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Periplocoside A ameliorated type II collagen-induced arthritis in mice via regulation of the balance of Th17/Treg cells
Affiliation:1. Laboratory of Immunology and Virology, Experiment Center For Science and Technology, Shanghai University of Traditional Chinese Medicine, China;2. State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, China;3. Department of Natural Products Chemistry, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, China;1. Shenzhen Key Laboratory of Marine Biotechnology and Ecology, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, Guangdong 518055, China;2. National R&D Center for Se-rich Agricultural Products Processing, Hubei Engineering Research Center for Deep Processing of Green Se-rich Agricultural Products, School of Modern Industry for Selenium Science and Engineering, Wuhan Polytechnic University, Wuhan 430023, China;3. Shenzhen Bay Laboratory, Shenzhen 518055, China;4. Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions 518055, China;1. Ph.D. Program in Translational Medicine, National Chung Hsing University, Taichung, Taiwan;2. Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung, Taiwan;3. Institute of Biomedical Science, National Chung-Hsing University, Taichung, Taiwan;4. Department of Pharmacy, College of Pharmacy, China Medical University, Taichung, Taiwan;5. Department of Emergency, Toxicology Center, China Medical University Hospital, Taichung, Taiwan;6. Division of Rheumatology/Immunology/Allergy, Department of Internal Medicine, Taichung Armed Forces General Hospital, Taichung, Taiwan;7. Department of Medical Research, China Medical University Hospital, Taichung, Taiwan
Abstract:Periplocoside A (PSA) has been extracted from the Chinese herbal medicine Periploca sepium Bge to treat rheumatoid arthritis (RA) via immune regulation. We previously found that PSA exhibits immunosuppressive activity both in vitro and in vivo. Balanced regulation of helper T 17 (Th17)/regulatory T (Treg) cells is the current therapeutic direction for the treatment of RA. The present study investigated the mechanism of PSA in treating collagen-induced arthritis (CIA). The therapeutic effects and potential pharmacological mechanisms of PSA were specifically clarified by examining its effects on CIA in DBA/1 mice. PSA administration significantly relieved the severity of the arthritis, and preventive administration of PSA reduced the incidence of arthritis in the mice with CIA and relieved joint damage in terms of morphology. PSA was also able to reduce the levels of anti-collagen II (CII) antibodies and pro-inflammatory cytokines in the serum. As a result, the proportion of Th17 cells decreased, and the proportion of Treg cells increased. A follow-up study of the ex vivo immunological reactions induced by a specific antigen found that PSA suppressed lymphocyte proliferation, inhibited the differentiation and reactivity of Th17 cells, and promoted the proportion of Treg cells among helper T cells. PSA also exhibited pharmacological effect in regulating the balance between Th17 and Treg cells in CIA through relevant signalling pathways. Thus, PSA played a specific role in CIA treatment. In particular, our results suggest that the therapeutic effects of PSA on RA are partially realized via the regulation of the balance of Th17/Treg cells.
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