The Inhibitory Effect of Nodakenin on Mast‐Cell‐Mediated Allergic Inflammation Via Downregulation of NF‐κB and Caspase‐1 Activation

ABSTRACT Nodakenin, a coumarin isolated from the roots of Angelicae gigas, is effective for treating function control disorders, bacterial infections, pain, diarrhea, vitamin E deficiency, and for relaxation of the uterus. The aim of this study was to investigate the antiallergic related inflammatory effects in phorbol‐12‐myristate 13‐acetate plus calcium ionophore A23187 (PMACI)‐stimulated human mast cells (HMC‐1) or anaphylactic activity in a mouse model. Nodakenin inhibited the mRNA expression and production of pro‐inflammatory cytokines such as tumor necrosis factor (TNF)‐α, interleukin (IL)‐6, and IL‐1β in PMACI‐stimulated HMC‐1. We also studied the inhibitory effects of nodakenin on the nuclear translocation of nuclear factor kappa B (NF‐κB) and activation of caspase‐1, inhibitory κB kinase (IKK), and Akt in PMACI‐stimulated HMC‐1. However, mitogen‐activated protein kinase (MAPK) activation was not sufficient to abrogate the stimulus. In addition, administration of nodakenin at 20 mg/kg inhibited histamine release and protected mice against compound 48/80‐induced anaphylactic mortality. Furthermore, Nodakenin inhibited the mRNA expression and production of pro‐inflammatory cytokines and caspase‐1 activation in compound 48/80‐induced anaphylactic mice. These results suggest new insight that nodakenin may be a promising antiallergic related inflammatory agent for inflammatory disorders. J. Cell. Biochem. 118: 3993–4001, 2017. © 2017 Wiley Periodicals, Inc. Nodakenin, a coumarin isolated from the roots of Angelicae gigas, is effective for treating function control disorders. In this study, we investigated the antiallergic related inflammatory effects in phorbol‐12‐myristate 13‐acetate plus calcium ionophore A23187 (PMACI)‐stimulated human mast cells (HMC‐1) or anaphylactic activity in a mouse model. Based on our data, we suggested new insight that nodakenin may be a promising antiallergic related inflammatory agent for inflammatory disorders.