Xihai Li1, Zhenli Zhang2, Wenna Liang3, Jianwei Zeng4, Xiang Shao5, Limei Xu6, Liangliang Jia7, Xiaojuan He8, Hui Li9, Chunsong Zheng10, Hongzhi Ye11, Tetsuya Asakawa12. 1. Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, PR China; Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fuzhou, 350122, PR China. Electronic address: lixihaifz@163.com. 2. SIPO Patent Examination (Beijing) Center, Beijing, 100160, PR China. Electronic address: zhangzhenli@sipo.gov.cn. 3. Research Base of Traditional Chinese Medicine Syndrome, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, China. Electronic address: liangwenna1979@163.com. 4. Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, PR China. Electronic address: zjwtcm@qq.com. 5. Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, PR China. Electronic address: 1105511810@qq.com. 6. Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, PR China. Electronic address: 251641769@qq.com. 7. Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, PR China. Electronic address: 1054897394@qq.com. 8. Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, PR China. Electronic address: 2360404594@qq.com. 9. Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, PR China. Electronic address: 1351427403@qq.com. 10. Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, PR China. Electronic address: 297161536@qq.com. 11. Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, PR China; Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fuzhou, 350122, PR China. Electronic address: yelin0930@163.com. 12. Research Base of Traditional Chinese Medicine Syndrome, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, China; Department of Neurosurgery, Hamamatsu University School of Medicine, Handayama, 1-20-1, Higashi-ku, Hamamatsu-city, Shizuoka, 431-3192, Japan. Electronic address: asakawat1971@gmail.com.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Tougu Xiaotong capsules (TXC) are an herbal compound commonly used to treat osteoarthritis (OA) in China. AIM OF THE STUDY: We attempted to verify TXC's therapeutic effects and mechanisms related to the p38 mitogen-activated protein kinase (MAPK) pathway in vivo and in vitro. MATERIALS AND METHODS: TXC's therapeutic effects were assessed by observing cartilage degeneration and inflammatory factors in a modified Hulth's model (in vivo) and a lipopolysaccharides (LPS)-exposed cellular model (in vitro). The expression of biomarkers related to p38 MAPK pathway-mediated inflammation was also investigated. RESULTS: TXC treatment reversed cartilage degeneration related biomarkers (ADAMTS 4, ADAMTS 5, Col I, Col V, MMP 3, MMP 9, and MMP 13) and inflammation factors (IL-1β, TNF-α, and IL-6) in both the animal and cellular OA models. Expression of p-p38 MAPK was downregulated following TXC administration, and changes to microRNAs in the cellular models were recovered. These results indicated that the p38 MAPK pathway-related mechanism may involve therapeutic effects of TXC. CONCLUSIONS: This study verified TXC's efficacy to treat OA in vivo and in vitro and suggests that p38 MAPK pathway-related mechanisms may be involved in TXC's therapeutic effects.
ETHNOPHARMACOLOGICAL RELEVANCE: Tougu Xiaotong capsules (TXC) are an herbal compound commonly used to treat osteoarthritis (OA) in China. AIM OF THE STUDY: We attempted to verify TXC's therapeutic effects and mechanisms related to the p38 mitogen-activated protein kinase (MAPK) pathway in vivo and in vitro. MATERIALS AND METHODS: TXC's therapeutic effects were assessed by observing cartilage degeneration and inflammatory factors in a modified Hulth's model (in vivo) and a lipopolysaccharides (LPS)-exposed cellular model (in vitro). The expression of biomarkers related to p38 MAPK pathway-mediated inflammation was also investigated. RESULTS: TXC treatment reversed cartilage degeneration related biomarkers (ADAMTS 4, ADAMTS 5, Col I, Col V, MMP 3, MMP 9, and MMP 13) and inflammation factors (IL-1β, TNF-α, and IL-6) in both the animal and cellular OA models. Expression of p-p38 MAPK was downregulated following TXC administration, and changes to microRNAs in the cellular models were recovered. These results indicated that the p38 MAPK pathway-related mechanism may involve therapeutic effects of TXC. CONCLUSIONS: This study verified TXC's efficacy to treat OA in vivo and in vitro and suggests that p38 MAPK pathway-related mechanisms may be involved in TXC's therapeutic effects.