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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Potential Cardioprotective Effect of a GRK5 Inhibitor Against NF-κB-Mediated Inflammation in an Animal Model of Isoproterenol-Induced Myocardial Infarction

by
Asma S. Alonazi
1,*,†,
Anfal F. Bin Dayel
1,†,
Bashayer A. Alkhathlan
1,
Lulu M. Alkaff
1,
Ahad T. Alrashed
1,
Reema A. Bin Klaib
1,
Doaa M. Elnagar
2,
Maha A. Alamin
1,
Rehab A. Ali
1,
Alaa Alnoor Alameen
1 and
Nouf M. Alrasheed
1
1
Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
2
Zoology Department, College of Science, King Saud University, Riyadh 11451, Saudi Arabia
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Int. J. Mol. Sci. 2026, 27(1), 53; https://doi.org/10.3390/ijms27010053 (registering DOI)
Submission received: 22 November 2025 / Revised: 15 December 2025 / Accepted: 16 December 2025 / Published: 20 December 2025
(This article belongs to the Special Issue Current Research for Heart Disease Biology and Therapeutics (Third Edition))
Versions Notes

Abstract

Myocardial infarction (MI) is a pathological condition associated with various cardiovascular diseases and leads to heart failure. Nuclear factor-kappa B (NF-κB) 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 NFκB-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-κB/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 < 0.001), troponin (p < 0.001), creatine kinase (p < 0.001), and LDH (p < 0.001). Treatment with AMX resulted in a significant reduction in cardiac injury biomarkers (p < 0.001) and IL-6 (p < 0.05). The protein level of NF-κB(p65) and NF-κB(p105) was significantly increased in cardiac myocytes of the MI group. Treatment with AMX led to a significant decrease in NF-κB(p65) and (p105) expression (p < 0.01 and p < 0.001, respectively), and GRK5 and MEF2α protein levels were also upregulated. In conclusion, AMX shows potential cardioprotective effects by modulating the GRK5/MEF2-mediated NF-κB inflammatory signaling pathway.
Keywords: GRK5; Amlexanox; NF-κB; inflammation; myocardial infarction GRK5; Amlexanox; NF-κB; inflammation; myocardial infarction

Share and Cite

MDPI and ACS Style

Alonazi, A.S.; Dayel, A.F.B.; Alkhathlan, B.A.; Alkaff, L.M.; Alrashed, A.T.; Klaib, R.A.B.; Elnagar, D.M.; Alamin, M.A.; Ali, R.A.; Alameen, A.A.; et al. Potential Cardioprotective Effect of a GRK5 Inhibitor Against NF-κB-Mediated Inflammation in an Animal Model of Isoproterenol-Induced Myocardial Infarction. Int. J. Mol. Sci. 2026, 27, 53. https://doi.org/10.3390/ijms27010053

AMA Style

Alonazi AS, Dayel AFB, Alkhathlan BA, Alkaff LM, Alrashed AT, Klaib RAB, Elnagar DM, Alamin MA, Ali RA, Alameen AA, et al. Potential Cardioprotective Effect of a GRK5 Inhibitor Against NF-κB-Mediated Inflammation in an Animal Model of Isoproterenol-Induced Myocardial Infarction. International Journal of Molecular Sciences. 2026; 27(1):53. https://doi.org/10.3390/ijms27010053

Chicago/Turabian Style

Alonazi, Asma S., Anfal F. Bin Dayel, Bashayer A. Alkhathlan, Lulu M. Alkaff, Ahad T. Alrashed, Reema A. Bin Klaib, Doaa M. Elnagar, Maha A. Alamin, Rehab A. Ali, Alaa Alnoor Alameen, and et al. 2026. "Potential Cardioprotective Effect of a GRK5 Inhibitor Against NF-κB-Mediated Inflammation in an Animal Model of Isoproterenol-Induced Myocardial Infarction" International Journal of Molecular Sciences 27, no. 1: 53. https://doi.org/10.3390/ijms27010053

APA Style

Alonazi, A. S., Dayel, A. F. B., Alkhathlan, B. A., Alkaff, L. M., Alrashed, A. T., Klaib, R. A. B., Elnagar, D. M., Alamin, M. A., Ali, R. A., Alameen, A. A., & Alrasheed, N. M. (2026). Potential Cardioprotective Effect of a GRK5 Inhibitor Against NF-κB-Mediated Inflammation in an Animal Model of Isoproterenol-Induced Myocardial Infarction. International Journal of Molecular Sciences, 27(1), 53. https://doi.org/10.3390/ijms27010053

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