Inhibitory effect of the Larix sibirica and its various flavonoids on the IgE-stimulated mast cell activation and anaphylaxis

Abstract

Larix sibirica (Siberian larch) is a deciduous tree native to Russia, Mongolia, and China and has been reported to possess anti-viral, anti-oxidant, and neuroprotective properties. In this study, we assessed the anti-allergic effects of an L. sibirica extract (LSE) and its various flavonoids using an IgE-sensitized mast cell-like cell line, rat basophilic leukaemia (RBL)-2H3, and a passive anaphylaxis mouse model. In IgE-sensitized RBL-2H3 cells, LSE and several flavonoids reduced release and production of β-hexosaminidase, histamine, and inflammatory mediators (prostaglandin D2, leukotriene C4, interleukin-4, and tumour necrosis factor-α), reduced expression of cyclooxygenase-2 and 5-lipoxygenase, and suppressed activation of nuclear factor-κB. LSE and several flavonoids reduced phosphorylation of downstream signalling molecules, such as Syk, protein kinase Cµ, phospholipase Cγ, and mitogen-activated protein kinases. Oral administration of LSE inhibited mast cell-dependent passive cutaneous anaphylactic reactions. These results suggest that LSE is a beneficial candidate for the prevention and treatment of allergic disorders.

Keywords

• Larix sibirica
• Flavonoids
• Mast cell RBL-2H3
• IgE
• FcεRI signalling