{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T18:00:01Z","timestamp":1792519201102,"version":"4.5.0"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T00:00:00Z","timestamp":1745539200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Biosci."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>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\u2018s 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\u2019s impact on M2 macrophage polarization and intestinal inflammation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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-PPAR\u03b3 axis, achieving therapeutic objectives for UC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The GGQL nano-preparation effectively promotes M2 macrophage polarization via the AMPK-PPAR\u03b3 axis, treating UC.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmolb.2025.1580874","type":"journal-article","created":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T04:12:27Z","timestamp":1745554347000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Mechanism study on the treatment of ulcerative colitis by Gegen Qinlian nano-preparation through promoting M2 macrophage polarization"],"prefix":"10.3389","volume":"12","author":[{"given":"Jilei","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiarui","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenyu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sizhe","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhui","family":"Ouyang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunzheng","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,4,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1184","DOI":"10.1093\/ecco-jcc\/jjab010","article-title":"Efficacy of oral, Topical, or combined oral and Topical 5-Aminosalicylates, in ulcerative colitis: Systematic review and network Meta-analysis","volume":"15","author":"Barberio","year":"2021","journal-title":"J. Crohns Colitis."},{"key":"B2","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1056\/NEJMc1915739","article-title":"Vedolizumab versus Adalimumab for Moderate-to-severe ulcerative colitis","volume":"382","author":"Biemans","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"B3","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1042\/ETLS20200350","article-title":"Biotechnology, nanotechnology and medicine","volume":"4","author":"Contera","year":"2020","journal-title":"Emerg. Top. Life Sci."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1035","DOI":"10.1016\/j.ijbiomac.2020.10.259","article-title":"Scutellaria baicalensis Georgi polysaccharide ameliorates DSS-induced ulcerative colitis by improving intestinal barrier function and modulating gut microbiota","volume":"166","author":"Cui","year":"2021","journal-title":"Int. J. Biol. Macromol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"2444","DOI":"10.1056\/NEJMoa2207940","article-title":"Mirikizumab as induction and Maintenance therapy for ulcerative colitis","volume":"388","author":"D'Haens","year":"2023","journal-title":"New Engl. J. Med."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1641","DOI":"10.1093\/ibd\/izab029","article-title":"Human intestinal macrophages are involved in the pathology of both ulcerative colitis and Crohn disease","volume":"27","author":"Dharmasiri","year":"2021","journal-title":"Inflamm. Bowel Dis."},{"key":"B7","doi-asserted-by":"publisher","first-page":"0441","DOI":"10.34133\/research.0441","article-title":"Aggravated ulcerative colitis via circNlgn-mediated suppression of nuclear actin Polymerization","volume":"7","author":"Du","year":"2024","journal-title":"Res. (Wash DC)"},{"key":"B8","doi-asserted-by":"publisher","first-page":"2696","DOI":"10.3390\/ijms24032696","article-title":"CD4 T-cell Subsets and the Pathophysiology of inflammatory bowel disease","volume":"24","author":"Gomez-Bris","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"B9","doi-asserted-by":"publisher","first-page":"CD007216","DOI":"10.1002\/14651858.CD007216.pub2","article-title":"Tacrolimus (FK506) for induction of remission in corticosteroid-refractory ulcerative colitis","volume":"4","author":"Gordon","year":"2022","journal-title":"Cochrane Database Syst. Rev."},{"key":"B10","doi-asserted-by":"publisher","first-page":"538","DOI":"10.1038\/s41575-023-00769-0","article-title":"Macrophages in intestinal homeostasis and inflammatory bowel disease","volume":"20","author":"Hegarty","year":"2023","journal-title":"Nat. Rev. Gastro. Hepat."},{"key":"B11","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1159\/000527422","article-title":"New and Emerging treatments for inflammatory bowel disease","volume":"104","author":"Higashiyama","year":"2023","journal-title":"Digestion"},{"key":"B12","doi-asserted-by":"publisher","first-page":"113571","DOI":"10.1016\/j.biopha.2022.113571","article-title":"Gegen Qinlian decoction ameliorates murine colitis by inhibiting the expansion of Enterobacteriaceae through activating PPAR-gamma signaling","volume":"154","author":"Hu","year":"2022","journal-title":"Biomed. Pharmacother."},{"key":"B13","doi-asserted-by":"publisher","first-page":"107100","DOI":"10.1016\/j.phrs.2024.107100","article-title":"Novel nano-drug delivery system for natural products and their application","volume":"201","author":"Huang","year":"2024","journal-title":"Pharmacol. Res."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1259","DOI":"10.3390\/antiox11071259","article-title":"Puerarin Attenuates oxidative stress and Ferroptosis via AMPK\/PGC1\u03b1\/Nrf2 pathway after Subarachnoid hemorrhage in Rats","volume":"11","author":"Huang","year":"2022","journal-title":"Antioxidants (Basel)"},{"key":"B15","doi-asserted-by":"publisher","first-page":"696","DOI":"10.1080\/19490976.2019.1589281","article-title":"Lactobacillus fermentum species ameliorate dextran sulfate sodium-induced colitis by regulating the immune response and altering gut microbiota","volume":"10","author":"Jang","year":"2019","journal-title":"Gut Microbes"},{"key":"B16","doi-asserted-by":"publisher","first-page":"118587","DOI":"10.1016\/j.lfs.2020.118587","article-title":"Changes in serum inflammatory cytokine levels and intestinal flora in a self-healing dextran sodium sulfate-induced ulcerative colitis murine model","volume":"263","author":"Jialing","year":"2020","journal-title":"Life Sci."},{"key":"B17","doi-asserted-by":"publisher","first-page":"14912","DOI":"10.1021\/acsami.4c20322","article-title":"TA-V Nanozymes with acid Resistance capabilities effectively target and alleviate ulcerative colitis lesions via oral delivery","volume":"17","author":"Jin","year":"2025","journal-title":"ACS Appl. Mater Interfaces"},{"key":"B18","doi-asserted-by":"publisher","first-page":"767456","DOI":"10.3389\/fimmu.2021.767456","article-title":"IL-1\u03b2 and the intestinal epithelial tight junction barrier","volume":"12","author":"Kaminsky","year":"2021","journal-title":"Front. Immunol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1396","DOI":"10.1053\/j.gastro.2022.01.023","article-title":"What Does disease progression Look like in ulcerative colitis, and How might it Be prevented?","volume":"162","author":"Krugliak","year":"2022","journal-title":"Gastroenterology"},{"key":"B20","doi-asserted-by":"publisher","first-page":"1381","DOI":"10.1016\/j.cgh.2020.01.046","article-title":"Dietary guidance from the International organization for the study of inflammatory bowel diseases","volume":"18","author":"Levine","year":"2020","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"105694","DOI":"10.1016\/j.phrs.2021.105694","article-title":"Main active components of Jiawei Gegen Qinlian decoction protects against ulcerative colitis under different dietary environments in a gut microbiota-dependent manner","volume":"170","author":"Li","year":"2021","journal-title":"Pharmacol. Res."},{"key":"B22","doi-asserted-by":"publisher","first-page":"154394","DOI":"10.1016\/j.phymed.2022.154394","article-title":"Sanguinarine ameliorates DSS induced ulcerative colitis by inhibiting NLRP3 inflammasome activation and modulating intestinal microbiota in C57BL\/6 mice","volume":"106","author":"Li","year":"2022","journal-title":"Phytomedicine"},{"key":"B23","doi-asserted-by":"publisher","first-page":"e2400206","DOI":"10.1002\/advs.202400206","article-title":"Gingerenone A Attenuates ulcerative colitis via targeting IL-17RA to inhibit inflammation and Restore intestinal barrier function","volume":"11","author":"Liang","year":"2024","journal-title":"Adv. Sci. (Weinh)"},{"key":"B24","doi-asserted-by":"publisher","first-page":"110917","DOI":"10.1016\/j.biopha.2020.110917","article-title":"The main bioactive compounds of Scutellaria baicalensis Georgi. for alleviation of inflammatory cytokines: a comprehensive review","volume":"133","author":"Liao","year":"2021","journal-title":"Biomed. Pharmacother."},{"key":"B25","doi-asserted-by":"publisher","first-page":"2934552","DOI":"10.1155\/2022\/2934552","article-title":"Gegen Qinlian decoction Relieves ulcerative colitis via adjusting dysregulated Nrf2\/ARE signaling","volume":"2022","author":"Lin","year":"2022","journal-title":"Evid.-based Compl. Alt."},{"key":"B26","doi-asserted-by":"publisher","first-page":"806148","DOI":"10.3389\/fphar.2022.806148","article-title":"Natural products modulate cell apoptosis: a Promising way for the treatment of ulcerative colitis","volume":"13","author":"Liu","year":"2022","journal-title":"Front. Pharmacol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1146\/annurev-pathmechdis-012418-012718","article-title":"Diversity, mechanisms, and significance of macrophage Plasticity","volume":"15","author":"Locati","year":"2020","journal-title":"Annu. Rev. Pathol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"174742","DOI":"10.1016\/j.ejphar.2022.174742","article-title":"Ginsenoside Rg1 ameliorated experimental colitis by regulating the balance of M1\/M2 macrophage polarization and the homeostasis of intestinal flora","volume":"917","author":"Long","year":"2022","journal-title":"Eur. J. Pharmacol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"103017","DOI":"10.1016\/j.autrev.2021.103017","article-title":"The influence of cytokines on the complex pathology of ulcerative colitis","volume":"21","author":"Nakase","year":"2022","journal-title":"Autoimmun. Rev."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1606","DOI":"10.1016\/S0140-6736(12)60150-0","article-title":"Ulcerative colitis","volume":"380","author":"Ordas","year":"2012","journal-title":"Lancet"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1007\/s11427-024-2768-y","article-title":"Targeting IGF1 to alleviate obesity through regulating energy expenditure and fat deposition","author":"Rong","year":"2025","journal-title":"Sci. China Life Sci."},{"key":"B32","doi-asserted-by":"publisher","first-page":"135","DOI":"10.7861\/clinmed.2021-0080","article-title":"Ulcerative colitis: an update","volume":"21","author":"Segal","year":"2021","journal-title":"Clin. Med. (Lond)."},{"key":"B33","doi-asserted-by":"publisher","first-page":"111580","DOI":"10.1016\/j.biopha.2021.111580","article-title":"Randomised clinical trial: efficacy and safety of Qing-Chang-Hua-Shi granules in a multicenter, randomized, and double-blind clinical trial of patients with moderately active ulcerative colitis","volume":"139","author":"Shen","year":"2021","journal-title":"Biomed. Pharmacother."},{"key":"B34","doi-asserted-by":"publisher","first-page":"114108","DOI":"10.1016\/j.jep.2021.114108","article-title":"Aloe vera mitigates dextran sulfate sodium-induced rat ulcerative colitis by potentiating colon mucus barrier","volume":"279","author":"Shi","year":"2021","journal-title":"J. Ethnopharmacol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1155077","DOI":"10.3389\/fimmu.2023.1155077","article-title":"A potential therapeutic approach for ulcerative colitis: targeted regulation of macrophage polarization through phytochemicals","volume":"14","author":"Wang","year":"2023","journal-title":"Front. Immunol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"7491","DOI":"10.7150\/thno.59196","article-title":"Microbial and genetic-based framework identifies drug targets in inflammatory bowel disease","volume":"11","author":"Wang","year":"2021","journal-title":"Theranostics"},{"key":"B37","doi-asserted-by":"publisher","first-page":"1373820","DOI":"10.3389\/fonc.2024.1373820","article-title":"Correlation between Tregs and ICOS-induced M2 macrophages polarization in colorectal cancer progression","volume":"14","author":"Xu","year":"2024","journal-title":"Front. Oncol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"S492-S502","DOI":"10.1080\/21691401.2018.1499665","article-title":"Research progress of novel inorganic nanometre materials carriers in nanomedicine for cancer diagnosis and treatment","volume":"46","author":"Xu","year":"2018","journal-title":"Artif. Cells Nanomed Biotechnol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"114562","DOI":"10.1016\/j.biopha.2023.114562","article-title":"Oligosaccharides of Polygonatum Cyrtonema Hua ameliorates dextran sulfate sodium-induced colitis and regulates the gut microbiota","volume":"161","author":"Xu","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"B40","doi-asserted-by":"publisher","first-page":"873382","DOI":"10.3389\/fimmu.2022.873382","article-title":"Adiponectin ameliorates GMH-induced brain Injury by regulating Microglia M1\/M2 polarization via AdipoR1\/APPL1\/AMPK\/PPAR\u03b3 signaling pathway in Neonatal Rats","volume":"13","author":"Xu","year":"2022","journal-title":"Front. Immunol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"3133","DOI":"10.1016\/j.ymthe.2022.01.046","article-title":"Role of exosomal non-coding RNAs from tumor cells and tumor-associated macrophages in the tumor microenvironment","volume":"30","author":"Xu","year":"2022","journal-title":"Mol. Ther."},{"key":"B42","doi-asserted-by":"publisher","first-page":"119157","DOI":"10.1016\/j.jep.2024.119157","article-title":"Luteolin modulates macrophage phenotypic switching via the AMPK-PPAR\u03b3 pathway to alleviate ulcerative colitis in mice","volume":"339","author":"Yang","year":"2025","journal-title":"J. Ethnopharmacol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"113304","DOI":"10.1016\/j.intimp.2024.113304","article-title":"Inhibition of hepatitis B virus through PPAR-JAK\/STAT pathway modulation by electroacupuncture and tenofovir disoproxil fumarate combination therapy","volume":"143","author":"Yang","year":"2024","journal-title":"Int. Immunopharmacol."},{"key":"B44","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.ijbiomac.2019.12.028","article-title":"The immunomodulatory role of irisin on osteogenesis via AMPK-mediated macrophage polarization","volume":"146","author":"Ye","year":"2020","journal-title":"Int. J. Biol. Macromol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"155056","DOI":"10.1016\/j.phymed.2023.155056","article-title":"Paeonol alleviates ulcerative colitis in mice by increasing short-chain fatty acids derived from Clostridium butyricum","volume":"120","author":"Zhao","year":"2023","journal-title":"Phytomedicine"},{"key":"B46","doi-asserted-by":"publisher","first-page":"153182","DOI":"10.1016\/j.phymed.2020.153182","article-title":"Gegen Qinlian decoction maintains colonic mucosal homeostasis in acute\/chronic ulcerative colitis via bidirectionally modulating dysregulated Notch signaling","volume":"68","author":"Zhao","year":"2020","journal-title":"Phytomedicine"},{"key":"B47","doi-asserted-by":"publisher","first-page":"153519","DOI":"10.1016\/j.phymed.2021.153519","article-title":"Gegen Qinlian decoction relieved DSS-induced ulcerative colitis in mice by modulating Th17\/Treg cell homeostasis via suppressing IL-6\/JAK2\/STAT3 signaling","volume":"84","author":"Zhao","year":"2021","journal-title":"Phytomedicine"},{"key":"B48","doi-asserted-by":"publisher","first-page":"588552","DOI":"10.3389\/fimmu.2020.588552","article-title":"PD-L1-Mediated immunosuppression in Glioblastoma is associated with the infiltration and M2-polarization of tumor-associated macrophages","volume":"11","author":"Zhu","year":"2020","journal-title":"Front. Immunol."}],"container-title":["Frontiers in Molecular Biosciences"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmolb.2025.1580874\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T04:12:27Z","timestamp":1745554347000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmolb.2025.1580874\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,25]]},"references-count":48,"alternative-id":["10.3389\/fmolb.2025.1580874"],"URL":"https:\/\/doi.org\/10.3389\/fmolb.2025.1580874","relation":{},"ISSN":["2296-889X"],"issn-type":[{"value":"2296-889X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,25]]},"article-number":"1580874"}}