Quercetagetin alleviates inflammatory osteoclastogenesis and collagen antibody-induced arthritis via Nrf2 signaling and Pten/AKT/Nfatc1 axis
Abstract Purpose Quercetagetin, a flavonoid derived from the natural herb Flos eriocauli, is used in traditional Chinese medicine for its fire-purging (anti-inflammation) and wind-expelling (pain-alleviating) properties. However, its potential effects concerning rheumatoid arthritis (RA) remain unde...
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BMC
2025-03-01
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| Series: | Arthritis Research & Therapy |
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| Online Access: | https://doi.org/10.1186/s13075-025-03522-x |
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| author | Haojue Wang Tao Yuan Jingpeng Wang Dengju Li Wayne Yuk-wai Lee Ziqing Li Shui Sun |
| author_facet | Haojue Wang Tao Yuan Jingpeng Wang Dengju Li Wayne Yuk-wai Lee Ziqing Li Shui Sun |
| author_sort | Haojue Wang |
| collection | DOAJ |
| description | Abstract Purpose Quercetagetin, a flavonoid derived from the natural herb Flos eriocauli, is used in traditional Chinese medicine for its fire-purging (anti-inflammation) and wind-expelling (pain-alleviating) properties. However, its potential effects concerning rheumatoid arthritis (RA) remain underexplored. This study was designed to elucidate the potential associations between Quercetagetin and RA, establishing the therapeutic potential of Quercetagetin and related mechanisms in RA treatment. Methods Network pharmacology was conducted to decipher related targets and signaling pathways between Quercetagetin and RA. In vitro assays were then conducted to explore the effects of Quercetagetin on osteoclast cell behaviors and corresponding signaling pathways. In vivo study further validated the therapeutic effect of Quercetagetin in collagen antibody-induced arthritis (CAIA) mice. Results The network pharmacological analysis indicated an intimate correlation of Quercetagetin with RA-related inflammatory osteolysis treatment. Pertaining to biological validations, 2 µM of Quercetagetin successfully inhibited LPS-driven osteoclast differentiation and function. qPCR assay and Western blot analyses denoted parallel changes in osteoclastic marker genes and proteins. Further mechanism study uncovered the effect of Quercetagetin in stimulating the Nrf2/Keap1 signaling pathway and moderating the Pten/AKT/Nfatc1 axis in osteoclasts. In vivo study revealed 40 mg/kg Quercetagetin every day could significantly relief joint destruction in CAIA mice. Conclusions Our study presents Quercetagetin ‘s therapeutic potential in treating RA, outlining its effects and potential mechanisms in suppressing LPS-induced osteoclast activity, and alleviating inflammatory bone destruction in CAIA model, thereby laying the groundwork for further translational research on Quercetagetin and Flos eriocauli in RA treatment. |
| format | Article |
| id | doaj-art-79af3a63eac04840b328494ae84bb7ff |
| institution | DOAJ |
| issn | 1478-6362 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Arthritis Research & Therapy |
| spelling | doaj-art-79af3a63eac04840b328494ae84bb7ff2025-08-20T03:05:49ZengBMCArthritis Research & Therapy1478-63622025-03-0127112010.1186/s13075-025-03522-xQuercetagetin alleviates inflammatory osteoclastogenesis and collagen antibody-induced arthritis via Nrf2 signaling and Pten/AKT/Nfatc1 axisHaojue Wang0Tao Yuan1Jingpeng Wang2Dengju Li3Wayne Yuk-wai Lee4Ziqing Li5Shui Sun6Department of Joint Surgery, Cheeloo College of Medicine, Shandong Provincial Hospital, Shandong UniversityDepartment of Joint Surgery, Cheeloo College of Medicine, Shandong Provincial Hospital, Shandong UniversityHeze Sports SchoolDepartment of Joint Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityDepartment of Orthopaedics and Traumatology, The Chinese University of Hong KongDepartment of Joint Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityDepartment of Joint Surgery, Cheeloo College of Medicine, Shandong Provincial Hospital, Shandong UniversityAbstract Purpose Quercetagetin, a flavonoid derived from the natural herb Flos eriocauli, is used in traditional Chinese medicine for its fire-purging (anti-inflammation) and wind-expelling (pain-alleviating) properties. However, its potential effects concerning rheumatoid arthritis (RA) remain underexplored. This study was designed to elucidate the potential associations between Quercetagetin and RA, establishing the therapeutic potential of Quercetagetin and related mechanisms in RA treatment. Methods Network pharmacology was conducted to decipher related targets and signaling pathways between Quercetagetin and RA. In vitro assays were then conducted to explore the effects of Quercetagetin on osteoclast cell behaviors and corresponding signaling pathways. In vivo study further validated the therapeutic effect of Quercetagetin in collagen antibody-induced arthritis (CAIA) mice. Results The network pharmacological analysis indicated an intimate correlation of Quercetagetin with RA-related inflammatory osteolysis treatment. Pertaining to biological validations, 2 µM of Quercetagetin successfully inhibited LPS-driven osteoclast differentiation and function. qPCR assay and Western blot analyses denoted parallel changes in osteoclastic marker genes and proteins. Further mechanism study uncovered the effect of Quercetagetin in stimulating the Nrf2/Keap1 signaling pathway and moderating the Pten/AKT/Nfatc1 axis in osteoclasts. In vivo study revealed 40 mg/kg Quercetagetin every day could significantly relief joint destruction in CAIA mice. Conclusions Our study presents Quercetagetin ‘s therapeutic potential in treating RA, outlining its effects and potential mechanisms in suppressing LPS-induced osteoclast activity, and alleviating inflammatory bone destruction in CAIA model, thereby laying the groundwork for further translational research on Quercetagetin and Flos eriocauli in RA treatment.https://doi.org/10.1186/s13075-025-03522-xQuercetagetinFlos eriocauliLipopolysaccharideRheumatoid arthritisOsteoclast |
| spellingShingle | Haojue Wang Tao Yuan Jingpeng Wang Dengju Li Wayne Yuk-wai Lee Ziqing Li Shui Sun Quercetagetin alleviates inflammatory osteoclastogenesis and collagen antibody-induced arthritis via Nrf2 signaling and Pten/AKT/Nfatc1 axis Arthritis Research & Therapy Quercetagetin Flos eriocauli Lipopolysaccharide Rheumatoid arthritis Osteoclast |
| title | Quercetagetin alleviates inflammatory osteoclastogenesis and collagen antibody-induced arthritis via Nrf2 signaling and Pten/AKT/Nfatc1 axis |
| title_full | Quercetagetin alleviates inflammatory osteoclastogenesis and collagen antibody-induced arthritis via Nrf2 signaling and Pten/AKT/Nfatc1 axis |
| title_fullStr | Quercetagetin alleviates inflammatory osteoclastogenesis and collagen antibody-induced arthritis via Nrf2 signaling and Pten/AKT/Nfatc1 axis |
| title_full_unstemmed | Quercetagetin alleviates inflammatory osteoclastogenesis and collagen antibody-induced arthritis via Nrf2 signaling and Pten/AKT/Nfatc1 axis |
| title_short | Quercetagetin alleviates inflammatory osteoclastogenesis and collagen antibody-induced arthritis via Nrf2 signaling and Pten/AKT/Nfatc1 axis |
| title_sort | quercetagetin alleviates inflammatory osteoclastogenesis and collagen antibody induced arthritis via nrf2 signaling and pten akt nfatc1 axis |
| topic | Quercetagetin Flos eriocauli Lipopolysaccharide Rheumatoid arthritis Osteoclast |
| url | https://doi.org/10.1186/s13075-025-03522-x |
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