Oxypeucedanin hydrate alleviates rheumatoid arthritis by inhibiting the TLR4-MD2/NF-κB/MAPK signaling axis
Rheumatoid arthritis (RA) is an idiopathic and chronic autoimmune disease for which there are currently no effective treatments. Oxypeucedanin hydrate (OXH) is a natural coumarin known for its potent anti-inflammatory properties. However, f...
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| Format: | Article |
| Language: | English |
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China Science Publishing & Media Ltd.
2024-05-01
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| Series: | Acta Biochimica et Biophysica Sinica |
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| Online Access: | https://www.sciengine.com/doi/10.3724/abbs.2024076 |
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| author | Liu Mengdan Huo Xueyan Li Congcong Hu Yunjie Lei Haoran Wang Dong Zhu Lin Gu Yucheng Guo Dale Huang Lijun Deng Yun |
| author_facet | Liu Mengdan Huo Xueyan Li Congcong Hu Yunjie Lei Haoran Wang Dong Zhu Lin Gu Yucheng Guo Dale Huang Lijun Deng Yun |
| author_sort | Liu Mengdan |
| collection | DOAJ |
| description | Rheumatoid arthritis (RA) is an idiopathic and chronic autoimmune disease for which there are currently no effective treatments. Oxypeucedanin hydrate (OXH) is a natural coumarin known for its potent anti-inflammatory properties. However, further investigations are needed to determine its therapeutic efficacy in treating RA. In this study, we evaluate the anti-inflammatory activity of OXH by treating LPS-induced RAW264.7 macrophages. Our results show that OXH treatment reverses the changes in iNOS, COX-2, IL-1β, IL-6, and TNF-α levels. Additionally, OXH reduces ROS production. Further analysis reveals that OXH suppresses the activation of the NF-κB/MAPK pathway. CETSA results show that OXH competes with LPS for binding to the TLR4/MD2 complex. MST experiments demonstrate the specific affinity of OXH for the TLR4/MD2 complex, with a Kd value of <sc>33.7 μM.</sc> Molecular docking analysis suggests that OXH binds to the pocket of the TLR4/MD2 complex and interacts with specific amino acids, such as GLY-343, LYS-388, and PHE-345. Molecular dynamics simulations further confirm this conclusion. Finally, we investigate the potential of OXH in treating RA using a collagen-induced arthritis (CIA) model in rats. OXH effectively ameliorates the symptoms of CIA, including improving body weight, reducing swelling and redness, increasing talus volume, and decreasing bone erosion. OXH also decreases the mRNA levels of pro-inflammatory factors in synovial tissue. Transcriptome enrichment analysis and western blot analysis confirm that OXH suppresses the NF-κB/MAPK pathway, which is consistent with our in vitro findings. |
| format | Article |
| id | doaj-art-fc1ab998c4ae416ab23adb229a6447d6 |
| institution | Kabale University |
| issn | 1672-9145 |
| language | English |
| publishDate | 2024-05-01 |
| publisher | China Science Publishing & Media Ltd. |
| record_format | Article |
| series | Acta Biochimica et Biophysica Sinica |
| spelling | doaj-art-fc1ab998c4ae416ab23adb229a6447d62025-01-17T05:58:25ZengChina Science Publishing & Media Ltd.Acta Biochimica et Biophysica Sinica1672-91452024-05-01561789180110.3724/abbs.202407620d259ccOxypeucedanin hydrate alleviates rheumatoid arthritis by inhibiting the TLR4-MD2/NF-κB/MAPK signaling axisLiu Mengdan0Huo Xueyan1Li Congcong2Hu Yunjie3Lei Haoran4Wang Dong5Zhu Lin6Gu Yucheng7Guo Dale8Huang Lijun9Deng Yun10["State Key Laboratory of Southwestern Chinese Medicine Resource, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China"]["State Key Laboratory of Southwestern Chinese Medicine Resource, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China"]["State Key Laboratory of Southwestern Chinese Medicine Resource, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China"]["State Key Laboratory of Southwestern Chinese Medicine Resource, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China"]["State Key Laboratory of Southwestern Chinese Medicine Resource, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China"]["State Key Laboratory of Southwestern Chinese Medicine Resource, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China","School of Basic Medical Science, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China"]["School of Medicine, Tsinghua University, Beijing 100084, China"]["Syngenta Jealott’s Hill International Research Centre, Berkshire RG426EY, UK"]["State Key Laboratory of Southwestern Chinese Medicine Resource, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China"]["State Key Laboratory of Southwestern Chinese Medicine Resource, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China","School of Basic Medical Science, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China"]["State Key Laboratory of Southwestern Chinese Medicine Resource, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China"]Rheumatoid arthritis (RA) is an idiopathic and chronic autoimmune disease for which there are currently no effective treatments. Oxypeucedanin hydrate (OXH) is a natural coumarin known for its potent anti-inflammatory properties. However, further investigations are needed to determine its therapeutic efficacy in treating RA. In this study, we evaluate the anti-inflammatory activity of OXH by treating LPS-induced RAW264.7 macrophages. Our results show that OXH treatment reverses the changes in iNOS, COX-2, IL-1β, IL-6, and TNF-α levels. Additionally, OXH reduces ROS production. Further analysis reveals that OXH suppresses the activation of the NF-κB/MAPK pathway. CETSA results show that OXH competes with LPS for binding to the TLR4/MD2 complex. MST experiments demonstrate the specific affinity of OXH for the TLR4/MD2 complex, with a Kd value of <sc>33.7 μM.</sc> Molecular docking analysis suggests that OXH binds to the pocket of the TLR4/MD2 complex and interacts with specific amino acids, such as GLY-343, LYS-388, and PHE-345. Molecular dynamics simulations further confirm this conclusion. Finally, we investigate the potential of OXH in treating RA using a collagen-induced arthritis (CIA) model in rats. OXH effectively ameliorates the symptoms of CIA, including improving body weight, reducing swelling and redness, increasing talus volume, and decreasing bone erosion. OXH also decreases the mRNA levels of pro-inflammatory factors in synovial tissue. Transcriptome enrichment analysis and western blot analysis confirm that OXH suppresses the NF-κB/MAPK pathway, which is consistent with our in vitro findings.https://www.sciengine.com/doi/10.3724/abbs.2024076oxypeucedanin hydraterheumatoid arthritisTLR4-MD2 complexNF-κB/MAPK pathway |
| spellingShingle | Liu Mengdan Huo Xueyan Li Congcong Hu Yunjie Lei Haoran Wang Dong Zhu Lin Gu Yucheng Guo Dale Huang Lijun Deng Yun Oxypeucedanin hydrate alleviates rheumatoid arthritis by inhibiting the TLR4-MD2/NF-κB/MAPK signaling axis Acta Biochimica et Biophysica Sinica oxypeucedanin hydrate rheumatoid arthritis TLR4-MD2 complex NF-κB/MAPK pathway |
| title | Oxypeucedanin hydrate alleviates rheumatoid arthritis by inhibiting the TLR4-MD2/NF-κB/MAPK signaling axis |
| title_full | Oxypeucedanin hydrate alleviates rheumatoid arthritis by inhibiting the TLR4-MD2/NF-κB/MAPK signaling axis |
| title_fullStr | Oxypeucedanin hydrate alleviates rheumatoid arthritis by inhibiting the TLR4-MD2/NF-κB/MAPK signaling axis |
| title_full_unstemmed | Oxypeucedanin hydrate alleviates rheumatoid arthritis by inhibiting the TLR4-MD2/NF-κB/MAPK signaling axis |
| title_short | Oxypeucedanin hydrate alleviates rheumatoid arthritis by inhibiting the TLR4-MD2/NF-κB/MAPK signaling axis |
| title_sort | oxypeucedanin hydrate alleviates rheumatoid arthritis by inhibiting the tlr4 md2 nf κb mapk signaling axis |
| topic | oxypeucedanin hydrate rheumatoid arthritis TLR4-MD2 complex NF-κB/MAPK pathway |
| url | https://www.sciengine.com/doi/10.3724/abbs.2024076 |
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