Silibinin modulates the NF-κb pathway and pro-inflammatory cytokine production by mononuclear cells from preeclamptic women

Abstract

Preeclampsia (PE) is a complication of human pregnancy associated with an intense inflammatory response involving leukocyte activation, as well as elevated production of pro-inflammatory cytokines. The nuclear transcription factor-kappa B (NF-κB) is present in cells of the immune system and is responsible for transcription of genes coding for pro-inflammatory proteins. Silibinin is the main component of silymarin, a polyphenolic extract obtained from fruits and seeds of Silybum marianum with potent hepatoprotective and anti-inflammatory activities. In this study, we assessed whether silibinin modulated NF-κB activity and the production of pro-inflammatory cytokines by peripheral blood mononuclear cells (PBMCs) from preeclamptic patients. PBMC from women with PE, normotensive (NT) pregnant women, and nonpregnant (NP) women were cultured with or without silibinin (5μM and 50μM) and 1μg/mL lipopolysaccharide (LPS) for 18h. The supernatants were assayed for tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) by ELISA. Cells were cultured for 30min to evaluate NF-κB activity. There was increased endogenous activation of NF-κB as well as TNF-α and IL-1β release by PBMC in the PE group compared with the NT and NP groups. A positive correlation between NF-κB activity and cytokine production was also observed in the PE group. Silibinin was capable of reducing, at least in part, the levels of NF-κB and cytokines TNF-α and IL-1β in preeclamptic women. We conclude that silibinin exhibits potent anti-inflammatory activity on PBMC from preeclamptic women by downmodulation of NF-κB activation and inflammatory cytokine production.