POSTER PRESENTATION ABSTRACTS
Please note: All posters will be displayed in
Salons 10-12.
THURSDAY, 5:30-6:15 PM
Funk JL, Beischel JA, Oyarzo-Somoza JN, Kiela PR, Kuscuoglu
N, Chen G, Lantz RC, Solyom AM, Jolad SD, Timmermann BN.
Turmeric prevents arthritis and bone resorption by blocking
multiple inflammatory pathways.
University of Arizona, AHSC jfunk@u.arizona.edu
PURPOSE: Scientific evidence demonstrating the
anti-inflammatory efficacy of turmeric in the treatment of arthritis
is lacking. However, its use is being promoted, particularly since the
withdrawal of COX-2 inhibitors from the market. Studies were therefore
undertaken to determine the efficacy and mechanism of action of a well-characterized
turmeric extract in the treatment of rheumatoid arthritis (RA) using
an animal model.
METHODS: A curcuminoid-containing turmeric extract
(TE) similar in composition to commercially available turmeric dietary
supplements was isolated and chemically and biologically characterized
for use in animals. Female Lewis rats were treated with: (1) vehicle
alone; (2) TE; (3) streptococcal cell wall (SCW) (25 mg/kg ip); or (4)
SCW + TE. Prevention of joint inflammation and destruction was assessed
clinically, histologically, and by BMD. Transcription factor activation
and gene _expression (Affymetrix Rat Genome 230 2.0 chips) were evaluated
to determine mechanism of action.
RESULTS: Daily TE treatment profoundly inhibited
joint inflammation and joint destruction (IC50 15 mg/kg/d with 90% inhibition
at 46 mg/kg/d). Remarkably, four days of pretreatment alone was equipotent
to daily (x 32d) treatment. Nuclear translocation of NF_B, an important
regulator of inflammatory gene _expression, was prevented by TE treatment
in arthritic joints. Consistent with this finding, the _expression of
over 600 genes in arthritic joints was also significantly inhibited
by TE. Among these were over 40 genes, such as IL-1_, known to be regulated
by NF_B as well as other genes indirectly regulated by NF_B (e.g. 70
genes regulated by IL-1_). Induced _expression of chemokines, the interleukin-1
signaling pathway, PGE2 production, and the bone-destructive RANK signaling
pathway in arthritic joints were important targets of TE action. TE
inhibition of inflammatory cell recruitment and PGE2 production in arthritic
joints verified the biological significance of these gene _expression
results. In addition, TE prevented periarticular osteoclast accumulation
while also blocking ex vivo osteoclast formation induced by mCSF and
a RANK activating antibody.
CONCLUSIONS: These translational studies suggest
that chemically complex curcuminoid containing extracts of turmeric,
because of their ability to block multiple pathways critical to inflammation
and inflammatory bone destruction, may have significant utility in the
treatment of RA, as well as diseases associated with RANK-mediated bone
resorption, such as osteoporosis.
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