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

Planta Med. 2005 May;71(5):429-34. doi: 10.1055/s-2005-864138.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Andrographis*
  • Animals
  • Apoptosis / drug effects
  • Concanavalin A
  • Diterpenes / administration & dosage
  • Diterpenes / pharmacology*
  • Diterpenes / therapeutic use
  • Dose-Response Relationship, Drug
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / pharmacology*
  • Immunosuppressive Agents / therapeutic use
  • Inhibitory Concentration 50
  • Interferon-gamma / biosynthesis*
  • Interleukin-2 / biosynthesis*
  • Mice
  • Phytotherapy*
  • Plant Extracts / administration & dosage
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / metabolism


  • Diterpenes
  • Immunosuppressive Agents
  • Interleukin-2
  • Plant Extracts
  • Concanavalin A
  • andrographolide
  • Interferon-gamma