J. Ishiwa et al., A citrus flavonoid, nobiletin, suppresses production and gene expression of matrix metalloproteinase 9/gelatinase B in rabbit synovial fibroblasts, J RHEUMATOL, 27(1), 2000, pp. 20-25
Objective. Flavonoids including nobiletin are known to exert many biologica
l actions in vitro. We investigated the chondroprotective effect of citrus
flavonoids, especially nobiletin, using cultured rabbit synovial fibroblast
s and articular chondrocytes.
Methods. We examined the effects of citrus flavonoids on the production and
gene expression of matrix metalloproteinases (MMP) and prostaglandin E-2 (
PGE(2)) production in rabbit synovial fibroblasts.
Results. Six flavonoids isolated from Citrus depressa Rutaceae including ta
ngeretin, 6-demethoxy-tangeretin, nobiletin, 5-demethylnobiletin, 6-demetho
xynobiletin, and sinensetin suppressed the interleukin 1 (IL-1) induced pro
duction of proMMP-9/progelatinase B in rabbit synovial cells in a dose depe
ndent manner (< 64 mu M); nobiletin most effectively suppressed proMMP-9 pr
oduction along with the decrease in its mRNA. Nobiletin also reduced IL-1 i
nduced production of PGE(2) in the synovial cells, but did not modi fy the
synthesis of total protein. These suppressive effects of nobiletin were als
o observed in rabbit articular chondrocytes. Nobiletin inhibited proliferat
ion of rabbit synovial fibroblasts in the growth phase.
Conclusion. These results suggest nobiletin is a novel antiinflammatory can
didate that has the potential to inhibit PGE(2) production. matrix degradat
ion of the articular cartilage, and pannus formation in osteoarthritis and