Huh Jeong-Eun, Baek Yong-Hyeon, Kim Yeo-Jin, Lee Jae-Dong, Choi Do-Young, Park Dong-Suk
Oriental Medicine Research Center for Bone and Joint Disease, KyungHee University, 149 Sangil-dong, Gangdong-gu, Seoul 134-727, Republic of Korea.
J Ethnopharmacol. 2009 Jun 25;123(3):515-21. doi: 10.1016/j.jep.2008.08.028. Epub 2008 Sep 4.
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).
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.
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.
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.
许多软骨保护剂已从天然产物中开发出来,并已促成骨关节炎治疗方法的发展。在本研究中,我们在胶原酶诱导的兔骨关节炎模型(CIA)中确定了白桦变种树皮丁醇提取物(BFBP)的骨关节炎疗效及作用机制。
兔右膝关节腔内注射胶原酶,在CIA诱导后,每天给兔口服蒸馏水(赋形剂)、BFBP(50、100和200mg/kg)或塞来昔布(100mg/kg),持续28天。
口服BFBP剂量依赖性地抑制了僵硬程度和整体组织学评分。蛋白聚糖强度以剂量依赖性方式显著增加。同样,MMP-1和MMP-3的mRNA表达降低。相反,BFBP治疗组滑液中TIMP-1水平显著升高。BFBP抑制了PGE2和COX-2等病理性炎症分子,但不影响COX-1表达。
我们认为BFBP在骨关节炎体内模型中通过MMPs/TIMP-1平衡对软骨改变发挥了保护作用,并调节了炎症相关分子,是骨关节炎治疗开发的极佳候选物。