Alleviation of osteoarthritis by calycosin-7-O -b-D-glucopyranoside (CG) isolated from Astragali radix (AR) in rabbit osteoarthritis (OA) model 1 S. I. Choi Ph.D.y a , T. R. Heo Ph.D.y, B.-H. Min M.D., Ph.D.z, J. H. Cui M.D.z, B. H. Choi Ph.D.xand S. R. Park M.D., Ph.D.k* y Department of Biological Engineering, Inha University, Incheon 402-751, South Korea z Department of Orthopedic Surgery, School of Medicine, Ajou University, Suwon 443-749, South Korea x Research Institute for Medical Sciences, Inha University College of Medicine, Incheon 400-712, South Korea k Department of Physiology, Inha University College of Medicine, Incheon 400-712, South Korea Summary Objective: This work was undertaken to assess the protective effect of an isoflavonoid, calycosin-7-O-b-D-glucopyranoside (CG), isolated from Astragali radix (AR) on the pathogenesis of osteoarthritis (OA)-like lesion in a rabbit model. Methods: Nine rabbits underwent an anterior cruciate ligament and menisectomy transection (ACLMT) of the rear knee joints to induce OA-like lesion. They were randomly divided into three groups (n ¼ 6/group): a negative control group treated with 200 ml of 0.5% (v/v) dimethyl sulfoxide (DMSO), a positive control group treated with 200 ml of 100 mM piroxicam, and a test group treated with 100 mg/500 ml of CG, where the test agents were administered by injection once a week for 4 weeks starting from the third week. Rabbits were then sacrificed to observe the progression of OA-like lesion. The synovial fluid was analyzed for the amounts of total proteins, glycosaminoglycans (GAG) and prostaglandin E 2 (PGE 2 ). In addition, histopathologic analyses were performed on the OA-like articular cartilage with or without therapeutic treatments. Results: The total synovial fluid volume (P < 0.05) was most strikingly reduced by the treatment with CG. Moreover, the CG treatment also significantly alleviated the OA-induced accumulation of prostaglandin (PG) (P < 0.001) and total proteins (P < 0.001) in the synovial fluid. The histopathologic analyses revealed that the CG treatment reduced the severity of the OA-like structural damages in the cartilage. However, the level of PGE 2 , a pathologic inflammatory molecule, was not diminished by CG or piroxicam. Conclusion: These results indicate that the isoflavonoid CG isolated from AR significantly alleviated the pathologic changes in the OA-like rabbit knee joints. This suggests that CG from AR could be a promising treatment for the therapy of OA. ª 2007 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved. Key words: Osteoarthritis, Astragali radix, Isoflavonoid, Calycosin-7-O -b-D-glucopyranoside, ACLMT. Introduction Osteoarthritis (OA) is a chronic and degenerative multi-fac- torial joint disease characterized by the fibrillation of articu- lar cartilage, bone remodeling, hypertrophy, inflammation of the synovial membrane, and in some cases sclerosis of subchondral bone and osteophyte formation 1 . OA is one of the most common joint disorders, affecting approximately 14.5% of the total population and nearly 80% of the geriatric population over the age of 60 2 . Under normal conditions, the maintenance of joint cartilage is predicated on a delicate balance between extracellular matrix (ECM) synthesis and degradation. In particular, hyaluronic acid (HA), an impor- tant component of the cartilage, is synthesized by the glyco- syltransferase, accumulated in the ECM, and then interacts with link proteins and aggrecan. Meanwhile, the cartilage matrix degradation is a multi-factorial process involving the progressive erosion of articular cartilage, prostaglandin (PG) degradation, disruption of the collagen network and eventually the functional loss 3 . Until now, the conservative treatment for OA is limited to a few classes of OA drugs such as paracetamol, non- steroidal anti-inflammatory drugs (NSAIDs), injectable intra-articular corticosteroids, anti-inflammatory steroids, cyclooxygenase (COX) inhibitory drugs and HA. These OA drugs provide general symptomatic relief, maintain the mobility and decrease pain and stiffness in the joint 4 . However, they also suffer from various side effects in the gastrointestinal system including nausea, vomiting, diar- rhea and drowsiness 5,6 . Astragali radix (AR) is a dried root of Astragalus mem- branaceus Bunge (Leguminosae) and has been used for centuries as an important medicine to reinforce vital en- ergy, strengthen superficial resistance and promote the discharge of pus and growth of new tissues. It has also been established that AR contains various active compo- nents including astragaloside, formononetin, calycosin, (3R)7,2 0 -dihydroxy-5 0 ,6 0 -dimethoxy-isofalvon-7-O -b-D-gluco- side, b-sitosterol, palmatic acid, isorhamnetin, quercetin, kaempferol, polyamine and daucosterol. In particular, fla- vonoids have been established as one of the most beneficial 1 Supported by a Biological Technology Research (No. 30762) grant from Inha University, South Korea, in 2004. a Present address: Plant Resource Research Institute, Duksung Women’s University, Seoul 132-714, South Korea. *Address correspondence and reprint requests to: So Ra Park, M.D., Ph.D., #7-206, Sinheung-dong, Joong-gu, Incheon 400-712, South Korea. Tel: 82-032-890-0922; Fax: 82-032-884-5997; E-mail: [email protected] Received 15 June 2006; revision accepted 10 February 2007. OsteoArthritis and Cartilage (2007) 15, 1086e1092 ª 2007 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.joca.2007.02.015 International Cartilage Repair Society 1086
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