Protective effects of butanol fraction from Betula platyphyla var. japonica on cartilage alterations in a rabbit collagenase-induced osteoarthritis.
OBJECTIVE
Many cartilage protective agents have been developed from natural products, and they have resulted in the development of treatments for osteoarthritis. In this study, we determined the osteoarthritic efficacy and mechanism of butanol fraction from the bark of Betula platyphylla var. japonica (BFBP) in collagenase-induced rabbit model of osteoarthritis (CIA).


METHODS
The right knees of rabbits were injected intra-articularly with collagenase, and rabbits were orally administrated with distilled water (vehicle), BFBP (50, 100 and 200 mg/kg) or celecoxib (100 mg/kg) once a day for 28 days after the initiation of the CIA.


RESULTS
Oral administration of BFBP dose-dependently suppressed the stiffness and global histologic score. Proteoglycan intensity was considerably increased in a dose-dependent manner. As well, the mRNA expression of MMP-1, and MMP-3 was decreased. On the contrary, the level of TIMP-1 in the synovial fluids was significantly increased in the BFBP treated group. The pathologic inflammatory molecules such as PGE2 and COX-2 were inhibited by BFBP, but COX-1 expression not affected.


CONCLUSIONS
We suggest that BFBP has shown the protective effect on cartilage alternations through balance of MMPs/TIMP-1 and regulates inflammatory-related molecules in vivo model of osteoarthritis, and great candidate for development of osteoarthritis treatment.
Huh
Jeong-Eun
JE
Oriental Medicine Research Center for Bone and Joint Disease, KyungHee University, 149 Sangil-dong, Gangdong-gu, Seoul 134-727, Republic of Korea.
Baek
Yong-Hyeon
YH
Kim
Yeo-Jin
YJ
Lee
Jae-Dong
JD
Choi
Do-Young
DY
Park
Dong-Suk
DS
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D029662:Betula; D002358:Cartilage, Articular / Q000187:drug effects* / Q000473:pathology; D000068579:Celecoxib; D017364:Collagenases; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000235:genetics / Q000378:metabolism; D010003:Osteoarthritis / Q000139:chemically induced / Q000188:drug therapy*; D008517:Phytotherapy; D024301:Plant Bark; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D010946:Plants, Medicinal; D011509:Proteoglycans / Q000378:metabolism; D011720:Pyrazoles; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D013449:Sulfonamides; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D010936:Plant Extracts; D011509:Proteoglycans; D011720:Pyrazoles; D012333:RNA, Messenger; D013449:Sulfonamides; D019715:Tissue Inhibitor of Metalloproteinase-1; D051546:Cyclooxygenase 2; D017364:Collagenases; D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1; D000068579:Celecoxib; D015232:Dinoprostone