Immunomodulatory effect of arctigenin, a lignan compound, on tumour necrosis factor-alpha and nitric oxide production, and lymphocyte proliferation

J Pharm Pharmacol. 1999 Nov;51(11):1267-73. doi: 10.1211/0022357991777001.


We have investigated the immunomodulatory effects of arctigenin, a dibenzyl butyrolactone lignan compound, on tumour necrosis factor (TNF)-alpha and nitric oxide (NO) production, and lymphocyte proliferation. Arctigenin inhibited strongly TNF-alpha production by lipopolysaccharide-stimulated murine macrophage RAW264.7 and differentiated human macrophage U937 with IC50 values of 5.0 and 3.9 microM, respectively, without displaying cytotoxicity. The TNF-alpha inhibitory effect of arctigenin in lipopolysaccharide-triggered RAW264.7 cells was increased by co-treatment with several known TNF-alpha inhibitors. It also potently attenuated T and B cell proliferation stimulated by concanavalin A and lipopolysaccharide in a dose-dependent manner with IC50 values of 2.9 and 14.6 microM, respectively. In contrast, the compound showed a different pattern in lipopolysaccharide- and interferon (IFN)-gamma-induced NO production from RAW264.7 cells. Arctigenin inhibited NO release by IFN-gamma signal, whereas it significantly enhanced lipopolysaccharide-triggered NO production in RAW264.7 cells. The results suggested that arctigenin may regulate immune responses in activated macrophages and lymphocytes including TNF-alpha and NO production and lymphocyte proliferation.

MeSH terms

  • Adjuvants, Immunologic / pharmacology*
  • Animals
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / metabolism*
  • Cell Differentiation / drug effects
  • Cell Division / drug effects
  • Cell Survival / drug effects
  • Cells, Cultured
  • Coloring Agents
  • Endotoxins / pharmacology
  • Escherichia coli / metabolism
  • Furans / pharmacology*
  • Lignans / pharmacology*
  • Lipopolysaccharides / pharmacology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Nitric Oxide / biosynthesis*
  • Spleen / cytology
  • Spleen / drug effects
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / metabolism*
  • Tetrazolium Salts
  • Thiazoles
  • Tumor Necrosis Factor-alpha / biosynthesis*


  • Adjuvants, Immunologic
  • Coloring Agents
  • Endotoxins
  • Furans
  • Lignans
  • Lipopolysaccharides
  • Tetrazolium Salts
  • Thiazoles
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide
  • endotoxin, Escherichia coli
  • thiazolyl blue
  • arctigenin