Betulin suppresses TNF-α and IL-1β production in osteoarthritis synovial fibroblasts by inhibiting the MEK/ERK/NF-κB pathway

Journal of Functional Foods

Yang-Chang Wu¹  Chih-Yang Lin²  Chih-Hsin Tang³  Lun-Chien Lo⁴  Ching-Liang Hsieh⁵  Hsiang-Ping Lee⁶  Chun-Hao Tsai⁷  Chin-Horng Su⁸  Wei-Chien Huang⁸ 

[1] Department of Chinese Medicine, China Medical University Hospital, Taichung, Taiwan;Department of Orthopedics, Yuan-Lin Christian Hospital, Changhua, Taiwan;School of Chinese Medicine, China Medical University, Taichung, Taiwan;School of Medicine, China Medical University, Taichung, Taiwan;Department of Chinese Medicine, China Medical University Hospital, Taichung, Taiwan;Department of Orthopedic Surgery, China Medical University Hospital, Taichung, Taiwan;Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan;Graduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan;

关键词: Betulin;    Osteoarthritis;    TNF-α;    IL-1β;    ACLT;    Proinflammatory cytokines;   

DOI  :  

来源: DOAJ

【 摘 要 】

Osteoarthritis (OA) is characterized by the infiltration of a number of proinflammatory cytokines into the joint microenvironment. Betulin is a natural analogue of betulinic acid, a lupane-type pentacyclic triterpene that displays many important biological activities, including anti-inflammatory activity, although the effects on inflammatory cytokine production in OA are unknown. Analyses of samples from the Gene Expression Omnibus (GEO) dataset and our own clinical samples revealed higher levels of tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β) in OA synovial tissue compared with normal healthy tissue. This was also the case in synovial tissue from normal healthy rats and rats subjected to anterior cruciate ligament transaction (ACLT)-induced OA. High-throughput screening of inflammatory cytokines in betulin-treated OA synovial fibroblasts (OASFs) identified TNF-α and IL-1β as potential targets of betulin. Further analyses found that betulin suppresses TNF-α and IL-1β production in OASFs by inhibiting mitogen-activated protein kinase (MEK), extracellular signal-regulated kinase (ERK) and nuclear factor kappa B (NF-κB) signaling cascades. Betulin shows promise for the treatment of OA.

【 授权许可】

Unknown