Gnetin H isolated from Paeonia anomala inhibits Fc epsilon RI-mediated mast cell signaling and degranulation

Abstract

Ethnopharmacological relevance: Paeonia anomala L. is used in Mongolian traditional medicine to treat various diseases including indigestion, abdominal pain, kidney disorders, inflammation, and female diseases. In this study we examined the effects of Paeonia anomala extract (PAE) and compounds derived from Paeonia anomala on immunoglobulin E (IgE)-mediated type I hypersensitivity responses in vitro. Materials and methods: Degranulation assay, reverse transcription PCR, enzyme-lined immunosorbent assays, western blot analyses were performed to measure allergic and proinflammatory mediators in IgE-stimulated rat basophilic leukemia (RBL)-2H3 mast cells treated with or without PAE or gnetin H. Results: Seventeen compounds were isolated, and p-hexosaminidase release from IgE-stimulated RBL-2H3 mast cells was measured. Of the seventeen isolated compounds, gnetin H, a resveratrol derivative, significantly inhibited beta-hexosaminidase release from RBL-2H3 cells with an IC50 value of 03 mu M. Notably, Gnetin H reduced beta-hexosaminidase release at lower concentrations than resveratrol. Furthermore, PAE and gnetin H inhibited histamine secretion, decreased the production and mRNA expression of tumor necrosis factor-alpha and interleukin-4 and suppressed translocation of nuclear factor kappa B. PAE and gnetin H also reduced the expression of cyclooxygenase-2 and production of prostaglandin E-2. PAE and gnetin H suppressed the phosphorylation of Syk, protein kinase C (PKC)mu, phospholipase C gamma, and the mitogen-activated protein kinases, c-Jun N-terminal kinase, p38, and extracellular signal-regulated kinase. Conclusions: These results suggest that PAE and its active compound gnetin H could be promising therapeutic agents for allergic disorders. (C) 2014 Elsevier Ireland Ltd. All rights reserved.