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

ObjectiveTo 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 (TC...

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Main Authors: Jilei Li, Jiarui Cao, Zhenyu Zhang, Sizhe Wang, Meng Zhu, Lili Yang, Wenhui Ouyang, Chunzheng Ma
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-04-01
Series:Frontiers in Molecular Biosciences
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Online Access:https://www.frontiersin.org/articles/10.3389/fmolb.2025.1580874/full
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author Jilei Li
Jiarui Cao
Zhenyu Zhang
Sizhe Wang
Meng Zhu
Lili Yang
Wenhui Ouyang
Chunzheng Ma
author_facet Jilei Li
Jiarui Cao
Zhenyu Zhang
Sizhe Wang
Meng Zhu
Lili Yang
Wenhui Ouyang
Chunzheng Ma
author_sort Jilei Li
collection DOAJ
description ObjectiveTo 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.MethodsWe 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.ResultsOur 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.ConclusionThe GGQL nano-preparation effectively promotes M2 macrophage polarization via the AMPK-PPARγ axis, treating UC.
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spelling doaj-art-55b17e8bbfaa4a08b444da05aadd44d72025-08-20T03:14:17ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2025-04-011210.3389/fmolb.2025.15808741580874Mechanism study on the treatment of ulcerative colitis by Gegen Qinlian nano-preparation through promoting M2 macrophage polarizationJilei Li0Jiarui Cao1Zhenyu Zhang2Sizhe Wang3Meng Zhu4Lili Yang5Wenhui Ouyang6Chunzheng Ma7Henan Province Hospital of TCM, Zhengzhou (The Second Affiliated Hospital of Henan University of Chinese Medicine), Zhengzhou, Henan, ChinaHenan University of Chinese Medicine (The Second Clinical Medical College of Henan University of Chinese Medicine), Zhengzhou, Henan, ChinaHenan University of Chinese Medicine (The Second Clinical Medical College of Henan University of Chinese Medicine), Zhengzhou, Henan, ChinaHenan University of Chinese Medicine (The Second Clinical Medical College of Henan University of Chinese Medicine), Zhengzhou, Henan, ChinaHenan University of Chinese Medicine (The Second Clinical Medical College of Henan University of Chinese Medicine), Zhengzhou, Henan, ChinaKaifeng Central Hospital, Kaifeng, Henan, ChinaHenan University of Chinese Medicine (The Second Clinical Medical College of Henan University of Chinese Medicine), Zhengzhou, Henan, ChinaHenan Province Hospital of TCM, Zhengzhou (The Second Affiliated Hospital of Henan University of Chinese Medicine), Zhengzhou, Henan, ChinaObjectiveTo 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.MethodsWe 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.ResultsOur 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.ConclusionThe GGQL nano-preparation effectively promotes M2 macrophage polarization via the AMPK-PPARγ axis, treating UC.https://www.frontiersin.org/articles/10.3389/fmolb.2025.1580874/fullulcerative colitisGegen Qinlian nano-preparationnanoparticle-targeted traditional Chinese medicinemacrophagespolarization
spellingShingle Jilei Li
Jiarui Cao
Zhenyu Zhang
Sizhe Wang
Meng Zhu
Lili Yang
Wenhui Ouyang
Chunzheng Ma
Mechanism study on the treatment of ulcerative colitis by Gegen Qinlian nano-preparation through promoting M2 macrophage polarization
Frontiers in Molecular Biosciences
ulcerative colitis
Gegen Qinlian nano-preparation
nanoparticle-targeted traditional Chinese medicine
macrophages
polarization
title Mechanism study on the treatment of ulcerative colitis by Gegen Qinlian nano-preparation through promoting M2 macrophage polarization
title_full Mechanism study on the treatment of ulcerative colitis by Gegen Qinlian nano-preparation through promoting M2 macrophage polarization
title_fullStr Mechanism study on the treatment of ulcerative colitis by Gegen Qinlian nano-preparation through promoting M2 macrophage polarization
title_full_unstemmed Mechanism study on the treatment of ulcerative colitis by Gegen Qinlian nano-preparation through promoting M2 macrophage polarization
title_short Mechanism study on the treatment of ulcerative colitis by Gegen Qinlian nano-preparation through promoting M2 macrophage polarization
title_sort mechanism study on the treatment of ulcerative colitis by gegen qinlian nano preparation through promoting m2 macrophage polarization
topic ulcerative colitis
Gegen Qinlian nano-preparation
nanoparticle-targeted traditional Chinese medicine
macrophages
polarization
url https://www.frontiersin.org/articles/10.3389/fmolb.2025.1580874/full
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