Inhibitory effect of silibinin on tumour necrosis factor-alpha and hydrogen peroxide production by human monocytes

Abstract

Silibinin is a chemically defined flavonoid and the main active component of silymarin, a polyphenolic complex from Silybum marianum, which has anti-inflammatory, hepatoprotective and anticarcinogenic properties. Monocytes obtained from healthy individuals were incubated with silibinin to evaluate cell viability, hydrogen peroxide (H(2)O(2)) release and tumour necrosis factor-alpha (TNF-α) production by these cells. The duration of treatment and different silibinin concentrations had no significant effect on cell viability. Monocytes showed a dose-dependent inhibitory effect on H(2)O(2) release by phorbol myristate acetate-stimulated monocytes in silibinin concentrations ranging from 6.25 to 50 µg mL(-1). Significant inhibition of TNF-α production by lipopolysaccharide-stimulated monocytes was observed at concentrations of 12.5, 50 and 100 µg mL(-1) of silibinin. These results suggest that silibinin exerts antioxidant and anti-inflammatory properties on human monocytes through an inhibitory effect on H(2)O(2) release and on TNF-α production, respectively.

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

“…Human monocytes cultured with silibinin (50 µM) and challenged with Pb18 or stimulated with LPS for 18 h were significantly inhibited in TNF-α production. These results confirm our previous data showing that silibinin suppresses TNF-α production by LPS-stimulated monocytes in a concentration-dependent manner, where the greatest inhibition was detected at 50 and 100 µg/mL silibinin (Bannwart et al 2010). Others have reported that, in mice, treatment with silymarin inhibited the biologically active form of TNF-α produced by peritoneal macrophages such that TNF-α production was detected at low concentrations ranging from 12.5 to 50 µg/mL (Zhang et al 1996).…”

“…Silibinin possesses more efficient anti-oxidant and anti-inflammatory properties on LPS-stimulated human monocytes due to inhibition of hydrogen peroxide (H 2 O 2 ) release and tumor necrosis factor-alpha (TNF-α) production, compared to silymarin (Bannwart et al 2010). Consistent with these activities, silibinin has been demonstrated to inhibit nuclear factor-kappa B (NF-κB) activation through suppression of inhibitory kappa B (IκB) degradation.…”

“…Thus, understanding the mechanisms involved in cytokine production by monocytes challenged with Pb18 and identifying therapeutic alternatives to minimize the deleterious effects of the inflammatory response is of utmost importance in the study of paracoccidioidomycosis. Human monocytes cultured with high doses of silibinin (50 and 100 µg/mL) exhibit viability above 95% (Bannwart et al 2010). Thus, the employment of a natural product such as silibinin, with antiinflammatory and anti-oxidant properties in ex vivo experiments, may lead to important advances in this area.…”

“…Thus, the employment of natural anti-inflammatory products in conjunction with conventional chemotherapy might be a useful alternative in overcoming the deleterious effects of systemic inflammation in paracoccidioidomycosis patients. Our previous results suggest that silibinin has anti-inflammatory activity over human monocytes (Bannwart et al 2010). The present study investigated whether the effect of this flavonoid on the NF-κB pathway affects the production of cytokines (TNF-α, IL-10 and TGF-β1) as well as inflammatory mediators (PGE 2 and NO) and whether the fungicidal activity of human monocytes against Pb18 is altered during in vitro challenge.…”

Anti-Inflammatory Activity of Silibinin in Animal Models of Chronic Inflammation

“…Among the natural active constituents, flavonoids are a family of polyphenolic substances whose members have exhibited a broad spectrum of biological activities including anti-inflammatory, anticancer, antimicrobial, antiviral, immunomodulatory, and antithrombotic activities [7,8,9,10]. Silibinin is a chemically defined flavonoid and the main active component of silymarin, a polyphenolic complex from Silybum marianum, which has anti-inflammatory, hepatoprotective and anticancer properties [11,12,13]. In spite of the presence of extensive medical literature that examining biological activity of silibinin, still insufficient data were reported on its anti-inflammatory effects in granuloma and rheumatoid arthritis.…”