alexa Andrographolide inhibits IFN-gamma and IL-2 cytokine production and protects against cell apoptosis.
Pharmaceutical Sciences

Pharmaceutical Sciences

Medicinal & Aromatic Plants

Author(s): Burgos RA, Seguel K, Perez M, Meneses A, Ortega M,

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Abstract Andrographolide is the main labdane diterpene present in Andrographis paniculata. Two lines of evidence report immunostimulant and anti-inflammatory 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 (CON-A), with an IC50 of 1.7 +/- 0.07 microM and 35.8 +/- 0.50 microM, respectively. Andrographolide, but not 14-DAP, inhibited partially the IL-2 production induced by CON-A. Andrographolide at doses of 5 and 10 microM 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-DAP, at doses of 50 microM and 100 microM, 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. This article was published in Planta Med and referenced in Medicinal & Aromatic Plants

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