Huh Jeong-Eun, Baek Yong-Hyeon, Lee Jae-Dong, Choi Do-Young, Park Dong-Suk
Oriental Medicine Research Center for Bone and Joint Disease, KyungHee University, Seoul, Korea.
J Pharmacol Sci. 2008 Jul;107(3):317-28. doi: 10.1254/jphs.08010fp.
Siegesbeckia pubescens (S. pubescens) was widely used to alleviate symptoms of osteoarthritis (OA) in traditional medicine. However, the mechanism of action of S. pubescens remains unresolved. In the present study, we determined the physiological relevance of S. pubescens on cartilage protection in collagenase-induced osteoarthritis (CIA) in rabbits. The right knees of rabbits were injected intra-articularly with collagenase, and rabbits were orally administered with distilled water (vehicle), S. pubescens (100, 400 mg/kg) or celecoxib (100 mg/kg) once a day for 28 days after the initiation of the CIA. S. pubescens significantly suppressed the stiffness and global histological score including articular cartilage and synovial layer in CIA. Proteoglycan, aggrecan, and type II collagen expression was significantly increased in the rabbit knee joints of the S. pubescens-treated group. However, celecoxib had no effect on cartilage protection in CIA. The expression level of ADAMTS-4, ADAMTS-5, MMP-1, MMP-3, and MMP-13 were dose-dependently decreased in the S. pubescens-treated group. In contrast, the level of TIMP-1 dose-dependently increased. The pro-inflammatory cytokines involved in cartilage destruction, such as IL-1beta, and inflammatory mediators containing PGE(2) and NO were also inhibited in the S. pubescens-treated group. These results indicate that the cartilage protective effect of S. pubescens works through down-regulation of inflammatory mediators and aggrecanases and MMPs, while up-regulating TIMP-1 in the CIA rabbit model.
毛梗稀莶（S. pubescens）在传统医学中被广泛用于缓解骨关节炎（OA）症状。然而，S. pubescens的作用机制仍未明确。在本研究中，我们确定了S. pubescens对胶原酶诱导的兔骨关节炎（CIA）中软骨保护的生理相关性。给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）、S. pubescens（100、400 mg/kg）或塞来昔布（100 mg/kg），持续28天。S. pubescens显著抑制了CIA中的僵硬程度和整体组织学评分，包括关节软骨和滑膜层。在S. pubescens治疗组的兔膝关节中，蛋白聚糖、聚集蛋白聚糖和II型胶原蛋白表达显著增加。然而，塞来昔布对CIA中的软骨保护没有作用。在S. pubescens治疗组中，ADAMTS-4、ADAMTS-5、MMP-1、MMP-3和MMP-13的表达水平呈剂量依赖性降低。相比之下，TIMP-1水平呈剂量依赖性升高。在S. pubescens治疗组中，参与软骨破坏的促炎细胞因子，如IL-1β，以及含有PGE(2)和NO的炎症介质也受到抑制。这些结果表明，在CIA兔模型中，S. pubescens的软骨保护作用是通过下调炎症介质、聚集蛋白聚糖酶和基质金属蛋白酶，同时上调TIMP-1来实现的。
