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 anaphylaxis-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-alpha and interleukin-6 in RPMC. Pretreatment of silibinin suppressed the antigen-stimulated calcium uptake and activation of nuclear factor-kappa B (NF-kappaB) in RPMC. Furthermore, silibinin increased the intracellular cAMP level. Increased cAMP, decreased calcium uptake and suppressed NF-kappaB 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.
Choi
Yun Ho
YH
Department of Anatomy, Chonbuk National University Medical School, Jeonbuk, Republic of Korea.
Yan
Guang Hai
GH
D000707:Anaphylaxis / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D000818:Animals; D018926:Anti-Allergic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D002118:Calcium / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D006636:Histamine Release / Q000187:drug effects*; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077385:Silybin; D012838:Silymarin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
D018926:Anti-Allergic Agents; D015850:Interleukin-6; D016328:NF-kappa B; D012838:Silymarin; D014409:Tumor Necrosis Factor-alpha; D000077385:Silybin; D002118:Calcium