A combination of Sinomenine and Methotrexate reduces joint damage of collagen induced arthritis in rats by modulating osteoclast-related cytokines |
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| Institution: | 1. Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Zhongshan Road 321#, 210008 Nanjing, China;2. Department of Pharmacy, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Zhongshan Road 321#, 210008 Nanjing, China;1. Department of Rheumatology, Clinical Medical College, Yangzhou University, Yangzhou 225000, China;2. Department of Pathology, Clinical Medical College, Yangzhou University, Yangzhou 225000, China;3. Institution of Traditional Chinese Medicine and Western Medicine, Medical College, Yangzhou University, Yangzhou 225000, China;4. Department of Physiology, School of Medicine, Showa University, Tokyo 142-8555, Japan;1. Department of Chemistry, Presidency University, 86/1 College Street, Kolkata 700073, India;2. Chemical Sciences Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata 700 064, India;1. Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, School of Pharmacy, Anhui Medical University, 81 Meishan Road, Hefei 230032, Anhui Province, P.R. China;2. Department of Pathology, School of Basic Medicine, Anhui Medical University, 81 Meishan Road, Hefei 230032, Anhui Province, P.R. China;3. Department of Pharmacy, the First Affiliated Hospital of University of Science and Technology of China, 17 Lujiang Road, Hefei 230026, Anhui Province, P.R. China;1. State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, Taipa, Macau (SAR);2. Faculty of Chinese Medicines, Macau University of Science and Technology, Taipa, Macau (SAR);3. Tianjin Institute of Pharmaceutical Research, New Drug Assessment Co. Ltd, Tianjin, China;4. Joint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People''s Republic of China, Macau University of Science and Technology, Taipa, Macau (SAR);1. College of Chemistry and Chemical Engineering, Hunan University, Changsha, Hunan 410082, PR China;2. Key Laboratory of Research and Utilization of Ethnomedicinal Plant Resources of Hunan Province, Huaihua University, Huaihua, Hunan 418008, PR China |
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| Abstract: | ObjectiveTo analyze the combination therapy of Sinomenine (SIN) and Methotrexate (MTX) in rheumatoid arthritis (RA), we herein demonstrated the combination effect of SIN and MTX on collagen-induced arthritis (CIA) in rats through their modulation on osteoclast-related cytokines.MethodsCIA was induced by the immunization of type II collagen (CII) in SD rats. SIN and MTX were administrated alone or in combination after the onset of arthritis. Arthritis index and histological analysis were used to evaluate the effect of treatments. Effects of SIN and MTX on expression of receptor activator of NF-κB ligand (RANKL) and osteopontin (OPN) in synovial tissues were assayed by immunohistochemistry. RANKL, osteoprotegerin (OPG), IL-6, IL-17 and matrix metalloproteinases (MMPs) in rat serum were measured by ELISA. The expression of osteoclast-related cytokines in fibroblast-like synoviocytes (FLS) from RA patients was assayed by RT-PCR.ResultsSIN and MTX combination additively reduced the inflammatory symptoms and joint damage in CIA. Combination of SIN and MTX significantly repressed synovial RANKL and OPN production. SIN and MTX exhibited complementary and synergistic effect upon down-regulating RANKL, IL-6, IL-17 and MMPs in rat serum. SIN and MTX also modulated the expression of RANKL and OPG in RA-FLS.ConclusionSIN and MTX have additive effects, decreasing inflammation and joint damage in CIA rats by modulating osteoclast-related cytokines. These results are indicative of the combined effect of SIN and MTX for anti-arthritic treatment in RA. |
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