Diacerein has proved to be effective in the treatment of
osteoarthritis. We investigated the effects of
diacerein in animal models of
carrageenin-,
zymosan-, or
dextran-induced paw
edema and adjuvant-induced
arthritis and in ovariectomized rats. In acute inflammatory models, unlike classical nonsteroidal anti-inflammatory drugs such as
naproxen and
ibuprofen,
diacerein inhibited the rat paw
edema induced by various agents. In the adjuvant-induced arthritic rats,
diacerein at 100 mg/kg/day significantly suppressed the paw
edema and the increase in serum mucoprotein. Addition of 3 mg/kg/day
naproxen to each
diacerein (3, 10, 30 mg/kg/day) dose resulted in significantly greater anti-inflammatory activity than with
naproxen alone. In the ovariectomized rats,
diacerein (10, 100 mg/kg/day) also significantly prevented bone loss and reduced the serum
alkaline phosphatase and decreased the excretion of urinary
hydroxyproline. In addition,
rhein (10, 30 microM) inhibited
calcium release from mouse calvaria induced by
interleukin-1 beta,
prostaglandin E(2) and
parathyroid hormone 1-34 human fragment. These findings indicate that
diacerein is a novel anti-inflammatory
drug with pharmacological properties different from those of classical nonsteroidal anti-inflammatory drugs and support the clinical investigation of the use of combination
therapy with
diacerein and nonsteroidal anti-inflammatory drugs in patients with not only
osteoarthritis but also
rheumatoid arthritis.