Immunosuppressive effect of silibinin in experimental autoimmune encephalomyelitis

Abstract

Silibinin is the major pharmacologically active compound of silymarin, the Silybum marianum fruit extract. Hepatoprotective activities of silibinin/silymarin are well-known, and recent studies demonstrated their anti-inflammatory and anti-carcinogenic effects which are due to inhibition of the transcription factor NF-kappaB. Based on this knowledge, we hypothesized that silibinin could be effective in the treatment of multiple sclerosis (MS) and so we tested its immunosuppressive effect in experimental autoimmune encephalomyelitis (EAE), the MS animal model. The process of spinal cord demyelination and inflammation were observed and T cell migration was determined by FACS analysis. The results showed that silibinin significantly reduced the histological signs of demyelination and inflammation in EAE. Since cytokines play an important role in inflammatory disease, the proliferative response and cytokine production were examined in lymphocytes from spleens and lymph nodes. We demonstrated that silibinin Ag-nonspecifically down-regulated the secretion of pro-inflammatory Th1 cytokines and up-regulated the anti-inflammatory Th2 cytokines in vitro. Silibinin also dose-dependently inhibited the production of Th1 cytokines ex vivo. These results indicate that silibinin is both immunosuppressive and immunomodulatory.

Effect of silymarin administration on TNF‐α serum concentration in peritoneal dialysis patients

“…It inhibits neutrophil migration, stabilizes mast cells and affects the synthesis of prostaglandins and leukotrienes (Min et al, 2007). In some studies, it has been reported that silymarin is also an immunomodulatory agent, increasing IFN-γ IL-4 and IL10, but decreasing the T-cell production of TNF-α (Saller et al, 2007).…”

“…Silymarin modulates the immune system by inhibition of neutrophil immigration, mast cell immobilization, prostaglandin production and leukotriene synthesis, and it suppresses the induction of TNF-α and modulates T-cell function (Kang et al, 2003;Manna et al, 1999;Min et al, 2007;Zi et al, 1997). A few studies on the effect of silymarin on TNF-α in dialysis patients has been published (Gazak et al, 2007;Walterova, 2005, Pradhan andGirish, 2006) TNF-α and IFN-γ inhibition effects of silymarin.…”

Silibinin: A novel inhibitor of Aβ aggregation

“…Recent studies have shown that silibinin has a strong antioxidant activity, increases cellular glutathione content, induces superoxide dismutase (SOD), antagonizes manganese-induced neurotoxicity in adult mice, and inhibits lipid peroxidation (Schumann et al, 2003). In addition, silibinin also possess anti-inflammatory (Min et al, 2007), growth-modulating and anti-carcinogenic effects (Chu et al, 2004). In the current study, we discovered, using a ThT assay and electron microscopic imaging analysis, that silibinin appears to be a strong inhibitor of Ab aggregation.…”

Candesartan modulates the antioxidant effect of silymarin against CCl4-induced liver injury in rats

“…It inhibits neutrophil migration, stabilizes mast cells and affects the synthesis of prostaglandins and leukotrienes. 24 Kim et al, 25 reported that silibinine, a component of SIL, is able to inhibit the production of TNF-α through inhibition of NF-κB pathway.…”