title: Tetrandrine suppresses articular inflammatory response by inhibiting pro-inflammatory factors via NF-κB inactivation.
abstract: Targeting activated macrophages using anti-inflammatory phytopharmaceuticals has been proposed as general therapeutic approaches for rheumatic diseases. Besides macrophages, chondrocytes are another promising target of anti-inflammatory agents. Tetrandrine is a major bisbenzylisoquinoline alkaloid isolated from Stephania tetrandrae S. Moore which has been used for 2,000 years as an antirheumatic herbal drug in China. Although, the anti-inflammatory effect of tetrandrine has been demonstrated, the mechanism has not been clearly clarified. In this study, we designed a comprehensive anti-inflammatory evaluation system for tetrandrine, including complete Freund's adjuvant (CFA)-induced arthritis rat, LPS-induced macrophage RAW 264.7 cells, and chondrogenic ATDC5 cells. The results showed that tetrandrine alleviated CFA-induced foot swelling, synovial inflammation, and pro-inflammatory cytokines secretion. Tetrandrine could inhibit IL-6, IL-1β, and TNF-α expression via blocking the nuclear translocation of nuclear factor (NF)-κB p65 in LPS-induced RAW 264.7 cells. Moreover, ATDC5 cells well responded to LPS induced pro-inflammatory mediators secretion and tissue degradation, and tetrandrine could also inhibit the production of nitric oxide and prostaglandin E2 , as well as the expression of matrix metalloproteinase (MMP)-3 and tissue inhibitor of metalloproteinase (TIMP)-1 via inhibiting IκBα phosphorylation and degradation. In conclusion, the results showed that one of the anti-inflammatory mechanisms of tetrandrine was inhibiting IκBα and NF-κB p65 phosphorylation in LPS-induced macrophage RAW 264.7 cells and chondrogenic ATDC5 cells. Moreover, we introduce a vigorous in vitro cell screening system, LPS-induced murine macrophage RAW 264.7 cells coupling chondrogenic ADTC5 cells, for screening anti-rheumatic drugs. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1557-1568, 2016.
authors.affiliation: Research Center of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, No. 88 YuQuan Road, Nankai District, Tianjin, 300193, China.|Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, No. 88 YuQuan Road, Nankai District, Tianjin, 300193, China.
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Gao
authors.affiliation: Research Center of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, No. 88 YuQuan Road, Nankai District, Tianjin, 300193, China.|Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, No. 88 YuQuan Road, Nankai District, Tianjin, 300193, China.|The Institute for Biomedical Engineering and Nano Science, Tongji University School of Medicine, 67 Chifeng Road, Shanghai, 200092, China.
authors.forename: Qi-Shuai
authors.initials: QS
authors.lastname: Feng
authors.affiliation: Research Center of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, No. 88 YuQuan Road, Nankai District, Tianjin, 300193, China.|Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, No. 88 YuQuan Road, Nankai District, Tianjin, 300193, China.
authors.forename: Xin-Fang
authors.initials: XF
authors.lastname: Zhang
authors.affiliation: Research Center of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, No. 88 YuQuan Road, Nankai District, Tianjin, 300193, China.|Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, No. 88 YuQuan Road, Nankai District, Tianjin, 300193, China.|Institute of Biomedical Engineering, Chinese Academy of Medical Science and Peking Union Medical College, No. 236 BaiDi Road, Nankai District, Tianjin, 300192, China.
authors.forename: Qiang-Song
authors.initials: QS
authors.lastname: Wang
authors.affiliation: Research Center of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, No. 88 YuQuan Road, Nankai District, Tianjin, 300193, China.|Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, No. 88 YuQuan Road, Nankai District, Tianjin, 300193, China.
authors.forename: Yuan-Lu
authors.initials: YL
authors.lastname: Cui
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000378:metabolism; D044182:Benzylisoquinolines / Q000494:pharmacology / Q000627:therapeutic use*; D002460:Cell Line; D004353:Drug Evaluation, Preclinical; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D018836:Inflammation Mediators / Q000378:metabolism; D053583:Interleukin-1beta / Q000097:blood; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D008517:Phytotherapy; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D044182:Benzylisoquinolines; C000594089:IL1B protein, rat; D007166:Immunosuppressive Agents; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; C009438:tetrandrine
keywords: anti-inflammatory; chondrocytes; nuclear factor-κB; rheumatoid arthritis; tetrandrine