Sull'argomento sono stati selezionati gli studi più rilevanti con una sintesi dei contenuti:

Shahina Z, Ndlovu E, Persaud O, Sultana T, Dahms TES. Candida albicans Reactive Oxygen Species (ROS)-Dependent Lethality and ROS-Independent Hyphal and Biofilm Inhibition by Eugenol and Citral. Microbiol Spectr. 2022 Nov 17:e0318322. doi: 10.1128/spectrum.03183-22.

Abstract. Candida albicans is part of the normal human flora but is most frequently isolated as the causative opportunistic pathogen of candidiasis. Plant-based essential oils and their components have been extensively studied as antimicrobials, but their antimicrobial impacts are poorly understood. Phenylpropenoids and monoterpenes, for example, eugenol from clove and citral from lemon grass, are potent antifungals against a wide range of pathogens. We report the cellular response of C. albicans to eugenol and citral, alone and combined, using biochemical and microscopic assays. The MICs of eugenol and citral were 1,000 and 256 μg/mL, respectively, with the two exhibiting additive effects based on a fractional inhibitory concentration index of 0.83 ± 0.14. High concentrations of eugenol caused membrane damage, oxidative stress, vacuole segregation, microtubule dysfunction and cell cycle arrest at the G1/S phase, and while citral had similar impacts, they were reactive oxygen species (ROS) independent. At sublethal concentrations (1/2 to 1/4 MIC), both oils disrupted microtubules and hyphal and biofilm formation in an ROS-independent manner. While both compounds disrupt the cell membrane, eugenol had a greater impact on membrane dysfunction. This study shows that eugenol and citral can induce vacuole and microtubule dysfunction, along with the inhibition of hyphal and biofilm formation. IMPORTANCE Candida albicans is a normal resident on and in the human body that can cause relatively benign infections. However, when our immune system is severely compromised (e.g., cancer chemotherapy patients) or underdeveloped (e.g., newborns), this fungus can become a deadly pathogen, infecting the bloodstream and organs. Since there are only a few effective antifungal agents that can be used to combat fungal infections, these fungi have been exposed to them over and over again, allowing the fungi to develop resistance. Instead of developing antifungal agents that kill the fungi, some of which have undesirable side effects on the human host, researchers have proposed to target the fungal traits that make the fungus more virulent. Here, we show how two components of plant-based essential oils, eugenol and citral, are effective inhibitors of C. albicans virulence traits.

Padhy I, Paul P, Sharma T, Banerjee S, Mondal A. Molecular Mechanisms of Action of Eugenol in Cancer: Recent Trends and Advancement. Life (Basel). 2022 Nov 6;12(11):1795. doi: 10.3390/life12111795. 

Abstract. Background: Cancer is, at present, among the leading causes of morbidity globally. Despite advances in treatment regimens for cancer, patients suffer from poor prognoses. In this context, the availability of vast natural resources seems to alleviate the shortcomings of cancer chemotherapy. The last decade has seen a breakthrough in the investigations related to the anticancer potential of dietary phytoconstituents. Interestingly, a handsome number of bioactive principles, ranging from phenolic acids, phenylpropanoids, flavonoids, stilbenes, and terpenoids to organosulphur compounds have been screened for their anticancer properties. Among the phenylpropanoids currently under clinical studies for anticancer activity, eugenol is a promising candidate. Eugenol is effective against cancers like breast, cervical, lung, prostate, melanomas, leukemias, osteosarcomas, gliomas, etc., as evident from preclinical investigations. Objective: The review aims to focus on cellular and molecular mechanisms of eugenol for cancer prevention and therapy..... Results: Different biochemical investigations reveal eugenol inducing cytotoxicity, inhibiting phases of the cell cycles, programmed cell death, and auto-phagocytosis in studied cancer lines; thus, portraying eugenol as a promising anticancer molecule. A survey of current literature has unveiled the molecular mechanisms intervened by eugenol in exercising its anticancer role. Conclusion: Based on the critical analysis of the literature, eugenol exhibits vivid signaling pathways to combat cancers of different origins. The reports also depict the advancement of novel nano-drug delivery approaches upgrading the therapeutic profile of eugenol. Therefore, eugenol nanoformulations may have enormous potential for both the treatment and prevention of cancer.

Jeanneau C, Giraud T, Milan JL, About I. Investigating unset endodontic sealers' eugenol and hydrocortisone roles in modulating the initial steps of inflammation. Clin Oral Investig. 2020 Feb;24(2):639-647. doi: 10.1007/s00784-019-02957-2. 

Abstract. Introduction: Endodontic treatment success is achieved not only when the cement provides a hermetic seal but also when the injured periapical tissue is regenerated. However, an exaggerated inflammatory reaction hinders tissue regeneration and it has been shown that dental materials affect the inflammatory response through modulation of cytokine secretion. This work was set to investigate the effects of the presence of hydrocortisone in zinc oxide eugenol sealers (Endomethasone N) on modulating the initial steps of inflammation in vitro....Results: Endomethasone N decreased secretion of IL-6 and TNF-α from hPDL cells. THP-1 adhesion to activated endothelial cells (HUVECs) and migration significantly decreased with Endomethasone N while no effect was observed with PCS. Activation of THP-1 decreased with both materials' extracts but was significantly lower with Endomethasone N than with PCS. Conclusion: These results performed in vitro show that Endomethasone N anti-inflammatory effects are due to the presence of hydrocortisone. Clinical relevance: Endomethasone N has potential local anti-inflammatory effects which appear to be due to its hydrocortisone rather than eugenol content. Decreasing the inflammatory response is a pre-requisite to initiate the periapical healing.

Lane T, Anantpadma M, Freundlich JS, Davey RA, Madrid PB, Ekins S. The Natural Product Eugenol Is an Inhibitor of the Ebola Virus In Vitro. Pharm Res. 2019 May 17;36(7):104. doi: 10.1007/s11095-019-2629-0.

Abstract. Purpose: Since the 2014 Ebola virus (EBOV) outbreak in West Africa there has been considerable effort towards developing drugs to treat Ebola virus disease and yet to date there is no FDA approved treatment. This is important as at the time of writing this manuscript there is an ongoing outbreak in the Democratic Republic of the Congo which has killed over 1000. Methods: We have evaluated a small number of natural products, some of which had shown antiviral activity against other pathogens. This is exemplified with eugenol, which is found in high concentrations in multiple essential oils, and has shown antiviral activity against feline calicivirus, tomato yellow leaf curl virus, Influenza A virus, Herpes Simplex virus type 1 and 2, and four airborne phages. Results: Four compounds possessed EC50 values less than or equal to 11 μM. Of these, eugenol, had an EC50 of 1.3 μM against EBOV and is present in several plants including clove, cinnamon, basil and bay. Eugenol is much smaller and structurally unlike any compound that has been previously identified as an inhibitor of EBOV, therefore it may provide new mechanistic insights. Conclusion: This compound is readily accessible in bulk quantities, is inexpensive, and has a long history of human consumption, which endorses the idea for further assessment as an antiviral therapeutic. This work also suggests that a more exhaustive assessment of natural product libraries against EBOV and other viruses is warranted to improve our ability to identify compounds that are so distinct from FDA approved drugs.

Uto T, Ohta T, Nakayama E, Nakagawa M, Hatada M, Shoyama Y. Bioassay-guided Fractionation of Clove Buds Extract Identifies Eugenol as Potent Melanogenic Inducer in Melanoma Cells. J Oleo Sci. 2022;71(9):1403-1412. doi: 10.5650/jos.ess22157.

Abstract. Clove, a dried flower buds of Syzygium aromaticum, is used in traditional medicine, for culinary purposes, and in essential oil production. In our preliminary screening of crude drugs used in Japanese Kampo formulas, a methanol (MeOH) extract of clove buds was found to exhibit a melanin induction. To date, the effects of clove buds or their constituents on the activation of melanogenesis remain unclear. Thus, this study aimed to isolate active compounds from the MeOH extract of clove buds associated with melanin synthesis in melanoma cells and to investigate the molecular mechanism involved. The MeOH extract of clove buds increased melanin content in murine B16-F1 melanoma cells. To identify the active compounds responsible for melanin induction, the MeOH extract was suspended in water and successively partitioned using hexane, ethyl acetate (EtOAc), and n-butanol (n-BuOH). Comparative analysis revealed that the EtOAc fraction induced melanin synthesis. Bioassay-guided separation of the EtOAc fraction isolated three compounds including eugenol. The analysis of structure-activity relationships of eugenol and structurally related compounds indicated that eugenol was the most potent melanin inducer among the 11 compounds, and that a hydroxyl group at C-1 and a methoxy group at C-2 may contribute to melanin induction. Eugenol induced melanin synthesis in human HMV-II melanoma cells as well as in B16-F1 cells. Further analysis indicated that eugenol may invoke intracellular tyrosinase activity and expression of tyrosinase, tyrosinaserelated protein (TRP)-1, TRP-2, and microphthalmia-associated transcription factor (MITF). These results suggest that eugenol enhances melanin synthesis by upregulating the expression of MITF and subsequent expression of melanogenic enzymes, and that it may be a potent therapeutic agent for hypopigmentation.

Olea AF, Bravo A, Martínez R, Thomas M, Sedan C, Espinoza L, Zambrano E, Carvajal D, Silva-Moreno E, Carrasco H. Antifungal Activity of Eugenol Derivatives against Botrytis Cinerea. Molecules. 2019 Mar 29;24(7):1239. doi: 10.3390/molecules24071239. 

Abstract. Botrytis cinerea is a worldwide spread fungus that causes the grey mold disease, which is considered the most important factor in postharvest losses in fresh fruit crops. Consequently, the control of gray mold is a matter of current and relevant interest for agricultural industries. In this work, a series of phenylpropanoids derived from eugenol were synthesized and characterized. Their effects on the mycelial growth of a virulent and multi-resistant isolate of B. cinerea (PN2) have been evaluated and IC50 values for the most active compounds range between 31⁻95 ppm. The antifungal activity exhibited by these compounds is strongly related to their chemical structure, i.e., increasing activity has been obtained by isomerization of the double bond or introduction of a nitro group on the aromatic ring. Based on the relationship between the fungicide activities and chemical structure, a mechanism of action is proposed. Finally, the activity of these compounds is higher than that reported for the commercial fungicide BC-1000 that is currently employed to combat this disease. Thus, our results suggest that these compounds are potential candidates to be used in the design of new and effective control with inspired natural compounds of this pathogen.

de Araújo Lopes A, da Fonseca FN, Rocha TM, de Freitas LB, Araújo EVO, Wong DVT, Lima Júnior RCP, Leal LKAM. Eugenol as a Promising Molecule for the Treatment of Dermatitis: Antioxidant and Anti-inflammatory Activities and Its Nanoformulation. Oxid Med Cell Longev. 2018 Dec 11;2018:8194849. doi: 10.1155/2018/8194849. 

Abstract. Contact dermatitis produces an inflammatory reaction primarily via stimulation of keratinocytes and cells of the immune system, which promote the release of cytokines, reactive oxygen species (ROS), and other chemical mediators. Eugenol (EUG, phenylpropanoid of essential oils) has attracted attention due to its anti-inflammatory properties, as well as antioxidant effect. On the other hand, it is volatile and insoluble and is a skin irritant. In this case, nanostructured systems have been successfully employed as a drug carrier for skin diseases since they improve both biological and pharmaceutical properties of active compounds. The cytotoxic, antioxidant, and anti-inflammatory effects of EUG were assessed in human neutrophils and keratinocytes. Additionally, polymeric nanocarries (NCEUG) were prepared to improve the chemical and irritant characteristics of EUG. EUG presented apparent safety and antioxidant and anti-inflammatory effects on human neutrophils, but presented cytotoxic effects on keratinocytes. However, the nanocapsules were able to reduce its cytotoxicity. An in vivo experiment of irritant contact dermatitis (ICD) in mice induced by TPA showed that NCEUG reduced significantly the ear edema in mice when compared to the EUG solution, as well as the leukocyte infiltration and IL-6 level, possibly due to better skin permeation and irritancy blockage. These findings suggest that EUG is a promising bioactive molecule, and its nanoencapsulation seems to be an interesting approach for the treatment of ICD.

arboza JN, da Silva Maia Bezerra Filho C, Silva RO, Medeiros JVR, de Sousa DP. An Overview on the Anti-inflammatory Potential and Antioxidant Profile of Eugenol. Oxid Med Cell Longev. 2018 Oct 22;2018:3957262. doi: 10.1155/2018/3957262.

Abstract. The bioactive compounds found in foods and medicinal plants are attractive molecules for the development of new drugs with action against several diseases, such as those associated with inflammatory processes, which are commonly related to oxidative stress. Many of these compounds have an appreciable inhibitory effect on oxidative stress and inflammatory response, and may contribute in a preventive way to improve the quality of life through the use of a diet rich in these compounds. Eugenol is a natural compound that has several pharmacological activities, action on the redox status, and applications in the food and pharmaceutical industry. Considering the importance of this compound, the present review discusses its anti-inflammatory and antioxidant properties, demonstrating its mechanisms of action and therapeutic potential for the treatment of inflammatory diseases.

Eugenolo (1-allyl-4-hydroxy-3-methoxybenzene)  è un composto fenolico che si trova in natura in molte piante, tra le quali la Melaleuca bracteata, o pianta del tè nero, nel basilico, nella noce moscata, nei chiodi di garofano, nei pesci come la carpa, il pesce gatto, gamberetti e il rombo (1) e si trova anche nel miele (2).

Industrialmente l'eugenolo si trova come polvere oppure come olio essenziale.

Allo stato solido Eugenolo si presenta come polvere dal colore bianco oppure marrone 

Allo stato liquido Eugenolo si presenta in forma di liquido giallastro, stabile. Infiammabile. Incompatibile con agenti ossidanti forti.

A cosa serve e dove si usa

Medicina

E' uno dei componenti attivi più importanti dei chiodi di garofano unitamente ad  isoeugenolo. Eugenolo è un componente molto interessante dal punto di vista clinico per il suo ruolo potenziale di prevenire  ed alleviare e le malattie croniche come  infiammazioni e tumori. Ha dimostrato attività antinfiammatoria e radical-scavenging (protegge le cellule dai danni che i radicali liberi, molecole instabili, producono nel corpo umano) con potenzialità di modulare malattie croniche (3). Inoltre Eugenolo inoltre, tramite le sue molteplici attività antiossidanti che comprendono la dimerizzazione (unione di due molecole in una doppia molecola che si chiama dimero) e l' effetto chelante (protezione da agenti indesiderati), può essere considerato efficace nel contrasto a malattie croniche.

 Il  e di eugenolo hanno dimostrato di modulare  in vitro e in vivo e quindi Eugenolo sembra possedere multiple attività antiossidanti (dimerizzazione, riciclaggio, ed effetto chelante) dimostrando così la possibilità di alleviare e prevenire le malattie croniche (3).

Possiede attività antimicrobica (4), è una potenziale strategia terapeutica contro l'epilessia del lobo temporale (5) e con la sua attività antinfiammatoria è una promettente molecola bioattiva per migliorare la dermatite da contatto.

In trattamento endodontico, ha inibito, unitamente ad altri componenti, l'ascesso peri apicale ed ha migliorato il riassorbimento osseo patologico (6).

Alimentazione

Fragranza e conservante. Nel settore alimentare, l'Eugenolo, unitamente al Caseinato di sodio ha dimostrato stabilità straordinaria durante lo stoccaggio ambientale (22 ° C) fino a 30 giorni e ha mantenuto una buona redispersibilità dopo l'essiccazione a spruzzo o il congelamento (7).

Cosmetica

L'Eugenolo è una fragranza molto diffusa nel settore cosmetico, alimentare e farmaceutico che serve a profumare di chiodi di garofano (da cui viene estratto) e cannella  i prodotti che lo contengono.

Sicurezza

E' una sostanza che può dare allergia per cui il suo nome deve essere obbligatoriamente scritto nell'etichetta dei componenti, però è considerato accettabile con un MOE (Margin of Exposure) inferiore a 100 (8).

Sull'argomento sono stati selezionati gli studi più rilevanti con una sintesi dei contenuti:

Eugenol studi

Caratteristiche tipiche del prodotto commerciale Eugenolo in forma di olio.

Appearance	Yellowish liquid
Boiling Point	255.0±0.0°C at 760 mmHg
Melting Point	−12-−10 °C(lit.)
Flash Point	119.8±8.1°C
Density	1.1±0.1 g/cm3
Refraction Index	1.536
Vapor Pressure	0.0±0.5 mmHg at 25°C
PSA	29.46000
LogP	2.20
Chemical Safety

• Formula molecolare   C₁₀H₁₂O₂
• Linear Formula        4-(H₂C=CHCH₂)C₆H₃-₂-(OCH₃)OH
• Peso molecolare    164.204 g/mol
• Massa esatta     164.083725
• UNII     3T8H1794QW
• CAS     97-53-0
• EC Number: 202-589-1
• DSSTox Substance ID  DTXSID9020617
• IUPAC  2-methoxy-4-prop-2-enylphenol
• InChl=1S/C10H12O2/c1-3-4-8-5-6-9(11)10(7-8)12-2/h3,5-7,11H,1,4H2,2H3
• InChl Key      RRAFCDWBNXTKKO-UHFFFAOYSA-N
• SMILES  COC1=C(C=CC(=C1)CC=C)O
• FEMA Number: 2467
• PubChem Substance ID 24894609
• MDL number MFCD00008654
• Beilstein Registry Number 1366759
• NSC    8895     209525     757030
• JECFA     1529

Sinonimi: 

• 4-Allyl-2-methoxyphenol
• 4-Allylguaiacol
• Eugenic acid
• Allylguaiacol
• Caryophyllic acid
• p-Allylguaiacol
• 2-methoxy-4-(prop-2-en-1-yl)phenol
• Eugenol (natural)
• 4-Hydroxy-3-methoxy-1-allylbenzene
• 2-Hydroxy-5-allylanisole
• 4-Hydroxy-3-methoxyallylbenzene
• Phenol, 4-allyl-2-methoxy-
• 2-Methoxy-4-(2-propen-1-yl)phenol
• Eugenol [USAN]
• NCI-C50453
• 4-Allylcatechol 2-methyl ether
• 1-allyl-4-hydroxy-3-methoxybenzene
• 1-Allyl-3-methoxy-4-hydroxybenzene
• 2-Metoksy-4-allilofenol
• p-Eugenol
• 2-Methoxy-4-prop-2-enylphenol
• Engenol
• 2-Methoxy-4-allylphenol
• 2-Methoxy-4-(2-propenyl)phenol
• Phenol, 2-methoxy-4-(2-propenyl)-
• 1,3,4-Eugenol
• 4-Allylcatechol-2-methyl ether
• Synthetic eugenol
• 1-Hydroxy-2-methoxy-4-allylbenzene
• 2-Methoxy-1-hydroxy-4-allylbenzene
• 4-Allyl-1-hydroxy-2-methoxybenzene
• 5-Allylguaiacol
• 1-Hydroxy-2-methoxy-4-prop-2-enylbenzene

Bibliografia____________________________________________________________________

(1) Li J, Liu H, Wang C, Wu L, Liu D. Determination of eugenol in fish and shrimp muscle tissue by stable isotope dilution assay and solid-phase extraction coupled gas chromatography-triple quadrupole mass spectrometry. Anal Bioanal Chem. 2016 Sep;408(24):6537-44. doi: 10.1007/s00216-016-9850-z. 

 (2) Tonello N, Moressi MB, Robledo SN, D'Eramo F, Marioli JM. Square wave voltammetry with multivariate calibration tools for determination of eugenol, carvacrol and thymol in honey. Talanta. 2016 Sep 1;158:306-314. doi: 10.1016/j.talanta.2016.05.071.

(3) Fujisawa S, Murakami Y. Eugenol and Its Role in Chronic Diseases. Adv Exp Med Biol. 2016;929:45-66. doi: 10.1007/978-3-319-41342-6_3. 

(4) Manrique Y, Gibis M, Schmidt H, Weiss J. Antimicrobial efficacy of sequentially applied eugenol against food spoilage micro-organisms. J Appl Microbiol. 2016 Dec;121(6):1699-1709. doi: 10.1111/jam.13294.

(5) Kim SR. Control of Granule Cell Dispersion by Natural Materials Such as Eugenol and Naringin: A Potential Therapeutic Strategy Against Temporal Lobe Epilepsy. J Med Food. 2016 Aug;19(8):730-6. doi: 10.1089/jmf.2016.3712. 

Abstract. The hippocampus is an important brain area where abnormal morphological characteristics are often observed in patients with temporal lobe epilepsy (TLE), typically showing the loss of the principal neurons in the CA1 and CA3 areas of the hippocampus. TLE is frequently associated with widening of the granule cell layer of the dentate gyrus (DG), termed granule cell dispersion (GCD), in the hippocampus, suggesting that the control of GCD with protection of hippocampal neurons may be useful for preventing and inhibiting epileptic seizures. We previously reported that eugenol (EUG), which is an essential component of medicinal herbs and has anticonvulsant activity, is beneficial for treating epilepsy through its ability to inhibit GCD via suppression of mammalian target of rapamycin complex 1 (mTORC1) activation in the hippocampal DG in a kainic acid (KA)-treated mouse model of epilepsy in vivo. In addition, we reported that naringin, a bioflavonoid in citrus fruits, could exert beneficial effects, such as antiautophagic stress and antineuroinflammation, in the KA mouse model of epilepsy, even though it was unclear whether naringin might also attenuate the seizure-induced morphological changes of GCD in the DG. Similar to the effects of EUG, we recently observed that naringin treatment significantly reduced KA-induced GCD and mTORC1 activation, which are both involved in epileptic seizures, in the hippocampus of mouse brain. Therefore, these observations suggest that the utilization of natural materials, which have beneficial properties such as inhibition of GCD formation and protection of hippocampal neurons, may be useful in developing a novel therapeutic agent against TLE.

(6) de Deus Moura Lde F, de Lima Mde D, Lima CC, Machado JI, de Moura MS, de Carvalho PV. Endodontic Treatment of Primary Molars with Antibiotic Paste: A Report of 38 Cases. J Clin Pediatr Dent. 2016;40(3):175-7. doi: 10.17796/1053-4628-40.3.175. 

Abstract. Objective: This study presents 38 cases of primary molars with necrotic pulps treated with antibiotics-based paste. Case report: The technique consisted of necrotic tissue removal of the pulp chamber, using spoons excavators and low speed drills. Pulp cavity was washed with saline solution and dried with sterile cotton balls. Then an antibiotic paste composed of chloramphenicol, tetracycline, zinc oxide and eugenol - CTZ paste - was inserted at the entrance of root canals. Patients were evaluated clinically and radiographically at different times. The criteria that defined clinical success were the lack of periapical abscess and mobility compatible with chronological age. Radiographic assessments consisted in absence of radiolucency in the region of root bifurcation and pathological bone resorption. Conclusion: There were 100% and 93% of clinical and radiographic success, respectively. The results suggest that the CTZ paste is an optional therapy for pulp of primary molars.

(7) Wang L, Zhang Y. Eugenol Nanoemulsion Stabilized with Zein and Sodium Caseinate by Self-Assembly. J Agric Food Chem. 2017 Apr 12;65(14):2990-2998. doi: 10.1021/acs.jafc.7b00194. 

(8) Api AM, Belsito D, Bhatia S, Bruze M, Calow P, Dagli ML, Dekant W, Fryer AD, Kromidas L, La Cava S, Lalko JF, Lapczynski A, Liebler DC, Miyachi Y, Politano VT, Ritacco G, Salvito D, Schultz TW, Shen J, Sipes IG, Wall B, Wilcox DK. RIFM fragrance ingredient safety assessment, Eugenol, CAS Registry Number 97-53-0. Food Chem Toxicol. 2016 Nov;97S:S25-S37. doi: 10.1016/j.fct.2015.12.013.