Andrographolide inhibits IFN-γ and IL-2 cytokine production and protects against cell apoptosis

Andrographolide is the main labdane diterpene present in Andrographis paniculata. Two lines of evidence report immunostimulant and anti-inflamatory properties for andrographolide in different models. Using murine T-cells in vitro we demonstrated that andrographolide and to a lesser extent, 14-deoxyandrographolide (14-DAP), reduced significantly, in a dose-dependent manner, the IFN-gamma production induced by concanavaline A (CONA), with an IC50 of 1.7 +/- 0.07 mu M and 35.8 +/- 0.50 mu M, respectively. Andrographolide, but not 14-DAP, inhibited partially the IL-2 production induced by CON-A. Andrographolide at doses of 5 and 10 mu M reduced the extracellular-signal-regulated protein kinase (ERK1/2) phosphorylation induced by CON-A, whereas 14-DAP only reduced ERK1 and partially the ERK2 phosphorylation. The inhibition of ERK1/2 phosphorylation was associated to a decrease in the IFN-gamma production, due that UO126, a specific ERK1/2 inhibitor, also reduced the IFN-gamma production in murine T-cells induced by CON-A. Additionally, andrographolide and to a lesser extent 14-DAR at doses of 50 mu M and 100 MM, respectively, reduced the apoptosis induced by hydrocortisone and PMA in thymocytes, which was associated to a decrease in caspase-3 like activity. We conclude that both diterpenic labdanes isolated from A. paniculata can exert potent immunosuppressant effects without affecting the viability of the cells.