title: Houttuynia cordata water extract suppresses anaphylactic reaction and IgE-mediated allergic response by inhibiting multiple steps of FcepsilonRI signaling in mast cells.
abstract: 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 beta-hexosaminidase, histamine, and reactive oxygen species in IgE-sensitized RBL-2H3 cells. In addition, HCWE inhibited antigen-induced IL-4 and TNF-alpha production and expression in IgE-sensitized RBL-2H3 cells. HCWE inhibited antigen-induced activation of NF-kappaB and degradation of IkappaB-alpha. To investigate the inhibitory mechanism of HCWE on degranulation and cytokine production, we examined the activation of intracellular FcepsilonRI signaling molecules. HCWE suppressed antigen-induced phosphorylation of Syk, Lyn, LAT, Gab2, and PLC gamma2. 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 FcepsilonRI-dependent signaling cascades in mast cells.
authors.affiliation: BK21 Project Team, Department of Pharmacy, College of Pharmacy, Chosun University, 375 Seosuk-dong, Gwangju 501-759, South Korea.
authors.forename: Eun Hee
authors.initials: EH
authors.lastname: Han
authors.forename: Jin Hee
authors.initials: JH
authors.lastname: Park
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Hye Gwang
authors.initials: HG
authors.lastname: Jeong
mesh_terms: D000707:Anaphylaxis / Q000188:drug therapy*; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D054819:Hexosaminidase B / Q000378:metabolism; D006636:Histamine Release / Q000187:drug effects; D052859:Houttuynia / Q000737:chemistry*; D006967:Hypersensitivity / Q000188:drug therapy*; D007073:Immunoglobulin E / Q000276:immunology / Q000502:physiology*; D008156:Luciferases / Q000235:genetics; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008813:Mice, Inbred ICR; D010323:Passive Cutaneous Anaphylaxis / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D017455:Receptors, IgE / Q000187:drug effects* / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D012997:Solvents; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism; D014162:Transfection; D014867:Water
chemical_list: D016207:Cytokines; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D017455:Receptors, IgE; D012997:Solvents; D014867:Water; D007073:Immunoglobulin E; D012313:RNA; D008156:Luciferases; D054819:Hexosaminidase B