{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T08:47:49Z","timestamp":1790758069608,"version":"4.1.0"},"reference-count":46,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,5,15]],"date-time":"2021-05-15T00:00:00Z","timestamp":1621036800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005888","name":"Uniwersytet Medyczny w Lodzi","doi-asserted-by":"publisher","award":["503\/1-156-04\/503-11-001-19-00"],"award-info":[{"award-number":["503\/1-156-04\/503-11-001-19-00"]}],"id":[{"id":"10.13039\/501100005888","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005888","name":"Uniwersytet Medyczny w Lodzi","doi-asserted-by":"publisher","award":["502-03\/1-156-04\/502-14-339"],"award-info":[{"award-number":["502-03\/1-156-04\/502-14-339"]}],"id":[{"id":"10.13039\/501100005888","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004569","name":"Ministerstwo Nauki i Szkolnictwa Wy\u017cszego","doi-asserted-by":"publisher","award":["0202\/DIA\/2015\/44"],"award-info":[{"award-number":["0202\/DIA\/2015\/44"]}],"id":[{"id":"10.13039\/501100004569","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004569","name":"Ministerstwo Nauki i Szkolnictwa Wy\u017cszego","doi-asserted-by":"publisher","award":["IP2015 089474"],"award-info":[{"award-number":["IP2015 089474"]}],"id":[{"id":"10.13039\/501100004569","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Introduction: Adiponectin is a hormone secreted by adipocytes, which exhibits insulin-sensitizing and anti-inflammatory properties and acts through adiponectin receptors: AdipoR1 and AdipoR2. The aim of the study was to evaluate whether activation of adiponectin receptors AdipoR1 and AdipoR2 with an orally active agonist AdipoRon has gastroprotective effect and to investigate the possible underlying mechanism. Methods: We used two well-established mouse models of gastric ulcer (GU) induced by oral administration of EtOH (80% solution in water) or diclofenac (30 mg\/kg, p.o.). Gastroprotective effect of AdipoRon (dose 5 and 50 mg \/kg p.o) was compared to omeprazole (20 mg\/kg p.o.) or 5% DMSO solution (control). Clinical parameters of gastroprotection were assessed using macroscopic (gastric lesion area) and microscopic (evaluation of the gastric mucosa damage) scoring. To establish the molecular mechanism, we measured: myeloperoxidase (MPO), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) activities; glutathione (GSH) level; and IL-1\u03b2, adenosine monophosphate-activated protein kinase (AMPK), and phosphorylated AMPK expression in gastric tissue. Results: AdipoRon produced a gastroprotective effect in both GU mouse models as evidenced by significantly lower macroscopic and microscopic damage scores. AdipoRon exhibited anti-inflammatory effect by reduction in MPO activity and IL-1\u03b2 expression in the gastric tissue. Moreover, AdipoRon induced antioxidative action, as demonstrated with higher GSH levels, and increased SOD and GPX activity. Conclusions: Activation of AdipoR1 and AdipoR2 using AdipoRon reduced gastric lesions and enhanced cell response to oxidative stress. Our data suggest that AdipoR1 and AdipoR2 activation may be an attractive therapeutic strategy to inhibit development of gastric ulcers.<\/jats:p>","DOI":"10.3390\/molecules26102946","type":"journal-article","created":{"date-parts":[[2021,5,16]],"date-time":"2021-05-16T23:17:16Z","timestamp":1621207036000},"page":"2946","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["AdipoRon, an Orally Active, Synthetic Agonist of AdipoR1 and AdipoR2 Receptors Has Gastroprotective Effect in Experimentally Induced Gastric Ulcers in Mice"],"prefix":"10.3390","volume":"26","author":[{"given":"Hubert","family":"Zatorski","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Medical University of Lodz, 92-215 Lodz, Poland"},{"name":"Department of Digestive Tract Diseases, Medical University of Lodz, 93-281 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5917-8749","authenticated-orcid":false,"given":"Maciej","family":"Salaga","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Medical University of Lodz, 92-215 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Zieli\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Medical University of Lodz, 92-215 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kinga","family":"Majchrzak","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Medical University of Lodz, 92-215 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1173-2966","authenticated-orcid":false,"given":"Agata","family":"Binienda","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Medical University of Lodz, 92-215 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radzis\u0142aw","family":"Kordek","sequence":"additional","affiliation":[{"name":"Department of Pathology, Medical University of Lodz, 92-215 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1825-1807","authenticated-orcid":false,"given":"Ewa","family":"Ma\u0142ecka-Panas","sequence":"additional","affiliation":[{"name":"Department of Digestive Tract Diseases, Medical University of Lodz, 93-281 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8443-4417","authenticated-orcid":false,"given":"Jakub","family":"Fichna","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Medical University of Lodz, 92-215 Lodz, Poland"},{"name":"Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Mazowiecka 6\/8, 92-215 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1007\/s00210-017-1402-3","article-title":"Highly selective CB2 receptor agonist A836339 has gastroprotective effect on experimentally induced gastric ulcers in mice","volume":"390","author":"Salaga","year":"2017","journal-title":"Naunyn Schmiedebergs Arch. Pharmacol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"S58","DOI":"10.1097\/00004836-199001001-00011","article-title":"The role of endogenous free radical scavengers on tissue recovery in the experimental ulcer model","volume":"12","author":"Oshima","year":"1990","journal-title":"J. Clin. Gastroenterol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"S131","DOI":"10.1097\/00004836-199206001-00023","article-title":"Changes in superoxide dismutase activity in the gastric mucosa of peptic ulcer patients","volume":"14","author":"Naito","year":"1992","journal-title":"J. Clin. Gastroenterol."},{"key":"ref_4","first-page":"971","article-title":"Role of neutrophils in a rat model of gastric ulcer recurrence caused by interleukin-1\u03b2","volume":"150","author":"Watanabe","year":"1997","journal-title":"Am. J. Pathol."},{"key":"ref_5","first-page":"177","article-title":"Helicobacter pylori infection as a cause of gastritis, duodenal ulcer, gastric cancer and nonulcer dyspepsia: A systematic overview","volume":"150","author":"Sherman","year":"1994","journal-title":"CMAJ"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1688","DOI":"10.1016\/j.cgh.2014.03.021","article-title":"Measures of Adiposity Are Associated with Increased Risk of Peptic Ulcer","volume":"12","author":"Boylan","year":"2014","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1007\/s11695-007-9002-9","article-title":"Endoscopic and histologic findings of the foregut in 426 patients with morbid obesity","volume":"17","author":"Csendes","year":"2007","journal-title":"Obes. Surg."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1159\/000334680","article-title":"Is obesity a new risk factor for gastritis?","volume":"85","author":"Yamamoto","year":"2012","journal-title":"Digestion"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1896","DOI":"10.2174\/138161210791208893","article-title":"Adiponectin: A Key Player in Obesity Related Disorders","volume":"16","author":"Matsuzawa","year":"2010","journal-title":"Curr. Pharm. Des."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1159\/000510342","article-title":"Expression of AdipoR1 and AdipoR2 and Serum Level of Adiponectin in Gastric Cancer","volume":"7","author":"Kordafshari","year":"2020","journal-title":"Gastrointest. Tumors"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1756-9966-30-107","article-title":"Adiponectin receptor-1 expression is associated with good prognosis in gastric cancer","volume":"30","author":"Tsukada","year":"2011","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_12","unstructured":"(2021, May 11). Tissue expression of ADIPOR2-Summary-The Human Protein Atlas. Available online: https:\/\/www.proteinatlas.org\/ENSG00000006831-ADIPOR2\/tissue."},{"key":"ref_13","unstructured":"(2021, May 11). Tissue expression of ADIPOR1-Summary-The Human Protein Atlas. Available online: https:\/\/www.proteinatlas.org\/ENSG00000159346-ADIPOR1\/tissue."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/j.physbeh.2015.06.016","article-title":"High fat diet induced changes in gastric vagal afferent response to adiponectin","volume":"152","author":"Kentish","year":"2015","journal-title":"Physiol. Behav."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4028","DOI":"10.3748\/wjg.v24.i35.4028","article-title":"Adiponectin affects the mechanical responses in strips from the mouse gastric fundus","volume":"24","author":"Idrizaj","year":"2018","journal-title":"World J. Gastroenterol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"G591","DOI":"10.1152\/ajpgi.00269.2014","article-title":"Effects of obesity on severity of colitis and cytokine expression in mouse mesenteric fat. Potential role of adiponectin receptor 1","volume":"308","author":"Sideri","year":"2015","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Di Zazzo, E., Polito, R., Bartollino, S., Nigro, E., Porcile, C., Bianco, A., Daniele, A., and Moncharmont, B. (2019). Adiponectin as link factor between adipose tissue and cancer. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20040839"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2461","DOI":"10.1074\/jbc.M209033200","article-title":"Globular adiponectin protected ob\/ob mice from diabetes and ApoE-deficient mice from atherosclerosis","volume":"278","author":"Yamauchi","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.cmet.2004.12.003","article-title":"AMP-activated protein kinase: Ancient energy gauge provides clues to modern understanding of metabolism","volume":"1","author":"Kahn","year":"2005","journal-title":"Cell Metab."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.1038\/nm788","article-title":"Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase","volume":"8","author":"Yamauchi","year":"2002","journal-title":"Nat. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1177\/0022034518818449","article-title":"An Adiponectin Receptor Agonist Reduces Type 2 Diabetic Periodontitis","volume":"98","author":"Wu","year":"2019","journal-title":"J. Dent. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/nature12656","article-title":"A small-molecule AdipoR agonist for type 2 diabetes and short life in obesity","volume":"503","author":"Yamauchi","year":"2013","journal-title":"Nature"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"E275","DOI":"10.1152\/ajpendo.00577.2014","article-title":"AdipoRon, the first orally active adiponectin receptor activator, attenuates postischemic myocardial apoptosis through both AMPK-mediated and AMPK-independent signalings","volume":"309","author":"Zhang","year":"2015","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1093\/aje\/kwj129","article-title":"Peptic ulcer disease in a general adult population: The kalixanda study: A random population-based study","volume":"163","author":"Aro","year":"2006","journal-title":"Am. J. Epidemiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1038\/nature01705","article-title":"Cloning of adiponectin receptors that mediate antidiabetic metabolic effects","volume":"423","author":"Yamauchi","year":"2003","journal-title":"Nature"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/ncpcardio1398","article-title":"Protective vascular and myocardial effects of adiponectin","volume":"6","author":"Goldstein","year":"2009","journal-title":"Nat. Clin. Pract. Cardiovasc. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"9534","DOI":"10.3390\/molecules16119534","article-title":"The effects of combined adiponectin-metformin on glucose and lipids levels in mice and acute toxicity and anti-ulcerogenic activity of adiponectin against ethanol-induced gastric mucosal injuries in rat","volume":"16","author":"Fard","year":"2011","journal-title":"Molecules"},{"key":"ref_28","first-page":"G773","article-title":"Protective role of adiponectin against ethanol-induced gastric injury in mice","volume":"302","author":"Yamamoto","year":"2012","journal-title":"Am. J. Physiol. Liver Physiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.jtcme.2018.05.001","article-title":"Protective activity of geraniol against acetic acid and Helicobacter pylori- induced gastric ulcers in rats","volume":"9","author":"Bhattamisra","year":"2019","journal-title":"J. Tradit. Complement. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"38","DOI":"10.2165\/00003088-199120010-00003","article-title":"Clinical Pharmacology of Omeprazole","volume":"20","author":"Howden","year":"1991","journal-title":"Clin. Pharmacokinet."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Ng, R.C.L., Jian, M., Ma, O.K.F., Bunting, M., Kwan, J.S.C., Zhou, G.J., Senthilkumar, K., Iyaswamy, A., Chan, P.K., and Li, M. (2020). Chronic oral administration of adipoRon reverses cognitive impairments and ameliorates neuropathology in an Alzheimer\u2019s disease mouse model. Mol. Psychiatry, 1\u201321.","DOI":"10.1038\/s41380-020-0701-0"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.pharep.2018.10.011","article-title":"High activity of endogenous opioid system protects against gastric damage development in mouse models of gastric mucosal injury","volume":"71","author":"Zatorski","year":"2019","journal-title":"Pharm. Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1177\/0748233710397421","article-title":"Gastroprotective effect of small centaury (Centaurium erythraea L) on aspirin-induced gastric damage in rats","volume":"27","author":"Tuluce","year":"2011","journal-title":"Toxicol. Ind. Health"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/j.jep.2013.01.015","article-title":"Gastroprotective activity of ethanolic root extract of Potentilla fulgens Wall. ex Hook","volume":"146","author":"Laloo","year":"2013","journal-title":"J. Ethnopharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0003-9861(86)90526-6","article-title":"Biological effects of the superoxide radical","volume":"247","author":"Fridovich","year":"1986","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"18097","DOI":"10.1161\/JAHA.120.018097","article-title":"AdipoRon Attenuates Inflammation and Impairment of Cardiac Function Associated With Cardiopulmonary Bypass\u2013Induced Systemic Inflammatory Response Syndrome","volume":"10","author":"Jenke","year":"2021","journal-title":"J. Am. Heart Assoc."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1007\/s10157-020-01944-2","article-title":"AdipoRon, an adiponectin receptor agonist, protects contrast-induced nephropathy by suppressing oxidative stress and inflammation via activation of the AMPK pathway","volume":"24","author":"Gu","year":"2020","journal-title":"Clin. Exp. Nephrol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1016\/j.metabol.2018.02.004","article-title":"Adiponectin receptor agonist AdipoRon decreased ceramide, and lipotoxicity, and ameliorated diabetic nephropathy","volume":"85","author":"Choi","year":"2018","journal-title":"Metabolism"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1007\/s00109-018-1696-8","article-title":"AdipoRon, an adiponectin receptor agonist, attenuates cardiac remodeling induced by pressure overload","volume":"96","author":"Zhang","year":"2018","journal-title":"J. Mol. Med."},{"key":"ref_40","first-page":"147","article-title":"Pterostilbene Decreases Cardiac Oxidative Stress and Inflammation via Activation of AMPK\/Nrf2\/HO-1 Pathway in Fructose-Fed Diabetic Rats. Cardiovasc","volume":"32","author":"Kosuru","year":"2018","journal-title":"Drugs Ther."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.1111\/j.1476-5381.2010.00873.x","article-title":"Guidelines for reporting experiments involving animals: The ARRIVE guidelines","volume":"160","author":"McGrath","year":"2010","journal-title":"Br. J. Pharmacol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/0016-5085(79)90002-7","article-title":"Cytoprotection by prostaglandins in rats. Prevention of gastric necrosis produced by alcohol, HCl, NaOH, hypertonic NaCl, and thermal injury","volume":"77","author":"Robert","year":"1979","journal-title":"Gastroenterology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1515\/znc-2006-5-605","article-title":"Antiulcerogenic activity of crude extract, fractions and populnoic acid isolated from Austroplenckia populnea (Celastraceae)","volume":"61","author":"Andrade","year":"2006","journal-title":"Z. Naturforsch."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1007\/s00210-012-0807-2","article-title":"Antiulcerogenic activity of chlorogenic acid in different models of gastric ulcer","volume":"386","author":"Shimoyama","year":"2013","journal-title":"Naunyn Schmiedebergs Arch. Pharmacol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1016\/0016-5085(88)90661-0","article-title":"Histology of alcoholic hemorrhagic &quot; gastritis &quot: A prospective evaluation","volume":"94","author":"Laine","year":"1988","journal-title":"Gastroenterology"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Krajewska, J.B., D\u0142ugosz, O., Sa\u0142aga, M., Banach, M., and Fichna, J. (2020). Silver nanoparticles based on blackcurrant extract show potent anti-inflammatory effect in vitro and in DSS-induced colitis in mice. Int. J. Pharm., 585.","DOI":"10.1016\/j.ijpharm.2020.119549"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/10\/2946\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:01:58Z","timestamp":1760162518000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/10\/2946"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,15]]},"references-count":46,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2021,5]]}},"alternative-id":["molecules26102946"],"URL":"https:\/\/doi.org\/10.3390\/molecules26102946","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,15]]}}}