Tomatidine Attenuates C48/80-induced Inflammatory Responses in HMC-1 Cells and is Associated with Modulation of the JNK/AP-1/NF-κB/Caspase-1 Pathway

Background: Existing research has suggested that the JNK/AP-1/NF-κB/Caspase-1 pathway may account for the activation of HMC-1 mast cells under inflammatory circumstances, and our current study aims to validate whether Tomatidine could act as the candidate to modulate this pathway in Allergic Rhinitis (AR). Objective: This study aimed to characterize the effect of Tomatidine on inflammation in C48/80- activated HMC-1 cells in vitro and to explore the underlying mechanisms involved. Methods: The inflammation in HMC-1 cells was triggered via C48/80 induction to mimic the AR, and the effects of Tomatidine on the viability of HMC-1 cells were tested using the Cell Counting Kit-8 assay. Thereafter, the concentrations of inflammation-related cytokines, Interleukin-1β, tumor necrosis factor-α, as well as the histamine and β-hexosaminidase, were quantified by enzymelinked immunosorbent assay. The activation status of the JNK/AP-1/NF-κB/Caspase-1 pathway in HMC-1 cells following C48/80 and/or Tomatidine intervention was determined based on immunoblotting assay. Results: The viability was elevated in HMC-1 cells following C48/80-induced activation, and the concentration of inflammation-related cytokines and mediators was increased as well. Meanwhile, the protein levels of active Caspase-1 and the phosphorylation of JNK/AP-1/NF-κB/Caspase-1 pathway-related proteins were also observed in HMC-1 cells after the treatment of C48/80. On the contrary, Tomatidine intervention suppressed the viability and the concentration of inflammationrelated cytokines and mediators of modeled HMC-1 cells and led to the inactivation of the JNK/AP-1/NF-κB/Caspase-1 pathway in modeled HMC-1 cells. Conclusion: Our study demonstrates that Tomatidine can attenuate C48/80-induced inflammatory responses in HMC-1 cells in vitro, potentially through modulation of the JNK/AP-1/NF- κB/Caspase-1 signaling pathway. These findings provide preliminary evidence supporting Tomatidine as a candidate for further investigation in allergic inflammation.