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Caudatin attenuates inflammatory reaction by suppressing JNK/AP-1/NF-κB/caspase-1 pathways in activated HMC-1 cells
Hee-Yun Kim1, Ho-Geun Kang2, Yu-Jin Choi3
1Asan, 31499 Republic of Korea Biochip Research Center, Hoseo University.
Insights
Caudatin, derived from Cynanchum auriculatum, effectively suppresses mast cell activation and reduces inflammatory cytokines linked to COVID-19 hyperinflammation. This compound may offer a natural approach for managing inflammatory conditions.
Area of Science:
- Immunology
- Pharmacology
- Natural Products
Background:
- Cytokine storm and mast cell activation contribute to COVID-19 hyperinflammation.
- Identifying natural compounds to modulate these inflammatory pathways is crucial.
Purpose of the Study:
- To investigate the anti-inflammatory effects of caudatin on human mast cell line HMC-1.
- To explore caudatin's potential in mitigating mast cell-mediated inflammation.
Main Methods:
- HMC-1 cells were treated with varying doses of caudatin.
- Key signaling molecules including JNK, AP-1, NF-κB, and caspase-1 were analyzed.
- mRNA expression and protein synthesis of pro-inflammatory cytokines were assessed.
Main Results:
- Caudatin suppressed JNK, AP-1, and NF-κB activation by inhibiting IκBα phosphorylation.
- Caudatin reduced activated-caspase-1 levels and inhibited its activation.
- Non-toxic doses of caudatin decreased pro-inflammatory cytokine mRNA and protein levels.
Conclusions:
- Caudatin effectively inhibits the JNK/AP-1/NF-κB/caspase-1 signaling pathway in mast cells.
- Caudatin reduces the secretion of inflammatory cytokines, offering potential therapeutic benefits.
- Caudatin may serve as a valuable ingredient in functional foods for inflammatory conditions like COVID-19.
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.
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