刺芒柄花素介导α7nAChR抑制巨噬细胞极化,改善动脉粥样硬化斑块。

IF 3.3 4区 医学 Q3 CHEMISTRY, MEDICINAL
Li Du, Shirong Li, Qiansong He, Min Zhang, Wenxiu Wang
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引用次数: 0

摘要

目的:探讨刺芒柄花素(FMN)介导的α7烟碱乙酰胆碱受体(α7nAChR)抑制巨噬细胞炎症极化、稳定动脉粥样硬化斑块的分子机制。方法:将SiRNA α7nAChR转染thp -1诱导的M0细胞,并用FMN处理。油红O染色评价巨噬细胞脂质沉积。RT-qPCR检测M1、M2巨噬细胞中α7nAChR、COX-2、IL-1β、IL-6、HO-1、SHIP1的表达。Western blot检测M1、M2巨噬细胞中α7nAChR、iNOS、CD206、CD68、p-JAK2、p-STAT3蛋白的表达。结果:与对照组相比,fmn介导的α7nAChR减少了M1和M2巨噬细胞的脂质沉积。RT-qPCR结果显示,FMN干预显著下调M1中COX-2和IL-1β的表达(P < 0.05)。α7nAChR的表达显著降低M2组织中COX-2、IL-6、IL-1β的表达(P < 0.05),显著升高HO-1、SHIP1的表达(P < 0.05)。Western blot结果显示,fmn介导的α7nAChR显著降低M1、M2巨噬细胞iNOS、CD68、P - jak2、P - stat3的表达,显著升高CD206蛋白的表达(P < 0.05)。讨论:本研究首次阐明了FMN通过α7nAChR/JAK2/STAT3轴调控巨噬细胞极化的机制,为胆碱能抗炎通路在心血管疾病中的作用提供了新的实验证据。但也存在一定的局限性,如THP-1细胞系适用性有限、剂量相关性研究有待加强、生物利用度和溶解度限制了临床转化、人体毒理学数据缺乏等。结论:FMN通过抑制JAK/STAT信号通路,促进α7nAChR表达,有效调节巨噬细胞极化。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Formononetin Mediates α7nAChR to Inhibit Macrophage Polarization and Ameliorate Atherosclerotic Plaque.

Objective: To explore the molecular mechanism of α7 nicotinic acetylcholine receptor (α7nAChR) mediated by Formononetin (FMN) in inhibiting macrophage inflammatory polarization and stabilizing atherosclerotic plaque.

Methods: SiRNA α7nAChR was transfected into THP-1-induced M0 cells and treated with FMN. Oil Red O staining was used to evaluate macrophage lipid deposition. RT-qPCR was used to detect α7nAChR, COX-2, IL-1β, IL-6, HO-1, and SHIP1 expression in M1 and M2 macrophages. Western blot was used to detect α7nAChR, iNOS, CD206, CD68, p-JAK2, and p-STAT3 protein expression in M1 and M2 macrophages.

Results: Compared with the control group, FMN-mediated α7nAChR reduced lipid deposition in M1 and M2 macrophages. RT-qPCR results showed that FMN intervention significantly downregulated COX-2 and IL-1β expression in M1 (P < 0.05). α7nAChR expression significantly reduced COX-2, IL-6, and IL-1β expression in M2 (P < 0.05) and significantly increased HO-1 and SHIP1 expression (P < 0.05). FMN-mediated α7nAChR significantly decreased the expression of iNOS, CD68, p-JAK2, and p-STAT3 in M1 and M2 macrophages and significantly increased the expression of CD206 protein by Western blot (P < 0.05).

Discussion: This study, for the first time, elucidated the mechanism of FMN regulating macrophage polarization through the α7nAChR/JAK2/STAT3 axis, providing new experimental evidence for the role of the cholinergic anti-inflammatory pathway in cardiovascular diseases. However, there are some limitations, such as the limited applicability of the THP-1 cell line, the need to strengthen the dose correlation study, the bioavailability and solubility limiting clinical translation, and the lack of human toxicological data.

Conclusion: FMN effectively modulates macrophage polarization through inhibition of the JAK/STAT signaling pathway while promoting α7nAChR expression.

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来源期刊
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.
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