| In vivo: |
| J Pharmacol Exp Ther. 2010 Feb;332(2):352-63. | | Inhibition of delayed-type hypersensitivity by Cucurbitacin R through the curbing of lymphocyte proliferation and cytokine expression by means of nuclear factor AT translocation to the nucleus.[Pubmed: 19846588 ] | Cucurbitacin R is known to exhibit an anti-inflammatory effect in different experimental models of inflammation.
METHODS AND RESULTS:
In this article, we outline the effect of Cucurbitacin R on T lymphocyte proliferation, cytokine production, and nuclear factor activation, as well as its influence on various experimental models of delayed-type hypersensitivity (DTH) in mice. Cucurbitacin R reduced the proliferation of phytohemagglutinin A-stimulated human T lymphocytes (IC(50), 18 microM), modifying the cell cycle, as well as the production of cytokines [interleukin (IL)-2, IL-4, IL-10, and especially interferon-gamma] and the induction of the principal cyclins implicated in the cell cycle (A(1), B(1), D(2), and E). These effects are brought on by a novel, selective inhibition of nuclear factor AT (NFAT) by Cucurbitacin R, with no concomitant effect on other transcription factors such as activator protein-1. In addition, we tested the in vivo effects of Cucurbitacin R in three experimental models of DTH, as well as its effects on T lymphocyte proliferation, the cell cycle, cytokines, and cyclins. Although Cucurbitacin R was found to reduce the inflammatory response brought on by both oxazolone and dinitrofluorobenzene, its activity was even more pronounced against sheep red blood cell-induced edema in mouse paws, with a clear reduction in the production of IL-1beta, IL-4, and tumor necrosis factor alpha in the inflamed paw.
CONCLUSIONS:
In conclusion, Cucurbitacin R has the potential to be a new immunosuppressive agent with antiproliferative effects through the inhibition of the NFAT with anti-inflammatory activity in DTH reactions. | | J Pharmacol Exp Ther. 2007 Feb;320(2):581-90. | | Cucurbitacin R reduces the inflammation and bone damage associated with adjuvant arthritis in lewis rats by suppression of tumor necrosis factor-alpha in T lymphocytes and macrophages.[Pubmed: 17065367 ] | The aim of this study was to investigate the effects of Cucurbitacin R on an experimental model of adjuvant-induced arthritis in rats.
METHODS AND RESULTS:
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-alpha (TNF-alpha) and prostaglandin E(2) 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 E(2), nitric oxide, and TNF-alpha production in RAW 264.7 macrophages, as well as that for TNF-alpha 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.
CONCLUSIONS:
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. |
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