{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T03:57:05Z","timestamp":1784779025474,"version":"3.55.0"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,3,25]],"date-time":"2025-03-25T00:00:00Z","timestamp":1742860800000},"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. Pharmacol."],"abstract":"<jats:p>Gut homeostasis is critical for human health, ulcerative colitis (UC) can disrupt gut homeostasis and cause disease. <jats:italic>Panax ginseng<\/jats:italic> C.A. Meyer is a widely used traditional herbal medicine known for its anti-inflammatory, antioxidant, and immunomodulatory effects. However, the protective mechanisms of total ginsenosides (TG) in treating UC remain unclear. In this study, we employed <jats:italic>Drosophila<\/jats:italic> melanogaster as a model organism to investigate the protective effects of TG on dextran sulfate sodium (DSS)-induced intestinal injury. Our data showed that TG significantly improved survival rates in female flies, restored intestinal length, maintained intestinal barrier integrity, and alleviated oxidative stress. Additionally, TG may protect against intestinal damage by activating the PI3K\/Akt signaling pathway and inhibiting the JAK\/STAT signaling pathway. These findings suggest that TG alleviates UC symptoms through multi-target regulation, highlighting its potential for developing novel therapeutic strategies for UC.<\/jats:p>","DOI":"10.3389\/fphar.2025.1556579","type":"journal-article","created":{"date-parts":[[2025,3,26]],"date-time":"2025-03-26T02:10:08Z","timestamp":1742955008000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Network analysis and in vivo experiments reveal the therapeutic mechanisms of total ginsenosides in a Drosophila model of ulcerative colitis"],"prefix":"10.3389","volume":"16","author":[{"given":"Gongchen","family":"He","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuexin","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanjie","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanyan","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,3,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"111628","DOI":"10.1016\/j.fct.2020.111628","article-title":"A phytopharmacological overview of medicinal plants used for prophylactic and treatment of colitis","volume":"144","author":"Akkol","year":"2020","journal-title":"Food. Chem. Toxicol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"6285099","DOI":"10.1155\/2022\/6285099","article-title":"Interference of interleukin-1\u03b2 mediated by lentivirus promotes functional recovery of spinal cord contusion injury in rats via the PI3K\/AKT1 signaling pathway","volume":"2022","author":"Cao","year":"2022","journal-title":"Mediat. Inflamm."},{"key":"B3","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1016\/j.stem.2009.01.009","article-title":"Intestinal stem cells in mammals and Drosophila","volume":"4","author":"Casali","year":"2009","journal-title":"Cell Stem Cell"},{"key":"B4","doi-asserted-by":"publisher","first-page":"101835","DOI":"10.1016\/j.redox.2020.101835","article-title":"Context-dependent responses of Drosophila intestinal stem cells to intracellular reactive oxygen species","volume":"39","author":"Chen","year":"2021","journal-title":"Redox Biol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"978558","DOI":"10.3389\/fphar.2022.978558","article-title":"Traditional chinese medicine prescription shenling BaiZhu powder to treat ulcerative colitis: Clinical evidence and potential mechanisms","volume":"13","author":"Chen","year":"2022","journal-title":"Front. Pharmocol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"23523","DOI":"10.1038\/srep23523","article-title":"Two phases of aging separated by the Smurf transition as a public path to death","volume":"6","author":"Dambroise","year":"2016","journal-title":"Sci. Rep."},{"key":"B7","doi-asserted-by":"publisher","first-page":"951","DOI":"10.1001\/jama.2023.15389","article-title":"Ulcerative colitis in adults: a review","volume":"330","author":"Gros","year":"2023","journal-title":"JAMA"},{"key":"B8","doi-asserted-by":"publisher","first-page":"7247238","DOI":"10.1155\/2019\/7247238","article-title":"A comprehensive review and update on the pathogenesis of inflammatory bowel disease","volume":"2019","author":"Guan","year":"2019","journal-title":"J. Immunol. Res."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1019594","DOI":"10.3389\/fphar.2022.1019594","article-title":"Protective effect of astragalus membranaceus and its bioactive compounds against the intestinal inflammation in Drosophila","volume":"13","author":"He","year":"2022","journal-title":"Front. Pharmacol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"897","DOI":"10.1007\/s00384-020-03536-8","article-title":"Cytomegalovirus infection is associated with worse outcomes in inflammatory bowel disease hospitalizations nationwide","volume":"35","author":"Hendler","year":"2020","journal-title":"Int. J. Colorectal Dis."},{"key":"B11","doi-asserted-by":"publisher","first-page":"33601","DOI":"10.18632\/oncotarget.26035","article-title":"Active ginseng components in cognitive impairment: therapeutic potential and prospects for delivery and clinical study","volume":"9","author":"Jakaria","year":"2018","journal-title":"Oncotarget"},{"key":"B12","doi-asserted-by":"publisher","first-page":"118215","DOI":"10.1016\/j.jep.2024.118215","article-title":"Orostachys malacophylla (pall.) fisch extracts alleviate intestinal inflammation in Drosophila","volume":"330","author":"Kim","year":"2024","journal-title":"J. Ethnopharmacol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1016\/j.jgr.2016.08.004","article-title":"Role of ginsenosides, the main active components of Panax ginseng, in inflammatory responses and diseases","volume":"41","author":"Kim","year":"2017","journal-title":"J. Ginseng Res."},{"key":"B14","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1016\/S0140-6736(23)00966-2","article-title":"Ulcerative colitis","volume":"402","author":"Le Berre","year":"2023","journal-title":"Lancet"},{"key":"B15","doi-asserted-by":"publisher","first-page":"115939","DOI":"10.1016\/j.taap.2022.115939","article-title":"The protective effect of safranal against intestinal tissue damage in Drosophila","volume":"439","author":"Lei","year":"2022","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"117578","DOI":"10.1016\/j.jep.2023.117578","article-title":"Protective effect of San Huang Pill and its bioactive compounds against ulcerative colitis in Drosophila via modulation of JAK\/STAT, apoptosis, Toll, and Nrf2\/Keap1 pathways","volume":"322","author":"Li","year":"2024","journal-title":"J. Ethnopharmacol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"117220","DOI":"10.1016\/j.jep.2023.117220","article-title":"Multi-omics revealed the mechanisms of Codonopsis pilosula aqueous extract in improving UC through blocking abnormal activation of PI3K\/Akt signaling pathway","volume":"319","author":"Li","year":"2024","journal-title":"J. Ethnopharmacol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"9867","DOI":"10.1021\/acs.jafc.4c00245","article-title":"Ginsenoside CK alleviates DSS-induced IBD in mice by regulating tryptophan metabolism and activating aryl hydrocarbon receptor via gut microbiota modulation","volume":"72","author":"Liu","year":"2024","journal-title":"J. Agric. Food. Chem."},{"key":"B19","doi-asserted-by":"publisher","first-page":"5601","DOI":"10.3892\/mmr.2016.5944","article-title":"Crocus sativus L. protects against SDS-induced intestinal damage and extends lifespan in Drosophila melanogaster","volume":"14","author":"Liu","year":"2016","journal-title":"Mol. Med. Rep."},{"key":"B20","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2\u2212\u0394\u0394CT method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"B21","doi-asserted-by":"publisher","first-page":"dmm049332","DOI":"10.1242\/dmm.049332","article-title":"Investigating local and systemic intestinal signalling in health and disease with Drosophila","volume":"15","author":"Medina","year":"2022","journal-title":"Dis. Model. Mech."},{"key":"B22","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/j.jgr.2017.01.008","article-title":"Molecular signaling of ginsenosides Rb1, Rg1, and Rg3 and their mode of actions","volume":"42","author":"Mohanan","year":"2018","journal-title":"J. Ginseng Res."},{"key":"B23","doi-asserted-by":"publisher","first-page":"4365","DOI":"10.1038\/s41467-019-12336-w","article-title":"Damage sensing by a Nox-Ask1-MKK3-p38 signaling pathway mediates regeneration in the adult Drosophila midgut","volume":"10","author":"Patel","year":"2019","journal-title":"Nat. Commun."},{"key":"B25","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/j.jgr.2020.02.004","article-title":"Pharmacological potential of ginseng and its major component ginsenosides","volume":"45","author":"Ratan","year":"2021","journal-title":"J. Ginseng Res."},{"key":"B26","doi-asserted-by":"publisher","first-page":"2831","DOI":"10.1093\/hmg\/ddaa170","article-title":"A Drosophila model of Friedreich ataxia with CRISPR\/Cas9 insertion of GAA repeats in the frataxin gene reveals in vivo protection by N-acetyl cysteine","volume":"29","author":"Russi","year":"2020","journal-title":"Hum. Mol. Genet."},{"key":"B44","doi-asserted-by":"publisher","first-page":"786","DOI":"10.1016\/j.biopha.2018.12.033","article-title":"Evodiamine prevents dextran sulfate sodium-induced murine experimental colitis via the regulation of NF-kappaB and NLRP3 inflammasome","volume":"110","author":"Shen","year":"2019","journal-title":"Biomed. Pharmacother"},{"key":"B27","doi-asserted-by":"publisher","first-page":"369","DOI":"10.3892\/etm.2023.12068","article-title":"Effect and mechanism of total ginsenosides repairing SDS-induced Drosophila enteritis model based on MAPK pathway","volume":"26","author":"Su","year":"2023","journal-title":"Exp. Ther. Med."},{"key":"B28","doi-asserted-by":"publisher","first-page":"155392","DOI":"10.1016\/j.cyto.2020.155392","article-title":"A centric view of JAK\/STAT5 in intestinal homeostasis, infection, and inflammation","volume":"139","author":"Surbek","year":"2021","journal-title":"Cytokine"},{"key":"B29","doi-asserted-by":"publisher","first-page":"8051870","DOI":"10.1155\/2017\/8051870","article-title":"Sex differences in the effect of resveratrol on DSS-induced colitis in mice","volume":"2017","author":"Wagnerova","year":"2017","journal-title":"Gastroenterol. Res. Pract."},{"key":"B30","doi-asserted-by":"publisher","first-page":"uhae170","DOI":"10.1093\/hr\/uhae170","article-title":"Panax notoginseng: panoramagram of phytochemical and pharmacological properties, biosynthesis, and regulation and production of ginsenosides","volume":"11","author":"Wei","year":"2024","journal-title":"Hortic. Res."},{"key":"B31","doi-asserted-by":"publisher","first-page":"426","DOI":"10.3390\/antiox11020426","article-title":"Ursolic acid protects sodium dodecyl sulfate-induced Drosophila ulcerative colitis model by inhibiting the JNK signaling","volume":"11","author":"Wei","year":"2022","journal-title":"Antioxidants"},{"key":"B32","doi-asserted-by":"publisher","first-page":"671","DOI":"10.7150\/jca.88783","article-title":"Ginsenosides and tumors: a comprehensive and visualized analysis of research hotspots and antitumor mechanisms","volume":"15","author":"Xia","year":"2024","journal-title":"J. Cancer"},{"key":"B33","doi-asserted-by":"publisher","first-page":"1072715","DOI":"10.3389\/fphar.2022.1072715","article-title":"Using Drosophila melanogaster as a suitable platform for drug discovery from natural products in inflammatory bowel disease","volume":"13","author":"Xiu","year":"2022","journal-title":"Front. Pharmacol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"114086","DOI":"10.1016\/j.biopha.2022.114086","article-title":"The role and mechanism of flavonoid herbal natural products in ulcerative colitis","volume":"158","author":"Xue","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"B35","doi-asserted-by":"publisher","first-page":"844","DOI":"10.1093\/ibd\/izad312","article-title":"Unveiling colitis: a journey through the dextran sodium sulfate-induced model","volume":"30","author":"Yang","year":"2024","journal-title":"Inflamm. Bowel Dis."},{"key":"B36","doi-asserted-by":"publisher","first-page":"140814","DOI":"10.1016\/j.chemosphere.2023.140814","article-title":"Selenium attenuated food borne cadmium-induced intestinal inflammation in red swamp crayfish (Procambarus clarkii) via regulating PI3K\/Akt\/NF-kappaB pathway","volume":"349","author":"Yang","year":"2024","journal-title":"Chemosphere"},{"key":"B37","doi-asserted-by":"publisher","first-page":"893758","DOI":"10.3389\/fphar.2022.893758","article-title":"Flos puerariae ameliorates the intestinal inflammation of Drosophila via modulating the Nrf2\/Keap1, JAK-STAT and Wnt signaling","volume":"13","author":"Yang","year":"2022","journal-title":"Front. Pharmacol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"10119","DOI":"10.1016\/j.eujim.2020.101119","article-title":"Six Gentlemen Decoction adding Aucklandia and Amomum (Xiangsha Liujunzi Tang) for the treatment of ulcerative colitis: A systematic review and meta-analysis of randomized clinical trials","volume":"36","author":"Yuan","year":"2020","journal-title":"Eur. J. Integr. Med"},{"key":"B38","first-page":"603","article-title":"Rectal administration of Panax notoginseng and Colla Corii Asini suppositories in ulcerative colitis: clinical effect and influence on immune function","volume":"14","author":"Zeng","year":"2022","journal-title":"Am. J. Transl. Res."},{"key":"B39","doi-asserted-by":"publisher","first-page":"2875","DOI":"10.3390\/nu14142875","article-title":"Protective effect of bilberry anthocyanin extracts on dextran sulfate sodium-induced intestinal damage in Drosophila melanogaster","volume":"14","author":"Zhang","year":"2022","journal-title":"Nutrients"},{"key":"B40","doi-asserted-by":"publisher","first-page":"946752","DOI":"10.3389\/fphar.2022.946752","article-title":"A review of neuroprotective effects and mechanisms of ginsenosides from panax ginseng in treating ischemic stroke","volume":"13","author":"Zhao","year":"2022","journal-title":"Front. Pharmacol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"1353614","DOI":"10.3389\/fimmu.2024.1353614","article-title":"Pharmacological effects of ginseng and ginsenosides on intestinal inflammation and the immune system","volume":"15","author":"Zhao","year":"2024","journal-title":"Front. Immunol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1007\/s13318-020-00645-1","article-title":"Differences in intestinal metabolism of ginseng between normal and immunosuppressed rats","volume":"46","author":"Zhu","year":"2021","journal-title":"Eur. J. Drug. Metab. Pharmacokinet."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2025.1556579\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,26]],"date-time":"2025-03-26T02:10:11Z","timestamp":1742955011000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2025.1556579\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,25]]},"references-count":43,"alternative-id":["10.3389\/fphar.2025.1556579"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2025.1556579","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,25]]},"article-number":"1556579"}}