Osteoarthritis (OA), a common degenerative
joint disease, is principally characterized by
inflammation and destruction of cartilage.
Nobiletin, an extract of the peel of citrus fruits, is known to have anti-inflammatory properties. However, the mechanisms by which
nobiletin plays a protective role in
osteoarthritis (OA) are not completely understood. In the present study, we investigated the anti-inflammatory effects of
nobiletin in the progression of OA in both in vitro and in vivo experiments. Mouse chondrocytes were pretreated with
nobiletin (0, 10, 20, 40 μM) for 24 h and then incubated with IL-1β (10 ng/ml, 24 h) in vitro. The generation of
PGE2 and NO was evaluated by the Griess reaction and ELISAs. The
protein expression of
inducible nitric oxide synthase, matrix metalloproteinase-3,
matrix metalloproteinase-13, A
disintegrin and
metalloproteinase with
thrombospondin motifs-5 (ADAMTS5),
cyclooxygenase-2,
collagen II, and
aggrecan was analyzed by Western blotting. Immunofluorescence and Western blot analysis were used to detect nuclear factor-κB (NF-κB) signaling molecules. Induction of proinflammatory and catabolic mediators by IL-1β stimulation of mouse chondrocytes could be partially blocked by treatment with
nobiletin or
ammonium pyrrolidine dithiocarbamate (an NF-κB inhibitor). Furthermore, our results indicated that
nobiletin exhibited a
therapeutic effect through active inhibition of the NF-κB signaling pathway. In a mouse model of OA, injection of
nobiletin (20 mg/kg) every 2 days for 8 weeks after surgery inhibited cartilage destruction and
synovitis. Taken together, our findings suggest that
nobiletin may be a potential therapeutic agent for the treatment of OA.