{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T21:03:55Z","timestamp":1790802235390,"version":"4.1.0"},"reference-count":44,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,20]],"date-time":"2025-12-20T00:00:00Z","timestamp":1766188800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002383","name":"King Saud University","doi-asserted-by":"crossref","award":["ORF-2025-1218"],"award-info":[{"award-number":["ORF-2025-1218"]}],"id":[{"id":"10.13039\/501100002383","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Myocardial infarction (MI) is a pathological condition associated with various cardiovascular diseases and leads to heart failure. Nuclear factor-kappa B (NF-\u03baB) is upregulated in the infarcted heart. G protein-coupled receptor kinase 5 (GRK5) also plays a complex role in both tissue repair and maladaptive hypertrophy in cardiovascular diseases; however, its effect on NF-\u03baB-mediated inflammation has not yet been elucidated. Thus, this study aims to investigate the effects of Amlexanox (AMX), a potential GRK5 inhibitor, in an animal model of MI by assessing its impact on GRK5-mediated NF-\u03baB\/inflammatory processes. Thirty-two male mice were randomly allocated into four groups: control, MI, (MI treated with vehicle (MI + V), and MI + AMX (AMX: 2.5 mg\/100 g\/day). MI was induced using ISO on days 21 and 22. The cardioprotective impacts of Amlexanox were verified by evaluating cardiac injury, inflammatory biomarker concentrations, and histopathological alterations in cardiomyocytes. MI induction was confirmed by increases in heart weight\/body weight ratio (HW\/BW) (p &lt; 0.001), troponin (p &lt; 0.001), creatine kinase (p &lt; 0.001), and LDH (p &lt; 0.001). Treatment with AMX resulted in a significant reduction in cardiac injury biomarkers (p &lt; 0.001) and IL-6 (p &lt; 0.05). The protein level of NF-\u03baB(p65) and NF-\u03baB(p105) was significantly increased in cardiac myocytes of the MI group. Treatment with AMX led to a significant decrease in NF-\u03baB(p65) and (p105) expression (p &lt; 0.01 and p &lt; 0.001, respectively), and GRK5 and MEF2\u03b1 protein levels were also upregulated. In conclusion, AMX shows potential cardioprotective effects by modulating the GRK5\/MEF2-mediated NF-\u03baB inflammatory signaling pathway.<\/jats:p>","DOI":"10.3390\/ijms27010053","type":"journal-article","created":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T14:27:47Z","timestamp":1766500067000},"page":"53","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Potential Cardioprotective Effect of a GRK5 Inhibitor Against NF-\u03baB-Mediated Inflammation in an Animal Model of Isoproterenol-Induced Myocardial Infarction"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3367-002X","authenticated-orcid":false,"given":"Asma S.","family":"Alonazi","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7138-414X","authenticated-orcid":false,"given":"Anfal F.","family":"Bin Dayel","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3981-1233","authenticated-orcid":false,"given":"Bashayer A.","family":"Alkhathlan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lulu M.","family":"Alkaff","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahad T.","family":"Alrashed","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reema A.","family":"Bin Klaib","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doaa M.","family":"Elnagar","sequence":"additional","affiliation":[{"name":"Zoology Department, College of Science, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4847-0840","authenticated-orcid":false,"given":"Maha A.","family":"Alamin","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rehab A.","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4073-2375","authenticated-orcid":false,"given":"Alaa Alnoor","family":"Alameen","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5283-1576","authenticated-orcid":false,"given":"Nouf M.","family":"Alrasheed","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"235101","DOI":"10.1155\/2015\/235101","article-title":"Prevalence of Cardiovascular Disease and Associated Risk Factors among Adult Population in the Gulf Region: A Systematic Review","volume":"2015","author":"Aljefree","year":"2015","journal-title":"Adv. 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