{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T20:14:16Z","timestamp":1787170456747,"version":"build-2736575974"},"reference-count":116,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T00:00:00Z","timestamp":1761868800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009687","name":"Wroclaw Medical University","doi-asserted-by":"crossref","award":["SUBK.A130.24.021"],"award-info":[{"award-number":["SUBK.A130.24.021"]}],"id":[{"id":"10.13039\/501100009687","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Phytotherapy is a growing field of modern medicine, offering natural alternatives with multidirectional pharmacological effects. Among plant-derived bioactive compounds, isoquinoline alkaloids exhibit antioxidant, anti-inflammatory, and antimicrobial properties. Our in vitro model of campylobacteriosis confirmed that berberine reduces pathological changes in colonocytes not only through its direct antibacterial (minimum inhibitory concentration for pure berberine against Campylobacter jejuni was 64 \u03bcg\/mL) and anti-biofilm (fourfold reduction in C. jejuni biomass) effects, but also through its protective effect on the morphostructure and secretory profile of host cells exposed to bacterial components. Furthermore, berberine stabilized intercellular junction proteins, modulated bile acid and arachidonic acid metabolism, and supported host-protective signaling pathways. These findings indicate that berberine acts through a dual mechanism\u2014directly reducing bacterial virulence while enhancing intestinal barrier integrity and metabolic homeostasis. In summary, berberine appears to be a multifunctional phytochemical in the development of new strategies for the prevention and treatment of C. jejuni-induced gastrointestinal infections and epithelial barrier dysfunctions. The protective effect we have demonstrated may contribute to alleviating the phenomenon of \u201cleaky gut,\u201d commonly associated with campylobacteriosis.<\/jats:p>","DOI":"10.3390\/ijms262110634","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T13:15:14Z","timestamp":1762175714000},"page":"10634","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Impact of Isoquinoline Alkaloids on the Intestinal Barrier in a Colonic Model of Campylobacter jejuni Infection"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8559-1695","authenticated-orcid":false,"given":"Anna","family":"Duda-Madej","sequence":"first","affiliation":[{"name":"Department of Microbiology, Faculty of Medicine, Wroclaw Medical University, Cha\u0142ubi\u0144skiego 4, 50-368 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9077-439X","authenticated-orcid":false,"given":"Przemys\u0142aw","family":"Gagat","sequence":"additional","affiliation":[{"name":"Faculty of Biotechnology, University of Wroclaw, Fryderyka Joliot-Curie 14a, 50-137 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2831-7643","authenticated-orcid":false,"given":"Jerzy","family":"Wi\u015bniewski","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Molecular Biology and Biotechnology, Faculty of Chemistry, Wroclaw University of Science and Technology, 50-370 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3668-6891","authenticated-orcid":false,"given":"Szymon","family":"Viscardi","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Wroclaw Medical University, Ludwika Pasteura 1, 50-367 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3117-8894","authenticated-orcid":false,"given":"Pawe\u0142","family":"Krzy\u017cek","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Medicine, Wroclaw Medical University, Cha\u0142ubi\u0144skiego 4, 50-368 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,31]]},"reference":[{"key":"ref_1","unstructured":"(2025, October 26). Foodborne Diseases Estimates. Available online: https:\/\/www.who.int\/data\/gho\/data\/themes\/who-estimates-of-the-global-burden-of-foodborne-diseases."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"941","DOI":"10.3201\/eid2106.140999","article-title":"Global Burden of Invasive Nontyphoidal Salmonella Disease, 2010","volume":"21","author":"Ao","year":"2015","journal-title":"Emerg. Infect. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1312","DOI":"10.1016\/S1473-3099(19)30418-9","article-title":"The Global Burden of Non-Typhoidal Salmonella Invasive Disease: A Systematic Analysis for the Global Burden of Disease Study 2017","volume":"19","author":"Stanaway","year":"2019","journal-title":"Lancet Infect. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2489","DOI":"10.1016\/S0140-6736(11)61752-2","article-title":"Invasive Non-Typhoidal Salmonella Disease: An Emerging and Neglected Tropical Disease in Africa","volume":"379","author":"Feasey","year":"2012","journal-title":"Lancet"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1128\/CMR.00006-15","article-title":"Global Epidemiology of Campylobacter Infection","volume":"28","author":"Kaakoush","year":"2015","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_6","unstructured":"Erkmen, O., and Bozoglu, T.F. (2016). Foodborne Invasive Infections. Food Microbiology Principles into Practice. Volume 1: Microorganisms Related to Foods, Foodborne Diseases and Food Spoilage, Wiley."},{"key":"ref_7","first-page":"69","article-title":"The Value of Plants Used in Traditional Medicine for Drug Discovery","volume":"109","author":"Fabricant","year":"2001","journal-title":"Environ. Health Perspect."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"127","DOI":"10.4081\/jphia.2011.e30","article-title":"Prevalence of Gastrointestinal Pathogens in Sub-Saharan Africa: Systematic Review and Meta-Analysis","volume":"2","author":"Fletcher","year":"2011","journal-title":"J. Public Health Afr."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Leonard, D. (2016). Gastrointestinal Infections. Molecular Pathology in Clinical Practice, Springer.","DOI":"10.1007\/978-3-319-19674-9"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Duda-Madej, A., Viscardi, S., Stecko, J., Szyma\u0144ska, N., Topola, E., Pacyga, K., and Szandruk-Bender, M. (2025). Can Nature Overcome Invasive Gastrointestinal Infections?. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26125795"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"143","DOI":"10.3201\/eid1401.070524","article-title":"Short- and Long-Term Effects of Bacterial Gastrointestinal Infections","volume":"14","author":"Ternhag","year":"2008","journal-title":"Emerg. Infect. Dis."},{"key":"ref_12","unstructured":"Fischer, G., Hashmi, M., and Paterek, E. (2005). Campylobacter Infection. StatPearls [Internet], StatPearls Publishing."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"105265","DOI":"10.1016\/j.micpath.2021.105265","article-title":"Virulence Factors of Foodborne Pathogen Campylobacter Jejuni","volume":"161","author":"Lopes","year":"2021","journal-title":"Microb. Pathog."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"786","DOI":"10.4315\/0362-028X-73.4.786","article-title":"An Overview of Methods Used to Clarify Pathogenesis Mechanisms of Campylobacter Jejuni","volume":"73","author":"Haddad","year":"2010","journal-title":"J. Food Prot."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1111\/j.1472-765X.2005.01694.x","article-title":"Persistence of Campylobacter jejuni on Surfaces in a Processing Environment and on Cutting Boards","volume":"40","author":"Cools","year":"2005","journal-title":"Lett. Appl. Microbiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1542\/pir.2017-0285","article-title":"Campylobacter Infections in Children","volume":"39","author":"Same","year":"2018","journal-title":"Pediatr. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e63309","DOI":"10.3897\/fmj.2.63309","article-title":"A Ready-to-Use Dose-Response Model of Campylobacter jejuni Implemented in the FSKX-Standard","volume":"2","author":"Sundermann","year":"2021","journal-title":"Food Model. J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1097\/QCO.0000000000000364","article-title":"Campylobacter jejuni and Associated Immune Mechanisms: Short-Term Effects and Long-Term Implications for Infants in Low Income Countries","volume":"30","author":"Schnee","year":"2017","journal-title":"Curr. Opin. Infect. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"G1","DOI":"10.1152\/ajpgi.00193.2009","article-title":"A Role for Campylobacter Jejuni-Induced Enteritis in Inflammatory Bowel Disease?","volume":"298","author":"Kalischuk","year":"2010","journal-title":"Am. J. Physiol.\u2014Gastrointest. Liver Physiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"102841","DOI":"10.1016\/j.eclinm.2024.102841","article-title":"The Epidemiology and Impact of Persistent Campylobacter Infections on Childhood Growth among Children 0\u201324 Months of Age in Resource-Limited Settings","volume":"76","author":"Schiaffino","year":"2024","journal-title":"eClinicalMedicine"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Heimesaat, M.M., Backert, S., Alter, T., and Bereswill, S. (2023). Molecular Targets in Campylobacter Infections. Biomolecules, 13.","DOI":"10.3390\/biom13030409"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.ebiom.2016.12.006","article-title":"Factors Associated with Sequelae of Campylobacter and Non-Typhoidal Salmonella Infections: A Systematic Review","volume":"15","author":"Esan","year":"2017","journal-title":"EBioMedicine"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Omarova, S., Awad, K., Moos, V., P\u00fcning, C., G\u00f6lz, G., Schulzke, J.D., and B\u00fccker, R. (2023). Intestinal Barrier in Post-Campylobacter jejuni Irritable Bowel Syndrome. Biomolecules, 13.","DOI":"10.3390\/biom13030449"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1053\/j.gastro.2009.04.001","article-title":"Increased Short- and Long-Term Risk of Inflammatory Bowel Disease After Salmonella or Campylobacter Gastroenteritis","volume":"137","author":"Gradel","year":"2009","journal-title":"Gastroenterology"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Finsterer, J. (2022). Triggers of Guillain\u2013Barr\u00e9 Syndrome: Campylobacter jejuni Predominates. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232214222"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1177\/0883073808325649","article-title":"Association of Campylobacter jejuni Infection with Childhood Guillain-Barr\u00e9 Syndrome: A Case-Control Study","volume":"24","author":"Kalra","year":"2009","journal-title":"J. Child Neurol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2080","DOI":"10.1016\/j.chom.2024.11.006","article-title":"Campylobacter Jejuni-Derived Cytolethal Distending Toxin Promotes Colorectal Cancer Metastasis","volume":"32","author":"He","year":"2024","journal-title":"Cell Host Microbe"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4","DOI":"10.4103\/wjcs.wjcs_19_22","article-title":"Campylobacter jejuni Causes Colorectal Cancer","volume":"11","author":"Gervaz","year":"2022","journal-title":"World J. Color. Surg."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Huang, G., Boesze-Battaglia, K., Walker, L.P., Zekavat, A., Schaefer, Z.P., Blanke, S.R., and Shenker, B.J. (2021). The Active Subunit of the Cytolethal Distending Toxin, CdtB, Derived From Both Haemophilus ducreyi and Campylobacter jejuni Exhibits Potent Phosphatidylinositol-3,4,5-Triphosphate Phosphatase Activity. Front. Cell. Infect. Microbiol., 11.","DOI":"10.3389\/fcimb.2021.664221"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1056\/NEJMoa031887","article-title":"Immunoproliferative Small Intestinal Disease Associated with Campylobacter jejuni","volume":"350","author":"Lecuit","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_31","first-page":"93","article-title":"Biofilms of Salmonella and Campylobacter in the Poultry Industry","volume":"15","author":"Rossi","year":"2017","journal-title":"Poult. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Whelan, M.V.X., Simpson, J.C., and Cr\u00f3in\u00edn, T.\u00d3. (2021). A Novel High-Content Screening Approach for the Elucidation of C. jejuni Biofilm Composition and Integrity. BMC Microbiol., 21.","DOI":"10.1186\/s12866-020-02062-5"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"10409","DOI":"10.1007\/s00253-020-10974-5","article-title":"Campylobacter Sp.: Pathogenicity Factors and Prevention Methods\u2014New Molecular Targets for Innovative Antivirulence Drugs?","volume":"104","author":"Kreling","year":"2020","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Tram, G., Day, C.J., and Korolik, V. (2020). Bridging the Gap: A Role for Campylobacter jejuni Biofilms. Microorganisms, 8.","DOI":"10.3390\/microorganisms8030452"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2725","DOI":"10.1007\/s00253-023-12456-w","article-title":"Campylobacter jejuni: Targeting Host Cells, Adhesion, Invasion, and Survival","volume":"107","author":"Kemper","year":"2023","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4","DOI":"10.3390\/biom12040521","article-title":"Campylobacter jejuni Serine Protease HtrA Induces Paracellular Transmigration of Microbiota across Polarized Intestinal Epithelial Cells","volume":"12","author":"Sharafutdinov","year":"2022","journal-title":"Biomolecules"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Sharafutdinov, I., Tegtmeyer, N., Rohde, M., Olofsson, A., Rehman, Z.U., Arnqvist, A., and Backert, S. (2024). Campylobacter jejuni Surface-Bound Protease HtrA, but Not the Secreted Protease nor Protease in Shed Membrane Vesicles, Disrupts Epithelial Cell-to-Cell Junctions. Cells, 13.","DOI":"10.3390\/cells13030224"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Sharafutdinov, I., Linz, B., Tegtmeyer, N., and Backert, S. (2025). Therapeutic and Protective Approaches to Combat Campylobacter jejuni Infections. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1572616"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1007\/BF02818693","article-title":"Antimicrobial Activity of Berberine\u2014A Constituent of Mahonia Aquifolium","volume":"47","year":"2002","journal-title":"Folia Microbiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"277","DOI":"10.2131\/jts.36.277","article-title":"The Mechanism of Action of Sanguinarine against Methicillin-Resistant Staphylococcus Aureus","volume":"36","author":"Kang","year":"2011","journal-title":"J. Toxicol. Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1016\/j.jep.2012.11.039","article-title":"Anti-Cancer, Anti-Inflammatory and Anti-Microbial Activities of Plant Extracts Used against Hematological Tumors in Traditional Medicine of Jordan","volume":"145","author":"Assaf","year":"2013","journal-title":"J. Ethnopharmacol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Li, X.L., Sun, Y.P., Wang, M., Wang, Z.B., and Kuang, H.X. (2024). Alkaloids in Chelidonium majus L.: A Review of Its Phytochemistry, Pharmacology and Toxicology. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1440979"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"36133","DOI":"10.1039\/C8RA06413J","article-title":"Inhibition of Biofilm Formation and Quorum Sensing Mediated Phenotypes by Berberine in Pseudomonas Aeruginosa and Salmonella Typhimurium","volume":"8","author":"Aswathanarayan","year":"2018","journal-title":"RSC Adv."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1080\/08927014.2021.1919649","article-title":"In Vitro Anti-Biofilm Efficacy of Sanguinarine against Carbapenem-Resistant Serratia Marcescens","volume":"37","author":"Fu","year":"2021","journal-title":"Biofouling"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Krzy\u017cek, P., Junka, A., S\u0142upski, W., Do\u0142owacka-J\u00f3\u017awiak, A., P\u0142achno, B., Sobiecka, A., Matkowski, A., Chodaczek, G., P\u0142usa, T., and Go\u015bciniak, G. (2021). Antibiofilm and Antimicrobial-Enhancing Activity of Chelidonium Majus and Corydalis Cheilanthifolia Extracts. Pathogens, 10.","DOI":"10.3390\/pathogens10081033"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1089\/mdr.2020.0207","article-title":"Antimicrobial and Antibiofilm Activities and Mechanism of Action of Chelerythrine Against Carbapenem-Resistant Serratia Marcescens In Vitro","volume":"27","author":"Qian","year":"2021","journal-title":"Microb. Drug Resist."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.canlet.2003.09.002","article-title":"The Anti-Inflammatory Potential of Berberine in Vitro and in Vivo","volume":"203","author":"Kuo","year":"2004","journal-title":"Cancer Lett."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1016\/j.ejphar.2012.05.039","article-title":"The Anti-Inflammatory Effects of Sanguinarine and Its Modulation of Inflammatory Mediators from Peritoneal Macrophages","volume":"689","author":"Niu","year":"2012","journal-title":"Eur. J. Pharmacol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.cbi.2013.11.011","article-title":"Protective Effect of Chelerythrine against Ethanol-Induced Gastric Ulcer in Mice","volume":"208","author":"Li","year":"2014","journal-title":"Chem. Biol. Interact."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"400","DOI":"10.5114\/ceji.2015.54607","article-title":"Evaluation of Anti-Inflammatory and Analgesic Activities of Extracts from Herb of Chelidonium majus L.","volume":"40","author":"Mikolajczak","year":"2015","journal-title":"Cent. Eur. J. Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"154314","DOI":"10.1016\/j.phymed.2022.154314","article-title":"Improvement of Anticancer Effect of Berberine by Salt Formation Modifications","volume":"104","author":"Xu","year":"2022","journal-title":"Phytomedicine"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"933","DOI":"10.4155\/fmc-2017-0041","article-title":"Anticancer Potential of Sanguinarine for Various Human Malignancies","volume":"9","author":"Achkar","year":"2017","journal-title":"Future Med. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1248\/bpb.b17-00451","article-title":"Chelerythrine Inhibits Human Hepatocellular Carcinoma Metastasis in Vitro","volume":"41","author":"Zhu","year":"2018","journal-title":"Biol. Pharm. Bull."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1016\/j.jep.2016.06.056","article-title":"Chelidonium Majus Crude Extract Inhibits Migration and Induces Cell Cycle Arrest and Apoptosis in Tumor Cell Lines","volume":"190","author":"Deljanin","year":"2016","journal-title":"J. Ethnopharmacol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1602","DOI":"10.1093\/infdis\/jir147","article-title":"Berberine Ameliorates Intestinal Epithelial Tight-Junction Damage and down-Regulates Myosin Light Chain Kinase Pathways in a Mouse Model of Endotoxinemia","volume":"203","author":"Gu","year":"2011","journal-title":"J. Infect. Dis."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ejps.2010.02.001","article-title":"Berberine Attenuates Pro-Inflammatory Cytokine-Induced Tight Junction Disruption in an in Vitro Model of Intestinal Epithelial Cells","volume":"40","author":"Li","year":"2010","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Peng, J., Li, H., Olaolu, O.A., Ibrahim, S., Ibrahim, S., and Wang, S. (2023). Natural Products: A Dependable Source of Therapeutic Alternatives for Inflammatory Bowel Disease through Regulation of Tight Junctions. Molecules, 28.","DOI":"10.3390\/molecules28176293"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Cao, M., Wang, P., Sun, C., He, W., and Wang, F. (2013). Amelioration of IFN-\u03b3 and TNF-\u03b1-Induced Intestinal Epithelial Barrier Dysfunction by Berberine via Suppression of MLCK-MLC Phosphorylation Signaling Pathway. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0061944"},{"key":"ref_59","unstructured":"National Center for Biotechnology Information (2025, October 24). PubChem Compound Summary for CID 5154, Sanguinarine, Available online: https:\/\/pubchem.ncbi.nlm.nih.gov\/compound\/sanguinarine."},{"key":"ref_60","unstructured":"National Center for Biotechnology Information (2025, October 24). PubChem Compound Summary for CID 2703, Chelerythrine, Available online: https:\/\/pubchem.ncbi.nlm.nih.gov\/compound\/chelerythrine."},{"key":"ref_61","unstructured":"National Center for Biotechnology Information (2025, October 24). PubChem Compound Summary for CID 2353, Berberine, Available online: https:\/\/pubchem.ncbi.nlm.nih.gov\/compound\/berberine."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Ekor, M. (2014). The Growing Use of Herbal Medicines: Issues Relating to Adverse Reactions and Challenges in Monitoring Safety. Front. Neurol., 4.","DOI":"10.3389\/fphar.2013.00177"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1021\/acs.jnatprod.9b01285","article-title":"Natural Products as Sources of New Drugs over the Nearly Four Decades from 01\/1981 to 09\/2019","volume":"83","author":"Newman","year":"2020","journal-title":"J. Nat. Prod."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.mayocpiqo.2023.08.005","article-title":"The Burden of Chronic Disease","volume":"8","author":"Hacker","year":"2024","journal-title":"Mayo Clin. Proc. Innov. Qual. Outcomes"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"E15","DOI":"10.5888\/pcd22.240539","article-title":"Trends in Multiple Chronic Conditions Among US Adults, By Life Stage, Behavioral Risk Factor Surveillance System, 2013\u20132023","volume":"22","author":"Watson","year":"2025","journal-title":"Prev. Chronic. Dis."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"E14","DOI":"10.5888\/pcd21.230267","article-title":"Chronic Disease Prevalence in the US: Sociodemographic and Geographic Variations by Zip Code Tabulation Area","volume":"21","author":"Benavidez","year":"2024","journal-title":"Prev. Chronic. Dis."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1177\/153473540200100313","article-title":"Integration of Herbal Medicine into Modern Medical Practices: Issues and Prospects","volume":"1","author":"Fong","year":"2002","journal-title":"Integr. Cancer Ther."},{"key":"ref_68","first-page":"180","article-title":"Mini Review Global Integration of Traditional and Modern Medicine: Policy Developments, Regulatory Frameworks, and Clinical Integration Model","volume":"4","author":"Thamizhoviya","year":"2025","journal-title":"Future Integr. Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"289264","DOI":"10.1155\/2014\/289264","article-title":"Antioxidant and Anti-Inflammatory Activities of Berberine in the Treatment of Diabetes Mellitus","volume":"2014","author":"Li","year":"2014","journal-title":"Evid. Based Complement. Alternat. Med."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Cheng, Z., Kang, C., Che, S., Su, J., Sun, Q., Ge, T., Guo, Y., Lv, J., Sun, Z., and Yang, W. (2022). Berberine: A Promising Treatment for Neurodegenerative Diseases. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.845591"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1016\/j.pharep.2015.03.002","article-title":"Berberine and Neurodegeneration: A Review of Literature","volume":"67","author":"Ahmed","year":"2015","journal-title":"Pharmacol. Rep."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Duda-Madej, A., Viscardi, S., Szewczyk, W., and Topola, E. (2024). Natural Alkaloids in Cancer Therapy: Berberine, Sanguinarine and Chelerythrine against Colorectal and Gastric Cancer. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25158375"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Duda-Madej, A., Lipska, P., Viscardi, S., Bazan, H., and Sobieraj, J. (2025). Targeting Skin Neoplasms: A Review of Berberine\u2019s Anticancer Properties. Cells, 14.","DOI":"10.3390\/cells14141041"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Pacyga, K., Pacyga, P., Topola, E., Viscardi, S., and Duda-Madej, A. (2024). Bioactive Compounds from Plant Origin as Natural Antimicrobial Agents for the Treatment of Wound Infections. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25042100"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Wu, S., Yang, K., Hong, Y., Gong, Y., Ni, J., Yang, N., and Ding, W. (2022). A New Perspective on the Antimicrobial Mechanism of Berberine Hydrochloride Against Staphylococcus Aureus Revealed by Untargeted Metabolomic Studies. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.917414"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"512947","DOI":"10.1155\/2015\/512947","article-title":"Effects of Hangeshashinto on Growth of Oral Microorganisms","volume":"2015","author":"Fukamachi","year":"2015","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"100436","DOI":"10.1016\/j.microb.2025.100436","article-title":"A Comprehensive Review on Biofilm-Associated Infections: Mechanisms, Diagnostic Challenges, and Innovative Therapeutic Strategies","volume":"8","author":"Grari","year":"2025","journal-title":"Microbe"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Krzy\u017cek, P. (2024). What Is a Biofilm? Lessons Learned from Interactions with Immune Cells. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms252111684"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1016\/j.tim.2020.03.016","article-title":"Biofilm Matrixome: Extracellular Components in Structured Microbial Communities","volume":"28","author":"Karygianni","year":"2020","journal-title":"Trends Microbiol."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Ma, L., Feng, J., Zhang, J., and Lu, X. (2022). Campylobacter Biofilms. Microbiol. Res., 264.","DOI":"10.1016\/j.micres.2022.127149"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Elgamoudi, B.A., and Korolik, V. (2021). Campylobacter Biofilms: Potential of Natural Compounds to Disrupt Campylobacter jejuni Transmission. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222212159"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Duda-Madej, A., Viscardi, S., Bazan, H., and Sobieraj, J. (2025). Exploring the Role of Berberine as a Molecular Disruptor in Antimicrobial Strategies. Pharmaceuticals, 18.","DOI":"10.3390\/ph18070947"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Veronese, P., and Dodi, I. (2024). Campylobacter jejuni\/Coli Infection: Is It Still a Concern?. Microorganisms, 12.","DOI":"10.3390\/microorganisms12122669"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1690","DOI":"10.1128\/IAI.06176-11","article-title":"Increase in Campylobacter jejuni Invasion of Intestinal Epithelial Cells under Low-Oxygen Coculture Conditions That Reflect the in Vivo Environment","volume":"80","author":"Mills","year":"2012","journal-title":"Infect. Immun."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Watson, R.O., and Gal\u00e1n, J.E. (2008). Campylobacter jejuni Survives within Epithelial Cells by Avoiding Delivery to Lysosomes. PLoS Pathog., 4.","DOI":"10.1371\/journal.ppat.0040014"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1556\/EuJMI.3.2013.3.3","article-title":"Extracellular Secretion of Protease HtrA from Campylobacter jejuni Is Highly Efficient and Independent of Its Protease Activity and Flagellum","volume":"3","author":"Boehm","year":"2013","journal-title":"Eur. J. Microbiol. Immunol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1556\/EuJMI-D-15-00003","article-title":"Campylobacter jejuni Serine Protease HtrA Plays an Important Role in Heat Tolerance, Oxygen Resistance, Host Cell Adhesion, Invasion, and Transmigration","volume":"5","author":"Boehm","year":"2015","journal-title":"Eur. J. Microbiol. Immunol."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Lobo de S\u00e1, F.D., Heimesaat, M.M., Bereswill, S., Nattramilarasu, P.K., Schulzke, J.D., and B\u00fccker, R. (2021). Resveratrol Prevents Campylobacter jejuni\u2014Induced Leaky Gut by Restoring Occludin and Claudin-5 in the Paracellular Leak Pathway. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.640572"},{"key":"ref_89","first-page":"20","article-title":"The Impact of Permeability Enhancers on Assessment for Monolayer of Colon Adenocarcinoma Cell Line (Caco-2) Used in in Vitro Permeability Assay","volume":"3","author":"Rastogi","year":"2013","journal-title":"J. Drug Deliv. Ther."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"5407","DOI":"10.1016\/j.psj.2020.08.014","article-title":"Campylobacter jejuni Increases the Paracellular Permeability of Broiler Chickens in a Dose-Dependent Manner","volume":"99","author":"Awad","year":"2020","journal-title":"Poult. Sci."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1177\/1753425914521648","article-title":"Campylobacter Infection in Chickens Modulates the Intestinal Epithelial Barrier Function","volume":"21","author":"Awad","year":"2015","journal-title":"Innate Immun."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"7345","DOI":"10.3748\/wjg.14.7345","article-title":"Disruption of Colonic Barrier Function and Induction of Mediator Release by Strains of Campylobacter jejuni That Invade Epithelial Cells","volume":"14","author":"Beltinger","year":"2008","journal-title":"World J. Gastroenterol."},{"key":"ref_93","unstructured":"(2025, May 12). Campylobacter. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/campylobacter."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Zhang, L., Wu, X., Yang, R., Chen, F., Liao, Y., Zhu, Z., Wu, Z., Sun, X., and Wang, L. (2021). Effects of Berberine on the Gastrointestinal Microbiota. Front. Cell. Infect. Microbiol., 10.","DOI":"10.3389\/fcimb.2020.588517"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"117865","DOI":"10.1016\/j.envpol.2021.117865","article-title":"Berberine Improves Intestinal Barrier Function and Reduces Inflammation, Immunosuppression, and Oxidative Stress by Regulating the NF-\u039aB\/MAPK Signaling Pathway in Deoxynivalenol-Challenged Piglets","volume":"289","author":"Tang","year":"2021","journal-title":"Environ. Pollut."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4196\/kjpp.2015.19.1.1","article-title":"Berberine Prevents Intestinal Mucosal Barrier Damage during Early Phase of Sepsis in Rat through the Toll-like Receptors Signaling Pathway","volume":"19","author":"Li","year":"2015","journal-title":"Korean J. Physiol. Pharmacol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1882","DOI":"10.1002\/ptr.8077","article-title":"Anti-Inflammatory, Antioxidant, and Immunomodulatory Effects of Berberis Vulgaris and Its Constituent Berberine, Experimental and Clinical, a Review","volume":"38","author":"Shakeri","year":"2024","journal-title":"Phyther. Res."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Jael Teresa de Jes\u00fas, Q.V., G\u00e1lvez-Ru\u00edz, J.C., M\u00e1rquez Ibarra, A.A., and Leyva-Peralta, M.A. (2025). Perspectives on Berberine and the Regulation of Gut Microbiota: As an Anti-Inflammatory Agent. Pharmaceuticals, 18.","DOI":"10.3390\/ph18020193"},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Wolf, P.G., Devendran, S., Doden, H.L., Ly, L.K., Moore, T., Takei, H., Nittono, H., Murai, T., Kurosawa, T., and Chlipala, G.E. (2021). Berberine Alters Gut Microbial Function through Modulation of Bile Acids. BMC Microbiol., 21.","DOI":"10.1186\/s12866-020-02020-1"},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Guo, Y., Zhang, Y.C., Huang, W.H., Selwyn, F.P., and Klaassen, C.D. (2016). Dose-Response Effect of Berberine on Bile Acid Profile and Gut Microbiota in Mice. BMC Complement. Altern. Med., 16.","DOI":"10.1186\/s12906-016-1367-7"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"7417","DOI":"10.1128\/JB.187.21.7417-7424.2005","article-title":"Bile Salts Modulate Expression of the CmeABC Multidrug Efflux Pump in Campylobacter jejuni","volume":"187","author":"Lin","year":"2005","journal-title":"J. Bacteriol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1042\/CS20220697","article-title":"Biological Tuners to Reshape the Bile Acid Pool for Therapeutic Purposes in Non-Alcoholic Fatty Liver Disease","volume":"137","author":"Gillard","year":"2023","journal-title":"Clin. Sci."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1124\/mol.116.106617","article-title":"Orally Administered Berberine Modulates Hepatic Lipid Metabolism by Altering Microbial Bile Acid Metabolism and the Intestinal FXR Signaling Pathway","volume":"91","author":"Sun","year":"2017","journal-title":"Mol. Pharmacol."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Liu, X., Wang, L., Tan, S., Chen, Z., Wu, B., and Wu, X. (2022). Therapeutic Effects of Berberine on Liver Fibrosis Are Associated With Lipid Metabolism and Intestinal Flora. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.814871"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"15","DOI":"10.2147\/JIR.S436653","article-title":"Protective Effect of Berberine on Acute Gastric Ulcer by Promotion of Tricarboxylic Acid Cycle-Mediated Arachidonic Acid Metabolism","volume":"17","author":"Guo","year":"2024","journal-title":"J. Inflamm. Res."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"2064","DOI":"10.1124\/dmd.106.011361","article-title":"Pharmacokinetics of Berberine and Its Main Metabolites in Conventional and Pseudo Germ-Free Rats Determined by Liquid Chromatography\/Ion Trap Mass Spectrometry","volume":"34","author":"Zuo","year":"2006","journal-title":"Drug Metab. Dispos."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.jconrel.2016.12.042","article-title":"Liposome Encapsulated Berberine Treatment Attenuates Cardiac Dysfunction after Myocardial Infarction","volume":"247","author":"Allijn","year":"2017","journal-title":"J. Control. Release"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1981","DOI":"10.1038\/s41467-019-09852-0","article-title":"Liver-Target Nanotechnology Facilitates Berberine to Ameliorate Cardio-Metabolic Diseases","volume":"10","author":"Guo","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Dewanjee, S., Chakraborty, P., Mukherjee, B., and De Feo, V. (2020). Plant-Based Antidiabetic Nanoformulations: The Emerging Paradigm for Effective Therapy. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21062217"},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Mbese, Z., Khwaza, V., and Aderibigbe, B.A. (2019). Curcumin and Its Derivatives as Potential Therapeutic Agents in Prostate, Colon and Breast Cancers. Molecules, 24.","DOI":"10.3390\/molecules24234386"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"112910","DOI":"10.1016\/j.ejmech.2020.112910","article-title":"Structure-Guided Modification of Isoxazole-Type FXR Agonists: Identification of a Potent and Orally Bioavailable FXR Modulator","volume":"209","author":"Luo","year":"2021","journal-title":"Eur. J. Med. Chem."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1696","DOI":"10.1021\/acsinfecdis.4c00045","article-title":"Targeting Intracellular Bacteria with Dual Drug-Loaded Lactoferrin Nanoparticles","volume":"10","author":"Andima","year":"2024","journal-title":"ACS Infect. Dis."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.dmpk.2017.11.003","article-title":"Organ\/Body-on-a-Chip Based on Microfluidic Technology for Drug Discovery","volume":"33","author":"Kimura","year":"2018","journal-title":"Drug Metab. Pharmacokinet."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1186\/s13321-016-0162-2","article-title":"Computational Methods for Prediction of in Vitro Effects of New Chemical Structures","volume":"8","author":"Banerjee","year":"2016","journal-title":"J. Cheminform."},{"key":"ref_115","first-page":"50767","article-title":"Anticancer Metal Complexes: Synthesis and Cytotoxicity Evaluation by the MTT Assay","volume":"1\u20136","author":"Ganot","year":"2013","journal-title":"J. Vis. Exp."},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Pires, C.L., Pra\u00e7a, C., Martins, P.A.T., Batista de Carvalho, A.L.M., Ferreira, L., Marques, M.P.M., and Moreno, M.J. (2021). Re-Use of Caco-2 Monolayers in Permeability Assays\u2014Validation Regarding Cell Monolayer Integrity. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13101563"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/21\/10634\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T05:28:48Z","timestamp":1762234128000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/21\/10634"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,31]]},"references-count":116,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["ijms262110634"],"URL":"https:\/\/doi.org\/10.3390\/ijms262110634","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,31]]}}}