Mechanism study on the treatment of ulcerative colitis by Gegen Qinlian nano-preparation through promoting M2 macrophage polarization.

IF 3.9 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Frontiers in Molecular Biosciences Pub Date : 2025-04-25 eCollection Date: 2025-01-01 DOI:10.3389/fmolb.2025.1580874

Jilei Li, Jiarui Cao, Zhenyu Zhang, Sizhe Wang, Meng Zhu, Lili Yang, Wenhui Ouyang, Chunzheng Ma

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引用次数: 0

Abstract

Objective: To address the core pathological features of intestinal barrier disruption and immune imbalance in ulcerative colitis (UC), we developed a nano-targeted formulation (GGQL nano-preparation) based on berberine, puerarin, baicalin, and glycyrrhizin by combining traditional Chinese medicine (TCM) and nanotechnology in this study. We aimed to investigate whether GGQL nano-preparation could promote M2 macrophage polarization, correct intestinal inflammation, and treat UC.

Methods: We used databases to identify M2 macrophage-related gene targets for GGQL nano-preparation in UC. Protein-protein interaction networks, topological analysis, and GO/KEGG enrichment analyses revealed GGQL nano-preparation's potential regulation of macrophage polarization via a specific pathway. We validated this using a dextran sulfate sodium (DSS)-induced UC model in C57BL/6 mice. Parameters assessed included the disease activity index (DAI), colon length, colitis macroscopic damage index (CMDI), spleen index, and pathological changes (via HE staining). Immunohistochemistry detected AMPK-PPAR axis factor changes to determine GGQL nano-preparation's impact on M2 macrophage polarization and intestinal inflammation.

Results: Our analyses suggested the GGQL nano-preparation reduced the DAI, enhanced colon length, improved CMDI scores, and mitigated splenic inflammation. HE staining showed GGQL nano-preparation alleviated inflammation in the spleen, lungs, and colon. Immunohistochemical findings indicated GGQL nano-preparation upregulated AMPK, PPAR, and SIRT1 expression. Mechanistically, GGQL nano-preparation promoted M2 macrophage polarization through the AMPK-PPARγ axis, achieving therapeutic objectives for UC.

Conclusion: The GGQL nano-preparation effectively promotes M2 macrophage polarization via the AMPK-PPARγ axis, treating UC.

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葛根芩连纳米制剂促进M2巨噬细胞极化治疗溃疡性结肠炎的机制研究。

目的：为了解决溃疡性结肠炎（UC）肠道屏障破坏和免疫失衡的核心病理特征，本研究采用中医药与纳米技术相结合的方法，以小檗碱、葛根素、黄芩苷、甘草酸苷为基础，研制了一种纳米靶向制剂（GGQL纳米制剂）。我们旨在研究GGQL纳米制剂是否能促进M2巨噬细胞极化，纠正肠道炎症，治疗UC。方法：利用数据库鉴定巨噬细胞M2相关基因靶点，用于UC中GGQL纳米制备。蛋白-蛋白相互作用网络、拓扑分析和GO/KEGG富集分析揭示了GGQL纳米制剂通过特定途径对巨噬细胞极化的潜在调节。我们用葡聚糖硫酸钠（DSS）诱导的C57BL/6小鼠UC模型验证了这一点。评估的参数包括疾病活动指数（DAI）、结肠长度、结肠炎宏观损伤指数（CMDI）、脾脏指数和病理变化（通过HE染色）。免疫组化检测AMPK-PPAR轴因子变化，确定GGQL纳米制剂对M2巨噬细胞极化和肠道炎症的影响。结果：我们的分析表明GGQL纳米制剂降低了DAI，增加了结肠长度，提高了CMDI评分，减轻了脾炎症。HE染色显示GGQL纳米制剂减轻了脾、肺和结肠的炎症。免疫组化结果显示GGQL纳米制剂上调AMPK、PPAR和SIRT1的表达。机制上，GGQL纳米制剂通过AMPK-PPARγ轴促进M2巨噬细胞极化，达到UC的治疗目的。结论：GGQL纳米制剂可通过AMPK-PPARγ轴促进M2巨噬细胞极化，治疗UC。

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

Frontiers in Molecular Biosciences Biochemistry, Genetics and Molecular Biology-Biochemistry

CiteScore

7.20

自引率

4.00%

发文量

1361

审稿时长

14 weeks

期刊介绍： Much of contemporary investigation in the life sciences is devoted to the molecular-scale understanding of the relationships between genes and the environment — in particular, dynamic alterations in the levels, modifications, and interactions of cellular effectors, including proteins. Frontiers in Molecular Biosciences offers an international publication platform for basic as well as applied research; we encourage contributions spanning both established and emerging areas of biology. To this end, the journal draws from empirical disciplines such as structural biology, enzymology, biochemistry, and biophysics, capitalizing as well on the technological advancements that have enabled metabolomics and proteomics measurements in massively parallel throughput, and the development of robust and innovative computational biology strategies. We also recognize influences from medicine and technology, welcoming studies in molecular genetics, molecular diagnostics and therapeutics, and nanotechnology. Our ultimate objective is the comprehensive illustration of the molecular mechanisms regulating proteins, nucleic acids, carbohydrates, lipids, and small metabolites in organisms across all branches of life. In addition to interesting new findings, techniques, and applications, Frontiers in Molecular Biosciences will consider new testable hypotheses to inspire different perspectives and stimulate scientific dialogue. The integration of in silico, in vitro, and in vivo approaches will benefit endeavors across all domains of the life sciences.