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

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.