A sinomenine derivative alleviates bone destruction in collagen-induced arthritis mice by suppressing mitochondrial dysfunction and oxidative stress via the NRF2/HO-1/NQO1 signaling pathway
Bone destruction in rheumatoid arthritis (RA) leads to significant disability, yet effective treatments are limited. Sinomenine (Sino) demonstrates anti-arthritic and bone-protective effects but requires high doses. In this study, we developed a Sino derivative, SINX, and evaluated its efficacy in R...
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Elsevier
2025-05-01
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| Series: | Pharmacological Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1043661825001112 |
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| author | Wan-Yi Guo Qi-Min Wu Hao-Feng Zeng Yu-Lian Chen Jie Xu Zhen-Yi Yu Yong-Kang Shu Xiao-Nan Yang Chuan-Hai Zhang Xi-Zi He Jia-Ning Mi Si Chen Xiao-Man Chen Jia-Qi Wu He-Quan Yao Liang Liu Hu-Dan Pan |
| author_facet | Wan-Yi Guo Qi-Min Wu Hao-Feng Zeng Yu-Lian Chen Jie Xu Zhen-Yi Yu Yong-Kang Shu Xiao-Nan Yang Chuan-Hai Zhang Xi-Zi He Jia-Ning Mi Si Chen Xiao-Man Chen Jia-Qi Wu He-Quan Yao Liang Liu Hu-Dan Pan |
| author_sort | Wan-Yi Guo |
| collection | DOAJ |
| description | Bone destruction in rheumatoid arthritis (RA) leads to significant disability, yet effective treatments are limited. Sinomenine (Sino) demonstrates anti-arthritic and bone-protective effects but requires high doses. In this study, we developed a Sino derivative, SINX, and evaluated its efficacy in RA. Safety assessments in mice confirmed its suitability for further study. In vitro, SINX inhibited osteoclast differentiation by reducing TRAP-positive cells, disrupting F-actin ring formation, and suppressing bone resorption pits, alongside downregulating osteoclast-specific genes. It also showed strong anti-inflammatory properties by reducing inflammatory cytokine levels. In vivo, using a collagen-induced arthritis (CIA) mouse model, SINX improved bone integrity by reducing joint inflammation, maintaining trabecular bone density, and preventing erosion. Histological and micro-CT analyses confirmed its effects, including suppressed osteoclast activity and reduced bone resorption-related gene expression. Mechanistically, SINX ameliorated mitochondrial dysfunction, decreased ROS levels, and activated the NRF2/HO-1/NQO1 pathway, enhancing antioxidant defenses. Compared to Sino, SINX achieved similar results at lower doses. These findings highlight the potential of SINX as a safe, effective treatment for RA-related bone destruction. |
| format | Article |
| id | doaj-art-9dfd8f882d854791b612c1d777b3242b |
| institution | OA Journals |
| issn | 1096-1186 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Pharmacological Research |
| spelling | doaj-art-9dfd8f882d854791b612c1d777b3242b2025-08-20T02:18:55ZengElsevierPharmacological Research1096-11862025-05-0121510768610.1016/j.phrs.2025.107686A sinomenine derivative alleviates bone destruction in collagen-induced arthritis mice by suppressing mitochondrial dysfunction and oxidative stress via the NRF2/HO-1/NQO1 signaling pathwayWan-Yi Guo0Qi-Min Wu1Hao-Feng Zeng2Yu-Lian Chen3Jie Xu4Zhen-Yi Yu5Yong-Kang Shu6Xiao-Nan Yang7Chuan-Hai Zhang8Xi-Zi He9Jia-Ning Mi10Si Chen11Xiao-Man Chen12Jia-Qi Wu13He-Quan Yao14Liang Liu15Hu-Dan Pan16State Key Laboratory of Traditional Chinese Medicine Syndrome /The Second Clinical College, Guangzhou University of Chinese Medicine, Guangdong Province 510405, China; Chinese Medicine Guangdong Laboratory (Hengqin Laboratory), Guangdong-Macao In-Depth Cooperation Zone in Hengqin, 519000, China; State Key Laboratory of Quality Research in Chinese Medicine (Macau University of Science and Technology), Taipa, MacaoState Key Laboratory of Natural Medicines and Department of Medicinal Chemistry, China Pharmaceutical University, Jiangning District, Nanjing 211198, ChinaState Key Laboratory of Traditional Chinese Medicine Syndrome /The Second Clinical College, Guangzhou University of Chinese Medicine, Guangdong Province 510405, ChinaState Key Laboratory of Traditional Chinese Medicine Syndrome /The Second Clinical College, Guangzhou University of Chinese Medicine, Guangdong Province 510405, ChinaState Key Laboratory of Quality Research in Chinese Medicine (Macau University of Science and Technology), Taipa, MacaoState Key Laboratory of Quality Research in Chinese Medicine (Macau University of Science and Technology), Taipa, MacaoState Key Laboratory of Quality Research in Chinese Medicine (Macau University of Science and Technology), Taipa, MacaoState Key Laboratory of Quality Research in Chinese Medicine (Macau University of Science and Technology), Taipa, MacaoState Key Laboratory of Quality Research in Chinese Medicine (Macau University of Science and Technology), Taipa, MacaoState Key Laboratory of Traditional Chinese Medicine Syndrome /The Second Clinical College, Guangzhou University of Chinese Medicine, Guangdong Province 510405, ChinaState Key Laboratory of Traditional Chinese Medicine Syndrome /The Second Clinical College, Guangzhou University of Chinese Medicine, Guangdong Province 510405, ChinaState Key Laboratory of Traditional Chinese Medicine Syndrome /The Second Clinical College, Guangzhou University of Chinese Medicine, Guangdong Province 510405, ChinaState Key Laboratory of Traditional Chinese Medicine Syndrome /The Second Clinical College, Guangzhou University of Chinese Medicine, Guangdong Province 510405, ChinaState Key Laboratory of Traditional Chinese Medicine Syndrome /The Second Clinical College, Guangzhou University of Chinese Medicine, Guangdong Province 510405, China; State Key Laboratory of Quality Research in Chinese Medicine (Macau University of Science and Technology), Taipa, MacaoState Key Laboratory of Natural Medicines and Department of Medicinal Chemistry, China Pharmaceutical University, Jiangning District, Nanjing 211198, ChinaState Key Laboratory of Traditional Chinese Medicine Syndrome /The Second Clinical College, Guangzhou University of Chinese Medicine, Guangdong Province 510405, China; Chinese Medicine Guangdong Laboratory (Hengqin Laboratory), Guangdong-Macao In-Depth Cooperation Zone in Hengqin, 519000, China; State Key Laboratory of Quality Research in Chinese Medicine (Macau University of Science and Technology), Taipa, MacaoState Key Laboratory of Traditional Chinese Medicine Syndrome /The Second Clinical College, Guangzhou University of Chinese Medicine, Guangdong Province 510405, China; Chinese Medicine Guangdong Laboratory (Hengqin Laboratory), Guangdong-Macao In-Depth Cooperation Zone in Hengqin, 519000, China; State Key Laboratory of Quality Research in Chinese Medicine (Macau University of Science and Technology), Taipa, Macao; Corresponding author at: State Key Laboratory of Traditional Chinese Medicine Syndrome /The Second Clinical College, Guangzhou University of Chinese Medicine, Guangdong Province 510405, China.Bone destruction in rheumatoid arthritis (RA) leads to significant disability, yet effective treatments are limited. Sinomenine (Sino) demonstrates anti-arthritic and bone-protective effects but requires high doses. In this study, we developed a Sino derivative, SINX, and evaluated its efficacy in RA. Safety assessments in mice confirmed its suitability for further study. In vitro, SINX inhibited osteoclast differentiation by reducing TRAP-positive cells, disrupting F-actin ring formation, and suppressing bone resorption pits, alongside downregulating osteoclast-specific genes. It also showed strong anti-inflammatory properties by reducing inflammatory cytokine levels. In vivo, using a collagen-induced arthritis (CIA) mouse model, SINX improved bone integrity by reducing joint inflammation, maintaining trabecular bone density, and preventing erosion. Histological and micro-CT analyses confirmed its effects, including suppressed osteoclast activity and reduced bone resorption-related gene expression. Mechanistically, SINX ameliorated mitochondrial dysfunction, decreased ROS levels, and activated the NRF2/HO-1/NQO1 pathway, enhancing antioxidant defenses. Compared to Sino, SINX achieved similar results at lower doses. These findings highlight the potential of SINX as a safe, effective treatment for RA-related bone destruction.http://www.sciencedirect.com/science/article/pii/S1043661825001112Rheumatoid arthritisReactive oxygen species (ROS)Mitochondrial functionSinomenine derivativesNRF2/HO-1/NQO1 |
| spellingShingle | Wan-Yi Guo Qi-Min Wu Hao-Feng Zeng Yu-Lian Chen Jie Xu Zhen-Yi Yu Yong-Kang Shu Xiao-Nan Yang Chuan-Hai Zhang Xi-Zi He Jia-Ning Mi Si Chen Xiao-Man Chen Jia-Qi Wu He-Quan Yao Liang Liu Hu-Dan Pan A sinomenine derivative alleviates bone destruction in collagen-induced arthritis mice by suppressing mitochondrial dysfunction and oxidative stress via the NRF2/HO-1/NQO1 signaling pathway Pharmacological Research Rheumatoid arthritis Reactive oxygen species (ROS) Mitochondrial function Sinomenine derivatives NRF2/HO-1/NQO1 |
| title | A sinomenine derivative alleviates bone destruction in collagen-induced arthritis mice by suppressing mitochondrial dysfunction and oxidative stress via the NRF2/HO-1/NQO1 signaling pathway |
| title_full | A sinomenine derivative alleviates bone destruction in collagen-induced arthritis mice by suppressing mitochondrial dysfunction and oxidative stress via the NRF2/HO-1/NQO1 signaling pathway |
| title_fullStr | A sinomenine derivative alleviates bone destruction in collagen-induced arthritis mice by suppressing mitochondrial dysfunction and oxidative stress via the NRF2/HO-1/NQO1 signaling pathway |
| title_full_unstemmed | A sinomenine derivative alleviates bone destruction in collagen-induced arthritis mice by suppressing mitochondrial dysfunction and oxidative stress via the NRF2/HO-1/NQO1 signaling pathway |
| title_short | A sinomenine derivative alleviates bone destruction in collagen-induced arthritis mice by suppressing mitochondrial dysfunction and oxidative stress via the NRF2/HO-1/NQO1 signaling pathway |
| title_sort | sinomenine derivative alleviates bone destruction in collagen induced arthritis mice by suppressing mitochondrial dysfunction and oxidative stress via the nrf2 ho 1 nqo1 signaling pathway |
| topic | Rheumatoid arthritis Reactive oxygen species (ROS) Mitochondrial function Sinomenine derivatives NRF2/HO-1/NQO1 |
| url | http://www.sciencedirect.com/science/article/pii/S1043661825001112 |
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