The Punicalagin Compound Mitigates Bronchial Epithelial Cell Senescence Induced by Cigarette Smoke Extract through the PAR2/mTOR Pathway.

IF 3.5 4区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Current medicinal chemistry Pub Date : 2024-10-03 DOI:10.2174/0109298673346794241001110826

Jianguo Xu, Xin Li, Xiaoli Zeng, Hairong Bao, Xiaoju Liu

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引用次数: 0

Abstract

Background: Tobacco smoke is an important inducer of airway epithelial cell aging. Punicalagin(PCG) is a natural anti-aging compound. The effect of PCG on tobacco smoke-induced airway epithelial cell senescence is unknown.

Objective: Our study investigated whether PCG can treat the human bronchial epithelial cell line (BEAS-2B) aging by inhibiting the protease-activated receptor 2 (PAR2)/m- TOR pathway.

Methods: Bioinformatics techniques were used to analyze the potential biological functions of PAR2. Molecular dynamics evaluated the binding ability of PCG and PAR2. The CCK8 assay was used to detect the cytotoxicity of CSE and PCG. The activity of the PAR2/mTOR pathway and the expression of the characteristic aging markers p16, p21, and SIRT1 are detected by qRT-PCR and Western blotting. Cell senescence was observed by Senescence-associated β-galactosidase (SA-β-gal) staining. The senescence-associated secretory phenotype (SASP): concentrations of interleukin IL-6, IL-8, and TNF- α were detected by ELISA.

Results: The GSE57148 bioinformatics analysis dataset showed that PAR2 regulates lung senescence through the mTOR signaling pathway. Molecular dynamics results found that PCG and PAR2 had a strong and stable binding force. CSE induces BEAS-2B cell senescence and activates the PAR2/mTOR pathway. Inhibition of PAR2 mitigated the senescence changes. In addition, PCG's pretreatment can significantly alleviate CSE-induced BEAS-2B cell senescence while inhibiting the PAR2/mTOR pathway.

Conclusion: PCG has a therapeutic effect on the senescence of airway epithelial cells.

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Punicalagin化合物通过PAR2/mTOR途径缓解香烟烟雾提取物诱导的支气管上皮细胞衰老

背景：烟草烟雾是气道上皮细胞老化的重要诱因。Punicalagin（PCG）是一种天然抗衰老化合物。PCG 对烟草烟雾诱导的气道上皮细胞衰老的影响尚不清楚：我们的研究探讨了PCG是否能通过抑制蛋白酶激活受体2（PAR2）/m- TOR通路来治疗人支气管上皮细胞系（BEAS-2B）的衰老：采用生物信息学技术分析 PAR2 的潜在生物功能。分子动力学评估了 PCG 与 PAR2 的结合能力。采用 CCK8 检测 CSE 和 PCG 的细胞毒性。通过 qRT-PCR 和 Western 印迹检测了 PAR2/mTOR 通路的活性以及特征性衰老标志物 p16、p21 和 SIRT1 的表达。通过衰老相关β-半乳糖苷酶（SA-β-gal）染色观察细胞衰老。衰老相关分泌表型（SASP）：通过 ELISA 检测白细胞介素 IL-6、IL-8 和 TNF- α 的浓度：GSE57148生物信息学分析数据集显示，PAR2通过mTOR信号通路调控肺衰老。分子动力学结果发现 PCG 与 PAR2 有很强且稳定的结合力。CSE诱导BEAS-2B细胞衰老并激活PAR2/mTOR通路。抑制 PAR2 可减轻衰老变化。此外，PCG预处理在抑制PAR2/mTOR通路的同时，还能显著缓解CSE诱导的BEAS-2B细胞衰老：结论：多氯化萘对气道上皮细胞的衰老具有治疗作用。

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 medicinal chemistry 医学-生化与分子生物学

CiteScore

8.60

自引率

2.40%

发文量

468

审稿时长

3 months

期刊介绍： Aims & Scope Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews and guest edited thematic issues written by leaders in the field covering a range of the current topics in medicinal chemistry. The journal also publishes reviews on recent patents. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.