title: Effects of SKI 306X, a new herbal agent, on proteoglycan degradation in cartilage explant culture and collagenase-induced rabbit osteoarthritis model.
abstract: OBJECTIVE
  Protective effects of SKI 306X, a natural herbal product extracted from three herbs Clematis mandshurica, Trichosanthes kirilowii, and Prunella vulgaris, on articular cartilage was examined and compared with other osteoarthritis (OA) drugs using in vitro and in vivo models.
  
  
  METHODS
  In vitro culture of rabbit articular cartilage explants was used as a model to measure the effects of drugs on the matrix degradation. The recombinant human interleukin-1alpha (rhIL-1alpha, 5 ng/ml) was added to induce proteoglycan (PG) degradation and the degree of PG degradation was assessed by measuring the amount of glycosaminoglycan (GAG) released into the culture medium. In in vivo experiment, collagenase was intraarticularly injected twice into the right knee joint of rabbits to induce OA-like change, and test agents were orally administered once a day for 28 days. The degrees of OA-like changes were evaluated through a histological examination.
  
  
  RESULTS
  In vitro study revealed SKI 306X inhibited the degradation of PG in a concentration-dependent manner. Trichosanthes kirilowii, which is one of the major components of SKI 306X, also significantly inhibited the GAG release in cartilage explant culture at 0.3 and 0.1 mg/ml. Dexamethasone and NSAIDs, such as diclofenac and rofecoxib, had no significant effects on the suppression of PG degradation. In in vivo studies, OA-like degeneration of the articular cartilage and synovial tissue was induced by injecting collagenase into the right knee joint of mature rabbits. At a dose of 200 mg/kg, SKI 306X reduced the OA-like histological changes, whereas diclofenac had no effect at 10 mg/kg.
  
  
  CONCLUSIONS
  These results indicate that SKI 306X inhibited PG degradation in cartilage explant culture, and its prophylactic administration significantly protected the knee joint of rabbit from OA-like change in collagenase-induced experimental OA model. This strongly suggests that SKI 306X can be a good OA agent with some cartilage protection activity.
authors.affiliation: College of Veterinary Medicine, School of Agricultural Biotechnology, Seoul National University, 103 Seodun-Dong, Suwon 441-744, Korea.
authors.forename: J-H
authors.initials: JH
authors.lastname: Choi
authors.forename: J-H
authors.initials: JH
authors.lastname: Choi
authors.forename: D-Y
authors.initials: DY
authors.lastname: Kim
authors.forename: J-H
authors.initials: JH
authors.lastname: Yoon
authors.forename: H-Y
authors.initials: HY
authors.lastname: Youn
authors.forename: J B
authors.initials: JB
authors.lastname: Yi
authors.forename: H-I
authors.initials: HI
authors.lastname: Rhee
authors.forename: K H
authors.initials: KH
authors.lastname: Ryu
authors.forename: K
authors.initials: K
authors.lastname: Jung
authors.forename: C-K
authors.initials: CK
authors.lastname: Han
authors.forename: W-J
authors.initials: WJ
authors.lastname: Kwak
authors.forename: Y-B
authors.initials: YB
authors.lastname: Cho
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D002358:Cartilage, Articular / Q000187:drug effects* / Q000378:metabolism; D017364:Collagenases / Q000008:administration & dosage; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D005109:Extracellular Matrix / Q000378:metabolism; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D010003:Osteoarthritis / Q000188:drug therapy*; D011509:Proteoglycans / Q000378:metabolism*; D011817:Rabbits; D029778:Trichosanthes
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004365:Drugs, Chinese Herbal; D006025:Glycosaminoglycans; D011509:Proteoglycans; C460104:SKI 306X; D017364:Collagenases