Abstract
Inflammation is a multifaceted biological reaction to a wide range of stimuli, and it has been linked to the onset and progression of chronic diseases such as heart disease, cancer, and diabetes. Inflammatory markers found in the blood, including C-reactive protein, serum amyloid A, fibrinogen, plasma viscosity, erythrocyte sedimentation rate, interleukin-6, and soluble adhesion molecules (like intercellular adhesion molecule-1 and vascular cell adhesion molecule-1), are risk factors for cardiovascular diseases such as coronary heart disease, stroke, and peripheral arterial disease. These markers play a crucial role in understanding and assessing cardiovascular health. Due to this complicated relationship between inflammation and cardiovascular disease, anti-inflammatory agents of natural origin have been the subject of many preclinical and clinical studies in recent years. Eugenol is a natural phenolic compound found in clove oil, nutmeg oil, cinnamon oil, and bay leaf oil, as well as other essential oils. Eugenol has been shown to have anti-inflammatory properties in many forms of experimental inflammation. It may scavenge free radicals, which contribute to inflammation and tissue damage. Various studies also suggest that eugenol can limit the production of inflammatory mediators such as prostaglandins, cytokines, and chemokines. Animal models of arthritis, colitis, and lung damage, as well as human clinical studies, have shown that eugenol has phenomenal anti-inflammatory properties. These properties suggest that eugenol may be able to reduce the risk of cardiovascular diseases.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Availability of data and materials
Not applicable.
References
Adeyemi DH, Obembe OO, Hamed MA, Akhigbe RE (2023) Sodium acetate ameliorates doxorubicin-induced cardiac injury via upregulation of Nrf2/HO-1 signaling and downregulation of NFkB-mediated apoptotic signaling in Wistar rats. Naunyn Schmiedebergs Arch Pharmacol. https://doi.org/10.1007/s00210-023-02620-4
Barboza JN, da Silva-Maia-Bezerra-Filho C, Silva RO et al (2018) An overview on the anti-inflammatory potential and antioxidant profile of eugenol. Oxid Med Cell Longev 2018:3957262. https://doi.org/10.1155/2018/3957262
Behl T, Bungau S, Kumar K et al (2020) Pleotropic effects of polyphenols in cardiovascular system. Biomed Pharmacother 130:110714. https://doi.org/10.1016/j.biopha.2020.110714
Bittencourt-Mernak MI, Pinheiro NM, da Silva RC et al (2021) Effects of eugenol and dehydrodieugenol b from nectandra leucantha against lipopolysaccharide (LPS)-induced experimental acute lung inflammation. J Nat Prod 84:2282–2294. https://doi.org/10.1021/acs.jnatprod.1c00386
Chen S-J, Huang Y-C, Wu B-N, Chen I-J (1997) Eugenolol: an eugenol-derived β-adrenoceptor blocker with partial β2-agonist and calcium mobilization inhibition associated vasorelaxant activities. Drug Dev Res 40:239–250. https://doi.org/10.1002/(SICI)1098-2299(199703)40:3%3c239::AID-DDR4%3e3.0.CO;2-L
Cho JS, Kim TH, Lim J-M, Song J-H (2008) Effects of eugenol on Na+ currents in rat dorsal root ganglion neurons. Brain Res 1243:53–62. https://doi.org/10.1016/j.brainres.2008.09.030
Choudhary R, Mishra KP, Subramanyam C (2006) Interrelations between oxidative stress and calcineurin in the attenuation of cardiac apoptosis by eugenol. Mol Cell Biochem 283:115–122. https://doi.org/10.1007/s11010-006-2386-3
Chung G, Rhee JN, Jung SJ et al (2008) Modulation of CaV2.3 calcium channel currents by eugenol. J Dent Res 87:137–141. https://doi.org/10.1177/154405910808700201
Comunanza V, Carbone E, Marcantoni A et al (2011) Calcium-dependent inhibition of T-type calcium channels by TRPV1 activation in rat sensory neurons. Pflugers Arch 462:709–722. https://doi.org/10.1007/s00424-011-1023-5
Corb Aron RA, Abid A, Vesa CM et al (2021) Recognizing the benefits of pre-/probiotics in metabolic syndrome and type 2 diabetes mellitus considering the influence of akkermansia muciniphila as a key gut bacterium. Microorganisms 9:618. https://doi.org/10.3390/microorganisms9030618
Cragg GM, Newman DJ (2013) Natural products: a continuing source of novel drug leads. Biochim Biophys Acta 1830:3670–3695. https://doi.org/10.1016/j.bbagen.2013.02.008
Damiani CEN, Rossoni LV, Vassallo DV (2003) Vasorelaxant effects of eugenol on rat thoracic aorta. Vascul Pharmacol 40:59–66. https://doi.org/10.1016/s1537-1891(02)00311-7
Daniel AN, Sartoretto SM, Becerra-Schmidt G et al (2009) Anti-inflammatory and antinociceptive activities A of eugenol essential oil in experimental animal models. Rev Bras. https://doi.org/10.1590/S0102-695X2009000200006
das Chagas Pereira de Andrade F, Mendes AN (2020) Computational analysis of eugenol inhibitory activity in lipoxygenase and cyclooxygenase pathways. Sci Rep 10:16204. https://doi.org/10.1038/s41598-020-73203-z
Das S, Das DK (2007) Resveratrol: a therapeutic promise for cardiovascular diseases. Recent Pat Cardiovasc Drug Discov 2:133–138. https://doi.org/10.2174/157489007780832560
de Dantas DM, de Silva AA, Pereira-de-Morais L et al (2022) Characterization of the vasodilator effect of eugenol in isolated human umbilical cord arteries. Chemico-Biol Interact 359:109890. https://doi.org/10.1016/j.cbi.2022.109890
de Fátima Leal Interaminense de Andrade L (2007) RI UFPE: Estudo dos efeitos cardiovasculares do óleo essencial do Ocimum gratissimum e de seu principal constituinte, Eugenol, em ratos hipertensos DOCA-sal, acordados
Earley S, Brayden JE (2015) Transient receptor potential channels in the vasculature. Physiol Rev 95:645–690. https://doi.org/10.1152/physrev.00026.2014
Elsebai MF, Albalawi MA (2022) Essential oils and COVID-19. Molecules. https://doi.org/10.3390/molecules27227893
Estevão-Silva CF, Kummer R, Fachini-Queiroz FC et al (2014) Anethole and eugenol reduce in vitro and in vivo leukocyte migration induced by fMLP, LTB4, and carrageenan. J Nat Med 68:567–575. https://doi.org/10.1007/s11418-014-0839-7
Feng W, Jin L, Xie Q et al (2018) Eugenol protects the transplanted heart against ischemia/reperfusion injury in rats by inhibiting the inflammatory response and apoptosis. Exp Ther Med 16:3464–3470. https://doi.org/10.3892/etm.2018.6598
Fischer IU, von Unruh GE, Dengler HJ (1990) The metabolism of eugenol in man. Xenobiotica 20:209–222. https://doi.org/10.3109/00498259009047156
Foudah AI, Devi S, Alqarni MH et al (2022) Quercetin attenuates nitroglycerin-induced migraine headaches by inhibiting oxidative stress and inflammatory mediators. Nutrients 14:4871. https://doi.org/10.3390/nu14224871
Fujisawa S, Atsumi T, Kadoma Y, Sakagami H (2002) Antioxidant and prooxidant action of eugenol-related compounds and their cytotoxicity. Toxicology 177:39–54. https://doi.org/10.1016/s0300-483x(02)00194-4
Gheorghe G, Toth PP, Bungau S et al (2020) Cardiovascular risk and statin therapy considerations in women. Diagnostics (basel) 10:483. https://doi.org/10.3390/diagnostics10070483
Guenette SA, Beaudry F, Marier JF, Vachon P (2006) Pharmacokinetics and anesthetic activity of eugenol in male Sprague-Dawley rats. J Vet Pharmacol Ther 29:265–270. https://doi.org/10.1111/j.1365-2885.2006.00740.x
Guénette SA, Ross A, Marier J-F et al (2007) Pharmacokinetics of eugenol and its effects on thermal hypersensitivity in rats. Eur J Pharmacol 562:60–67. https://doi.org/10.1016/j.ejphar.2007.01.044
Halliwell B (2001) Food-derived antioxidants: how to evaluate their importance in food and in vivo. Handbook of antioxidants, 2nd edn. CRC Press, p 46
Hamdin CD, Utami SW, Muliasari H et al (2019) Histological pattern on pancreas and liver of diabetic rats after treatment of eugenol isolated from leaves of Syzygium aromaticum. AIP Conf Proc 2199:060004. https://doi.org/10.1063/1.5141313
Han X, Parker TL (2017) Anti-inflammatory activity of clove (Eugenia caryophyllata) essential oil in human dermal fibroblasts. Pharm Biol 55:1619–1622. https://doi.org/10.1080/13880209.2017.1314513
Harb AA, Bustanji YK, Almasri IM, Abdalla SS (2019) Eugenol reduces LDL cholesterol and hepatic steatosis in hypercholesterolemic rats by modulating TRPV1 receptor. Sci Rep 9:14003. https://doi.org/10.1038/s41598-019-50352-4
Hosseinzadeh S, Jafarikukhdan A, Hosseini A, Armand R (2015) The application of medicinal plants in traditional and modern medicine: a review of Thymus vulgaris. Int J Clin Med 06:635. https://doi.org/10.4236/ijcm.2015.69084
Hu G, Li X, Zhang S, Wang X (2016) Association of rat thoracic aorta dilatation by astragaloside IV with the generation of endothelium-derived hyperpolarizing factors and nitric oxide, and the blockade of Ca2+ channels. Biomed Rep 5:27–34. https://doi.org/10.3892/br.2016.680
Hu S, Liu B, Yang M et al (2023) Carnosic acid protects against doxorubicin-induced cardiotoxicity through enhancing the Nrf2/HO-1 pathway. Food Funct 14:3849–3862. https://doi.org/10.1039/D2FO03904D
Huang M-Z, Yang Y-J, Liu X-W et al (2019) Aspirin eugenol ester attenuates oxidative injury of vascular endothelial cells by regulating NOS and Nrf2 signalling pathways. Br J Pharmacol 176:906–918. https://doi.org/10.1111/bph.14592
Hussain S, Rahman R, Mushtaq A, Zerey-Belaskri AE (2017) Clove: a review of a precious species with multiple uses
Hwang S-M, Lee K, Im S-T et al (2020) Co-application of eugenol and QX-314 elicits the prolonged blockade of voltage-gated sodium channels in nociceptive trigeminal ganglion neurons. Biomolecules 10:1513. https://doi.org/10.3390/biom10111513
Isaksson M, Rustemeyer T, Antelmi A (2020) Dental materials and implants. In: Contact dermatitis. pp 1–40
Jiao K, Su P, Li Y (2023) FGFR2 modulates the Akt/Nrf2/ARE signaling pathway to improve angiotensin II-induced hypertension-related endothelial dysfunction. Clin Exp Hypertens 45:2208777. https://doi.org/10.1080/10641963.2023.2208777
Jirovetz L, Buchbauer G, Stoilova I et al (2006) Chemical composition and antioxidant properties of clove leaf essential oil. J Agric Food Chem 54:6303–6307. https://doi.org/10.1021/jf060608c
Johnston GAR (2005) GABA(A) receptor channel pharmacology. Curr Pharm Des 11:1867–1885. https://doi.org/10.2174/1381612054021024
Karuppasamy V, Sekar SK, Kandhasamy S, et al (2022) The anti-integrity activity of eugenol on inflammatory markers of chronic atherosclerosis (In Review)
Kouidhi B, Zmantar T, Bakhrouf A (2010) Anticariogenic and cytotoxic activity of clove essential oil (Eugenia caryophyllata) against a large number of oral pathogens. Ann Microbiol 60:599–604. https://doi.org/10.1007/s13213-010-0092-6
Kuang B, Wang Z, Hou S et al (2023) Methyl eugenol protects the kidney from oxidative damage in mice by blocking the Nrf2 nuclear export signal through activation of the AMPK/GSK3β axis. Acta Pharmacol Sin 44:367–380. https://doi.org/10.1038/s41401-022-00942-2
Kumar S, Behl T, Sachdeva M et al (2021) Implicating the effect of ketogenic diet as a preventive measure to obesity and diabetes mellitus. Life Sci 264:118661. https://doi.org/10.1016/j.lfs.2020.118661
Kummer R, Estevão-Silva CF, Bastos RL et al (2015) Alpha-pinene reduces in vitro and in vivo leukocyte migration during acute inflammation. Int J Appl Res Nat Prod 8:12–17
Magalhães CB, Riva DR, DePaula LJ et al (2010) In vivo anti-inflammatory action of eugenol on lipopolysaccharide-induced lung injury. J Appl Physiol 108:845–851. https://doi.org/10.1152/japplphysiol.00560.2009
Marchese A, Barbieri R, Coppo E et al (2017) Antimicrobial activity of eugenol and essential oils containing eugenol: a mechanistic viewpoint. Crit Rev Microbiol 43:668–689. https://doi.org/10.1080/1040841X.2017.1295225
Markowitz K, Moynihan M, Liu M, Kim S (1992) Biologic properties of eugenol and zinc oxide-eugenol. A clinically oriented review. Oral Surg Oral Med Oral Pathol 73:729–737. https://doi.org/10.1016/0030-4220(92)90020-q
Mnafgui K, Kaanich F, Derbali A et al (2013) Inhibition of key enzymes related to diabetes and hypertension by eugenol in vitro and in alloxan-induced diabetic rats. Arch Physiol Biochem 119:225–233. https://doi.org/10.3109/13813455.2013.822521
Mohammadi Nejad S, Özgüneş H, Başaran N (2017) Pharmacological and toxicological properties of eugenol. Turk J Pharm Sci 14:201–206. https://doi.org/10.4274/tjps.62207
Nagababu E, Sesikeran B, Lakshmaiah N (1995) The protective effects of eugenol on carbon tetrachloride induced hepatotoxicity in rats. Free Radic Res 23:617–627. https://doi.org/10.3109/10715769509065281
Nagababu E, Rifkind JM, Boindala S, Nakka L (2010) Assessment of antioxidant activity of eugenol in vitro and in vivo. Methods Mol Biol 610:165–180. https://doi.org/10.1007/978-1-60327-029-8_10
Nisar MF, Khadim M, Rafiq M et al (2021) Pharmacological properties and health benefits of eugenol: a comprehensive review. Oxid Med Cell Longev 2021:2497354. https://doi.org/10.1155/2021/2497354
Ohkubo T, Kitamura K (1997) Eugenol activates Ca(2+)-permeable currents in rat dorsal root ganglion cells. J Dent Res 76:1737–1744. https://doi.org/10.1177/00220345970760110401
Pan C, Dong Z (2015) Antiasthmatic effects of eugenol in a mouse model of allergic asthma by regulation of vitamin D3 upregulated protein 1/NF-κB pathway. Inflammation 38:1385–1393. https://doi.org/10.1007/s10753-015-0110-8
Parija SC, Jandhyam H, Mohanty BP, et al (2020) Eugenol induces potent vasorelaxation in uterine arteries from pregnant goats—a promising natural therapeutic agent for hypertensive disorders of pregnancy. 2020.09.22.307629
Patel RV, Mistry BM, Shinde SK et al (2018) Therapeutic potential of quercetin as a cardiovascular agent. Eur J Med Chem 155:889–904. https://doi.org/10.1016/j.ejmech.2018.06.053
Pramod K, Ansari SH, Ali J (2010) Eugenol: a natural compound with versatile pharmacological actions. Nat Prod Commun 5:1999–2006
Qar J, Al-Trad B, Khmaiseh A et al (2022) The effect of eugenol treatment on diabetic cardiomyopathy in streptozotocin-induced diabetic rats. Biomed Pharmacol J 15:623–633
Rameshrad M, Babaei H, Azarmi Y, Fouladi DF (2016) Rat aorta as a pharmacological tool for in vitro and in vivo studies. Life Sci 145:190–204. https://doi.org/10.1016/j.lfs.2015.12.043
Rathod P, Yadav RP (2021) Anti-diabesity potential of various multifunctional natural molecules. J Herb Med 27:100430. https://doi.org/10.1016/j.hermed.2021.100430
Rodrigues TG, Fernandes A, Sousa JPB et al (2009) In vitro and in vivo effects of clove on pro-inflammatory cytokines production by macrophages. Nat Prod Res 23:319–326. https://doi.org/10.1080/14786410802242679
Sankhyan A, Pawar PK (2013) Metformin loaded non-ionic surfactant vesicles: optimization of formulation, effect of process variables and characterization. Daru 21:7. https://doi.org/10.1186/2008-2231-21-7
Sarnak MJ, Levey AS (2000) Cardiovascular disease and chronic renal disease: a new paradigm. Am J Kidney Dis 35:S117-131. https://doi.org/10.1016/s0272-6386(00)70239-3
Savsani HH (2020) Pharmacological modulation of calcium in selective cardiovascular disorders through store operated calcium entry inhibitors. Vadodara
Sensch O, Vierling W, Brandt W, Reiter M (2000) Effects of inhibition of calcium and potassium currents in guinea-pig cardiac contraction: comparison of beta-caryophyllene oxide, eugenol, and nifedipine. Br J Pharmacol 131:1089–1096. https://doi.org/10.1038/sj.bjp.0703673
Sharma JN, Srivastava KC, Gan EK (1994) Suppressive effects of eugenol and ginger oil on arthritic rats. Pharmacology 49:314–318. https://doi.org/10.1159/000139248
Singh A, Singh KS (2022) Bioactive compounds from polar regions: an account of chemical ecology and biotechnological applications. Curr Org Chem 26:1055–1087
Srivastava KC, Mustafa T (1989) Spices: antiplatelet activity and prostanoid metabolism. Prostaglandins Leukot Essent Fatty Acids 38:255–266. https://doi.org/10.1016/0952-3278(89)90129-4
Tan J, Yadav MK, Devi S, Kumar M (2022) Neuroprotective effects of arbutin against oxygen and glucose deprivation-induced oxidative stress and neuroinflammation in rat cortical neurons. Acta Pharm 72:123–134. https://doi.org/10.2478/acph-2022-0002
Tedeschi LO, Muir JP, Naumann HD et al (2021) Nutritional aspects of ecologically relevant phytochemicals in ruminant production. Front Vet Sci 8:628445. https://doi.org/10.3389/fvets.2021.628445
Thakur G, Singh A, Singh I (2016) Chitosan-montmorillonite polymer composites: formulation and evaluation of sustained release tablets of aceclofenac. Sci Pharm 84:603–618. https://doi.org/10.3390/scipharm84040603
Touyz RM, Alves-Lopes R, Rios FJ et al (2018) Vascular smooth muscle contraction in hypertension. Cardiovasc Res 114:529–539. https://doi.org/10.1093/cvr/cvy023
Ugbogu OC, Emmanuel O, Agi GO et al (2021) A review on the traditional uses, phytochemistry, and pharmacological activities of clove basil (Ocimum gratissimum L.). Heliyon 7:e08404. https://doi.org/10.1016/j.heliyon.2021.e08404
Venkadeswaran K, Thomas PA, Geraldine P (2016) An experimental evaluation of the anti-atherogenic potential of the plant, Piper betle, and its active constitutent, eugenol, in rats fed an atherogenic diet. Biomed Pharmacother 80:276–288. https://doi.org/10.1016/j.biopha.2016.03.028
Wong ZW, Thanikachalam PV, Ramamurthy S (2017) Molecular understanding of the protective role of natural products on isoproterenol-induced myocardial infarction: a review. Biomed Pharmacother 94:1145–1166. https://doi.org/10.1016/j.biopha.2017.08.009
Xiao-Rong L, Ning M, Xi-Wang L et al (2021) Untargeted and targeted metabolomics reveal the underlying mechanism of aspirin eugenol ester ameliorating rat hyperlipidemia via inhibiting FXR to induce CYP7A1. Front Pharmacol 12:733789. https://doi.org/10.3389/fphar.2021.733789
Xu G-Y, Winston JH, Shenoy M et al (2007) Transient receptor potential vanilloid 1 mediates hyperalgesia and is up-regulated in rats with chronic pancreatitis. Gastroenterology 133:1282–1292. https://doi.org/10.1053/j.gastro.2007.06.015
Yamamoto S, Shimizu S, Kiyonaka S et al (2008) TRPM2-mediated Ca2+ influx induces chemokine production in monocytes that aggravates inflammatory neutrophil infiltration. Nat Med 14:738–747. https://doi.org/10.1038/nm1758
Yang BH, Piao ZG, Kim Y-B et al (2003) Activation of vanilloid receptor 1 (VR1) by eugenol. J Dent Res 82:781–785. https://doi.org/10.1177/154405910308201004
Yeh JL, Hsu JH, Hong YS et al (2011) Eugenolol and glyceryl-isoeugenol suppress LPS-induced iNOS expression by down-regulating NF-kappaB AND AP-1 through inhibition of MAPKS and AKT/IkappaBalpha signaling pathways in macrophages. Int J Immunopathol Pharmacol 24:345–356. https://doi.org/10.1177/039463201102400208
Yogalakshmi B, Viswanathan P, Anuradha CV (2010) Investigation of antioxidant, anti-inflammatory and DNA-protective properties of eugenol in thioacetamide-induced liver injury in rats. Toxicology 268:204–212. https://doi.org/10.1016/j.tox.2009.12.018
Acknowledgements
The authors are grateful to the Chitkara College of Pharmacy, Chitkara University, Rajpura, Patiala, Punjab, India for providing the necessary facilities to carry out the research work.
Funding
Nil.
Author information
Authors and Affiliations
Contributions
TGS, SD conceptualising, editing and execution of manuscript. AM, SC: literature survey, wrote manuscript, medical writing and designing the review. All authors read and approved the manuscript.
Corresponding author
Ethics declarations
Conflict of interest
There are no conflicts of interest.
Ethical approval
Not applicable.
Consent to Publish
The paper is submitted with the consent of all listed authors.
Compliance with ethical standards
Not applicable.
Consent to participate
Not applicable.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Devi, S., Chauhan, S., Mannan, A. et al. Targeting cardiovascular risk factors with eugenol: an anti-inflammatory perspective. Inflammopharmacol 32, 307–317 (2024). https://doi.org/10.1007/s10787-023-01392-w
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10787-023-01392-w