帕马汀通过STAT1/CXCL10轴改善N-甲基-N'-亚硝基胍诱导的慢性萎缩性胃炎

IF 4.4 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY FASEB Journal Pub Date : 2024-09-17 DOI:10.1096/fj.202401624R
Yuan Zhou, Qiaojiao Wang, Wanyu Tang, Zhengcai Ma, Zhipeng Yang, Xuegang Li, Wanqun Chen, Hang Ma, Xiaoli Ye
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引用次数: 0

摘要

慢性萎缩性胃炎(CAG)是一种常见的胃癌前病变。棕榈碱(PAL)是从黄连(RC)中分离出来的一种异喹啉生物碱,具有显著的抗炎特性,常用于治疗胃肠道疾病。然而,PAL 对 CAG 的作用机制仍不清楚。本研究采用 N-甲基-N'-亚硝基胍(MNNG)在体内和体外诱导 CAG 炎症模型。在两个动物实验中评估了五种生物碱对 RC 的疗效以及最有效的 PAL 对 CAG 小鼠的剂量依赖性作用。RNA-seq和Western印迹显示,PAL能显著改善IL-17、TNF和NF-kappa B炎症相关信号通路。进一步的中枢基因预测和实验验证显示,PAL调节了STAT1/CXCL10轴,从而通过调节IL-17、TNF-α和p-p65的表达来减轻CAG。总之,PAL 可通过 STAT1/CXCL10 轴抑制氧化应激和炎症反应,从而减轻 MNNG 诱导的 CAG。这种方法是使用 PAL 治疗 CAG 的有效补充。
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Palmatine ameliorates N-methyl-N'-nitrosoguanidine-induced chronic atrophic gastritis through the STAT1/CXCL10 axis

Chronic atrophic gastritis (CAG) is a prevalent preneoplastic condition of the stomach. Palmatine (PAL), an isoquinoline alkaloid isolated from Rhizoma Coptidis (RC), has significant anti-inflammatory properties and is often used to treat gastrointestinal disorders. However, the mechanism of PAL on CAG remains unclear. In this study, N-methyl-N'-nitrosoguanidine (MNNG) was used to induce CAG inflammatory disease models in vivo and in vitro. The efficacy of five alkaloids in RC and the dose-dependent effects of the most effective PAL in CAG mice were evaluated in two animal experiments. RNA-seq and western blot revealed that PAL significantly improved IL-17, TNF, and NF-kappa B inflammation-related signaling pathways. Further hub gene prediction and experimental validation revealed that PAL modulated the STAT1/CXCL10 axis, thereby exerting attenuation of CAG through the regulation of IL-17, TNF-α, and p-p65 expression. In conclusion, PAL was proposed to mitigate MNNG-induced CAG, potentially through the inhibition of oxidative stress and inflammatory responses via the STAT1/CXCL10 axis. This approach is an effective complement to the use of PAL in the treatment of CAG.

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来源期刊
FASEB Journal
FASEB Journal 生物-生化与分子生物学
CiteScore
9.20
自引率
2.10%
发文量
6243
审稿时长
3 months
期刊介绍: The FASEB Journal publishes international, transdisciplinary research covering all fields of biology at every level of organization: atomic, molecular, cell, tissue, organ, organismic and population. While the journal strives to include research that cuts across the biological sciences, it also considers submissions that lie within one field, but may have implications for other fields as well. The journal seeks to publish basic and translational research, but also welcomes reports of pre-clinical and early clinical research. In addition to research, review, and hypothesis submissions, The FASEB Journal also seeks perspectives, commentaries, book reviews, and similar content related to the life sciences in its Up Front section.
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