Silibinin attenuates mast cell-mediated anaphylaxis-like reactions

Silibinin is known to have hepatoprotective, anti-carcinogenic and anti-inflammatory effects. However, roles of silibinin in the immediate-type allergic reactions (anaphylaxis) have not fully been investigated. In the present study, we have demonstrated that silibinin attenuated mast cell-mediated anaphylaxis-like reactions involved in allergic diseases. Oral administration of silibinin inhibited compound 48/80-induced passive cutaneous anaphy- laxis-like reaction in mice. Silibinin also attenuated anti-dinitrophenyl (DNP) immunoglobulin (Ig) E-mediated passive systemic and cutaneous anaphylaxis. Silibinin had no cytotoxicity on rat peritoneal mast cells (RPMC). Silibinin dose-dependently reduced histamine release from RPMC activated by compound 48/80 or anti-DNP IgE. Moreover, silibinin inhibited the secretion of pro-inflammatory cytokines, such as tumor necrosis factor-a and interleukin-6 in RPMC. Pretreatment of silibinin suppressed the antigen-stimulated calcium uptake and activation of nuclear factor-kappa B (NF-xB) in RPMC. Furthermore, silibinin increased the intracellular cAMP level. Increased cAMP, decreased calcium uptake and suppressed NF-xB activity might be involved in the inhibitory effect of silibinin on the secretory response. Our findings provide possibility that silibinin may serve as an effective therapeutic agent for allergic diseases.