, Chunyan Min, Xiaogang Jiang, Song Zhu, Haixin Zhao, Zhenyu Xuan, Jianzhong Yu, Jian Zhang
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:Annals of Medicine
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Online Access:https://www.tandfonline.com/doi/10.1080/07853890.2025.2519684
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author Yun Yang
Lengqiu Guo
Jinghua Yu
Wei Peng
Qi Wang
Lan Wei
Xihua Chen
Chunyan Min
Xiaogang Jiang
Song Zhu
Haixin Zhao
Zhenyu Xuan
Jianzhong Yu
Jian Zhang
author_facet Yun Yang
Lengqiu Guo
Jinghua Yu
Wei Peng
Qi Wang
Lan Wei
Xihua Chen
Chunyan Min
Xiaogang Jiang
Song Zhu
Haixin Zhao
Zhenyu Xuan
Jianzhong Yu
Jian Zhang
author_sort Yun Yang
collection DOAJ
description Background Da-Yuan-Yin Decoction (DYY), used since the early Qing Dynasty in China for damp-heat syndrome, was evaluated for its comprehensive protective effects.Materials and methods Rats received a high-fat/high-sugar diet for 14 days, then daily exposure to high temperature/humidity (31.0 ± 0.5°C, 85%-95%) for 10 hours over 14 days. Damp-heat syndrome was induced on day 29 via intraperitoneal lipopolysaccharide (LPS) injections (1 mg/kg and 0.5 mg/kg after 4 hours). Two hours post-modeling, rats received DYY (400 or 800 mg/kg/day) orally for 5 days. Symptoms were scored. On day 33, kidney, spleen, tongue, lung, liver, stomach, and colon tissues underwent histopathological and immunochemical/immunofluorescence analysis. Serum levels of inflammation factors, C-reactive protein (CRP), cell-free DNA (cfDNA), myeloperoxidase (MPO), and superoxide dismutase (SOD) were quantified. Complete blood count (CBC), blood biochemistry, short-chain fatty acids (SCFAs), gut microbiota composition in the colon, and metabolites in the cecum were analyzed.Results DYY significantly reduced symptom scores and decreased CRP level, while also regulating parameters in CBC and biochemical profiles. The treatment ameliorated tissue damage in the kidney, spleen, tongue, lung, liver, stomach, and colon. DYY downregulated citrullinated histone H3 (Cit H3), polyclonal peptidylarginine deiminase 4 (PADI4), and MPO expressions in the lung, stomach, and colon. Furthermore, it modulated inflammatory responses, suppressed the interleukin-23 (IL-23)/janus kinase-2 (JAK2)/signal transduction and transcription activator-3 (STAT3) signaling pathway and enhanced antioxidant activity. DYY administration significantly increased total SCFA content. The intervention restored gut microbiota diversity and abundance, while ameliorating metabolic dysregulation.Conclusion Systemic pathophysiological alterations were observed in rats with damp-heat syndrome. The comprehensive protective effects of DYY involved suppression of neutrophil extracellular traps (NETs) formation through downregulation of PADI4 expression, modulation of inflammatory responses, inhibition of the IL-23/JAK2/STAT3 signaling pathway, restoration of intestinal microecological balance and metabolic homeostasis, and enhancement of antioxidant.
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spelling doaj-art-c3fb145b24174d65835c85f96a9352f22025-08-20T02:07:27ZengTaylor & Francis GroupAnnals of Medicine0785-38901365-20602025-12-0157110.1080/07853890.2025.2519684Da-Yuan-Yin decoction suppresses NETs formation, inhibits the IL-23/JAK2/STAT3 signalling pathway, and modulates metabolic profiles and gut microbiota composition in damp-heat syndromeYun Yang0Lengqiu Guo1Jinghua Yu2Wei Peng3Qi Wang4Lan Wei5Xihua Chen6Chunyan Min7Xiaogang Jiang8Song Zhu9Haixin Zhao10Zhenyu Xuan11Jianzhong Yu12Jian Zhang13College of Pharmaceutical Science, Soochow University, Suzhou, ChinaJiangsu Province Engineering Research Center of Molecular Target Therapy and Companion Diagnostics in Oncology, Suzhou Vocational Health College, Suzhou, ChinaCollege of Pharmaceutical Science, Soochow University, Suzhou, ChinaDepartment of the Gastrointestinal Surgery, Second Affiliated Hospital of Soochow University, Suzhou, ChinaJiangsu Province Engineering Research Center of Molecular Target Therapy and Companion Diagnostics in Oncology, Suzhou Vocational Health College, Suzhou, ChinaCollege of Pharmaceutical Science, Soochow University, Suzhou, ChinaCollege of Pharmaceutical Science, Soochow University, Suzhou, ChinaPharmaceutical Standards Laboratory, Suzhou Institute for Drug Control, Suzhou, ChinaCollege of Pharmaceutical Science, Soochow University, Suzhou, ChinaCollege of Pharmaceutical Science, Soochow University, Suzhou, ChinaSchool of International Studies, Shaanxi Normal University, Xian, ChinaCollege of Pharmaceutical Science, Soochow University, Suzhou, ChinaDepartment of Internal Medicine of Traditional Chinese Medicine, Haian Hospital of Traditional Chinese Medicine, Nantong, ChinaCollege of Pharmaceutical Science, Soochow University, Suzhou, ChinaBackground Da-Yuan-Yin Decoction (DYY), used since the early Qing Dynasty in China for damp-heat syndrome, was evaluated for its comprehensive protective effects.Materials and methods Rats received a high-fat/high-sugar diet for 14 days, then daily exposure to high temperature/humidity (31.0 ± 0.5°C, 85%-95%) for 10 hours over 14 days. Damp-heat syndrome was induced on day 29 via intraperitoneal lipopolysaccharide (LPS) injections (1 mg/kg and 0.5 mg/kg after 4 hours). Two hours post-modeling, rats received DYY (400 or 800 mg/kg/day) orally for 5 days. Symptoms were scored. On day 33, kidney, spleen, tongue, lung, liver, stomach, and colon tissues underwent histopathological and immunochemical/immunofluorescence analysis. Serum levels of inflammation factors, C-reactive protein (CRP), cell-free DNA (cfDNA), myeloperoxidase (MPO), and superoxide dismutase (SOD) were quantified. Complete blood count (CBC), blood biochemistry, short-chain fatty acids (SCFAs), gut microbiota composition in the colon, and metabolites in the cecum were analyzed.Results DYY significantly reduced symptom scores and decreased CRP level, while also regulating parameters in CBC and biochemical profiles. The treatment ameliorated tissue damage in the kidney, spleen, tongue, lung, liver, stomach, and colon. DYY downregulated citrullinated histone H3 (Cit H3), polyclonal peptidylarginine deiminase 4 (PADI4), and MPO expressions in the lung, stomach, and colon. Furthermore, it modulated inflammatory responses, suppressed the interleukin-23 (IL-23)/janus kinase-2 (JAK2)/signal transduction and transcription activator-3 (STAT3) signaling pathway and enhanced antioxidant activity. DYY administration significantly increased total SCFA content. The intervention restored gut microbiota diversity and abundance, while ameliorating metabolic dysregulation.Conclusion Systemic pathophysiological alterations were observed in rats with damp-heat syndrome. The comprehensive protective effects of DYY involved suppression of neutrophil extracellular traps (NETs) formation through downregulation of PADI4 expression, modulation of inflammatory responses, inhibition of the IL-23/JAK2/STAT3 signaling pathway, restoration of intestinal microecological balance and metabolic homeostasis, and enhancement of antioxidant.https://www.tandfonline.com/doi/10.1080/07853890.2025.2519684Da-Yuan-Yin decoctiondamp-heat syndromeneutrophil extracellular trapsfaecal metabolitesgut microbiotainflammation
spellingShingle Yun Yang
Lengqiu Guo
Jinghua Yu
Wei Peng
Qi Wang
Lan Wei
Xihua Chen
Chunyan Min
Xiaogang Jiang
Song Zhu
Haixin Zhao
Zhenyu Xuan
Jianzhong Yu
Jian Zhang
Da-Yuan-Yin decoction suppresses NETs formation, inhibits the IL-23/JAK2/STAT3 signalling pathway, and modulates metabolic profiles and gut microbiota composition in damp-heat syndrome
Annals of Medicine
Da-Yuan-Yin decoction
damp-heat syndrome
neutrophil extracellular traps
faecal metabolites
gut microbiota
inflammation
title Da-Yuan-Yin decoction suppresses NETs formation, inhibits the IL-23/JAK2/STAT3 signalling pathway, and modulates metabolic profiles and gut microbiota composition in damp-heat syndrome
title_full Da-Yuan-Yin decoction suppresses NETs formation, inhibits the IL-23/JAK2/STAT3 signalling pathway, and modulates metabolic profiles and gut microbiota composition in damp-heat syndrome
title_fullStr Da-Yuan-Yin decoction suppresses NETs formation, inhibits the IL-23/JAK2/STAT3 signalling pathway, and modulates metabolic profiles and gut microbiota composition in damp-heat syndrome
title_full_unstemmed Da-Yuan-Yin decoction suppresses NETs formation, inhibits the IL-23/JAK2/STAT3 signalling pathway, and modulates metabolic profiles and gut microbiota composition in damp-heat syndrome
title_short Da-Yuan-Yin decoction suppresses NETs formation, inhibits the IL-23/JAK2/STAT3 signalling pathway, and modulates metabolic profiles and gut microbiota composition in damp-heat syndrome
title_sort da yuan yin decoction suppresses nets formation inhibits the il 23 jak2 stat3 signalling pathway and modulates metabolic profiles and gut microbiota composition in damp heat syndrome
topic Da-Yuan-Yin decoction
damp-heat syndrome
neutrophil extracellular traps
faecal metabolites
gut microbiota
inflammation
url https://www.tandfonline.com/doi/10.1080/07853890.2025.2519684
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