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.

IF 2.9 4区医学 Q3 CHEMISTRY, MEDICINAL

Current topics in medicinal chemistry Pub Date : 2025-05-27 DOI:10.2174/0115680266392868250527045507

Xiyan Xiao, Shiyin Yang

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引用次数: 0

Abstract

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.

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番茄碱可减弱HMC-1细胞中c48 /80诱导的炎症反应，并与JNK/AP-1/NF-κB/Caspase-1通路的调节有关。

背景：已有研究表明JNK/AP-1/NF-κB/Caspase-1通路可能是炎症环境下HMC-1肥大细胞激活的原因，我们的研究旨在验证番茄碱是否可以作为变应性鼻炎（AR）中调节该通路的候选药物。目的：本研究旨在表征番茄碱对体外C48/80活化的hcc -1细胞炎症的影响，并探讨其潜在机制。方法：采用C48/80诱导法模拟AR诱导HMC-1细胞炎症反应，采用细胞计数试剂盒-8检测番茄碱对HMC-1细胞活力的影响。随后，采用酶联免疫吸附法测定炎症相关细胞因子、白细胞介素-1β、肿瘤坏死因子-α以及组胺和β-己糖氨酸酶的浓度。采用免疫印迹法检测C48/80和/或Tomatidine干预后hcc -1细胞中JNK/AP-1/NF-κB/Caspase-1通路的激活情况。结果：c48 /80诱导活化后，HMC-1细胞活力升高，炎症相关细胞因子和介质浓度升高。同时观察C48/80处理后hcc -1细胞中活性Caspase-1蛋白水平及JNK/AP-1/NF-κB/Caspase-1通路相关蛋白磷酸化情况。相反，Tomatidine干预抑制了模型hcc -1细胞的活力和炎症相关细胞因子和介质的浓度，导致模型hcc -1细胞JNK/AP-1/NF-κB/Caspase-1通路失活。结论：我们的研究表明，番茄碱可以减轻体外HMC-1细胞c48 /80诱导的炎症反应，可能是通过调节JNK/AP-1/NF- κB/Caspase-1信号通路。这些发现为支持番茄碱作为进一步研究过敏性炎症的候选药物提供了初步证据。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current topics in medicinal chemistry 医学-医药化学

CiteScore

6.40

自引率

2.90%

发文量

186

审稿时长

3-8 weeks

期刊介绍： Current Topics in Medicinal Chemistry is a forum for the review of areas of keen and topical interest to medicinal chemists and others in the allied disciplines. Each issue is solely devoted to a specific topic, containing six to nine reviews, which provide the reader a comprehensive survey of that area. A Guest Editor who is an expert in the topic under review, will assemble each issue. The scope of Current Topics in Medicinal Chemistry will cover all areas of medicinal chemistry, including current developments in rational drug design, synthetic chemistry, bioorganic chemistry, high-throughput screening, combinatorial chemistry, compound diversity measurements, drug absorption, drug distribution, metabolism, new and emerging drug targets, natural products, pharmacogenomics, and structure-activity relationships. Medicinal chemistry is a rapidly maturing discipline. The study of how structure and function are related is absolutely essential to understanding the molecular basis of life. Current Topics in Medicinal Chemistry aims to contribute to the growth of scientific knowledge and insight, and facilitate the discovery and development of new therapeutic agents to treat debilitating human disorders. The journal is essential for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important advances.