Houttuynia cordata water extract suppresses anaphylactic reaction and IgE-mediated allergic response by inhibiting multiple steps of FcεRI signaling in mast cells

Houttuynia cordata has been used as a traditional medicine in Korea and is known to have antioxidant, anti-cancer and anti-allergic activities. The precise effect of H. cordata, however, remains unknown. In this study, we investigated the effects of H. cordata water extract (HCWE) on passive cutaneous anaphylaxis (PCA) in mice and on IgE-mediated allergic response in rat mast RBL-2H3 cells. Oral administration of HCWE inhibited IgE-mediated systemic PCA in mice. HCWE also reduced antigen (DNP-BSA)-induced release of β-hexosaminidase, histamine, and reactive oxygen species in IgE-sensitized RBL-2H3 cells. In addition, HCWE inhibited antigen-induced IL-4 and TNF-α production and expression in IgE-sensitized RBL-2H3 cells. HCWE inhibited antigen-induced activation of NF-κB and degradation of IκB-α. To investigate the inhibitory mechanism of HCWE on degranulation and cytokine production, we examined the activation of intracellular FcεRI signaling molecules. HCWE suppressed antigen-induced phosphorylation of Syk, Lyn, LAT, Gab2, and PLC γ2. Further downstream, antigen-induced phosphorylation of Akt and MAP kinases (ERK1/2 and JNK1/2 but not p38 MAP kinase) were inhibited by HCWE. Taken together, the in vivo/in vitro anti-allergic effect of HCWE suggests possible therapeutic applications of this agent in inflammatory allergic diseases through inhibition of cytokines and multiple events of FcεRI-dependent signaling cascades in mast cells.