Hongyuyin attenuates intestinal fibrosis in ulcerative colitis in mice revealed by transcriptomic and network pharmacology analyses
Abstract Ulcerative colitis (UC) is a chronic, idiopathic inflammatory disease affecting the gastrointestinal tract. Hongyuyin (HYY), a traditional Chinese botanical formulation, has been effectively treating UC for over three decades; however, its underlying biological mechanism of action in UC-ass...
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Nature Portfolio
2025-07-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-06021-w |
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| author | Qin Qin Qingjun Dong Yan Pan Chen Wang Jingen Lu |
| author_facet | Qin Qin Qingjun Dong Yan Pan Chen Wang Jingen Lu |
| author_sort | Qin Qin |
| collection | DOAJ |
| description | Abstract Ulcerative colitis (UC) is a chronic, idiopathic inflammatory disease affecting the gastrointestinal tract. Hongyuyin (HYY), a traditional Chinese botanical formulation, has been effectively treating UC for over three decades; however, its underlying biological mechanism of action in UC-associated intestinal fibrosis (IF) remains unclear. This study investigated the mechanisms of action of HYY on IF through in vivo experiments using a dextran sulfate sodium (DSS)-induced mouse colitis model. Clinical symptoms, colonic pathological damage, inflammation, and fibrosis were monitored across all groups. Both transcriptomic analysis and network pharmacology (NP) techniques were utilized to elucidate the mechanistic insights. HYY treatment substantially reduced inflammation, fibroblast activation, and collagen deposition in UC mice. KEGG analyses suggested that HYY treatment modulated multiple signaling pathways, notably the TNF, IL-17, and PI3K-Akt signaling pathways. Combined analysis identified the PI3K-Akt signaling pathway as a major contributor, with high enrichment factors and numerous enrichment genes involved (IL-6, CSF3, SPP1, AKT1, PIK3CA, and so on) in UC-associated IF. Western blotting confirmed significant reductions in both p-AKT/AKT and p-mTOR/mTOR ratios after HYY treatment. Collectively, HYY alleviates UC-associated IF by reducing the phosphorylation of PI3K-Akt pathway factors, thereby inhibiting fibroblast activation and collagen deposition. This research provides novel insights into HYY’s mechanism of action in UC-associated IF management. |
| format | Article |
| id | doaj-art-172fda35403546c7b6e427a3dd393fcd |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-172fda35403546c7b6e427a3dd393fcd2025-08-20T04:01:34ZengNature PortfolioScientific Reports2045-23222025-07-0115111810.1038/s41598-025-06021-wHongyuyin attenuates intestinal fibrosis in ulcerative colitis in mice revealed by transcriptomic and network pharmacology analysesQin Qin0Qingjun Dong1Yan Pan2Chen Wang3Jingen Lu4Institute of Chinese Traditional Surgery, Longhua Hospital, Shanghai University of Traditional Chinese MedicineDepartment of Anal & Intestinal Disease, Longhua Hospital, Shanghai University of Traditional Chinese MedicineDepartment of Anal & Intestinal Disease, Longhua Hospital, Shanghai University of Traditional Chinese MedicineDepartment of Anal & Intestinal Disease, Longhua Hospital, Shanghai University of Traditional Chinese MedicineDepartment of Anal & Intestinal Disease, Longhua Hospital, Shanghai University of Traditional Chinese MedicineAbstract Ulcerative colitis (UC) is a chronic, idiopathic inflammatory disease affecting the gastrointestinal tract. Hongyuyin (HYY), a traditional Chinese botanical formulation, has been effectively treating UC for over three decades; however, its underlying biological mechanism of action in UC-associated intestinal fibrosis (IF) remains unclear. This study investigated the mechanisms of action of HYY on IF through in vivo experiments using a dextran sulfate sodium (DSS)-induced mouse colitis model. Clinical symptoms, colonic pathological damage, inflammation, and fibrosis were monitored across all groups. Both transcriptomic analysis and network pharmacology (NP) techniques were utilized to elucidate the mechanistic insights. HYY treatment substantially reduced inflammation, fibroblast activation, and collagen deposition in UC mice. KEGG analyses suggested that HYY treatment modulated multiple signaling pathways, notably the TNF, IL-17, and PI3K-Akt signaling pathways. Combined analysis identified the PI3K-Akt signaling pathway as a major contributor, with high enrichment factors and numerous enrichment genes involved (IL-6, CSF3, SPP1, AKT1, PIK3CA, and so on) in UC-associated IF. Western blotting confirmed significant reductions in both p-AKT/AKT and p-mTOR/mTOR ratios after HYY treatment. Collectively, HYY alleviates UC-associated IF by reducing the phosphorylation of PI3K-Akt pathway factors, thereby inhibiting fibroblast activation and collagen deposition. This research provides novel insights into HYY’s mechanism of action in UC-associated IF management.https://doi.org/10.1038/s41598-025-06021-wUlcerative colitisIntestinal fibrosisPI3KAKTTranscriptomicsNetwork pharmacology |
| spellingShingle | Qin Qin Qingjun Dong Yan Pan Chen Wang Jingen Lu Hongyuyin attenuates intestinal fibrosis in ulcerative colitis in mice revealed by transcriptomic and network pharmacology analyses Scientific Reports Ulcerative colitis Intestinal fibrosis PI3K AKT Transcriptomics Network pharmacology |
| title | Hongyuyin attenuates intestinal fibrosis in ulcerative colitis in mice revealed by transcriptomic and network pharmacology analyses |
| title_full | Hongyuyin attenuates intestinal fibrosis in ulcerative colitis in mice revealed by transcriptomic and network pharmacology analyses |
| title_fullStr | Hongyuyin attenuates intestinal fibrosis in ulcerative colitis in mice revealed by transcriptomic and network pharmacology analyses |
| title_full_unstemmed | Hongyuyin attenuates intestinal fibrosis in ulcerative colitis in mice revealed by transcriptomic and network pharmacology analyses |
| title_short | Hongyuyin attenuates intestinal fibrosis in ulcerative colitis in mice revealed by transcriptomic and network pharmacology analyses |
| title_sort | hongyuyin attenuates intestinal fibrosis in ulcerative colitis in mice revealed by transcriptomic and network pharmacology analyses |
| topic | Ulcerative colitis Intestinal fibrosis PI3K AKT Transcriptomics Network pharmacology |
| url | https://doi.org/10.1038/s41598-025-06021-w |
| work_keys_str_mv | AT qinqin hongyuyinattenuatesintestinalfibrosisinulcerativecolitisinmicerevealedbytranscriptomicandnetworkpharmacologyanalyses AT qingjundong hongyuyinattenuatesintestinalfibrosisinulcerativecolitisinmicerevealedbytranscriptomicandnetworkpharmacologyanalyses AT yanpan hongyuyinattenuatesintestinalfibrosisinulcerativecolitisinmicerevealedbytranscriptomicandnetworkpharmacologyanalyses AT chenwang hongyuyinattenuatesintestinalfibrosisinulcerativecolitisinmicerevealedbytranscriptomicandnetworkpharmacologyanalyses AT jingenlu hongyuyinattenuatesintestinalfibrosisinulcerativecolitisinmicerevealedbytranscriptomicandnetworkpharmacologyanalyses |