Author: Darssheela Ramasamy
Affiliation: Department of Microbiology, Universiti Putra Malaysia.
Cardiovascular diseases (CVDs) remain the leading cause of global morbidity and mortality claiming 20.5 million lives in 2021 alone, accounting for over one-third of worldwide deaths (Di Cesare et al., 2024). Low and middle-income countries bear a disproportionate burden, contributing to 32% of all CVD-related deaths (Hasani et al., 2023). These diseases impose a significant economic strain, with treatment costs for conditions like hypertension averaging between $500 and $1500 per episode, while managing coronary heart disease or stroke can exceed $5000 per episode (Gheorghe et al., 2018). This underscores the urgent need for cost effective, accessible interventions to address CVD’s globally.
Several factors contribute to cardiovascular disease (CVD) prevalence, including diabetes, obesity, sedentary lifestyle, hypertension, poor diet, smoking, and excessive alcohol intake (Hasani et al., 2023). Moreover, aging populations, environmental challenges, and healthcare disparities exacerbate crisis (Roth et al., 2020). Against this backdrop, natural compounds like linalool offer a glimmer of hope.
Linalool, a monoterpene phytochemical commonly found in the essential oils of aromatic plants like lavender, has demonstrated a wide array of pharmacological benefits, including antidepressant, antimicrobial, gastroprotective, antinociceptive, and antitumor effects (dos Santos et al., 2021; Kamatou & Viljoen, 2008). Importantly, it is considered safe for consumption, with no significant toxicological or mutagenic effects observed in studies (Letizia et al., 2003).
Cardioprotective Effects of Linalool
Recent research highlights linalool’s remarkable potential in mitigating cardiovascular risks thanks to its anti-inflammatory, antioxidant, and vasodilatory properties. Mohamed et al. (2021) demonstrated linalool’s ability to reduce myocardial infarction (MI)-related damage, including lowering infarct size and improving critical cardiac parameters such as heart rate, blood pressure, and electrocardiographic readings. Linalool’s antihypertensive effects stem from its ability to induce vasodilation by directly acting on vascular smooth muscles and engaging endothelial pathways involving guanylyl cyclase and potassium channels.
The study also noted its role in enhancing antioxidant markers (SOD, CAT, and GPx), reducing oxidative stress, and combating inflammation by decreasing pro-inflammatory cytokines like TNF-α and IL-6 and inhibiting NF-κB activation. Additionally, linalool modulates apoptosis, increasing anti-apoptotic Bcl-2 and decreasing pro-apoptotic factors like Bax and caspases, thereby protecting heart cells from myocardial infarction (MI) induced damage (Mohamed et al., 2021).
Jianlin Ke and colleagues explored linalool’s antiarrhythmic properties, emphasising its ability to preserve Connexin 43, a critical protein for cardiac electrical signal conduction. This reduced the risk of arrhythmias by stabilising the resting membrane potential of heart cells. Additionally, linalool induced vascular endothelial growth factor B (VEGF-B) levels supporting blood vessel survival and preventing ischemia-induced damage (damage due to restricted blood flow) (Ke et al., 2020).
Complementing these findings, another line of research confirmed linalool’s efficacy in improving heart function by reducing infarct size, cardiac tissue necrosis, and Troponin-T levels, a marker of cardiac injury. It also countered oxidative stress by reducing malondialdehyde (MDA) levels and restoring antioxidant enzymes. Linalool’s anti-inflammatory effects were evident through reduced polymorphonuclear leukocyte infiltration, and myeloperoxidase activity. Molecularly, it activated the cell survival pathways via Akt protein and inhibited glycogen synthase kinase-3β, further boosting cardioprotective benefits (Zheng et al., 2017).
Linalool also demonstrated the ability to induce vascular relaxation and lower blood pressure by blocking calcium influx through voltage-dependent calcium channels and inhibiting calcium release from intracellular stores. These mechanisms reduce vascular smooth muscle contraction and promote vascular health. In hypertensive models, linalool prevented vascular remodeling by inhibiting smooth muscle cells proliferation (Anjos et al., 2013).
Overcoming Limitations
Despite its promising profile, linalool’s volatility and liposolubility pose challenges. Complexation with β-cyclodextrin (LIN-β-CD) has been shown to enhance stability, bioavailability and antihypertensive efficacy (Brito et al., 2023). With minimal toxicity and proven safety during fetal development in animal studies, linalool is well positioned for further exploration.
Conclusion
Linalool’s multifaceted cardioprotective effects including oxidative stress, inflammation, arrythymias and vascular remodelling, highlights its potential as natural therapeutic for cardiovascular diseases. While preclinical evidence is robust, further research, particularly human trials, is essential to integrate linalool into CVD management strategies effectively.
References
Anjos, P. J. C., Lima, A. O., Cunha, P. S., De Sousa, D. P., Onofre, A. S. C., Ribeiro, T. P., Medeiros, I. A., Antoniolli, Â. R., Quintans-Júnior, L. J., & Santos, M. R. V. (2013). Cardiovascular effects induced by linalool in normotensive and hypertensive rats. Zeitschrift Fur Naturforschung – Section C Journal of Biosciences, 68 C(5–6), 181–190. https://doi.org/10.1515/znc-2013-5-603
Brito, D. S. de, Moraes, R. dos A., Jesus, R. L. C. de, Araújo, F. A. de, Silva, L. B. da, Lima, G. B. de C., Camargo, S. B., Silva, I. L. P. da, & Silva, D. F. (2023). Cardiovascular effects of free or complexed linalool to β-cyclodextrin: a focus for antihypertensive action. Revista de Medicina, 102(6), 0–2. http://dx.doi.org/10.11606/issn.1679-9836.v102i6e-203574
Di Cesare, M., McGhie, D. V., Perel, P., Mwangi, J., Taylor, S., Pervan, B., Kabudula, C., Narula, J., Bixby, H., Pineiro, D., Gaziano, T. A., & Pinto, F. J. (2024). The Heart of the World. Global Heart, 19(1). https://doi.org/10.5334/gh.1288
dos Santos, É. R. Q., Maia, J. G. S., Fontes-Júnior, E. A., & do Socorro Ferraz Maia, C. (2022). Linalool as a Therapeutic and Medicinal Tool in Depression Treatment: A Review. Current Neuropharmacology, 20(6), 1073–1092. https://doi.org/10.2174/1570159×19666210920094504
Gheorghe, A., Griffiths, U., Murphy, A., Legido-Quigley, H., Lamptey, P., & Perel, P. (2018). The economic burden of cardiovascular disease and hypertension in low- and middle-income countries: A systematic review. BMC Public Health, 18(1), 1–11. https://doi.org/10.1186/s12889-018-5806-x
Hasani, W. S. R., Musa, K. I., Cheng, K. Y., & Dass, S. C. (2023). Exploring the trend of age-standardized mortality rates from cardiovascular disease in Malaysia: A joinpoint analysis (2010-2021). 1–12. https://doi.org/10.1186/s12889-024-19103-7
Kamatou, G. P. P., & Viljoen, A. M. (2008). Linalool – a Review of a Biologically Active Compound of Commercial Importance. Natural Product Communications, 3(7), 1934578X0800300727. https://doi.org/10.1177/1934578X0800300727
Ke, J., Zhu, C., Zhang, Y., & Zhang, W. (2020). Anti‐Arrhythmic Effects of Linalool via Cx43 Expression in a Rat Model of Myocardial Infarction. Frontiers in Pharmacology, 11(June), 1–8. https://doi.org/10.3389/fphar.2020.00926
Letizia, C. S., Cocchiara, J., Lalko, J., & Api, A. M. (2003). Fragrance material review on linalool. Food and Chemical Toxicology, 41(7), 943–964. https://doi.org/10.1016/S0278-6915(03)00015-2
Mohamed, M. E., Abduldaium, M. S., & Younis, N. S. (2021). Cardioprotective effect of linalool against isoproterenol-induced myocardial infarction. Life, 11(2), 1–17. https://doi.org/10.3390/life11020120
Roth, G. A., Mensah, G. A., Johnson, C. O., Addolorato, G., Ammirati, E., Baddour, L. M., Barengo, N. C., Beaton, A., Benjamin, E. J., Benziger, C. P., Bonny, A., Brauer, M., Brodmann, M., Cahill, T. J., Carapetis, J. R., Catapano, A. L., Chugh, S., Cooper, L. T., Coresh, J., … Fuster, V. (2020). Global Burden of Cardiovascular Diseases and Risk Factors, 1990-2019: Update From the GBD 2019 Study. Journal of the American College of Cardiology, 76(25), 2982–3021. https://doi.org/10.1016/j.jacc.2020.11.010
Zheng, X. H., Liu, C. P., Hao, Z. G., Wang, Y. F., & Li, X. L. (2017). Protective effect and mechanistic evaluation of linalool against acute myocardial ischemia and reperfusion injury in rats. RSC Advances, 7(55), 34473–34481. https://doi.org/10.1039/c7ra00743d
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