Abstract
Coronary artery diseases are the major causes of disabilities and death worldwide. Evidence from the literature has demonstrated that Origanum majorana L. (marjoram) acts as an antioxidant, anti-inflammatory, antiplatelet, and assists in hormonal regulation. However, there is limited scientific evidence describing the signaling pathways associated with the marjoram’s positive effect on cardiac injury. Therefore, we aimed to understand the mechanistic protective effects of marjoram on isoproterenol (ISO)-induced myocardial injury in rats. Sprague Dawley rats were randomly assigned into six groups. Marjoram was administrated by oral gavage and isoproterenol was administrated subcutaneously (ISO; 85 mg/kg). Heart weight, cardiac enzymes, inflammatory, and oxidative stress biomarkers were measured. The ISO-induced cardiac injury was confirmed by the significant increase in the levels of cardiac enzymes (P value < 0.05), whereas pre-treatment with marjoram normalized these cardiac injury parameters. We also determined that marjoram had a protective effect against ISO-induced increase in C-reactive protein (CRP), IL-6, IL-13, and TNF-α. Additionally, marjoram significantly decreased cardiac thiobarbituric acid reactive substances (TBARS) levels (P value < 0.05) and protected against ISO-induced oxidative stress. We have demonstrated that marjoram decreased both cardiac oxidative stress and inflammation, thus establishing the beneficial effects of marjoram on ISO-induced cardiac injury in rats.
Similar content being viewed by others
Data Availability
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Abbreviations
- CVDs:
-
Cardiovascular diseases
- ACUC:
-
Animal Care and Use Committee
- IL:
-
Interleukin
- CRP:
-
C-reactive protein
- CK:
-
Creatine kinase
- LDH:
-
Lactate dehydrogenase
- AST:
-
Aspartate transaminase
- ALT:
-
Alanine transaminase
- TNF-α:
-
Tumor necrosis factor-alpha
- SOD:
-
Superoxide dismutase
- TBARS:
-
Thiobarbituric acid reactive substances
- GPx:
-
Glutathione peroxidase
- ISO:
-
Isoproterenol
References
Joseph, P., Leong, D., McKee, M., Anand, S. S., Schwalm, J.-D., Teo, K., et al. (2017). Reducing the global burden of cardiovascular disease, part 1: The epidemiology and risk factors. Circulation Research, 121, 677–694.
Roth, G. A., Forouzanfar, M. H., Moran, A. E., Barber, R., Nguyen, G., Feigin, V. L., et al. (2015). Demographic and epidemiologic drivers of global cardiovascular mortality. New England Journal of Medicine., 372, 1333–1341.
Vos, T., Abajobir, A. A., Abate, K. H., Abbafati, C., Abbas, K. M., Abd-Allah, F., et al. (2017). Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990–2016: A systematic analysis for the Global Burden of Disease Study 2016. The Lancet., 390, 1211–1259.
Saleh, A. I., Abdel Maksoud, S. M., El-Maraghy, S. A., & Gad, M. Z. (2011). Protective effect of L-arginine in experimentally induced myocardial ischemia: Comparison with aspirin. Journal of Cardiovascular Pharmacology and Therapeutics., 16, 53–62.
Kannan, M. M., & Quine, S. D. (2013). Ellagic acid inhibits cardiac arrhythmias, hypertrophy and hyperlipidaemia during myocardial infarction in rats. Metabolism, 62, 52–61.
Rababa’h, A., Singh, S., Suryavanshi, S. V., Altarabsheh, S. E., Deo, S. V., & McConnell, B. K. (2014). Compartmentalization role of A-kinase anchoring proteins (AKAPs) in mediating protein kinase A (PKA) signaling and cardiomyocyte hypertrophy. International Journal of Molecular Sciences, 16, 218–229.
Panda, V. S., & Naik, S. R. (2008). Cardioprotective activity of Ginkgo biloba phytosomes in isoproterenol-induced myocardial necrosis in rats: A biochemical and histoarchitectural evaluation. Experimental and Toxicologic Pathology., 60, 397–404.
Mert, H., Yılmaz, H., Irak, K., Yıldırım, S., & Mert, N. (2018). Investigation of the protective effect of kefir against isoproterenol induced myocardial infarction in rats. Korean Journal for Food Science of Animal Resources, 38, 259.
Guillory, A. N., Yin, X., Wijaya, C. S., Diaz Diaz, A. C., Rababa’h, A., Singh, S., et al. (2013). Enhanced cardiac function in Gravin mutant mice involves alterations in the beta-adrenergic receptor signaling cascade. PLoS ONE, 8, e74784.
Rababa’h, A. M., Guillory, A. N., Mustafa, R., & Hijjawi, T. (2018). Oxidative stress and cardiac remodeling: an updated edge. Current Cardiology Reviews, 14, 53–59.
Jering, K. S., Zannad, F., Claggett, B., Mc Causland, F. R., Ferreira, J. P., Desai, A., et al. (2020). Cardiovascular and renal outcomes of mineralocorticoid receptor antagonist use in PARAGON-HF. JACC Heart Failure, 9, 13.
Nakaya, M., Chikura, S., Watari, K., Mizuno, N., Mochinaga, K., Mangmool, S., et al. (2012). Induction of cardiac fibrosis by beta-blocker in G protein-independent and G protein-coupled receptor kinase 5/beta-arrestin2-dependent signaling pathways. The Journal of Biological Chemistry., 287, 35669–35677.
Waller, S. B., Madrid, I. M., Hoffmann, J. F., Picoli, T., Cleff, M. B., Chaves, F. C., et al. (2017). Chemical composition and cytotoxicity of extracts of marjoram and rosemary and their activity against Sporothrix brasiliensis. Journal of Medical Microbiology, 66, 1076–1083.
Bina, F., & Rahimi, R. (2017). Sweet marjoram: A review of ethnopharmacology, phytochemistry, and biological activities. Journal of Evidence-Based Complementary and Alternative Medicine, 22, 175–185.
Ramadan, G., Nadia, M., & Zahra, M. M. (2012). Egyptian sweet marjoram leaves protect against genotoxicity, immunosuppression and other complications induced by cyclophosphamide in albino rats. British Journal of Nutrition, 108, 1059–1068.
Novak, J., Bitsch, C., Langbehn, J., Pank, F., Skoula, M., Gotsiou, Y., et al. (2000). Ratios of cis-and trans-sabinene hydrate in Origanum majorana L. and Origanum microphyllum (Bentham) Vogel. Biochemical Systematics and Ecology, 28, 697–704.
Rodriguez-Garcia, I., Silva-Espinoza, B. A., Ortega-Ramirez, L. A., Leyva, J. M., Siddiqui, M. W., Cruz-Valenzuela, M. R., et al. (2016). Oregano essential oil as an antimicrobial and antioxidant additive in food products. Critical Reviews in Food Science and Nutrition, 56, 1717–1727.
Leri, M., Scuto, M., Ontario, M. L., Calabrese, V., Calabrese, E. J., Bucciantini, M., et al. (2020). Healthy effects of plant polyphenols: Molecular mechanisms. International Journal of Molecular Sciences, 21, 1250.
Rababa’h, A. M., Matani, B. R., & Ababneh, M. A. (2020). The ameliorative effects of marjoram in dehydroepiandrosterone induced polycystic ovary syndrome in rats. Life Sciences., 261, 118353.
Tveden-Nyborg, P., Bergmann, T. K., & Lykkesfeldt, J. (2018). Basic & clinical pharmacology & toxicology policy for experimental and clinical studies. Basic & Clinical Pharmacology & Toxicology, 123, 233–235.
Rababa’h, A. M., Alzoubi, K. H., Ababneh, M., & Khabour, O. F. (2020). Awareness of Jordanian investigators about the importance of ethics review committees: a pilot study. Science and Engineering Ethics., 26, 821–831.
Soliman, M. M., Nassan, M. A., & Ismail, T. A. (2016). Origanum Majoranum extract modulates gene expression, hepatic and renal changes in a rat model of type 2 diabetes. Iranian Journal of Pharmaceutical Research: IJPR., 15, 45.
Meeran, M. F. N., Azimullah, S., Al Ahbabi, M. M., Jha, N. K., Lakshmanan, V. K., Goyal, S. N., et al. (2020). Nootkatone, a dietary fragrant bioactive compound, attenuates dyslipidemia and intramyocardial lipid accumulation and favorably alters lipid metabolism in a rat model of myocardial injury: An in vivo and in vitro study. Molecules., 25, 5656.
Feng, W., & Li, W. (2010). The study of ISO induced heart failure rat model. Experimental and Molecular Pathology, 88, 299–304.
Afroz, R., Tanvir, E. M., Karim, N., Hossain, M. S., Alam, N., Gan, S. H., et al. (2016). Sundarban honey confers protection against isoproterenol-induced myocardial infarction in wistar rats. BioMed Research International., 2016, 6437641.
Ortendahl, J. D., Diamant, A. L., Toth, P. P., Cherepanov, D., Harmon, A. L., & Broder, M. S. (2019). Protecting the gains: What changes are needed to prevent a reversal of the downward cardiovascular disease mortality trend? Clinical Cardiology., 42, 47–55.
Faulx, M. D., Chandler, M. P., Zawaneh, M. S., Stanley, W. C., & Hoit, B. D. (2007). Mouse strain-specific differences in cardiac metabolic enzyme activities observed in a model of isoproterenol-induced cardiac hypertrophy. Clinical and Experimental Pharmacology and Physiology., 34, 77–80.
Besbasi, F., & Hamlin, R. (1990). Influence of phenytoin on isoproterenol-induced myocardial fibrosis in rats. American Journal of Veterinary Research., 51, 36–39.
Panda, V., Laddha, A., Nandave, M., & Srinath, S. (2016). Dietary phenolic acids of Macrotyloma uniflorum (Horse Gram) protect the rat heart against isoproterenol-induced myocardial infarction. Phytotherapy Research., 30, 1146–1155.
Apple, F. S., Falahati, A., Paulsen, P. R., Miller, E. A., & Sharkey, S. W. (1997). Improved detection of minor ischemic myocardial injury with measurement of serum cardiac troponin I. Clinical Chemistry., 43, 2047–2051.
Ramadan, G., Nadia, M., Arafa, N. M., & Zahra, M. M. (2013). Preventive effects of egyptian sweet marjoram (Origanum majorana L.) leaves on haematological changes and cardiotoxicity in isoproterenol-treated albino rats. Cardiovascular Toxicology, 13, 100–9.
Tiwari, R., Mohan, M., Kasture, S., Maxia, A., & Ballero, M. (2009). Cardioprotective potential of myricetin in isoproterenol-induced myocardial infarction in Wistar rats. Phytotherapy Research: An International Journal Devoted to Pharmacological and Toxicological Evaluation of Natural Product Derivatives., 23, 1361–1366.
Suchalatha, S., & Devi, C. S. (2004). Effect of arogh—a polyherbal formulation on the marker enzymes in isoproterenol induced myocardial injury. Indian Journal of Clinical Biochemistry., 19, 184–189.
Thygesen, K., Alpert, J. S., Jaffe, A. S., Chaitman, B. R., Bax, J. J., Morrow, D. A., et al. (2019). Fourth universal definition of myocardial infarction (2018). European Heart Journal, 40, 237–269.
Goyal, B. R., & Mehta, A. A. (2012). Benefi cial role of spironolactone, telmisartan and their combination on isoproterenol-induced cardiac hypertrophy. Acta Cardiologica, 67, 203–211.
Meeran, M. F. N., Jagadeesh, G. S., & Selvaraj, P. (2015). Thymol attenuates inflammation in isoproterenol induced myocardial infarcted rats by inhibiting the release of lysosomal enzymes and downregulating the expressions of proinflammatory cytokines. European Journal of Pharmacology., 754, 153–161.
Mansoury, M. M. (2019). Marjoram (Origanum majorana L.) Alleviate Myocardial Damage Induced by Doxorubicin in Rats. Journal of Biochemical Technology., 10, 82.
Arranz, E., Jaime, L., de las Hazas, M. L., Reglero, G., & Santoyo, S. (2015). Supercritical fluid extraction as an alternative process to obtain essential oils with anti-inflammatory properties from marjoram and sweet basil. Industrial Crops and Products, 67, 121–9.
Arranz, E., Jaime, L., López de las Hazas, M. C., Reglero, G., & Santoyo, S. (2015). Supercritical fluid extraction as an alternative process to obtain essential oils with anti-inflammatory properties from marjoram and sweet basil, Industrial Crops and Products. Industrial Crops and Products, 67, 121–9.
Puhakka, M., Magga, J., Hietakorpi, S., Penttilä, I., Uusimaa, P., Risteli, J., et al. (2003). Interleukin-6 and tumor necrosis factor alpha in relation to myocardial infarct size and collagen formation. Journal of Cardiac Failure, 9, 325–332.
Thygesen, K., Alpert, J. S., Jaffe, A. S., Chaitman, B. R., Bax, J. J., Morrow, D. A., et al. (2019). Fourth universal definition of myocardial infarction (2018). European Heart Journal., 40, 237–269.
Ramadan, G., El-Beih, N. M., Arafa, N. M., & Zahra, M. M. (2013). Preventive effects of Egyptian sweet marjoram (Origanum majorana L) leaves on haematological changes and cardiotoxicity in isoproterenol-treated albino rats. Cardiovasc Toxicol, 13, 100–9.
Mossa, A., Heikal, T. M., Mohafrash, S. M., & Refaie, A. A. (2015). Antioxidant potential and hepatoprotective activity of Origanum majorana leaves extract against oxidative damage and hepatotoxicity induced by pirimiphos-methyl in male mice. Journal of Applied Sciences, 15, 69–79.
Wong, Z. W., Thanikachalam, P. V., & Ramamurthy, S. (2017). Molecular understanding of the protective role of natural products on isoproterenol-induced myocardial infarction: A review. Biomedicine & Pharmacotherapy., 94, 1145–1166.
Refaie, A. A., Ramadan, A., & Mossa, A. T. (2014). Oxidative damage and nephrotoxicity induced by prallethrin in rat and the protective effect of Origanum majorana essential oil. Asian Pacific Journal of Tropical Medicine, 7–1, S506–S513.
Mossa, A. T., Refaie, A. A., Ramadan, A., & Bouajila, J. (2013). Amelioration of prallethrin-induced oxidative stress and hepatotoxicity in rat by the administration of Origanum majorana essential oil. BioMed Research International., 2013, 859085.
Vasudeva, N., Singla, P., Das, S., & Sharma, S. K. (2014). Antigout and antioxidant activity of stem and root of Origanum Majorana Linn. American Journal of Drug Discovery and Development., 4, 102–112.
Prakash, N. K. U., Sripriya, N. S., Raj, D. D., Deepa, S., & Bhuvaneswari, S. (2019). Antioxidant potency and GC-MS composition of Origanum majorana Linn. Pakistan Journal of Pharmaceutical Sciences, 32, 2117–2122.
Leyva-López, N., Gutiérrez-Grijalva, E. P., Vazquez-Olivo, G., & Heredia, J. B. (2017). Essential oils of oregano: biological activity beyond their antimicrobial properties. Molecules (Basel, Switzerland)., 22, 989.
Quiroga, P. R., Riveros, C. G., Zygadlo, J. A., Grosso, N. R., & Nepote, V. (2011). Antioxidant activity of essential oil of oregano species from Argentina in relation to their chemical composition. International Journal of Food Science & Technology., 46, 2648–2655.
El-Ashmawy, I. M., Saleh, A., & Salama, O. M. (2007). Effects of marjoram volatile oil and grape seed extract on ethanol toxicity in male rats. Basic & Clinical Pharmacology & Toxicology, 101, 320–327.
Acknowledgment
This work was supported by the Deanship of Research at Jordan University of Science and Technology to AR [Project Number: 451/2019]. We would like to thank Professor Bradley McConnell (Department of Pharmacological and Pharmaceutical Sciences, University of Houston) for proofreading the final version of the manuscript.
Funding
Financial support was via grant number 451/2019 from the Deanship of Research at the Jordan University of Science and Technology to AR.
Author information
Authors and Affiliations
Contributions
AR: conceptualization; AR and MA designed the study; AR provided the plant; AR and MA conducted the experimental work; AR and MA drafted the manuscript; AR and MA conducted the field research; AR contributed new reagents or analytic tools; AR and MA performed data analysis and interpreted the results; AR and MA contributed to the discussion. All authors read and approved the final manuscript.
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Additional information
Handling Editor: Y. James Kang.
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Rababa’h, A.M., Alzoubi, M.A. Origanum majorana L. Extract Protects Against Isoproterenol-Induced Cardiotoxicity in Rats. Cardiovasc Toxicol 21, 543–552 (2021). https://doi.org/10.1007/s12012-021-09645-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12012-021-09645-2