Triptolide, a diterpenoid triepoxide, suppresses inflammation and cartilage destruction in collagen-induced arthritis mice
Authors: Hongwei Jia
Na Lin
Akira Ito
Chunfang Liu
Hao Wu
Keisuke Imada
Cheng Xiao
Journal: Biochemical pharmacology (2007)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Chinese herbal remedy; Tripterygium wilfordii Hook. f.; TWHF; rheumatoid arthritis; triptolide
Affiliations: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, No. 16, Nanxiaojie, Dongzhimennei, Beijing 100700, China. 

Abstract:  Chinese herbal remedy Tripterygium wilfordii Hook. f. (TWHF) has been reported to be therapeutically efficacious in the treatment of rheumatoid arthritis (RA), but its in vivo actions have not been clarified. The purpose of this study was to investigate the effects of triptolide, a diterpenoid triepoxide extracted from TWHF, on inflammation and cartilage destruction in collagen-induced arthritis (CIA) model mice. Histological examination demonstrated that triptolide significantly reduced the inflammatory responses and cartilage damage in the joint tissues. Interestingly, triptolide interfered with CIA-augmented expression of matrix metalloproteinases-13 and -3, which are considered to be key enzymes in the pathological destruction of cartilage, and simultaneously augmented CIA-reduced tissue inhibitors of metalloproteinases-1 and -2 expression in the joints. Moreover, triptolide inhibited prostaglandin E(2) production via selective suppression of the production and gene expression of cyclooxygenase (COX)-2, but not COX-1. The levels of interleukin (IL)-1beta, tumor necrosis factor alpha and IL-6 were also decreased by triptolide in the joint tissues and sera as well as the suppression of CIA-mediated expression of their mRNAs in the joints. In addition, triptolide treatment in vivo was able to reduce an abundance of nuclear factor-kappaB, the transcriptional factor closely related to the inflammatory process, in articular cartilage and synovium in CIA mice. These results suggest that triptolide exerts novel chondroprotective and anti-inflammatory effects on RA, and the therapeutic action of TWHF on RA is, in part, due to the triptolide activities. 

Retracted: No

PubPeer comments:
 Figure 1C shows the knee of a Normal mouse (left), the knee of a mouse with induced arthritis (middle), and the knee of a mouse with induced arthritis treated with Triptolide (right). * Blue boxes: the Normal and Triptolide panels appear to show an overlap if one of the panels is in mirror image and slightly rotated. ![file] , 
 Fig 6Bb:  . (B) shows NF-kB p65 mRNA in cartilage (b) from  Trip (32 mg kg)-treated... mice. ![file] Endarkened version for clarity: ![file] , 
 Fig 6 B(c,d): NF-kB p65 mRNA in synovium from vehicle-treated and Trip (32 mg kg)-treated mice. ![file] ![file] , 
 #1  Fig. 1 u2013 Effects of triptolide on arthritis progression and joint histology of CIA mice. Mice were orally administered triptolide (Trip) or vehicle for 21 days from the first day of the onset of the clinical symptoms of arthritis. At the end of the experiment, the clinical onset and histology of the joints were evaluated. ... (C) displays histological observation of the joints in mice. **In normal mice**, there is normal knee joint architecture... ![] The image later appeared as  Nobiletin-treated in Fig. 3 D of [Imada et al (2008)] .  Histological evaluation of the joint tissues of CIA mice treated with nobiletin. Paraffin sections of ankle (A,C) and** knee (B,D)** joints were stained with hematoxylin and eosin, and joint histology was evaluated. (A,B) Sections from vehicle-treated mice. (C,**D) Sections from nobiletin** (60 mg kg)-treated mice. Here rotated through 90 deg: ![] ,