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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 β-hexosaminidase release from IgE-stimulated RBL-2H3 mast cells was measured. Of the seventeen isolated compounds, gnetin H, a resveratrol derivative, significantly inhibited β-hexosaminidase release from RBL-2H3 cells with an IC50 value of 0.3μM. Notably, Gnetin H reduced β-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-α and interleukin-4 and suppressed translocation of nuclear factor κB. PAE and gnetin H also reduced the expression of cyclooxygenase-2 and production of prostaglandin E2. PAE and gnetin H suppressed the phosphorylation of Syk, protein kinase C (PKC)μ, phospholipase Cγ, 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. [Copyright &y& Elsevier]