{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T16:26:48Z","timestamp":1788280008453,"version":"build-2803163510"},"reference-count":43,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2023,7,7]],"date-time":"2023-07-07T00:00:00Z","timestamp":1688688000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program","doi-asserted-by":"publisher","award":["2022YFD1801101"],"award-info":[{"award-number":["2022YFD1801101"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Ulcerative colitis (UC) is an inflammatory bowel disease (IBD), and its pathogenesis is related to intestinal mucosal barrier damage and gut microbiota imbalance. Protopine (PRO), an isoquinoline alkaloid, is one of the main anti-inflammatory ingredients of traditional Chinese medicine Macleaya cordata\u00a0(Willd.) R. Br. This study investigated the effects of PRO on the intestinal mucosal barrier and gut microbiota in dextran sodium sulfate (DSS)-induced colitis mice. C57BL\/6J mice were treated with 3% DSS in drinking water to induce acute colitis, while PRO was administered orally once daily for 7 days. The results showed that PRO administration significantly alleviated the symptoms of DSS-induced colitis in mice and inhibited the expression of inflammation-related genes. In addition, PRO restored the integrity of the intestinal barrier in colitis mice by restoring colonic mucin secretion and promoting the expression of tight junction proteins. Furthermore, PRO alleviated the DSS-induced gut microbiota dysbiosis by decreasing the abundance of Proteobacteria, Escherichia-Shigella and Enterococcus, as well as enhancing the abundance of beneficial bacteria, such as Firmicutes and Akkermansia. These findings suggested that PRO effectively alleviated DSS-induced ulcerative colitis by suppressing the expression of inflammation-related genes, maintaining the intestinal mucosal barrier and regulating the intestinal microbiota.<\/jats:p>","DOI":"10.3390\/molecules28135277","type":"journal-article","created":{"date-parts":[[2023,7,10]],"date-time":"2023-07-10T00:54:23Z","timestamp":1688950463000},"page":"5277","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Protopine Alleviates Dextran Sodium Sulfate-Induced Ulcerative Colitis by Improving Intestinal Barrier Function and Regulating Intestinal Microbiota"],"prefix":"10.3390","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-0813-9056","authenticated-orcid":false,"given":"Meishan","family":"Yue","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong 030801, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jialu","family":"Huang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong 030801, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolan","family":"Ma","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong 030801, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Huang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Hunan Agricultural University, Changsha 410128, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yisong","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Hunan Agricultural University, Changsha 410128, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianguo","family":"Zeng","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong 030801, China"},{"name":"College of Veterinary Medicine, Hunan Agricultural University, Changsha 410128, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1756","DOI":"10.1016\/S0140-6736(16)32126-2","article-title":"Ulcerative colitis","volume":"389","author":"Ungaro","year":"2017","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s12276-018-0126-x","article-title":"Mechanisms regulating intestinal barrier integrity and its pathological implications","volume":"50","author":"Chelakkot","year":"2018","journal-title":"Exp. Mol. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1016\/j.gtc.2020.07.005","article-title":"Epidemiology and Pathogenesis of Ulcerative Colitis","volume":"49","author":"Du","year":"2020","journal-title":"Gastroenterol. Clin. N. Am."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"26","DOI":"10.5217\/ir.2018.16.1.26","article-title":"Immunological pathogenesis of inflammatory bowel disease","volume":"16","author":"Lee","year":"2018","journal-title":"Intest. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1515\/jbcpp-2018-0036","article-title":"Immune response and inflammatory pathway of ulcerative colitis","volume":"30","author":"Chatuphonprasert","year":"2018","journal-title":"J. Basic Clin. Physiol. Pharmacol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"6016","DOI":"10.3748\/wjg.v23.i33.6016","article-title":"Dextran sodium sulfate colitis murine model: An indispensable tool for advancing our understanding of inflammatory bowel diseases pathogenesis","volume":"23","author":"Eichele","year":"2017","journal-title":"World J. Gastroenterol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1111\/imr.12182","article-title":"The mucus and mucins of the goblet cells and enterocytes provide the first defense line of the gastrointestinal tract and interact with the immune system","volume":"260","author":"Pelaseyed","year":"2014","journal-title":"Immunol. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Pei, L.Y., Ke, Y.S., Zhao, H.H., Wang, L., Jia, C., Liu, W.Z., Fu, Q.H., Shi, M.N., Cui, J., and Li, S.C. (2019). Role of colonic microbiota in the pathogenesis of ulcerative colitis. BMC Gastroenterol., 19.","DOI":"10.1186\/s12876-019-0930-3"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"818902","DOI":"10.3389\/fnut.2021.818902","article-title":"Gut Microbiota Is a Potential Biomarker in Inflammatory Bowel Disease","volume":"8","author":"Guo","year":"2021","journal-title":"Front. Nutr."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2652","DOI":"10.1056\/NEJMra2002697","article-title":"Pathophysiology of Inflammatory Bowel Diseases","volume":"383","author":"Chang","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1016\/j.immuni.2014.05.013","article-title":"Inflammatory bowel disease as a model for translating the microbiome","volume":"40","author":"Huttenhower","year":"2014","journal-title":"Immunity"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1504929","DOI":"10.1155\/2022\/1504929","article-title":"Sanguinarine-Chelerythrine Fraction of Coptis chinensis Exerts Anti-inflammatory Activity in Carrageenan Paw Oedema Test in Rats and Reveals Reduced Gastrotoxicity","volume":"2022","author":"Danielewski","year":"2022","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1080\/14786419.2015.1017490","article-title":"Chemical composition, antioxidant and antimicrobial activity of the essential oil from the leaves of Macleaya cordata (Willd) R","volume":"30","author":"Li","year":"2016","journal-title":"Br. Nat. Prod. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.pestbp.2017.08.016","article-title":"Molluscicidal activity and physiological toxicity of Macleaya cordata alkaloids components on snail Oncomelania hupensis","volume":"143","author":"Ke","year":"2017","journal-title":"Pestic. Biochem. Physiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"708597","DOI":"10.3389\/fvets.2021.708597","article-title":"Effects of Combined Supplementation of Macleaya cordata Extract and Benzoic Acid on the Growth Performance, Immune Responses, Antioxidant Capacity, Intestinal Morphology, and Microbial Composition in Weaned Piglets","volume":"8","author":"Wang","year":"2021","journal-title":"Front. Vet. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Wang, M., Zhang, J., Huang, X., Liu, Y., and Zeng, J. (2022). Effects of Dietary Macleaya cordata Extract on Growth Performance, Biochemical Indices, and Intestinal Microbiota of Yellow-Feathered Broilers Subjected to Chronic Heat Stress. Animals, 12.","DOI":"10.3390\/ani12172197"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"935201","DOI":"10.3389\/fvets.2022.935201","article-title":"Exploring the Anti-inflammatory Effects of Protopine Total Alkaloids of Macleaya Cordata (Willd.) R","volume":"9","author":"Dong","year":"2022","journal-title":"Br. Front. Vet. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.ejphar.2008.06.045","article-title":"Protective effects of protopine on hydrogen peroxide-induced oxidative injury of PC12 cells via Ca(2+) antagonism and antioxidant mechanisms","volume":"591","author":"Xiao","year":"2008","journal-title":"Eur. J. Pharmacol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1186\/s12935-021-02105-5","article-title":"Protopine triggers apoptosis via the intrinsic pathway and regulation of ROS\/PI3K\/Akt signalling pathway in liver carcinoma","volume":"21","author":"Nie","year":"2021","journal-title":"Cancer Cell Int."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Zhang, B., Zeng, M., Li, M., Kan, Y., Li, B., Xu, R., Wu, Y., Wang, S., Zheng, X., and Feng, W. (2019). Protopine Protects Mice against LPS-Induced Acute Kidney Injury by Inhibiting Apoptosis and Inflammation via the TLR4 Signaling Pathway. Molecules, 25.","DOI":"10.3390\/molecules25010015"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"110583","DOI":"10.1016\/j.fct.2019.110583","article-title":"Protopine attenuates inflammation stimulated by carrageenan and LPS via the MAPK\/NF-kappaB pathway","volume":"131","author":"Alam","year":"2019","journal-title":"Food Chem. Toxicol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"108","DOI":"10.5483\/BMBRep.2012.45.2.108","article-title":"Protopine reduces the inflammatory activity of lipopolysaccharide-stimulated murine macrophages","volume":"45","author":"Bae","year":"2012","journal-title":"BMB Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1689","DOI":"10.1002\/ptr.6357","article-title":"Protopine isolated from Nandina domestica induces apoptosis and autophagy in colon cancer cells by stabilizing p53","volume":"33","author":"Son","year":"2019","journal-title":"Phytother. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"84","DOI":"10.15586\/aei.v50i6.669","article-title":"Protopine alleviates lipopolysaccharide-triggered intestinal epithelial cell injury through retarding the NLRP3 and NF-kappaB signaling pathways to reduce inflammation and oxidative stress","volume":"50","author":"Li","year":"2022","journal-title":"Allergol. Immunopathol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.7150\/ijbs.65476","article-title":"Berberine ameliorates DSS-induced intestinal mucosal barrier dysfunction through microbiota-dependence and Wnt\/beta-catenin pathway","volume":"18","author":"Dong","year":"2022","journal-title":"Int. J. Biol. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"961885","DOI":"10.3389\/fmicb.2022.961885","article-title":"Therapeutic Mechanisms of Berberine to Improve the Intestinal Barrier Function via Modulating Gut Microbiota, TLR4\/NF-kappa B\/MTORC Pathway and Autophagy in Cats","volume":"13","author":"Cao","year":"2022","journal-title":"Front. Microbiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"154321","DOI":"10.1016\/j.phymed.2022.154321","article-title":"Sanguinarine ameliorates DSS induced ulcerative colitis by inhibiting NLRP3 inflammasome activation and modulating intestinal microbiota in C57BL\/6 mice","volume":"104","author":"Li","year":"2022","journal-title":"Phytomedicine"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Yang, Y., Ding, T., Xiao, G., Huang, J., Luo, D., Yue, M., Su, Y., Jiang, S., Zeng, J., and Liu, Y. (2023). Anti-Inflammatory Effects of Allocryptopine via the Target on the CX3CL1-CX3CR1 axis\/GNB5\/AKT\/NF-kappaB\/Apoptosis in Dextran Sulfate-Induced Mice. Biomedicines, 11.","DOI":"10.3390\/biomedicines11020464"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1016\/j.immuni.2019.03.017","article-title":"Cytokine Networks in the Pathophysiology of Inflammatory Bowel Disease","volume":"50","author":"Friedrich","year":"2019","journal-title":"Immunity"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3498310","DOI":"10.1155\/2022\/3498310","article-title":"Jatrorrhizine Alleviates DSS-Induced Ulcerative Colitis by Regulating the Intestinal Barrier Function and Inhibiting TLR4\/MyD88\/NF-kappaB Signaling Pathway","volume":"2022","author":"Niu","year":"2022","journal-title":"Evid. Based Complement. Alternat. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1007\/s00109-017-1557-x","article-title":"Layered defense: How mucus and tight junctions seal the intestinal barrier","volume":"95","author":"Capaldo","year":"2017","journal-title":"J. Mol. Med."},{"key":"ref_32","doi-asserted-by":"crossref","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":"ref_33","doi-asserted-by":"crossref","first-page":"2394","DOI":"10.1097\/MIB.0000000000000204","article-title":"Intestinal inflammation and mucosal barrier function","volume":"20","author":"Mascaraque","year":"2014","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"679897","DOI":"10.3389\/fimmu.2021.679897","article-title":"Kaempferol Alleviates Murine Experimental Colitis by Restoring Gut Microbiota and Inhibiting the LPS-TLR4-NF-kappaB Axis","volume":"12","author":"Qu","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1016\/j.tibtech.2015.06.011","article-title":"Proteobacteria: Microbial signature of dysbiosis in gut microbiota","volume":"33","author":"Shin","year":"2015","journal-title":"Trends Biotechnol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1002\/ibd.20903","article-title":"Low counts of Faecalibacterium prausnitzii in colitis microbiota","volume":"15","author":"Sokol","year":"2009","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"115537","DOI":"10.1016\/j.jep.2022.115537","article-title":"Sanhuang Xiexin decoction ameliorates DSS-induced colitis in mice by regulating intestinal inflammation, intestinal barrier, and intestinal flora","volume":"297","author":"Wu","year":"2022","journal-title":"J. Ethnopharmacol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3142","DOI":"10.1039\/D0FO03061A","article-title":"The dietary supplement Rhodiola crenulata extract alleviates dextran sulfate sodium-induced colitis in mice through anti-inflammation, mediating gut barrier integrity and reshaping the gut microbiome","volume":"12","author":"Wang","year":"2021","journal-title":"Food Funct."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"840245","DOI":"10.3389\/fimmu.2022.840245","article-title":"Lactobacillus spp. for Gastrointestinal Health: Current and Future Perspectives","volume":"13","author":"Dempsey","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3964","DOI":"10.1038\/s41467-022-31312-5","article-title":"Imbalanced gut microbiota fuels hepatocellular carcinoma development by shaping the hepatic inflammatory microenvironment","volume":"13","author":"Schneider","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1136\/gutjnl-2016-313432","article-title":"Recovery of ethanol-induced Akkermansia muciniphila depletion ameliorates alcoholic liver disease","volume":"67","author":"Grander","year":"2018","journal-title":"Gut"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1002\/ibd.20753","article-title":"Distinct cytokine patterns identified from multiplex profiles of murine DSS and TNBS-induced colitis","volume":"15","author":"Alex","year":"2009","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_43","first-page":"4557","article-title":"A guide to histomorphological evaluation of intestinal inflammation in mouse models","volume":"7","author":"Erben","year":"2014","journal-title":"Int. J. Clin. Exp. Pathol."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/13\/5277\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:08:09Z","timestamp":1760126889000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/13\/5277"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,7]]},"references-count":43,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2023,7]]}},"alternative-id":["molecules28135277"],"URL":"https:\/\/doi.org\/10.3390\/molecules28135277","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,7]]}}}