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Tetrandrine suppresses articular inflammatory response by inhibiting pro‐inflammatory factors via NF‐κB inactivation
Author(s) -
Gao LiNa,
Feng QiShuai,
Zhang XinFang,
Wang QiangSong,
Cui YuanLu
Publication year - 2016
Publication title -
journal of orthopaedic research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.041
H-Index - 155
eISSN - 1554-527X
pISSN - 0736-0266
DOI - 10.1002/jor.23155
Subject(s) - tetrandrine , inflammation , pharmacology , iκbα , nf κb , tumor necrosis factor alpha , macrophage , matrix metalloproteinase , chemistry , anti inflammatory , medicine , immunology , in vitro , biochemistry
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 E 2 , 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.