Downregulation of nuclear factor-kappa B (NF-κB) pathway by silibinin in human monocytes challenged with Paracoccidioides brasiliensis

Aims: Silibinin is the major active component of silymarin, a polyphenolic plant flavonoid that has anti-inflammatory effects. The modulatory effect of silibinin on monocyte function against Paracoccidioides brasiliensis (Pb18) has not yet been demonstrated. The present study investigated whether the effect of silibinin on nuclear factor-kappa B (NF-kappa B) pathways may affect the production of tumor necrosis factor-alpha (TNF-alpha), interleukin-10 (IL-10), transforming growth factor beta (TGF-beta 1), prostaglandin E-2 (PGE(2)), nitric oxide (NO) and fungicidal activity of human monocytes challenged in vitro with Pb18. Main methods: Peripheral blood monocytes from healthy individuals were treated with silibinin and challenged with Pb18 for 18 h. TNF-alpha, IL-10, TGF-beta 1 and PGE(2) expression were determined by immunoenzymatic assay (ELISA) and NO release was determined by the accumulation of nitrite in culture supernatants. Fungicidal activity of monocytes was analyzed after treatment with interferon-gamma plus silibinin and challenge with Pb18. NF-kappa B activation in cultured monocytes was evaluated by flow cytometry and ELISA. Key findings: Silibinin partially inhibited p65NF-kappa B activation as the number of cells expressing this factor was reduced and the concentration of nuclear p65NF-kappa B was low, compared to untreated controls. The addition of silibinin also resulted in suppression of TNF-alpha, IL-10, TGF-beta 1, PGE(2) and NO production but did not affect the fungicidal activity of monocytes against Pb18. Significance: Silibinin exerts anti-inflammatory and anti-fibrotic effects on CD14 +/- human monocytes challenged by Pb18 by partial inhibition of p65NF-kappa B activation. (C) 2010 Elsevier Inc. All rights reserved.