In vitro anti-inflammatory and immunomodulatory properties of umbelliprenin and methyl galbanate.

Ferula species (Apiaceae) are considered important medicinal plants. The present in vitro study sought to investigate the immunomodulatory and anti-inflammatory properties of terpenoid coumarins isolated from Ferula szowitsiana on immune cells isolated from naïve mice and to elucidate possible underlying mechanisms of action. With splenocytes, effects of the agents on PHA-induced proliferation and interleukin (IL)-4 and interferon (IFN)-γ release were assessed. With peritoneal macrophages, anti-inflammatory potentials were evaluated in lipopolysaccharide (LPS)/IFNγ-stimulated cells via measures of changes in nitric oxide (NO) and PGE(2) secretion. Expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) was also determined via Western blot analysis. The results indicated that umbelliprenin (UMB) and methyl galbanate (MG) reduced remarkably PHA-induced splenocyte proliferation and both preferentially induced T(H)2 IL-4 and suppressed T(H)1 IFNγ secretion. Each also significantly suppressed LPS-induced production of NO and PGE(2) apparently and also led to reductions in inducible iNOS and COX-expression. To the authors' knowledge, the present study is the first to report on anti-inflammatory and immunomodulatory effects of UMB and MG in vitro. The present results suggest that each could potentially be exploited as a natural immunosuppressant against inflammatory and autoimmune diseases once substantial further toxicological analyses have been done to confirm overall safety in vivo.