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

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 mu M, 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 mu M, 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 INF-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.