The Effect of Ferulic Acid on Inflammation in a Myocardial Ischemia-Reperfusion Experimental Model: The Effect of Ferulic Acid on Inflammation

Naseer Ahmed; Ayesha Ihsan Qazi; Mazhar Mehmood; Meera Tanveer; Romaisa Kiran; Mohsin Shabir

doi:10.54393/pjhs.v6i7.3447

Authors

Naseer Ahmed Department of Pharmacology, Rehman College of Dentistry, Peshawar, Pakistan
Ayesha Ihsan Qazi Department of Pharmaceutical Sciences, Khyber Medical University, Peshawar, Pakistan
Mazhar Mehmood Department of Cardiology, Rehman Medical Institute, Peshawar, Pakistan
Meera Tanveer Department of Research, Rehman College of Dentistry, Peshawar, Pakistan
Romaisa Kiran Clinical Trial Unit, Rehman Medical Institute, Peshawar, Pakistan
Mohsin Shabir Department of Cardiology, Rehman Medical Institute, Peshawar, Pakistan

DOI:

https://doi.org/10.54393/pjhs.v6i7.3447

Keywords:

Ferulic Acid, Inflammation, Mitochondrial Dysfunction, Ischemia-Reperfusion, Serum IL-6 Levels

Abstract

Cardiovascular disease is a leading cause of death globally, with ischemia-reperfusion injury (IRI) causing tissue damage through oxidative stress and inflammation. Interleukin-6 (IL-6) plays a role in IRI-related myocardial damage. Ferulic acid, a plant-derived phenolic compound, shows potential as an anti-inflammatory and antioxidant therapy to reduce IRI. Objectives: To investigate the dose-dependent protective effect of ferulic acid in an experimental myocardial ischemia-reperfusion injury model, focusing on its impact on serum IL-6 levels. Methods: This experimental study was conducted over 6 months by the Department of Pharmacology at Rehman College of Dentistry, Peshawar, Pakistan, utilizing healthy male Sprague Dawley rats weighing 300–350 grams (g). Rats showing signs of illness were excluded from the study. Twenty rats were randomly allocated to control (n=10) and treatment (n=10) groups. Preceding the induction of ischemia-reperfusion injury, the treatment group was administered oral ferulic acid for 15 days; controls were untreated. Data were analyzed using SPSS version 23.0. Results are presented as mean ± standard deviation, and the mean difference was compared by an independent sample t-test, taking<0.05. Results: IL-6 levels in serum were measured using ELISA, with control rats showing higher IL-6 (66–80 ng/l) than ferulic acid-treated rats (46–55 ng/l). There was a significant reduction in IL-6 levels in the treated group. This indicates ferulic acid lowers inflammation in myocardial ischemia-reperfusion injury. Conclusions: It was concluded that the ability to lower the IL-6 level and modulate oxidative-inflammatory pathways, ferulic acid can be a promising therapeutic agent to attenuate myocardial inflammatory responses and reperfusion injury.

References

World Health Organization. Cardiovascular Diseases (CVDS). [Internet]. 2021 Aug.

Roth GA, Mensah GA, Johnson CO, Addolorato G, Ammirati E, Baddour LM, et al. Global Burden of Cardiovascular Diseases and Risk Factors, 1990–2019: Update from the GBD 2019 Study. Journal of the American College of Cardiology. 2020 Dec; 76(25): 2982-3021. doi: 10.1016/j.jacc.2020.11.010. DOI: https://doi.org/10.1016/j.jacc.2020.11.021

Algoet M, Janssens S, Himmelreich U, Gsell W, Pusovnik M, Van den Eynde J, et al. Myocardial Ischemia-Reperfusion Injury and the Influence of Inflammation. Trends in Cardiovascular Medicine. 2023 Aug; 33(6): 357-366. doi: 10.1016/j.tcm.2022.06.007. DOI: https://doi.org/10.1016/j.tcm.2022.02.005

He J, Liu D, Zhao L, Zhou D, Rong J, Zhang L, et al. Myocardial Ischemia/Reperfusion Injury: Mechanisms of Injury and Implications for Management. Experimental and Therapeutic Medicine. 2022 Jun; 23(6): 430. doi: 10.3892/etm.2022.11326. DOI: https://doi.org/10.3892/etm.2022.11357

Lindsey ML, Brunt KR, Kirk JA, Kleinbongard P, Calvert JW, de Castro Brás LE, et al. Guidelines for in Vivo Mouse Models of Myocardial Infarction. American Journal of Physiology - Heart and Circulatory Physiology. 2021 Nov; 321(6): H1056-H1103. doi: 10.1152/ajpheart.00462.2021. DOI: https://doi.org/10.1152/ajpheart.00459.2021

Zhang H, Yan Q, Wang X, Chen X, Chen Y, Du J, et al. The Role of Mitochondria in Liver Ischemia-Reperfusion Injury: From Aspects of Mitochondrial Oxidative Stress, Mitochondrial Fission, Mitochondrial Membrane Permeable Transport Pore Formation, Mitophagy, and Mitochondria-Related Protective Measures. Oxidative Medicine and Cellular Longevity. 2021: 6670579. doi: 10.1155/2021/6670579. DOI: https://doi.org/10.1155/2021/6670579

Yang HM. Mitochondrial Dysfunction in Cardiovascular Diseases. International Journal of Molecular Sciences. 2025 Feb; 26(5): 1917. doi: 10.3390/ijms26051917. DOI: https://doi.org/10.3390/ijms26051917

Villar-Fincheira P, Sanhueza-Olivares F, Norambuena-Soto I, Cancino-Arenas N, Hernández-Vargas F, Troncoso R, et al. Role of Interleukin-6 in Vascular Health and Disease. Frontiers in Molecular Biosciences. 2021 Mar; 8: 641734. doi: 10.3389/fmolb.2021.641734. DOI: https://doi.org/10.3389/fmolb.2021.641734

Feng Y, Ye D, Wang Z, Pan H, Lu X, Wang M, et al. The Role of Interleukin-6 Family Members in Cardiovascular Diseases. Frontiers in Cardiovascular Medicine. 2022 Mar; 9: 818890. doi: 10.3389/fcvm.2022.818890. DOI: https://doi.org/10.3389/fcvm.2022.818890

Georgakis MK, Malik R, Gill D, Franceschini N, Sudlow CL, Dichgans M. Interleukin-6 Signaling Effects on Ischemic Stroke and Other Cardiovascular Outcomes: A Mendelian Randomization Study. Circulation: Genomic and Precision Medicine. 2020 Jun; 13(3): e002872. doi: 10.1161/CIRCGEN.119.002872. DOI: https://doi.org/10.1101/19007682

Ridker PM, Rane M. Interleukin-6 Signaling and Anti-Interleukin-6 Therapeutics in Cardiovascular Disease. Circulation Research. 2021 May; 128(11): 1728-1746. doi: 10.1161/CIRCRESAHA.121.318209. DOI: https://doi.org/10.1161/CIRCRESAHA.121.319077

Heusch G. Myocardial Ischemia/Reperfusion: Translational Pathophysiology of Ischemic Heart Disease. Med. 2024 Jan; 5(1): 10-31. doi: 10.1016/j.medj.2023.12.001. DOI: https://doi.org/10.1016/j.medj.2023.12.007

Marcato DC, Spagnol CM, Salgado HR, Isaac VL, Corrêa MA. New and Potential Properties, Characteristics, and Analytical Methods of Ferulic Acid: A Review. Brazilian Journal of Pharmaceutical Sciences. 2022 Apr; 58: e18747. doi: 10.1590/s2175-97902022e18747. DOI: https://doi.org/10.1590/s2175-97902020000118747

Mehrabani M, Amirkhosravi A, Aminzadeh A, Tekiyeh Maroof N, Ab Aziz A, Kamarul T. Ferulic Acid Mitigates H2O2-Induced Oxidative Stress by Hindering the Activity of Reactive Oxygen Species and Programmed Cell Death in Rat PC12 Cells. Physiology and Pharmacology. 2024 Dec; 28(4): 486-495. DOI: https://doi.org/10.61186/phypha.28.4.486

Cebova M and Pechanova O. Protective Effects of Polyphenols Against Ischemia/Reperfusion Injury. Molecules. 2020 Jul; 25(15): 3469. doi: 10.3390/molecules25153469. DOI: https://doi.org/10.3390/molecules25153469

Mancuso C and Santangelo R. Ferulic Acid: Pharmacological and Toxicological Aspects. Food and Chemical Toxicology. 2014 Mar; 65: 185-195. doi: 10.1016/j.fct.2013.12.024. DOI: https://doi.org/10.1016/j.fct.2013.12.024

Verma H, Bhattacharjee A, Shivavedi N, Nayak PK. Evaluation of Rosmarinic Acid Against Myocardial Infarction in Maternally Separated Rats. Naunyn-Schmiedeberg's Archives of Pharmacology. 2022 Oct; 395(10): 1189-1207. doi: 10.1007/s00210-022-02219-3. DOI: https://doi.org/10.1007/s00210-022-02273-9

Lv D, Cheng X, Tang L, Jiang M. The Cardioprotective Effect of Total Flavonoids on Myocardial Ischemia/Reperfusion in Rats. Biomedicine and Pharmacotherapy. 2017 Apr; 88: 277-284. doi: 10.1016/j.biopha.2017.01.035. DOI: https://doi.org/10.1016/j.biopha.2017.01.060

Gao Y, Hao J, Zhang H, Qian G, Jiang R, Hu J, et al. Protective Effect of the Combinations of Glycyrrhizic, Ferulic and Cinnamic Acid Pretreatment on Myocardial Ischemia-Reperfusion Injury in Rats. Experimental and Therapeutic Medicine. 2015 Feb; 9(2): 435-445. doi: 10.3892/etm.2014.2113. DOI: https://doi.org/10.3892/etm.2014.2134

Mahmoud ES, Shams GE. The Possible Protective Effect of Ferulic Acid Against Cisplatin-Induced Renal Toxicity in Rats. Zagazig Veterinary Journal. 2024 Dec; 52(4): 380-395. DOI: https://doi.org/10.21608/zvjz.2024.307340.1255

Liu X, Qi K, Gong Y, Long X, Zhu S, Lu F, et al. Ferulic Acid Alleviates Myocardial Ischemia Reperfusion Injury via Upregulating AMPKα2 Expression-Mediated Ferroptosis Depression. Journal of Cardiovascular Pharmacology. 2022 Apr; 79(4): 489-500. doi: 10.1097/FJC.0000000000001216. DOI: https://doi.org/10.1097/FJC.0000000000001199

Shah AK, Bhullar SK, Elimban V, Dhalla NS. Oxidative Stress as a Mechanism for Functional Alterations in Cardiac Hypertrophy and Heart Failure. Antioxidants. 2021 Jun; 10(6): 931. doi: 10.3390/antiox10060931. DOI: https://doi.org/10.3390/antiox10060931