The multicomponent phytopharmaceutical SKI306X inhibits in vitro cartilage degradation and the production of inflammatory mediators.
Clinical studies have demonstrated that SKI306X, a purified preparation of three medicinal plants, relieves joint pain and improves functionality in osteoarthritis patients. To study the biological action of SKI306X, bovine cartilage explants and human peripheral blood mononuclear cells (PBMC) were stimulated with IL-1 beta and lipopolysaccharide (LPS) respectively, in the presence or absence of SKI306X and its individual composites. All tested compounds inhibited dose-dependently IL-1 beta-induced proteoglycan release and nitric oxide production by cartilage, indicating cartilage protective activity. SKI306X and two of its compounds inhibited PGE(2), TNF-alpha and IL-1 beta production by LPS-stimulated PBMC, indicating anti-inflammatory activity. These results demonstrate that the biological effect of SKI306X is at least bipartite: (1) cartilage protective and (2) anti-inflammatory. The observed anti-inflammatory effects may provide an explanation for the outcome of the clinical studies. Long-term clinical trails are necessary to elucidate whether the in vitro cartilage protective activity results in disease-modifying effects.
Hartog
A
A
Numico Research, P.O. Box 7005, 6700 CA Wageningen, The Netherlands. anita.hartog@numico-research.nl
Hougee
S
S
Faber
J
J
Sanders
A
A
Zuurman
C
C
Smit
H F
HF
van der Kraan
P M
PM
Hoijer
M A
MA
Garssen
J
J
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002356:Cartilage / Q000187:drug effects* / Q000378:metabolism*; D002417:Cattle; D039324:Clematis / Q000737:chemistry; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology*; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D053583:Interleukin-1beta / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D031347:Prunella / Q000737:chemistry; D029778:Trichosanthes / Q000737:chemistry; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D004365:Drugs, Chinese Herbal; D006025:Glycosaminoglycans; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; C460104:SKI 306X; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D015232:Dinoprostone