Caudatin attenuates inflammatory reaction by suppressing JNK/AP-1/NF-κB/caspase-1 pathways in activated HMC-1 cells

One of the interfering factors in Coronavirus disease 2019 (COVID-19) is the cytokine storm, which contributes to hyperinflammation. Mast cells cause COVID-19 hyperinflammation by increasing inflammatory cytokine levels. We investigated whether caudatin, an active compound of Cynanchum auriculatum, could suppress inflammatory response signaling in human mast cell line, HMC-1 cells. Caudatin suppressed activation of c-Jun N-terminal kinase (JNK) and activator protein-1 (AP-1) in HMC-1 cells. Caudatin suppressed nuclear translocation of catalytic subunit (p65) of nuclear factor (NF)-κB by blocking IκBα phosphorylation and degradation. Caudatin also reduced levels of activated-caspase-1 protein and activation of caspase-1. Non-toxic caudatin doses inhibited the mRNA expression and protein synthesis of pro-inflammatory cytokines. A significant finding was that caudatin inhibited JNK/AP-1/NF-κB/caspase-1 signaling molecules, reducing the secretion of inflammatory cytokines. Consequently, we propose that caudatin might be used as a material in health functional foods to alleviate mast cell-mediated inflammatory conditions like COVID-19.