Qufeng epimedium decoction alleviates rheumatoid arthritis through CYLD-antagonized NF-kB activation by deubiquitinating Sirt1
Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease that markedly limits the patients´ day-to-day functional abilities and life quality. Currently, there is no known cure for RA. Qufeng epimedium decoction, a traditional Chinese medicine, is widely used in China to treat RA. Howeve...
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Elsevier
2025-03-01
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| Series: | Immunobiology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0171298525000099 |
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| author | Zhiming Wu Peng Zhang Wenyan Huang Yifen Zhou Zhengliu Cao Chunhong Wu |
| author_facet | Zhiming Wu Peng Zhang Wenyan Huang Yifen Zhou Zhengliu Cao Chunhong Wu |
| author_sort | Zhiming Wu |
| collection | DOAJ |
| description | Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease that markedly limits the patients´ day-to-day functional abilities and life quality. Currently, there is no known cure for RA. Qufeng epimedium decoction, a traditional Chinese medicine, is widely used in China to treat RA. However, its underlying mechanism remains elusive. Methods: The RA animal model was established to investigate the anti-RA effect and regulatory effect on fibroblast-like synoviocytes (FLS) pyroptosis, qRT-PCR, Western blot, flow cytometry, histology staining, and ELISA were utilized to confirm the gene and protein expressions. The interactions between Sirt1 and CYLD were validated through Co-immunoprecipitation (Co-IP) and RNA-FISH assay. Results: Administration with Qufeng epimedium decoction attenuated inflammatory damage, excessive proliferation, and FLSs pyroptosis in an RA rat model. Moreover, treatment of Qufeng epimedium decoction reduced the ubiquitination modification level of Sirt1 in FLSs isolated from an RA rat model. Mechanistically, CYLD, an intermediation for linking Qufeng epimedium decoction and RA, was responsible for Sirt1 deubiquitination to its protein stabilization, thereby deactivating the NF-kB /GSDMD signaling pathway. Conclusion: Our findings indicate that Qufeng epimedium decoction suppresses FLSs pyroptosis and RA progression via CYLD-mediated Sirt1 deubiquitination and deactivation of the NF-kB /GSDMD signaling pathway. This study sheds light on the underlying mechanism of Qufeng epimedium decoction's effectiveness in RA treatment. |
| format | Article |
| id | doaj-art-87934a52661f44a58572d829920da71d |
| institution | Kabale University |
| issn | 0171-2985 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Immunobiology |
| spelling | doaj-art-87934a52661f44a58572d829920da71d2025-02-05T04:31:05ZengElsevierImmunobiology0171-29852025-03-012302152875Qufeng epimedium decoction alleviates rheumatoid arthritis through CYLD-antagonized NF-kB activation by deubiquitinating Sirt1Zhiming Wu0Peng Zhang1Wenyan Huang2Yifen Zhou3Zhengliu Cao4Chunhong Wu5Chinese Medicine Department, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330000, Jiangxi Province, PR China; Corresponding author at: Chinese Medicine Department, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, No. 1519, Dongyue Avenue, Nanchang County, Nanchang 330000, Jiangxi Province, PR China.Chinese Medicine Department, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330000, Jiangxi Province, PR ChinaDay Surgery Center, Jiangxi Maternal and Child Health Care Hospital, Nanchang 330000, Jiangxi Province, PR ChinaChinese Medicine Department, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330000, Jiangxi Province, PR ChinaChinese Medicine Department, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330000, Jiangxi Province, PR ChinaOutpatient Department, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330000, Jiangxi Province, PR ChinaBackground: Rheumatoid arthritis (RA) is a chronic autoimmune disease that markedly limits the patients´ day-to-day functional abilities and life quality. Currently, there is no known cure for RA. Qufeng epimedium decoction, a traditional Chinese medicine, is widely used in China to treat RA. However, its underlying mechanism remains elusive. Methods: The RA animal model was established to investigate the anti-RA effect and regulatory effect on fibroblast-like synoviocytes (FLS) pyroptosis, qRT-PCR, Western blot, flow cytometry, histology staining, and ELISA were utilized to confirm the gene and protein expressions. The interactions between Sirt1 and CYLD were validated through Co-immunoprecipitation (Co-IP) and RNA-FISH assay. Results: Administration with Qufeng epimedium decoction attenuated inflammatory damage, excessive proliferation, and FLSs pyroptosis in an RA rat model. Moreover, treatment of Qufeng epimedium decoction reduced the ubiquitination modification level of Sirt1 in FLSs isolated from an RA rat model. Mechanistically, CYLD, an intermediation for linking Qufeng epimedium decoction and RA, was responsible for Sirt1 deubiquitination to its protein stabilization, thereby deactivating the NF-kB /GSDMD signaling pathway. Conclusion: Our findings indicate that Qufeng epimedium decoction suppresses FLSs pyroptosis and RA progression via CYLD-mediated Sirt1 deubiquitination and deactivation of the NF-kB /GSDMD signaling pathway. This study sheds light on the underlying mechanism of Qufeng epimedium decoction's effectiveness in RA treatment.http://www.sciencedirect.com/science/article/pii/S0171298525000099Qufeng epimedium decoctionRheumatoid arthritisSirt1CYLDAlleviates fibroblast-like synoviocyte pyroptosis |
| spellingShingle | Zhiming Wu Peng Zhang Wenyan Huang Yifen Zhou Zhengliu Cao Chunhong Wu Qufeng epimedium decoction alleviates rheumatoid arthritis through CYLD-antagonized NF-kB activation by deubiquitinating Sirt1 Immunobiology Qufeng epimedium decoction Rheumatoid arthritis Sirt1 CYLD Alleviates fibroblast-like synoviocyte pyroptosis |
| title | Qufeng epimedium decoction alleviates rheumatoid arthritis through CYLD-antagonized NF-kB activation by deubiquitinating Sirt1 |
| title_full | Qufeng epimedium decoction alleviates rheumatoid arthritis through CYLD-antagonized NF-kB activation by deubiquitinating Sirt1 |
| title_fullStr | Qufeng epimedium decoction alleviates rheumatoid arthritis through CYLD-antagonized NF-kB activation by deubiquitinating Sirt1 |
| title_full_unstemmed | Qufeng epimedium decoction alleviates rheumatoid arthritis through CYLD-antagonized NF-kB activation by deubiquitinating Sirt1 |
| title_short | Qufeng epimedium decoction alleviates rheumatoid arthritis through CYLD-antagonized NF-kB activation by deubiquitinating Sirt1 |
| title_sort | qufeng epimedium decoction alleviates rheumatoid arthritis through cyld antagonized nf kb activation by deubiquitinating sirt1 |
| topic | Qufeng epimedium decoction Rheumatoid arthritis Sirt1 CYLD Alleviates fibroblast-like synoviocyte pyroptosis |
| url | http://www.sciencedirect.com/science/article/pii/S0171298525000099 |
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