{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T21:46:13Z","timestamp":1785188773263,"version":"3.55.0"},"reference-count":90,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,9,18]],"date-time":"2024-09-18T00:00:00Z","timestamp":1726617600000},"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>Ulcerative colitis (UC) is a debilitating chronic disease marked by persistent inflammation and intestinal fibrosis. Despite the availability of various treatments, many patients fail to achieve long-term remission, underscoring a significant unmet therapeutic need. BMS-477118, a reversible inhibitor of dipeptidyl peptidase 4 (DPP4), has demonstrated anti-inflammatory properties in preclinical and clinical studies with minimal adverse effects compared to other antidiabetic agents. However, the potential benefits of BMS-477118 in chronic UC have not yet been explored. In this study, we aimed to investigate the effects of BMS-477118 in rats subjected to chronic dextran sodium sulfate (DSS) administration. Our findings indicate that BMS-477118 activates the interconnected positive feedback loop involving AMPK, SIRT1, and FOXO3a, improving histological appearance in injured rat colons. BMS-477118 also reduced fibrotic changes associated with the chronic nature of the animal model, alleviated macroscopic damage and disease severity, and improved the colon weight-to-length ratio. Additionally, BMS-477118 prevented DSS-induced weight loss and enhanced tight junction proteins. These effects, in conjunction with reduced oxidative stress and its potential anti-inflammatory, antiapoptotic, and autophagy-inducing properties, fostered prolonged survival in rats with chronic UC. To conclude, BMS-477118 has the potential to activate the AMPK\/SIRT1\/FOXO3a signaling pathway in inflamed colons. These results suggest that the AMPK\/SIRT1\/FOXO3a pathway could be a new therapeutic target for UC. Further research is mandatory to explore the therapeutic possibilities of this pathway. Additionally, continued studies on the therapeutic potential of BMS-477118 and other DPP4 inhibitors are promising for creating new treatments for various conditions, including UC in diabetic patients.<\/jats:p>","DOI":"10.3389\/fphar.2024.1456058","type":"journal-article","created":{"date-parts":[[2024,9,18]],"date-time":"2024-09-18T08:34:42Z","timestamp":1726648482000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Activation of AMPK\/SIRT1\/FOXO3a signaling by BMS-477118 (saxagliptin) mitigates chronic colitis in rats: uncovering new anti-inflammatory and antifibrotic roles"],"prefix":"10.3389","volume":"15","author":[{"given":"Elsayed A.","family":"Elmorsy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmoud E.","family":"Youssef","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed R.","family":"Abdel-Hamed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maha M.","family":"Amer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sahar R.","family":"Elghandour","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdullah S.","family":"Alkhamiss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nahla B.","family":"Mohamed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mostafa M.","family":"Khodeir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hossam A.","family":"Elsisi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thamir Saad","family":"Alsaeed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manal M.","family":"Kamal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abousree T.","family":"Ellethy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Basem H.","family":"Elesawy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sameh","family":"Saber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,9,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e23480","DOI":"10.1096\/fj.202302461RR","article-title":"Linagliptin, a DPP-4 inhibitor, activates AMPK\/FOXO3a and suppresses NF\u03baB to mitigate the debilitating effects of diethylnitrosamine exposure in rat liver: novel mechanistic insights","volume":"38","author":"Abdelhady","year":"2024","journal-title":"The FASEB J."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1239025","DOI":"10.3389\/fphar.2023.1239025","article-title":"Unveiling the therapeutic potential of exogenous \u03b2-hydroxybutyrate for chronic colitis in rats: novel insights on autophagy, apoptosis, and pyroptosis","volume":"14","author":"Abdelhady","year":"2023","journal-title":"Front. Pharmacol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"887233","DOI":"10.3389\/fphar.2022.887233","article-title":"Carbocisteine as a modulator of Nrf2\/HO-1 and NF\u03baB interplay in rats: new inspiration for the revival of an old drug for treating ulcerative colitis","volume":"13","author":"Abdelhamid","year":"2022","journal-title":"Front. Pharmacol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1186\/s13098-015-0095-3","article-title":"DPP-4 inhibitor sitagliptin prevents inflammation and oxidative stress of heart and kidney in two kidney and one clip (2K1C) rats","volume":"7","author":"Alam","year":"2015","journal-title":"Diabetology and Metabolic Syndrome"},{"key":"B5","doi-asserted-by":"publisher","first-page":"e16100","DOI":"10.1371\/journal.pone.0016100","article-title":"TNF-\u0391 contributes to caspase-3 independent apoptosis in neuroblastoma cells: role of NFAT","volume":"6","author":"\u00c1lvarez","year":"2011","journal-title":"PLOS ONE"},{"key":"B6","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1038\/s41419-020-2308-4","article-title":"SIRT1 inhibits chemoresistance and cancer stemness of gastric cancer by initiating an AMPK\/FOXO3 positive feedback loop","volume":"11","author":"An","year":"2020","journal-title":"Cell. Death and Dis."},{"key":"B7","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1517\/14728222.2016.1086752","article-title":"The AMPK enzyme-complex: from the regulation of cellular energy homeostasis to a possible new molecular target in the management of chronic inflammatory disorders","volume":"20","author":"Antonioli","year":"2016","journal-title":"Expert Opin. Ther. Targets"},{"key":"B8","doi-asserted-by":"publisher","first-page":"119743","DOI":"10.1016\/j.lfs.2021.119743","article-title":"Activation of AMPK\/mTOR-driven autophagy and inhibition of NLRP3 inflammasome by saxagliptin ameliorate ethanol-induced gastric mucosal damage","volume":"280","author":"Arab","year":"2021","journal-title":"Life Sci."},{"key":"B9","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1007\/s00109-022-02281-5","article-title":"FoxO3 and oxidative stress: a multifaceted role in cellular adaptation","volume":"101","author":"Bernardo","year":"2023","journal-title":"J. Mol. Med."},{"key":"B10","doi-asserted-by":"publisher","first-page":"233","DOI":"10.3390\/antiox9030233","article-title":"Effect of dipeptidyl-peptidase 4 inhibitors on circulating oxidative stress biomarkers in patients with type 2 diabetes mellitus","volume":"9","author":"Bigagli","year":"2020","journal-title":"Antioxidants (Basel)"},{"key":"B11","doi-asserted-by":"publisher","first-page":"e000227","DOI":"10.1136\/bmjdrc-2016-000227","article-title":"Dipeptidyl peptidase-4 inhibition by Saxagliptin prevents inflammation and renal injury by targeting the Nlrp3\/ASC inflammasome","volume":"4","author":"Birnbaum","year":"2016","journal-title":"BMJ Open Diabetes Res. Care"},{"key":"B12","doi-asserted-by":"publisher","first-page":"e64","DOI":"10.1097\/01.hjh.0000548249.66849.5c","article-title":"A11466 Protective effect of Saxagliptin, a DPP-4 inhibitor, on myocardial ischemia reperfusion injury in STZ induced diabetic rats","volume":"36","author":"Bisht","year":"2018","journal-title":"J. Hypertens."},{"key":"B13","doi-asserted-by":"publisher","first-page":"2011","DOI":"10.1126\/science.1094637","article-title":"Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase","volume":"303","author":"Brunet","year":"2004","journal-title":"Science"},{"key":"B14","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1189\/jlb.1202629","article-title":"Decisions on life and death: FOXO Forkhead transcription factors are in command when PKB\/Akt is off duty","volume":"73","author":"Burgering","year":"2003","journal-title":"J. Leukoc. Biol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1056","DOI":"10.1038\/nature07813","article-title":"AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity","volume":"458","author":"Cant\u00f3","year":"2009","journal-title":"Nature"},{"key":"B16","doi-asserted-by":"publisher","first-page":"121877","DOI":"10.1016\/j.lfs.2023.121877","article-title":"The rules and regulatory mechanisms of FOXO3 on inflammation, metabolism, cell death and aging in hosts","volume":"328","author":"Cao","year":"2023","journal-title":"Life Sci."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1467","DOI":"10.1038\/mi.2014.35","article-title":"Defective expression of SIRT1 contributes to sustain inflammatory pathways in the gut","volume":"7","author":"Caruso","year":"2014","journal-title":"Mucosal Immunol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"e22496","DOI":"10.1096\/fj.202200749R","article-title":"Ambroxol, a mucolytic agent, boosts HO-1, suppresses NF-\u03baB, and decreases the susceptibility of the inflamed rat colon to apoptosis: a new treatment option for treating ulcerative colitis","volume":"36","author":"Cavalu","year":"2022","journal-title":"The FASEB J."},{"key":"B19","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1002\/0471142735.im1525s104","article-title":"Dextran sulfate sodium (DSS)-induced colitis in mice","volume":"104","author":"Chassaing","year":"2014","journal-title":"Curr. Protoc. Immunol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"5457","DOI":"10.2147\/JIR.S380285","article-title":"DPP4 as a potential candidate in cardiovascular disease","volume":"15","author":"Chen","year":"2022","journal-title":"J. Inflamm. Res."},{"key":"B21","doi-asserted-by":"publisher","first-page":"113951","DOI":"10.1016\/j.bcp.2020.113951","article-title":"Dipeptidyl peptidase-4 inhibition improves endothelial senescence by activating AMPK\/SIRT1\/Nrf2 signaling pathway","volume":"177","author":"Chen","year":"2020","journal-title":"Biochem. Pharmacol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"122901","DOI":"10.1016\/j.lfs.2024.122901","article-title":"Cyclic adenosine 3\u2019, 5\u2019-monophosphate (cAMP) signaling is a crucial therapeutic target for ulcerative colitis","volume":"353","author":"Cheng","year":"2024","journal-title":"Life Sci."},{"key":"B23","doi-asserted-by":"publisher","first-page":"230","DOI":"10.4103\/0976-500X.85934","article-title":"Saxagliptin: a dipeptidyl peptidase-4 inhibitor in the treatment of type 2 diabetes mellitus","volume":"2","author":"Dave","year":"2011","journal-title":"J. Pharmacol. Pharmacother."},{"key":"B24","doi-asserted-by":"publisher","first-page":"1065","DOI":"10.1016\/j.xkme.2021.07.007","article-title":"Dipeptidyl peptidase-4 inhibitors and diabetic kidney disease: a narrative review","volume":"3","author":"Daza-Arnedo","year":"2021","journal-title":"Kidney Med."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1422","DOI":"10.3390\/cancers11101422","article-title":"The emerging roles of mTORC1 in macromanaging autophagy","volume":"11","author":"Dossou","year":"2019","journal-title":"Cancers (Basel)"},{"key":"B26","doi-asserted-by":"publisher","first-page":"1110","DOI":"10.3390\/cells8091110","article-title":"FOXO3a from the nucleus to the mitochondria: a round trip in cellular stress response","volume":"8","author":"Fasano","year":"2019","journal-title":"Cells"},{"key":"B27","doi-asserted-by":"publisher","first-page":"3100","DOI":"10.1523\/JNEUROSCI.4012-14.2015","article-title":"SIRT1-FOXO3a regulate cocaine actions in the nucleus accumbens","volume":"35","author":"Ferguson","year":"2015","journal-title":"J. Neurosci."},{"key":"B28","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1080\/15548627.2021.1909406","article-title":"How autophagy controls the intestinal epithelial barrier","volume":"18","author":"Foerster","year":"2022","journal-title":"Autophagy"},{"key":"B29","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1007\/s00380-020-01711-z","article-title":"DPP-4 inhibitor induces FGF21 expression via sirtuin 1 signaling and improves myocardial energy metabolism","volume":"36","author":"Furukawa","year":"2021","journal-title":"Heart Vessels"},{"key":"B30","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1161\/HYPERTENSIONAHA.119.13778","article-title":"Activation of transient receptor potential channel vanilloid 4 by DPP-4 (dipeptidyl peptidase-4) inhibitor vildagliptin protects against diabetic endothelial dysfunction","volume":"75","author":"Gao","year":"2020","journal-title":"Hypertension"},{"key":"B31","doi-asserted-by":"publisher","first-page":"117017","DOI":"10.1016\/j.lfs.2019.117017","article-title":"Saxagliptin mitigates airway inflammation in a mouse model of acute asthma via modulation of NF-kB and TLR4","volume":"239","author":"Helal","year":"2019","journal-title":"Life Sci."},{"key":"B32","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1016\/j.lfs.2018.07.021","article-title":"Nephroprotective effect of saxagliptin against gentamicin-induced nephrotoxicity, emphasis on anti-oxidant, anti-inflammatory and anti-apoptic effects","volume":"208","author":"Helal","year":"2018","journal-title":"Life Sci."},{"key":"B33","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1159\/000068143","article-title":"Animal models of inflammatory bowel disease: an overview","volume":"70","author":"Hoffmann","year":"2003","journal-title":"Pathobiology"},{"key":"B34","doi-asserted-by":"publisher","first-page":"3335","DOI":"10.1021\/acschemneuro.2c00733","article-title":"DPP-4 inhibitors suppress tau phosphorylation and promote neuron autophagy through the AMPK\/mTOR pathway to ameliorate cognitive dysfunction in diabetic mellitus","volume":"14","author":"Hu","year":"2023","journal-title":"ACS Chem. Neurosci."},{"key":"B35","doi-asserted-by":"publisher","first-page":"796","DOI":"10.1111\/cns.13114","article-title":"Exercise activates lysosomal function in the brain through AMPK-SIRT1-TFEB pathway","volume":"25","author":"Huang","year":"2019","journal-title":"CNS Neurosci. and Ther."},{"key":"B36","doi-asserted-by":"publisher","first-page":"2120","DOI":"10.2337\/db13-1029","article-title":"Linagliptin-mediated DPP-4 inhibition ameliorates kidney fibrosis in streptozotocin-induced diabetic mice by inhibiting endothelial-to-mesenchymal transition in a therapeutic regimen","volume":"63","author":"Kanasaki","year":"2014","journal-title":"Diabetes"},{"key":"B37","doi-asserted-by":"publisher","first-page":"1005","DOI":"10.1016\/j.clinthera.2011.06.016","article-title":"Saxagliptin: a clinical review in the treatment of type 2 diabetes mellitus","volume":"33","author":"Kania","year":"2011","journal-title":"Clin. Ther."},{"key":"B38","doi-asserted-by":"publisher","first-page":"23","DOI":"10.3390\/ijms23169344","article-title":"Inflammatory bowel disease: a review of pre-clinical murine models of human disease","author":"Katsandegwaza","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"B39","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1186\/s12950-020-00246-4","article-title":"Ulcerative colitis: understanding its cellular pathology could provide insights into novel therapies","volume":"17","author":"Kaur","year":"2020","journal-title":"J. Inflamm. (Lond)"},{"key":"B40","doi-asserted-by":"publisher","first-page":"e32084","DOI":"10.1371\/journal.pone.0032084","article-title":"Dextran sodium sulfate (DSS) induces colitis in mice by forming nano-lipocomplexes with medium-chain-length fatty acids in the colon","volume":"7","author":"Laroui","year":"2012","journal-title":"PLoS One"},{"key":"B41","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":"The Lancet"},{"key":"B42","doi-asserted-by":"publisher","first-page":"e1004987","DOI":"10.1371\/journal.pgen.1004987","article-title":"Phototoxic stress induces phosphorylation of p62\/SQSTM1 by ULK1 to regulate selective autophagic clearance of protein aggregates","volume":"11","author":"Lim","year":"2015","journal-title":"PLoS Genet."},{"key":"B43","doi-asserted-by":"publisher","first-page":"56","DOI":"10.3892\/mmr.2020.11694","article-title":"AMPK-SIRT1 pathway dysfunction contributes to neuron apoptosis and cognitive impairment induced by sevoflurane","volume":"23","author":"Liu","year":"2021","journal-title":"Mol. Med. Rep."},{"key":"B44","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1111\/j.1582-4934.2009.00632.x","article-title":"NF-kappaB regulation: the nuclear response","volume":"13","author":"Mankan","year":"2009","journal-title":"J. Cell. Mol. Med."},{"key":"B45","doi-asserted-by":"publisher","first-page":"4995","DOI":"10.1007\/s12010-023-04470-5","article-title":"Potent FOXO3a activators from biologically active compound library for cancer therapeutics: an in silico approach","volume":"195","author":"Manoharan","year":"2023","journal-title":"Appl. Biochem. Biotechnol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"305","DOI":"10.5009\/gnl.2012.6.3.305","article-title":"Cellular and molecular basis of intestinal barrier dysfunction in the irritable bowel syndrome","volume":"6","author":"Mart\u00ednez","year":"2012","journal-title":"Gut Liver"},{"key":"B47","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1097\/FJC.0b013e31826be204","article-title":"Dipeptidyl peptidase-4 inhibition with saxagliptin enhanced nitric oxide release and reduced blood pressure and sICAM-1 levels in hypertensive rats","volume":"60","author":"Mason","year":"2012","journal-title":"J. Cardiovasc Pharmacol."},{"key":"B48","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1111\/cns.13042","article-title":"DPP-4 inhibitors promote proliferation and migration of rat brain microvascular endothelial cells under hypoxic\/high-glucose conditions, potentially through the SIRT1\/HIF-1\/VEGF pathway","volume":"25","author":"Mi","year":"2019","journal-title":"CNS Neurosci. and Ther."},{"key":"B49","doi-asserted-by":"publisher","first-page":"547","DOI":"10.4103\/1735-5362.323920","article-title":"Anti-inflammatory effects of saxagliptin and vildagliptin against doxorubicin-induced nephrotoxicity in rats: attenuation of NLRP3 inflammasome up-regulation and tubulo-interstitial injury","volume":"16","author":"Mostafa","year":"","journal-title":"Res. Pharm. Sci."},{"key":"B50","doi-asserted-by":"publisher","first-page":"547","DOI":"10.4103\/1735-5362.323920","article-title":"Anti-inflammatory effects of saxagliptin and vildagliptin against doxorubicin-induced nephrotoxicity in rats: attenuation of NLRP3 inflammasome up-regulation and tubulo-interstitial injury","volume":"16","author":"Mostafa","year":"","journal-title":"Res. Pharm. Sci."},{"key":"B51","doi-asserted-by":"publisher","first-page":"144","DOI":"10.3390\/ph14020144","article-title":"Novel potent and selective DPP-4 inhibitors: design, synthesis and molecular docking study of dihydropyrimidine phthalimide hybrids","volume":"14","author":"Mourad","year":"2021","journal-title":"Pharm. [Online]"},{"key":"B52","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1186\/s12933-015-0264-6","article-title":"Inhibition of DPP-4 reduces acute mortality after myocardial infarction with restoration of autophagic response in type 2 diabetic rats","volume":"14","author":"Murase","year":"","journal-title":"Cardiovasc Diabetol."},{"key":"B53","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1186\/s12933-015-0264-6","article-title":"Inhibition of DPP-4 reduces acute mortality after myocardial infarction with restoration of autophagic response in type 2 diabetic rats","volume":"14","author":"Murase","year":"","journal-title":"Cardiovasc. Diabetol."},{"key":"B54","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/j.jphs.2016.12.003","article-title":"The effects of DPP-4 inhibitor on hypoxia-induced apoptosis in human umbilical vein endothelial cells","volume":"133","author":"Nagamine","year":"2017","journal-title":"J. Pharmacol. Sci."},{"key":"B55","doi-asserted-by":"publisher","first-page":"113409","DOI":"10.1016\/j.biopha.2022.113409","article-title":"Canagliflozin-loaded chitosan-hyaluronic acid microspheres modulate AMPK\/NF-\u03baB\/NLRP3 axis: a new paradigm in the rectal therapy of ulcerative colitis","volume":"153","author":"Nasr","year":"2022","journal-title":"Biomed. and Pharmacother."},{"key":"B56","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1038\/ncb2708","article-title":"mTOR inhibits autophagy by controlling ULK1 ubiquitylation, self-association and function through AMBRA1 and TRAF6","volume":"15","author":"Nazio","year":"2013","journal-title":"Nat. Cell. Biol."},{"key":"B57","doi-asserted-by":"publisher","first-page":"346","DOI":"10.4331\/wjbc.v5.i3.346","article-title":"FoxO3a and disease progression","volume":"5","author":"Nho","year":"2014","journal-title":"World J. Biol. Chem."},{"key":"B58","doi-asserted-by":"publisher","first-page":"1446","DOI":"10.1038\/s41401-020-0413-7","article-title":"Dipeptidyl peptidase 4 inhibitor sitagliptin protected against dextran sulfate sodium-induced experimental colitis by potentiating the action of GLP-2","volume":"41","author":"Ning","year":"2020","journal-title":"Acta Pharmacol. Sin."},{"key":"B59","doi-asserted-by":"publisher","first-page":"5380638","DOI":"10.1155\/2017\/5380638","article-title":"A double-blinded randomized study investigating a possible anti-inflammatory effect of saxagliptin versus placebo as add-on therapy in patients with both type 2 diabetes and stable coronary artery disease","volume":"2017","author":"Njerve","year":"2017","journal-title":"Mediat. Inflamm."},{"key":"B60","doi-asserted-by":"publisher","first-page":"3300","DOI":"10.3390\/biomedicines11123300","article-title":"The safety and efficacy of combining saxagliptin and pioglitazone therapy in streptozocin-induced diabetic rats","volume":"11","author":"Othman","year":"2023","journal-title":"Biomedicines"},{"key":"B61","doi-asserted-by":"publisher","first-page":"1418","DOI":"10.3390\/antiox11071418","article-title":"Antioxidant effects of DPP-4 inhibitors in early stages of experimental diabetic retinopathy","volume":"11","author":"Ramos","year":"2022","journal-title":"Antioxidants"},{"key":"B62","doi-asserted-by":"publisher","first-page":"3443","DOI":"10.2147\/JIR.S315938","article-title":"The supportive role of NSC328382, a P2X7R antagonist, in enhancing the inhibitory effect of CRID3 on NLRP3 inflammasome activation in rats with dextran sodium sulfate-induced colitis","volume":"14","author":"Saber","year":"2021","journal-title":"J. Inflamm. Res."},{"key":"B63","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1007\/s00109-011-0748-0","article-title":"AMP-activated protein kinase inhibits NF-\u03baB signaling and inflammation: impact on healthspan and lifespan","volume":"89","author":"Salminen","year":"2011","journal-title":"J. Mol. Med. Berl."},{"key":"B64","doi-asserted-by":"publisher","first-page":"1719","DOI":"10.1111\/bcp.13955","article-title":"Dipeptidyl peptidase-4 inhibitors lower the risk of autoimmune disease in patients with type 2 diabetes mellitus: a nationwide population-based cohort study","volume":"85","author":"Seong","year":"2019","journal-title":"Br. J. Clin. Pharmacol."},{"key":"B65","doi-asserted-by":"publisher","first-page":"1845","DOI":"10.2147\/DMSO.S369712","article-title":"Potential effect of DPP-4 inhibitors towards hepatic diseases and associated glucose intolerance","volume":"15","author":"Sharma","year":"2022","journal-title":"Diabetes Metab. Syndr. Obes."},{"key":"B66","doi-asserted-by":"publisher","first-page":"586","DOI":"10.3390\/ph14060586","article-title":"Dipeptidyl peptidase (DPP)-IV inhibitors with antioxidant potential isolated from natural sources: a novel approach for the management of diabetes","volume":"14","author":"Singh","year":"2021","journal-title":"Pharm. (Basel)"},{"key":"B67","doi-asserted-by":"publisher","first-page":"1185","DOI":"10.3389\/fphar.2020.01185","article-title":"DPP-4 inhibitors in the prevention\/treatment of pulmonary fibrosis, heart and kidney injury caused by COVID-19-A therapeutic approach of choice in type 2 diabetic patients?","volume":"11","author":"Smelcerovic","year":"2020","journal-title":"Front. Pharmacol."},{"key":"B68","doi-asserted-by":"publisher","first-page":"5517","DOI":"10.1038\/s41598-024-55944-3","article-title":"Identified S100A9 as a target for diagnosis and treatment of ulcerative colitis by bioinformatics analysis","volume":"14","author":"Tan","year":"2024","journal-title":"Sci. Rep."},{"key":"B69","doi-asserted-by":"publisher","first-page":"101762","DOI":"10.1016\/j.trim.2022.101762","article-title":"Protective effect of Saxagliptin on diabetic rats with renal ischemia reperfusion injury by targeting oxidative stress and mitochondrial apoptosis pathway through activating Nrf-2\/HO-1 signaling","volume":"76","author":"Tang","year":"2023","journal-title":"Transpl. Immunol."},{"key":"B70","doi-asserted-by":"publisher","first-page":"608","DOI":"10.1080\/13813455.2020.1715442","article-title":"Protective effect of saxagliptin against renal ischaemia reperfusion injury in rats","volume":"128","author":"Tekin","year":"2022","journal-title":"Archives Physiology Biochem."},{"key":"B71","doi-asserted-by":"publisher","first-page":"759","DOI":"10.2174\/138955710791572424","article-title":"Saxagliptin: a new drug for the treatment of type 2 diabetes","volume":"10","author":"Thareja","year":"2010","journal-title":"Mini Rev. Med. Chem."},{"key":"B72","doi-asserted-by":"publisher","first-page":"3125","DOI":"10.3390\/ijms19103125","article-title":"The role of AMPK in the regulation of skeletal muscle size, hypertrophy, and regeneration","volume":"19","author":"Thomson","year":"2018","journal-title":"Int. J. Mol. Sci."},{"key":"B73","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/j.ejphar.2016.04.005","article-title":"Glucose-independent renoprotective mechanisms of the tissue dipeptidyl peptidase-4 inhibitor, saxagliptin, in Dahl salt-sensitive hypertensive rats","volume":"783","author":"Uchii","year":"2016","journal-title":"Eur. J. Pharmacol."},{"key":"B74","doi-asserted-by":"publisher","first-page":"e37095","DOI":"10.1097\/MD.0000000000037095","article-title":"Global trends and hotspots of ulcerative colitis based on bibliometric and visual analysis from 1993 to 2022","volume":"103","author":"Wang","year":"2024","journal-title":"Med. Baltim."},{"key":"B75","doi-asserted-by":"publisher","first-page":"1015500","DOI":"10.3389\/fphys.2022.1015500","article-title":"Role of AMPK in autophagy","volume":"13","author":"Wang","year":"2022","journal-title":"Front. Physiology"},{"key":"B76","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1038\/s41392-021-00528-0","article-title":"Targeting cellular senescence prevents glucocorticoid-induced bone loss through modulation of the DPP4-GLP-1 axis","volume":"6","author":"Wang","year":"","journal-title":"Signal Transduct. Target. Ther."},{"key":"B77","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1038\/s41420-021-00625-7","article-title":"Dipeptidyl peptidase-4 (DPP4) inhibitor sitagliptin alleviates liver inflammation of diabetic mice by acting as a ROS scavenger and inhibiting the NF\u03baB pathway","volume":"7","author":"Wang","year":"","journal-title":"Cell. Death Discov."},{"key":"B78","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1186\/s13058-019-1150-z","article-title":"Nicotinamide N-methyltransferase enhances chemoresistance in breast cancer through SIRT1 protein stabilization","volume":"21","author":"Wang","year":"2019","journal-title":"Breast Cancer Res."},{"key":"B79","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1186\/s12974-019-1411-x","article-title":"AMPK activation attenuates inflammatory pain through inhibiting NF-\u03baB activation and IL-1\u03b2 expression","volume":"16","author":"Xiang","year":"2019","journal-title":"J. Neuroinflammation"},{"key":"B80","doi-asserted-by":"publisher","first-page":"990","DOI":"10.3892\/etm.2021.10422","article-title":"Saxagliptin protects against diabetic nephropathy by inhibiting caspase 3\/PARP-1-dependent nephrocele apoptosis","volume":"22","author":"Xing","year":"2021","journal-title":"Exp. Ther. Med."},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.831168","article-title":"Regulation of SIRT1 and its roles in inflammation","volume":"13","author":"Yang","year":"","journal-title":"Front. Immunol."},{"key":"B82","doi-asserted-by":"publisher","first-page":"831168","DOI":"10.3389\/fimmu.2022.831168","article-title":"Regulation of SIRT1 and its roles in inflammation","volume":"13","author":"Yang","year":"","journal-title":"Front. Immunol."},{"key":"B83","doi-asserted-by":"publisher","first-page":"1618","DOI":"10.1016\/j.bbrc.2018.07.090","article-title":"Saxagliptin regulates M1\/M2 macrophage polarization via CaMKK\u03b2\/AMPK pathway to attenuate NAFLD","volume":"503","author":"Yang","year":"","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B84","doi-asserted-by":"publisher","first-page":"1618","DOI":"10.1016\/j.bbrc.2018.07.090","article-title":"Saxagliptin regulates M1\/M2 macrophage polarization via CaMKK\u03b2\/AMPK pathway to attenuate NAFLD","volume":"503","author":"Yang","year":"","journal-title":"Biochem. Biophysical Res. Commun."},{"key":"B85","doi-asserted-by":"publisher","first-page":"3055","DOI":"10.3390\/molecules27103055","article-title":"Role of dipeptidyl peptidase 4 inhibitors in antidiabetic treatment","volume":"27","author":"Yin","year":"2022","journal-title":"Molecules"},{"key":"B86","doi-asserted-by":"publisher","first-page":"25723","DOI":"10.1007\/s11356-021-17831-6","article-title":"Electrocardiographic and histopathological characterizations of diabetic cardiomyopathy in rats","volume":"29","author":"Youssef","year":"2022","journal-title":"Environ. Sci. Pollut. Res."},{"key":"B87","doi-asserted-by":"publisher","first-page":"2086","DOI":"10.3892\/ijmm.2018.3393","article-title":"Autophagy regulates the degeneration of the auditory cortex through the AMPK-mTOR-ULK1 signaling pathway","volume":"41","author":"Yuan","year":"2018","journal-title":"Int. J. Mol. Med."},{"key":"B88","doi-asserted-by":"publisher","first-page":"778674","DOI":"10.3389\/fcvm.2021.778674","article-title":"Longevity factor FOXO3: a key regulator in aging-related vascular diseases","volume":"8","author":"Zhao","year":"2021","journal-title":"Front. Cardiovasc Med."},{"key":"B89","doi-asserted-by":"publisher","first-page":"113651","DOI":"10.1016\/j.biopha.2022.113651","article-title":"Diacetylrhein, an anthraquinone antiarthritic agent, suppresses dextran sodium sulfate-induced inflammation in rats: a possible mechanism for a protective effect against ulcerative colitis","volume":"154","author":"Zohny","year":"","journal-title":"Biomed. and Pharmacother."},{"key":"B90","doi-asserted-by":"publisher","first-page":"112723","DOI":"10.1016\/j.biopha.2022.112723","article-title":"Coomassie brilliant blue G-250 dye attenuates bleomycin-induced lung fibrosis by regulating the NF-\u03baB and NLRP3 crosstalk: a novel approach for filling an unmet medical need","volume":"148","author":"Zohny","year":"","journal-title":"Biomed. and Pharmacother."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2024.1456058\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,18]],"date-time":"2024-09-18T08:34:45Z","timestamp":1726648485000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2024.1456058\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,18]]},"references-count":90,"alternative-id":["10.3389\/fphar.2024.1456058"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2024.1456058","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,18]]},"article-number":"1456058"}}