RT Journal Article
SR Electronic
T1 Cucurbitacin R Reduces the Inflammation and Bone Damage Associated with Adjuvant Arthritis in Lewis Rats by Suppression of Tumor Necrosis Factor-α in T Lymphocytes and Macrophages
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 581
OP 590
DO 10.1124/jpet.106.107003
VO 320
IS 2
A1 José M. Escandell
A1 M. Carmen Recio
A1 Salvador Máñez
A1 Rosa M. Giner
A1 Miguel Cerdá-Nicolás
A1 José Luis Ríos
YR 2007
UL http://jpet.aspetjournals.org/content/320/2/581.abstract
AB The aim of this study was to investigate the effects of cucurbitacin R on an experimental model of adjuvant-induced arthritis in rats. The treatment of arthritic rats with cucurbitacin R (1 mg/kg p.o. daily) modified the evolution of the clinical symptoms, whereas the histopathology of paws demonstrated a reduction in the signs of arthritis. Compared with the control group, radiography of the tibiotarsal joints of cucurbitacin R-treated rats showed a decrease in joint damage and soft tissue swelling of the footpad. The in vivo study of the expression of proinflammatory enzymes (nitric-oxide synthase-2 and cyclooxygenase-2) with the aid of the Western blot technique, and that of tumor necrosis factor-α (TNF-α) and prostaglandin E2 by means of enzyme-linked immunosorbent assays demonstrated a clear decrease in both the enzymes and the mediators in paw homogenates. The analysis for prostaglandin E2, nitric oxide, and TNF-α production in RAW 264.7 macrophages, as well as that for TNF-α in human lymphocytes, indicated a reduction of all mediators. The expression of cyclooxygenase-2 was not modified in RAW 264.7 macrophages, whereas the expression of nitric-oxide synthase-2 was clearly diminished. Moreover, cucurbitacin R was found to inhibit signal transducer and activator of transcription 3 activation in the lymphocytes of both healthy and arthritic men. These experimental data on the chronic model, together with previously reported activity on acute and subchronic experimental models, justify the anti-inflammatory activity of cucurbitacin R and provide further evidence for the therapeutic potential of a group of natural products as anti-inflammatory agents. The American Society for Pharmacology and Experimental Therapeutics