Abstract

We have studied the effects of dihydrocucurbitacin B, a triterpene isolated from Cayaponia tayuya roots, on different models of delayed type hypersensitivity (DTH) in mice, as well as on T-lymphocyte proliferation and the mediators involved. In experiments with mice, dihydrocucurbitacin B inhibited the inflammatory reactions induced by oxazolone, dinitrofluorobenzene, and sheep red blood cells, reducing both the edema and cell infiltration. Moreover, the analysis of inflamed tissues showed that dihydrocucurbitacin B reduced the presence of the most relevant cytokines implicated in these processes, including interleukin-1β, interleukin-4, and tumor necrosis factor-α. Dihydrocucurbitacin B was also found to inhibit the proliferation of phytohemagglutinin-stimulated human T lymphocytes (IC₅₀ = 1.48 μM), halting the cell cycle in the G₀ phase. In addition, the triterpene reduced the production of interleukin-2, interleukin-4, interleukin-10, and interferon-γ in human T lymphocytes, and it hampered the induction of the principal cyclins involved in the cell cycle, including A₁, B₁, D₂, and E₁. Finally, dihydrocucurbitacin B was found to exert a selective inhibition on the nuclear factor of activated T cells (NFAT) in human lymphocytes without affecting the calcium influx. Taken together, these results suggest that dihydrocucurbitacin B curbs DTH reactions by inhibiting NFAT, which in turn suppresses the proliferation of the most relevant cells involved in DTH reactions, namely the T cells.