[Methanol extract of Celastrus orbiculatu suppresses synovial hyperplasia and cartilage erosion and degradation in rheumatoid arthritis].
OBJECTIVE
To investigate the effects of methanol extract of Celastrus orbiculatu (MECO) on synovial hyperplasia and cartilage erosion and degradation in rheumatoid arthritis (RA), and explore the possible mechanisms to provide clues for new drug development for RA treatment.


METHODS
The articular synovium from patients with RA and normal articular cartilage were co-implanted into the back of severe combined immunodeficient (SCID)mice to establish the chimeric model SCID- HuRAg. Four weeks later, the mice were given MECO intragastrically at 30 mg/day, leflunomide at 500 microg/day or distilled water, respectively, for 4 consecutive weeks. After completion of the treatments, the histological scores of the grafts for synovial hyperplasia, cartilage invasion by synoviocyte and cartilage degradation around the chondrocytes were evaluated, and serum level of tumor necrosis factor-alpha (TNF-alpha) was measured with radioimmunoassay. The expression of TNF-alpha mRNA and the cell apoptosis in the synovium were detected with in situ hybridization (ISH) and TUNEL, respectively, and the results were analyzed with the image analysis system.


RESULTS
The grafts survived in the mice till the end of experiment. MECO and leflunomide, in comparison with distilled water, significantly lowered the scores for synovial hyperlasia (2.00+/-0.76 and 2.25+/-0.89 vs 3.63+/-0.52), cartilage erosion (1.69+/-0.80 and 2.00+/-1.36 vs 3.75+/-0.53), cartilage degradation (1.88+/-0.83 and 2.13+/-0.83 vs 3.63+/-0.74) and serum TNF-alpha level (0.84+/-0.09 and 0.83+/-0.12 vs 0.99+/-0.11 ng/ml). Cell apoptosis of the synovium increased significantly with MECO and leflunomide treatments, but the expression of TNF-alpha mRNA in the synovium decreased significantly in MECO group.


CONCLUSIONS
MECO can effectively suppress synovial hyperplasia and cartilage erosion and degradation SCID-HuRAg mice by reducing TNF-alpha production in the synovium and promoting synovial apoptosis. MECO can be comparable with leflunomide in their effect, but the former is more effective in suppressing TNF-alpha expression in the synovium.
Xiao
Chang-hong
CH
College of Traditional Chinese Medicine, Laboratory Animal Center, Southern Medical University, Guangzhou 510515, and Department of Rheumatology, First People's Hospital of Foshan, China. chnghngxiao@yahoo.com.cn
Gu
Wei-wang
WW
Zhang
Jia-ning
JN
Chen
Guo-qiang
GQ
Huang
Shi-feng
SF
Yang
Min
M
Chen
De-chao
DC
Chen
Jie
J
Xiao
Dan
D
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002357:Cartilage Diseases / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D031247:Celastrus / Q000737:chemistry*; D017690:Cell Transplantation; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006965:Hyperplasia / Q000150:complications / Q000188:drug therapy; D008297:Male; D000432:Methanol / Q000737:chemistry*; D051379:Mice; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013583:Synovial Membrane / Q000187:drug effects* / Q000473:pathology* / Q000637:transplantation; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000235:genetics
D010936:Plant Extracts; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D000432:Methanol