Silibinin polarizes Th1/Th2 immune responses through the inhibition of immunostimulatory function of dendritic cells

Abstract

Silibinin is the primary active compound in silymarin. It has been demonstrated to exert anti-carcinogenic effects and hepato-protective effects. However, the effects of silibinin on the maturation and immunostimulatory activities exhibited by dendritic cells (DCs) remain, for the most part, unknown. In this study, we have attempted to determine whether silibinin can influence surface molecule expression, dextran uptake, cytokine production, capacity to induce T-cell differentiation, and the signaling pathways underlying these phenomena in murine bone marrow-derived DCs. Silibinin was shown to significantly suppress the expression of CD80, CD86, MHC class I, and MHC class II in the DCs, and was also associated with impairments of LPS-induced IL-12 expression in the DCs. Silibinin-treated DCs proved highly efficient with regard to Ag capture via mannose receptor-mediated endocytosis. Silibinin also inhibited the LPS-induced activation of MAPKs and the nuclear translocation of the NF-kappaB p65 subunit. Additionally, silibinin-treated DCs evidenced an impaired induction of Th1 response, and a normal cell-mediated immune response. These findings provide new insight into the immunopharmacological functions of silibinin, especially with regard to their impact on the DCs. These findings expand our current understanding of the immunopharmacological functions of silibinin, and may prove useful in the development of therapeutic adjuvants for acute and chronic DC-associated diseases.

Polyphenolic phytochemicals – just antioxidants or much more?

“…Silibinin can suppress the expression of inflammatory genes such as CD80 and MHC class I and inhibit the lipopolysaccharide (LPS)-induced activation of mitogen-activated protein (MAP) kinases (important in vascular gene regulation) and the nuclear translocation of the NF-kB p65 subunit in murine dendritic cells [101]. Tangeretin and nobiletin, polymethylated flavonoids from citrus peel, inhibit IL-1b-induced COX-2 expression in human lung carcinoma cells [102].…”

d-pinitol inhibits Th1 polarization via the suppression of dendritic cells

“…We reported previously that a variety of phytochemicals exhibit profound immunoregulatory activity, particularly in DC [8][9][10][11]. D-pinitol (3-O-methyl-chiroinositol), an active principle of the traditional antidiabetic plant, Bougainvillea spectabilis, reportedly exerts insulin-like effects [12].…”

Immunosuppressive Effect of Quercetin on Dendritic Cell Activation and Function

“…The immunomodulatory activity of quercetin has been investigated in NK cells (17), macrophages (18), mast cells (19), neutrophils (20), B cells (21), and T cells (22). Although a number of studies have reported the activity of flavonoids in the modulation of DC activation (23)(24)(25)(26)(27), the effect of quercetin on DCs remains unknown. In this study, we examined the immunomodulatory effect of quercetin on DC activation.…”