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

Abstract

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.

Expression of SARS-CoV-2 receptor angiotensin-converting enzyme 2 by activating protein-1 in human mast cells

“…The hallmark of COVID-19 pathogenesis is the cytokine storm with elevated levels of inflammatory cytokines including tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, IL-1β, and TSLP [7] , [22] , [23] , [24] . TNF-α is released by mast cells [25] , [26] and considered one of the leading mediators of acute inflammation, the activation of which can also trigger IL-1 and IL-6 production [27] . High concentrations of TNF-α were reported in both plasma and tissues of patients with COVID-19 [22] .…”

“…Mast cells produce IL-6 in response to viruses, and increased IL-6 is a biomarker for COVID-19 [23] . Moreover, mast cells secrete IL-1 and TSLP, which cause mast cells to release cytokines and chemokines that are inflammatory chemical mediators [26] , [28] , [29] . Additionally, tryptase released by mast cells causes vascular barrier failure, lung fibrosis, and airway inflammation and encourages the spread of SARS-CoV-2 infection [21] .…”