Physiological Responses to a Natural Antioxidant Flavonoid Mixture, Silymarin, in BALB/c Mice: II. Alterations in Thymic Differentiation Correlate with Changes in c-mycGene Expression

Abstract

Silymarin is a mixture of bioactive flavonoids isolated from the seeds and fruits of Milk Thistle [ Silybum marianum (L.) Gaertner]. We tested the hypothesis that exposure to silymarin will modulate differentiation and cell selection in the thymus via alterations in gene expression. Male BALB/c mice were treated intraperitoneally once daily for five days with 0, 10, 50 or 250 mg/kg of silymarin. Flow cytometric examination of thymic lymphocyte populations showed that the absolute numbers of CD4 + and CD8 + positive T-lymphocytes were increased by silymarin. The c- myc proto-oncogene is important in controlling differentiation and functions of thymocytes. Treatment with silymarin resulted in increased c- myc expression in the thymus. In contrast, the expressions of IL-2 and IL-4 were decreased by silymarin, while MHC II expression did not change. These results indicate that in vivo exposure to silymarin influences phenotypic selection processes in the thymus at doses that may be encountered in natural medicinal use. Further studies investigating the effects of silymarin on the immune system are warranted.

Deleterious effects of silymarin on the expression of genes controlling endothelial nitric oxide synthase activity in carbon tetrachloride-treated rat livers

“…In addition to the therapeutic activities of improving liver function and fibrosis, silymarin has anti-inflammatory and antioxidant activities (Flores et al 2005;Johnson et al 2002;Saliou et al 1998). We have shown that the expression of iNOS and HO-1, both highly induced in the proinflammatory response against CCl 4 treatment, was decreased significantly in both the acute and the chronic treatment models, although HO-1 was undetected in the spontaneously restored CMC-treated group using the chronic model (Figs.…”

Silymarin treatment reduces granuloma and hepatic fibrosis in experimental schistosomiasis

“…The best dosage of silymarin was established using curveresponse assays. We standardized 10 mgkg −1 , which was also used by other authors Johnson et al 2003;Johnson et al 2002).…”

Plant-derived medicines: A novel class of immunological adjuvants

“…The purified component of T. wilfordii hook F, triptolide, is reported to elicit this activity, and could inhibit peripheral CD4+ T-lymphocytes but increased CD8+ T-lymphocyte numbers in Peyer's patches of mice in a collagen-induced mouse arthritis model of inflammation, indicating a bimodal mechanism of action [102]. Paradoxically, while increased IL-2 and IL-4 mRNA expression in murine thymocytes was reported with silymarin (derived from S. marianum), treatment of ConA-stimulated mouse spleen cells with silibinin, the active component of silymarin, exhibited lower IFNγ and IL-2 production in vitro [103][104][105][106]. Taken together, these results suggest a synergistic action between multiple components in silymarin, modulating T-lymphocyte responses by regulating T H 1 and T H 2 cytokine levels important for host protection.…”