{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T06:06:50Z","timestamp":1790662010274,"version":"4.1.0"},"reference-count":45,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,11,21]],"date-time":"2023-11-21T00:00:00Z","timestamp":1700524800000},"content-version":"vor","delay-in-days":324,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BioMed Research International"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:p><jats:italic>Introduction<\/jats:italic>. <jats:italic>Helicobacter pylori<\/jats:italic> (<jats:italic>H. pylori<\/jats:italic>) induces gastritis by stimulating Th17 cells and related cytokines. The aim of our study was to investigate the synergistic effect of metformin with amoxicillin as an antibiotic in inhibiting <jats:italic>H. pylori<\/jats:italic> and modulating the immune response in a rat model. <jats:italic>Methods<\/jats:italic>. Forty\u2010five male Sprague\u2010Dawley rats were divided into seven groups and infected with <jats:italic>H. pylori<\/jats:italic>. Over the course of 14 days, all animals were treated with metformin and amoxicillin alone and in combination. The antibacterial activity of metformin was evaluated by growth curves and colony counts. The immunoregulatory effect on Treg\/Th17 balance was assessed by flow cytometry, and the cytokine profile of IL\u201017A, IL\u20101<jats:italic>\u03b2<\/jats:italic>, IL\u20106, IL\u20108, TGF\u2010<jats:italic>\u03b2<\/jats:italic>, and IL\u201010 was determined by ELISA. The effect of metformin on gene expression of <jats:italic>cagA<\/jats:italic> and IL\u20108 was investigated by RT\u2010PCR. Pathological changes were assessed by hematoxylin and eosin (H&amp;E) staining and immunohistochemical (IHC) staining. <jats:italic>Results<\/jats:italic>. Metformin showed weak antibacterial activity against clinically isolated <jats:italic>H. pylori<\/jats:italic>. However, the combination of metformin and amoxicillin (AMX) showed strong synergistic antibacterial activity (<jats:italic>\u03a3<\/jats:italic>FIC = 0.24). Compared with AMX, metformin reduced inflammation and tissue damage but resulted in increased bacterial growth. During metformin administration, both TGF\u2010<jats:italic>\u03b2<\/jats:italic> levels and Treg cells increased dramatically (<jats:italic>P<\/jats:italic> = 0.002). In synergy with AMX, metformin decreased the effective dose of antibiotic to eradicate <jats:italic>H. pylori<\/jats:italic>. <jats:italic>Conclusions<\/jats:italic>. The combination of metformin with potential antibiotics such as AMX had a positive effect on the relief of <jats:italic>H. pylori<\/jats:italic>\u2010related inflammation by inducing Treg cells while successfully eliminating <jats:italic>H. pylori<\/jats:italic>.<\/jats:p>","DOI":"10.1155\/2023\/5583286","type":"journal-article","created":{"date-parts":[[2023,11,21]],"date-time":"2023-11-21T22:20:08Z","timestamp":1700605208000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Antibacterial and Immunoregulatory Effects of Metformin against <i>Helicobacter pylori<\/i> Infection in Rat Model"],"prefix":"10.1155","volume":"2023","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0473-8742","authenticated-orcid":false,"given":"Hassan","family":"Valadbeigi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5143-3178","authenticated-orcid":false,"given":"Saeed","family":"Khoshnood","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8742-9138","authenticated-orcid":false,"given":"Babak","family":"Negahdari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohd Azmuddin","family":"Abdullah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3387-9379","authenticated-orcid":false,"given":"Mohammad Hossein","family":"Haddadi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,11,21]]},"reference":[{"key":"e_1_2_9_1_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10120-019-00952-w"},{"key":"e_1_2_9_2_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0135858"},{"key":"e_1_2_9_3_2","first-page":"2393","article-title":"Metformin mitigates autoimmune insulitis by inhibiting Th1 and Th17 responses while promoting Treg production","volume":"11","author":"Duan W.","year":"2019","journal-title":"American Journal of Translational Research"},{"key":"e_1_2_9_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijtb.2018.04.003"},{"key":"e_1_2_9_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/advs.201902227"},{"key":"e_1_2_9_6_2","doi-asserted-by":"publisher","DOI":"10.2147\/CPAA.S297903"},{"key":"e_1_2_9_7_2","doi-asserted-by":"publisher","DOI":"10.15414\/jmbfs.4232"},{"key":"e_1_2_9_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12275-022-2130-z"},{"key":"e_1_2_9_9_2","doi-asserted-by":"publisher","DOI":"10.2217\/fmb-2018-0184"},{"key":"e_1_2_9_10_2","first-page":"595","article-title":"Cellular immunity induced by H. pylori vaccine with chitosan as adjuvant","volume":"23","author":"Gong Y.","year":"2007","journal-title":"Xi bao yu fen zi Mian yi xue za zhi= Chinese Journal of Cellular and Molecular Immunology"},{"key":"e_1_2_9_11_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2009.11.043"},{"key":"e_1_2_9_12_2","doi-asserted-by":"publisher","DOI":"10.1097\/MPG.0000000000000194"},{"key":"e_1_2_9_13_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2249.2003.02177.x"},{"key":"e_1_2_9_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-019-06041-3"},{"key":"e_1_2_9_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.meegid.2018.02.020"},{"key":"e_1_2_9_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micpath.2018.01.040"},{"key":"e_1_2_9_17_2","doi-asserted-by":"publisher","DOI":"10.1080\/00365529850170991"},{"key":"e_1_2_9_18_2","doi-asserted-by":"publisher","DOI":"10.1186\/1476-511X-13-115"},{"key":"e_1_2_9_19_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00380-008-1137-7"},{"key":"e_1_2_9_20_2","doi-asserted-by":"publisher","DOI":"10.1039\/C8RA08204A"},{"key":"e_1_2_9_21_2","doi-asserted-by":"publisher","DOI":"10.1080\/13813455.2018.1461233"},{"key":"e_1_2_9_22_2","doi-asserted-by":"publisher","DOI":"10.1055\/a-1031-7328"},{"key":"e_1_2_9_23_2","doi-asserted-by":"publisher","DOI":"10.1097\/00000478-199610000-00001"},{"key":"e_1_2_9_24_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12275-021-1136-2"},{"key":"e_1_2_9_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00363-19"},{"key":"e_1_2_9_26_2","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics11020162"},{"key":"e_1_2_9_27_2","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms10010124"},{"key":"e_1_2_9_28_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12866-021-02291-2"},{"key":"e_1_2_9_29_2","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27144559"},{"key":"e_1_2_9_30_2","article-title":"Synergistic benefits: exploring the anti-virulence effects of metformin\/vildagliptin antidiabetic combination against Pseudomonas aeruginosa via controlling quorum sensing systems","volume":"11","author":"Khayat M. 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