title: Andrographolide inhibits IFN-gamma and IL-2 cytokine production and protects against cell apoptosis.
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.
authors.affiliation: Laboratory of Molecular Pharmacology, Institute of Pharmacology, Faculty of Veterinary Science, Universidad Austral de Chile, Valdivia, Chile. rburgos1@uach.cl
authors.forename: Rafael A
authors.initials: RA
authors.lastname: Burgos
authors.forename: Karina
authors.initials: K
authors.lastname: Seguel
authors.forename: Mirna
authors.initials: M
authors.lastname: Perez
authors.forename: Ada
authors.initials: A
authors.lastname: Meneses
authors.forename: Marcela
authors.initials: M
authors.lastname: Ortega
authors.forename: María I
authors.initials: MI
authors.lastname: Guarda
authors.forename: Anitsi
authors.initials: A
authors.lastname: Loaiza
authors.forename: Juan L
authors.initials: JL
authors.lastname: Hancke
mesh_terms: D035685:Andrographis; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D003208:Concanavalin A; D004224:Diterpenes / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D020128:Inhibitory Concentration 50; D007371:Interferon-gamma / Q000096:biosynthesis*; D007376:Interleukin-2 / Q000096:biosynthesis*; D051379:Mice; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism
chemical_list: D004224:Diterpenes; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D010936:Plant Extracts; D003208:Concanavalin A; C030419:andrographolide; D007371:Interferon-gamma