Geniposide Stabilized Atherosclerosis Plaque by Induced M2 Polarization via PPARγ Signaling Pathway.

IF 5.1 2区医学 Q1 CHEMISTRY, MEDICINAL

Drug Design, Development and Therapy Pub Date : 2025-09-30 eCollection Date: 2025-01-01 DOI:10.2147/DDDT.S499890

Zheng Jin, Qingmin Chu, Zhiyi Du, Junlong Li, Wei Wu, Xiaoxiong Zhou, Huanyi Zhao

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引用次数: 0

Abstract

Objective: The instability of atherosclerotic (AS) plaque constitutes a critical trigger for acute intravascular thrombosis and cardiovascular disease. Prior studies have found that Geniposide (Gen) is capable of regulating macrophage polarization and stabilizing AS plaque. However, its potential mechanism is not clear. Given the role of peroxisome proliferator-activated receptor γ (PPARγ) in mediating macrophage polarization, this study aims to investigate the relationship between Gen, PPARγ and macrophage polarization.

Methods: In vitro, RAW264.7 was used to investigate the effects of Gen on polarization phenotype, anti-inflammatory activity, and its correlation with PPARγ. In vivo, ApoE^-/- mice were fed with a high-fat diet to induce AS and were used to evaluate the pharmacological effects of Gen. Additionally, the relationship between Gen, PPARγ and M2 polarization in AS was verified.

Results: In vitro, Gen upregulated the expressions of M2 macrophage markers (CD163, IL-10, Arg-1). Moreover, Gen increased the expressions of PPARγ target genes (CD36, ABCG1) and activated PPARγ activity, which could be inhibited by PPARγ antagonist GW9662. In vivo, the intervention of Gen on AS model of ApoE^-/- mice played a role in reducing the blood lipid, stabilizing AS plaques and down-regulating the level of inflammatory factors. Consistent with the results in vitro, Gen was able to regulate the expression of macrophage polarization and increase the expression of PPARγ, while GW9662 treatment inhibited the expression of M2 phenotypic markers.

Conclusion: Gen regulates macrophage polarization to M2 phenotype and plays a role in inhibiting inflammation and stabilizing plaque by mediating PPARγ activation, which suggests that Gen may be a promising agent for AS.

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京尼平苷通过PPARγ信号通路诱导M2极化稳定动脉粥样硬化斑块。

目的：动脉粥样硬化（AS）斑块的不稳定性是急性血管内血栓形成和心血管疾病的关键触发因素。既往研究发现Geniposide （Gen）具有调节巨噬细胞极化和稳定AS斑块的作用。然而，其潜在机制尚不清楚。鉴于过氧化物酶体增殖物激活受体γ (PPARγ)在巨噬细胞极化中的作用，本研究旨在探讨Gen、PPARγ与巨噬细胞极化的关系。方法：采用RAW264.7体外实验研究Gen对极化表型、抗炎活性的影响及其与PPARγ的相关性。在体内，采用高脂饲料喂养ApoE-/-小鼠诱导AS，并评价Gen的药理作用。此外，验证Gen、PPARγ与AS中M2极化之间的关系。结果：在体外，Gen上调了M2巨噬细胞标志物（CD163、IL-10、Arg-1）的表达。此外，Gen增加了PPARγ靶基因CD36、ABCG1的表达，激活了PPARγ活性，而这种活性可被PPARγ拮抗剂GW9662抑制。在体内，Gen对ApoE-/-小鼠AS模型的干预具有降低血脂、稳定AS斑块、下调炎症因子水平的作用。与体外实验结果一致，Gen能够调节巨噬细胞极化的表达，增加PPARγ的表达，而GW9662则抑制M2表型标记物的表达。结论：Gen调节巨噬细胞向M2表型的极化，并通过介导PPARγ活化，发挥抑制炎症和稳定斑块的作用，提示Gen可能是一种有前景的AS药物。

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

Drug Design, Development and Therapy CHEMISTRY, MEDICINAL-PHARMACOLOGY & PHARMACY

CiteScore

9.00

自引率

0.00%

发文量

382

审稿时长

>12 weeks

期刊介绍： Drug Design, Development and Therapy is an international, peer-reviewed, open access journal that spans the spectrum of drug design, discovery and development through to clinical applications. The journal is characterized by the rapid reporting of high-quality original research, reviews, expert opinions, commentary and clinical studies in all therapeutic areas. Specific topics covered by the journal include: Drug target identification and validation Phenotypic screening and target deconvolution Biochemical analyses of drug targets and their pathways New methods or relevant applications in molecular/drug design and computer-aided drug discovery* Design, synthesis, and biological evaluation of novel biologically active compounds (including diagnostics or chemical probes) Structural or molecular biological studies elucidating molecular recognition processes Fragment-based drug discovery Pharmaceutical/red biotechnology Isolation, structural characterization, (bio)synthesis, bioengineering and pharmacological evaluation of natural products** Distribution, pharmacokinetics and metabolic transformations of drugs or biologically active compounds in drug development Drug delivery and formulation (design and characterization of dosage forms, release mechanisms and in vivo testing) Preclinical development studies Translational animal models Mechanisms of action and signalling pathways Toxicology Gene therapy, cell therapy and immunotherapy Personalized medicine and pharmacogenomics Clinical drug evaluation Patient safety and sustained use of medicines.