RESUMEN
BACKGROUND: Chicken coccidiosis is an intracellular parasitic disease that presents major challenges to the development of the commercial poultry industry. Perennial drug selective pressure has led to the multi-drug resistance of chicken coccidia, which makes the prevention and control of chicken coccidiosis extremely difficult. In recent years, natural plant products have attracted the attention of researchers due to their inherent advantages, such as the absence of veterinary drug residues. The development of these natural products provides a new direction for the prevention and treatment of chicken coccidiosis. METHODS: The anticoccidial effect of a natural plant product combination formulation (eucalyptus oil + apigenin + eugenol essential oil) was tested against Eimeria tenella in broilers. To search for the optimal concentration of the combination formulation, we screened 120 broilers in a chicken cage trial in which 100 broilers were infected with 5 × 104 sporulated Eimeria tenella oocysts; broilers receiving a decoquinate solution was set up as a chemical control. The optimal anticoccidial concentration was determined by calculating the anticoccidial index (ACI), and the suitable concentration was used as the recommended dose for a series of safety dose assessment tests, such as feed conversion ratio (FCR), hematological indices and serum biochemical indices, as well as liver and kidney sections, at onefold (low dose), threefold (medium dose) and sixfold (high dose) the recommended dose (RD). RESULTS: The results showed that this combination formulation of three plant natural products had a better anticoccidial effect than formulations containing two plant natural products or a single one, with an ACI of 169.3. The dose gradient anticoccidial test revealed that the high-dose formulation group had a better anticoccidial effect (ACI = 169.2) than the medium- and low-dose groups. The safety evaluation test showed that concentrations of the formulation at one-, three- and sixfold the RD were non-toxic to Arbor Acres broilers, indicating the high safety of the combination formulation. CONCLUSIONS: The combination formulation showed not only a moderate anticoccidial effect but also had a high safety profile for broilers. The results of this study indicate a new alternative for the prevention and control of coccidiosis in broilers.
Asunto(s)
Pollos , Coccidiosis , Coccidiostáticos , Eimeria tenella , Eucalyptus , Eugenol , Enfermedades de las Aves de Corral , Animales , Pollos/parasitología , Eimeria tenella/efectos de los fármacos , Coccidiosis/tratamiento farmacológico , Coccidiosis/veterinaria , Coccidiosis/parasitología , Enfermedades de las Aves de Corral/tratamiento farmacológico , Enfermedades de las Aves de Corral/parasitología , Coccidiostáticos/farmacología , Coccidiostáticos/uso terapéutico , Coccidiostáticos/administración & dosificación , Eugenol/farmacología , Eugenol/administración & dosificación , Eucalyptus/química , Productos Biológicos/farmacología , Productos Biológicos/administración & dosificación , Oocistos/efectos de los fármacos , Extractos Vegetales/farmacología , Extractos Vegetales/química , Extractos Vegetales/administración & dosificación , Aceites Volátiles/farmacología , Aceites Volátiles/química , Aceites Volátiles/administración & dosificaciónRESUMEN
Plantar fasciitis is the most common cause of heel pain in adults with an overall prevalence of 0.85% in the adult population of the US, affecting over 2 million adults annually. Most current treatment modalities are not supported by sufficient evidence to recommend one particular strategy over another. Topical application of analgesics for soft tissue pain is well established, however the plantar fascia presents challenges in this regard due to thick skin, fibrotic tissue, and an often thickened fat pad. Sixty-two patients with plantar fasciitis were randomized to a placebo controlled trial testing the efficacy of a topical solution of plant terpenes containing camphor, menthol, eugenol, eucalyptol, and vanillin. Skin permeation of the mixture was enhanced with 15% dimethylsulfoxide (DMSO), 1% limonene, and rosemary oil. One ml of solution was applied topically twice daily, and pain scores evaluated on Day 0, Day 1, Day 3, and Day 10. Using the validated foot function index 78.1% of patients reported an 85% or greater decrease in their total pain score by day 10 while placebo treatment was without effect (One Way ANOVA, P < 0.01). This study adapts the treatment modality of topical analgesia for soft tissue pain to a problematic area of the body and shows therapeutic promise.ClinicalTrials.gov Identifier: NCT05467631.
Asunto(s)
Dimetilsulfóxido , Fascitis Plantar , Humanos , Femenino , Masculino , Fascitis Plantar/tratamiento farmacológico , Persona de Mediana Edad , Adulto , Dimetilsulfóxido/uso terapéutico , Dimetilsulfóxido/administración & dosificación , Dimetilsulfóxido/química , Terpenos/uso terapéutico , Resultado del Tratamiento , Anciano , Mentol/administración & dosificación , Mentol/uso terapéutico , Benzaldehídos/administración & dosificación , Benzaldehídos/uso terapéutico , Benzaldehídos/química , Eugenol/uso terapéutico , Eugenol/administración & dosificación , Eugenol/farmacología , Alcanfor/uso terapéutico , Alcanfor/administración & dosificación , Dimensión del Dolor , Aceites VolátilesRESUMEN
Eugenol (Eug) holds potential as a treatment for bacterial rhinosinusitis by nasal powder drug delivery. To stabilization and solidification of volatile Eug, herein, nasal inhalable γ-cyclodextrin metal-organic framework (γ-CD-MOF) was investigated as a carrier by gas-solid adsorption method. The results showed that the particle size of Eug loaded by γ-CD-MOF (Eug@γ-CD-MOF) distributed in the range of 10-150 µm well. In comparison to γ-CD and ß-CD-MOF, γ-CD-MOF has higher thermal stability to Eug. And the intermolecular interactions between Eug and the carriers were verified by characterizations and molecular docking. Based on the bionic human nasal cavity model, Eug@γ-CD-MOF had a high deposition distribution (90.07 ± 1.58%). Compared with free Eug, the retention time Eug@γ-CD-MOF in the nasal cavity was prolonged from 5 min to 60 min. In addition, the cell viability showed that Eug@γ-CD-MOF (Eug content range 3.125-200 µg/mL) was non-cytotoxic. And the encapsulation of γ-CD-MOF could not reduce the bacteriostatic effect of Eug. Therefore, the biocompatible γ-CD-MOF could be a potential and valuable carrier for nasal drug delivery to realize solidification and nasal therapeutic effects of volatile oils.
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Administración Intranasal , Portadores de Fármacos , Sistemas de Liberación de Medicamentos , Eugenol , Estructuras Metalorgánicas , Polvos , Estructuras Metalorgánicas/química , Polvos/química , Humanos , Eugenol/química , Eugenol/administración & dosificación , Eugenol/farmacología , Administración Intranasal/métodos , Sistemas de Liberación de Medicamentos/métodos , Portadores de Fármacos/química , Tamaño de la Partícula , Supervivencia Celular/efectos de los fármacos , Simulación del Acoplamiento Molecular/métodos , gamma-Ciclodextrinas/química , Estabilidad de Medicamentos , Antibacterianos/administración & dosificación , Antibacterianos/química , Antibacterianos/farmacología , Ciclodextrinas/química , Cavidad Nasal/metabolismoRESUMEN
This study was designed to examine the impact of aspirin eugenol ester (AEE) on the growth performance, serum antioxidant capacity, jejunal barrier function, and cecal microbiota of broilers raised under stressful high density (HD) stocking conditions compared with normal density broilers (ND). A total of 432 one-day-old AA+ male broilers were randomly divided into 4 groups: normal density (ND, 14 broilers /m2), high density (HD, 22 broilers /m2), ND + AEE, and HD + AEE. The results of the study revealed a significant decrease in the growth performance of broiler chickens as a result of HD stress (P < 0.05). The total antioxidant capacity (T-AOC) in serum demonstrated a significant decrease (P < 0.05) at both 28 and 35 d. Conversely, the serum level of malondialdehyde (MDA) exhibited a significant increase (P < 0.05). Dietary supplementation of AEE resulted in a significant elevation (P < 0.05) of serum GSH-PX, SOD and T-AOC activity at both 28 and 35 d. Moreover, exposure to HD stress resulted in a considerable reduction in the height of intestinal villi and mRNA expression of tight junction proteins in the jejunum, along with, a significant elevation in the mRNA expression of inflammatory cytokines (P < 0.05). However, the administration of AEE reversed the adverse effects of HD-induced stress on villus height and suppressed the mRNA expression of the pro-inflammatory genes, COX-2 and mPGES-1. Additionally, the exposure to HD stress resulted in a substantial reduction in the α-diversity of cecal microbiota and disruption in the equilibrium of intestinal microbial composition, with a notable decrease in the relative abundance of Bacteroides and Faecalibacterium (P < 0.05). In contrast, the addition of AEE to the feed resulted in a notable increase in the relative abundance of Phascolarctobacterium and enhanced microbial diversity (P < 0.05). The inclusion of AEE in the diet has been demonstrated to enhance intestinal integrity and growth performance of broilers by effectively mitigating disruptions in gut microbiota induced by HD stress.
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Alimentación Animal , Antioxidantes , Aspirina , Ciego , Pollos , Dieta , Suplementos Dietéticos , Eugenol , Microbioma Gastrointestinal , Animales , Pollos/crecimiento & desarrollo , Masculino , Microbioma Gastrointestinal/efectos de los fármacos , Antioxidantes/metabolismo , Dieta/veterinaria , Ciego/microbiología , Ciego/efectos de los fármacos , Aspirina/administración & dosificación , Aspirina/farmacología , Aspirina/análogos & derivados , Alimentación Animal/análisis , Suplementos Dietéticos/análisis , Eugenol/análogos & derivados , Eugenol/administración & dosificación , Eugenol/farmacología , Distribución Aleatoria , Crianza de Animales Domésticos , Inflamación/veterinaria , Inflamación/inducido químicamenteRESUMEN
Orodispersible films (ODFs) have emerged as an advanced and patient-friendly delivery system due to ease of administration, improved patient compliance, quick release and taste-masking of active pharmaceutical ingredients. This research reports the preparation of the ODF containing eugenol and borax (EB-ODF) by a solvent casting technique for treating mouth ulcers. The EB-ODF consisted of vinyl pyrrolidone/vinyl acetate copolymer (Kollidon® VA64, VA64) and hydroxypropyl methylcellulose (HPMC-K250) as the film formers where eugenol and borax were loaded. The thickness of the EB-ODF obtained was 0.119 ± 0.001 mm and the tensile strength was 13.1 ± 1.1 N/mm2 (p > 0.05). The prepared films disintegrated in the oral cavity within 30 s and over 90% of the eugenol was released from the film in the first 5 min. Furthermore, the combined application of eugenol and borax, loaded in EB-ODF, displayed notable synergetic antibacterial property against both gram-negative and gram-positive bacteria. In an in-vivo study on a rat model with chemical burn-induced oral ulcers, the EB-ODF treatment group had a 100% reduction in ulcer area (p > 0.05) after 10 days of treatment and demonstrated a 38.7% higher reduction in oral ulcer area compared to the Dingpeng Cream treatment group (p < 0.0001). The EB-ODF treatment group showed minimal oral irritation, scoring only 1 point and a 65% preference in the taste tests (p < 0.0001). In summary, EB-ODF had successfully overcome the poor palatability of commercially available formulation and provided notable potential for further ulcer treatment product development.
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Boratos , Eugenol , Úlceras Bucales , Eugenol/administración & dosificación , Eugenol/farmacología , Animales , Ratas , Boratos/administración & dosificación , Úlceras Bucales/tratamiento farmacológico , Masculino , Administración Oral , Sistemas de Liberación de Medicamentos/métodos , Liberación de Fármacos , Derivados de la Hipromelosa/química , Ratas Wistar , Resistencia a la TracciónRESUMEN
BACKGROUND: Eugenol has various curative properties. It affects the dilatation of cerebral arteries through voltage-dependent Ca2+ channel inhibition. This study is the first to explore the impact of eugenol on neuroprotection and vasospasm in an experimental subarachnoid hemorrhage (SAH) model. METHODS: Twenty-four adult male Sprague-Dawley rats were indiscriminately separated into 3 groups: the control group (n = 8), the SAH group (n = 8), and the eugenol group (n = 8). A double-bleeding method was used. The eugenol group received intracisternal eugenol (Sigma-Aldrich, St. Louis, MO, USA) at 30 µg/20 µl after induction of SAH. On the day 7, all groups were euthanized. Measurements were taken for basilar artery wall thickness, lumen diameter, serum endothelin-1 (ET-1), and caspase-3 levels. RESULTS: The eugenol group exhibited significantly lower wall thickness, ET-1, oxidative stress index, and caspase-3 levels compared to the SAH group. In comparison to the control group, the eugenol group showed a higher oxidative stress index along with higher ET-1 and caspase-3 levels, but these differences were not statistically significant. Wall thickness was significantly higher in the eugenol group than in the control group. CONCLUSIONS: This study represents the first literature exploration of intrathecal eugenol's impact on vasospasm induced after experimental SAH. Administration of intrathecal eugenol demonstrates a positive effect on the treatment of experimental vasospasm as well as on the reduction of oxidative stress and apoptosis.
Asunto(s)
Modelos Animales de Enfermedad , Eugenol , Ratas Sprague-Dawley , Hemorragia Subaracnoidea , Vasoespasmo Intracraneal , Animales , Eugenol/administración & dosificación , Eugenol/farmacología , Hemorragia Subaracnoidea/complicaciones , Hemorragia Subaracnoidea/tratamiento farmacológico , Vasoespasmo Intracraneal/tratamiento farmacológico , Vasoespasmo Intracraneal/etiología , Masculino , Ratas , Inyecciones Espinales , Estrés Oxidativo/efectos de los fármacos , Arteria Basilar/efectos de los fármacos , Arteria Basilar/patología , Fármacos Neuroprotectores/administración & dosificación , Endotelina-1/sangre , Caspasa 3/metabolismoRESUMEN
Background: Heat stress (HS) is a main abiotic stress factor for the health and welfare of animals. Recently, the use of nano-emulsion essential oils exhibited a promising approach to mitigate the detrimental impacts of abiotic and biotic stresses, ultimately contributing to the global aim of sustainable livestock production. Aim: The current study was piloted to assess the impact of eugenol nano-emulsion (EUGN) supplementation on growth performance, serum metabolites, redox homeostasis, immune response, and pro-inflammatory reactions in growing rabbits exposed to HS. Methods: A total of 100 male weaning rabbits aged 35 days were divided into 4 treatments. Rabbits were fed the diet with EUGN at different concentrations: 0 (control group; EUGN0), 50 (EUGN50), 100 (EUGN100), and 150 (EUGN150) mg/kg diet for 8 weeks under summer conditions. Results: Dietary EUGN levels significantly improved (p < 0.05) the body weight, body weight gain, carcass weights, and improved feed conversion ratio of rabbits. EUGN supplementation significantly increased Hb, platelets, and red blood cells , while the mean corpuscular hemoglobin and eosinophils were significantly decreased compared to the control one. Compared with EUGN0 stressed rabbits, all EUGN-experimental groups had a reduction in levels of total glycerides (p < 0.01), uric acid, total bilirubin, direct bilirubin, and gamma-glutamyl transpeptidase (p < 0.01). Total antioxidant capacity and glutathione peroxidase were significantly improved by EUGN treatment when compared to the control one (p < 0.01), while the EUGN100 exhibited the greatest levels of catalase. Lipid peroxidation (malondialdehyde) was significantly decreased in EUGN-treated groups. All pro-inflammatory cytokines serum interleukin 4, Interleukin 1ß, and tumor necrosis factor alpha were considerably decreased after dietary EUGN supplementation (p < 0.05). The serum concentrations of immunoglobulins (IgG and IgM) were significantly improved in rabbits of the EUGN150 group. Conclusion: This study shows that EUGN can be used as a novel feed additive to enhance the growth performance, immune variables, and antioxidants, and reduce the inflammatory response of growing rabbits exposed to thermal stress.
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Alimentación Animal , Dieta , Suplementos Dietéticos , Eugenol , Homeostasis , Animales , Conejos , Eugenol/administración & dosificación , Eugenol/farmacología , Masculino , Suplementos Dietéticos/análisis , Alimentación Animal/análisis , Homeostasis/efectos de los fármacos , Dieta/veterinaria , Oxidación-Reducción/efectos de los fármacos , Emulsiones , Inflamación/veterinaria , Respuesta al Choque Térmico/efectos de los fármacosRESUMEN
The most common form of psycho-social dysfunction is anxiety with depression being related closely without any age bar. They are present with combined state of sadness, confusion, stress, fear etc. Glyoxalase system contains enzyme named glyoxalase 1 (GLO1).It is a metabolic pathway which detoxifies alpha-oxo-aldehydes, particularly methylglyoxal (MG). Methylglyoxal is mainly made by the breakdown of the glycolytic intermediates, glyceraldehyde-3-phosphates and dihydroxyacetone phosphate. Glyoxylase-1 expression is also related with anxiety behavior. A casual role or GLO-1 in anxiety behavior by using viral vectors for over expression in the anterior cingulate cortex was found and it was found that local GLO-1 over expression increased anxiety behavior. The present study deals with the molecular mechanism of protective activity of eugenol against anxiolytic disorder. A pre-clinical animal study was performed on 42 BALB/c mice. Animals were given stress through conventional restrain model. The mRNA expression of GLO-1 was analyzed by real time RT-PCR. Moreover, the GLO-1 protein expression was also examined by immunohistochemistry in whole brain and mean density was calculated. The mRNA and protein expressions were found to be increased in animals given anxiety as compared to the normal control. Whereas, the expressions were decreased in the animals treated with eugenol and its liposome-based nanocarriers in a dose dependent manner. However, the results were better in animals treated with nanocarriers as compared to the compound alone. It is concluded that the eugenol and its liposome-based nanocarriers exert anxiolytic activity by down-regulating GLO-1 protein expression in mice.
A forma mais comum de disfunção psicossocial é a ansiedade intimamente relacionada com a depressão, sem qualquer barreira de idade. Elas estão presentes em um estado combinado de tristeza, confusão, estresse, medo etc. O sistema de glioxalase contém uma enzima chamada glioxalase 1 (GLO1). É uma via metabólica que desintoxica alfa-oxo-aldeídos, particularmente metilglioxal (MG). O metilglioxal é produzido principalmente pela quebra dos intermediários glicolíticos, gliceraldeído-3-fosfatos e fosfato de diidroxiacetona. A expressão da glioxalase 1 também está relacionada ao comportamento de ansiedade. Um papel casual ou GLO1 no comportamento de ansiedade usando vetores virais para superexpressão no córtex cingulado anterior foi encontrado e descobriu-se que a superexpressão local de GLO1 aumentava o comportamento de ansiedade. O presente estudo trata do mecanismo molecular da atividade protetora do eugenol contra o transtorno ansiolítico. Um estudo pré-clínico em animais foi realizado em 42 camundongos BALB / c. Os animais foram submetidos ao estresse por meio do modelo de contenção convencional. A expressão de mRNA de GLO1 foi analisada por RT-PCR em tempo real. Além disso, a expressão da proteína GLO1 também foi examinada por imuno-histoquímica em todo o cérebro e a densidade média foi calculada. Verificou-se que as expressões de mRNA e proteínas estavam aumentadas em animais que receberam ansiedade em comparação com o controle normal. Considerando que as expressões foram diminuídas nos animais tratados com eugenol e seus nanocarreadores baseados em lipossomas de forma dependente da dose. No entanto, os resultados foram melhores em animais tratados com nanocarreadores em comparação com o composto sozinho. Conclui-se que o eugenol e seus nanocarreadores baseados em lipossomas exercem atividade ansiolítica por regulação negativa da expressão da proteína GLO1 em camundongos.
Asunto(s)
Masculino , Animales , Ratones , Ansiedad/tratamiento farmacológico , Eugenol/administración & dosificación , Lactoilglutatión LiasaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Syzygium aromaticum L. volatile oil (clove oil) has been traditionally used for various stomach disorders including inflammatory conditions. Eugenol is the major constituent present in the volatile oil, and it has been established as a gastroprotective agent through many published studies, but the exact and complete mechanism of ulcer protection is not delineated yet. Moreover, it plays precisely the opposite effect in higher dose in antiulcer properties with worsening the ulcer at a higher dose. AIM: This study aims to carry out the prophylactic cytoprotective effect of eugenol with single low doses and explore the probable interrelated underlying transcriptional and translational level mechanism of cytoprotection such as antioxidative, anti-inflammatory, mucous generation in rats using ethanol-induced ulcer model. METHODS: Rats were administered with different doses of eugenol before ethanol intragastrically. The effects of the eugenol on mucous production, Nitric oxide generation, PGE2 synthesis, lipid peroxidation were recorded together with cytokines measurement in the blood. TNF-α and IL-6, two key cytokines, were also studied in specific. In addition, studies on the immunohistochemical and gene expression of HSP70 and iNOS indicators have been conducted. RESULTS: According to our findings, Eugenol substantially reduced the ulcer index and completely protected the mucosa from lesions. By restoring the lowered GSH and NP-SH levels, the protective effect of the eugenol was found to be augmented at both doses. This finding has corresponded to an increase in MDA, which was lowered by ethanol administration. Pre-treatment with eugenol on the ethanol-induced ulcer reduced the plasma NO levels and increased PGE2 along with a decreased TNF-α and IL-6 concentration. Additionally, significant transcriptional and translational upregulation of HSP70 and downregulation of iNOS were detected in the eugenol-treated rat stomach tissue. CONCLUSION: Our findings demonstrated that eugenol had a considerable gastroprotective impact at low doses, which could be attributed to its ability to regulate inflammatory reactions and antioxidant capacity.
Asunto(s)
Antiinflamatorios/farmacología , Antioxidantes/farmacología , Eugenol/farmacología , Úlcera Gástrica/prevención & control , Animales , Antiinflamatorios/administración & dosificación , Antiulcerosos/administración & dosificación , Antiulcerosos/farmacología , Antioxidantes/administración & dosificación , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Etanol/toxicidad , Eugenol/administración & dosificación , Masculino , Malondialdehído/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Tsantan Sumtang (TS), a traditional Tibetan medicine, has been used in the clinic for the treatment of myocardial ischemia (MI) for ages, however, the bioactive ingredients that are responsible for improving MI remain unknown. AIM OF THE STUDY: This study investigated the chemical components of TS and their medicinal efficacies at cell levels, in order to expound the bioactive ingredients in TS. MATERIALS AND METHODS: First, a response-surface methodology was employed to determine the optimum ethanol reflux extraction process of polyphenols in TS (PTS) due to their close correlation with MI improvement. Second, a serum pharmacochemistry technique was used to analyze the compounds of PTS absorbed into the blood of rats. Third, hypoxia-, H2O2-, and adriamycin (ADM)-induced H9c2 cell injury models were used to investigate the cardioprotective effects of these compounds in vitro. Fourth, protective effects of isovitexin, quercitrin, and isoeugenol on mitochondrial function were further tested. RESULTS: The optimum extraction conditions for obtaining PTS were an ethanol concentration of 78.22%, an extraction time of 67.4 min, and a material-liquid ratio of 1:72.60 mL/g. Serum pharmacochemistry analysis detected 21 compounds, of which 11 compounds were always present in the blood within 5 h. Cytotoxicity and the protective effect of 11 compounds in hypoxia-, H2O2-, and ADM-induced H9c2 cell injury models shown that isovitexin, quercitrin, and isoeugenol had almost no cytotoxicity, and they could elevate the survival rate in injured H9c2 cells. Furthermore, isovitexin, quercitrin, and isoeugenol could decrease mitochondrial reactive oxygen species (ROS) releasion, inhibite mitochondrial permeability transition pore (mPTP) opening, ameliorate the change of mitochondrial membrane potential (MMP) to exert mitochondrial protection effect. CONCLUSION: Isovitexin, quercitrin, and isoeugenol exhibited cardioprotective effect at cell levles, these three compounds might be the bioactive ingredients in TS. These findings elucidate the pharmacodynamic substances and mechanisms of TS, guiding its clinical use.
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Medicina Tradicional Tibetana , Mioblastos/efectos de los fármacos , Isquemia Miocárdica/tratamiento farmacológico , Polifenoles/farmacología , Animales , Antibióticos Antineoplásicos/toxicidad , Apigenina/administración & dosificación , Apigenina/química , Apigenina/farmacología , Línea Celular , Relación Dosis-Respuesta a Droga , Doxorrubicina/toxicidad , Eugenol/administración & dosificación , Eugenol/análogos & derivados , Eugenol/química , Eugenol/farmacología , Peróxido de Hidrógeno/toxicidad , Mioblastos/fisiología , Fitoterapia , Polifenoles/sangre , Polifenoles/química , Polifenoles/farmacocinética , Quercetina/administración & dosificación , Quercetina/análogos & derivados , Quercetina/química , Quercetina/farmacología , Ratas , Ratas Sprague-DawleyRESUMEN
Conventional cancer treatments have shown several unfavourable adverse effects, as well as an increase in anticancer drug resistance, which worsens the impending cancer therapy. Thus, the emphasis is currently en route for natural products. There is currently great interest in the natural bioactive components from medicinal plants possessing anticancer characteristics. For example, clove (Syzygium aromaticum L.) (Family Myrtaceae) is a highly prized spice that has been historically utilized as a food preservative and for diverse medical uses. It is reckoned amongst the valued sources of phenolics. It is indigenous to Indonesia but currently is cultivated in various places of the world. Among diverse active components, eugenol, the principal active component of S. aromaticum, has optimistic properties comprising antioxidant, anti-inflammatory, and anticancer actions. Eugenol (4-allyl-2-methoxyphenol) is a musky oil that is mainly obtained from clove. It has long been utilized all over the world as a result of its broad properties like antioxidant, anticancer, anti-inflammatory, and antimicrobial activities. Eugenol continues to pique investigators' interest because of its multidirectional activities, which suggests it could be used in medications to treat different ailments. Anticancer effects of eugenol are accomplished by various mechanisms like inducing cell death, cell cycle arrest, inhibition of migration, metastasis, and angiogenesis on several cancer cell lines. Besides, eugenol might be utilized as an adjunct remedy for patients who are treated with conventional chemotherapy. This combination leads to a boosted effectiveness with decreased toxicity. The present review focuses on the anticancer properties of eugenol to treat several cancer types and their possible mechanisms.
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Antiinflamatorios/administración & dosificación , Antineoplásicos/administración & dosificación , Antioxidantes/administración & dosificación , Eugenol/administración & dosificación , Neoplasias/tratamiento farmacológico , Fitoquímicos/administración & dosificación , Fitoterapia/métodos , Syzygium/química , Animales , Antiinflamatorios/química , Antineoplásicos/química , Antioxidantes/química , Apoptosis/efectos de los fármacos , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Aceite de Clavo/química , Eugenol/química , Humanos , Neoplasias/patología , Aceites Volátiles/química , Fitoquímicos/química , Plantas Medicinales/química , Resultado del TratamientoRESUMEN
Active cancer-associated fibroblasts (CAFs) are major components of the tumor microenvironment, which promote carcinogenesis and modulate response to therapy. Therefore, targeting these cells or reducing their paracrine pro-carcinogenic effects could be of great therapeutic value. To this end, we sought to investigate the effect of eugenol, a natural phenolic molecule, on active breast CAFs. We have shown that decitabine (5-Aza-2'-deoxycytidine, DAC) and eugenol inhibit the expression of the DNA methyltransferase genes DNMT1 and DNMT3A at both the protein and mRNA levels in breast CAF cells. While the effect of eugenol was persistent, DAC had only a transient inhibitory effect on the mRNA level of both DNMT genes. Furthermore, eugenol and DAC suppressed the invasive/migratory and proliferative potential of CAF cells as well as their paracrine pro-carcinogenic effects both in vitro and in humanized orthotopic tumor xenografts. Interestingly, these inhibitory effects of decitabine and eugenol were mediated through E2F1 downregulation. Indeed, ectopic expression of E2F1 upregulated both genes and attenuated the effects of eugenol. Additionally, we provide clear evidence that eugenol, like DAC, strongly modulates the methylation pattern in active CAF cells, through methylating several oncogenes and demethylating various important tumor suppressor genes, which affected their mRNA expression levels. Importantly, the E2F1 promoter was also hypermethylated and the gene downregulated in response to eugenol. Together, these findings show that the active features of breast CAF cells can be normalized through eugenol-dependent targeting of DNMT1/DNMT3A and the consequent modulation in gene methylation.
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Neoplasias de la Mama/tratamiento farmacológico , Fibroblastos Asociados al Cáncer/efectos de los fármacos , ADN (Citosina-5-)-Metiltransferasa 1/genética , ADN Metiltransferasa 3A/genética , Decitabina/administración & dosificación , Factor de Transcripción E2F1/genética , Eugenol/administración & dosificación , Animales , Neoplasias de la Mama/genética , Fibroblastos Asociados al Cáncer/metabolismo , Fibroblastos Asociados al Cáncer/patología , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , ADN (Citosina-5-)-Metiltransferasa 1/metabolismo , Metilación de ADN/efectos de los fármacos , ADN Metiltransferasa 3A/metabolismo , Decitabina/farmacología , Regulación hacia Abajo , Sinergismo Farmacológico , Factor de Transcripción E2F1/metabolismo , Eugenol/farmacología , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Células MCF-7 , Ratones , Comunicación Paracrina/efectos de los fármacos , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Anaesthetics are commonly applied in pharmacokinetic (PK) studies to assure smooth handling of experimental procedures or to promote animal welfare. However, the influence of anaesthetics on the PK of co-administered drug is generally unknown but assumes ignorable. The goal of the study was to investigate the effect of tricaine methanesulfonate (MS-222), 2-phenoxyethanol (2-PE) and eugenol (EUG) on the PK of florfenicol (FF) in Nile tilapia. Twenty-eight fish were repeatedly exposed to 90 ppm EUG, 300 ppm MS-222 or 900 ppm 2-PE before FF oral administration (15 mg/kg) and each successive blood sampling. The serum concentration-time profiles were analysed by a 2-compartmental model, and the generated parameters in the control (without anaesthetic) and anaesthetic groups were statistically compared. The results demonstrated that the serum concentrations of each anaesthetic were similar at every FF sampling times (70 µg/ml for MS-222; 277 µg/ml for 2-PE; and 61 µg/ml for EUG). In comparison with the control group, the repeated use of MS-222 did not result in a statistical difference in most of the PK parameters. In contrast, the elimination half-lives of the 2-PE and EUG groups were significantly longer whereas the absorption and distribution half-lives of the 2-PE group were significantly shorter than the control, resulting in altered optimal dosages in the simulation modelling. Whether or not the numbers and extent of PK parameters change mitigate subsequent estimations of other PK-derived secondary values such as dosing regimen and withdrawal time remains to be elucidated, but the auxiliary use of anaesthetics in PK studies should not assume uninfluential.
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Aminobenzoatos/administración & dosificación , Anestésicos/administración & dosificación , Antibacterianos/farmacocinética , Cíclidos/fisiología , Glicoles de Etileno/administración & dosificación , Eugenol/administración & dosificación , Tianfenicol/análogos & derivados , Animales , Distribución Aleatoria , Tianfenicol/farmacocinéticaRESUMEN
Conventional therapy of visceral leishmaniasis (VL) remains challenging with the pitfall of toxicity, drug resistance, and expensive. Hence, urgent need for an alternative approach is essential. In this study, we evaluated the potential of combination therapy with eugenol oleate and miltefosine in Leishmania donovani infected macrophages and in the BALB/c mouse model. The interactions between eugenol oleate and miltefosine were found to be additive against promastigotes and amastigotes with xΣFIC 1.13 and 0.68, respectively. Significantly (p < 0.001) decreased arginase activity, increased nitrite generation, improved pro-inflammatory cytokines, and phosphorylated p38MAPK were observed after combination therapy with eugenol oleate and miltefosine. >80% parasite clearance in splenic and hepatic tissue with concomitant nitrite generation, and anti-VL cytokines productions were observed after orally administered miltefosine (5 mg/kg body weight) and eugenol oleate (15 mg/kg body weight) in L. donovani-infected BALB/c mice. Altogether, this study suggested the possibility of an oral combination of miltefosine with eugenol oleate against visceral leishmaniasis.
Asunto(s)
Citocinas/metabolismo , Eugenol/uso terapéutico , Inmunidad , Leishmaniasis Visceral/tratamiento farmacológico , Leishmaniasis Visceral/inmunología , Óxido Nítrico/biosíntesis , Fosforilcolina/análogos & derivados , Administración Oral , Animales , Muerte Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Citocinas/biosíntesis , Interacciones Farmacológicas , Quimioterapia Combinada , Eugenol/administración & dosificación , Eugenol/farmacología , Femenino , Inmunidad/efectos de los fármacos , Concentración 50 Inhibidora , Leishmania donovani/efectos de los fármacos , Leishmania donovani/crecimiento & desarrollo , Leishmania donovani/inmunología , Leishmania donovani/ultraestructura , Leishmaniasis Visceral/parasitología , Estadios del Ciclo de Vida/efectos de los fármacos , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Macrófagos/parasitología , Macrófagos/ultraestructura , Masculino , Ratones Endogámicos BALB C , Óxido Nítrico Sintasa de Tipo II/metabolismo , Parásitos/efectos de los fármacos , Parásitos/crecimiento & desarrollo , Parásitos/inmunología , Parásitos/ultraestructura , Fosforilación/efectos de los fármacos , Fosforilcolina/administración & dosificación , Fosforilcolina/farmacología , Fosforilcolina/uso terapéutico , Linfocitos T/efectos de los fármacos , Linfocitos T/inmunología , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
Asarum is a traditional medicine and has been widely used as remedies for inflammatory diseases, toothache, headache, local anesthesia, and aphthous stomatitis in China, Japan, and Korea. Our previous research found that safrole and methyl eugenol were vital compounds that contribute to distinguish the different species and raw Asarum and its processed products apart. The pharmacokinetics of safrole and methyl eugenol after oral administration of Asarum extract has not been reported yet. In this study, a rapid and simple gas chromatography-mass spectroscopy (GC-MS) method that has a complete run time of only 4.5 min was developed and validated for the simultaneous determination and pharmacokinetic study of safrole and methyl eugenol in rat plasma after administration of Asarum extracts. The chromatographic separation was realized on a DB-17 column (30 m × 0.25 mm × 0.25 µm). And detection was carried out under selected ion monitoring (SIM) mode. Plasma samples were pretreated by n-hexane. The pharmacokinetic parameters provided by this study will be beneficial for further developments and clinical applications of Asarum.
Asunto(s)
Asarum/química , Eugenol/análogos & derivados , Cromatografía de Gases y Espectrometría de Masas , Aceites Volátiles/administración & dosificación , Extractos Vegetales/administración & dosificación , Safrol/administración & dosificación , Safrol/farmacocinética , Administración Oral , Animales , Calibración , Eugenol/administración & dosificación , Eugenol/sangre , Eugenol/química , Eugenol/farmacocinética , Límite de Detección , Masculino , Ratas Sprague-Dawley , Estándares de Referencia , Reproducibilidad de los Resultados , Safrol/sangre , Safrol/químicaRESUMEN
The transient receptor potential vanilloid 1 (TRPV1) channel is a polymodal receptor in sensory nerves and involved in pain sensation. TRPV1 has at least three distinct activation modes that are selectively induced by different stimuli capsaicin, noxious heat, and protons. Although many mode-selective TRPV1 antagonists have been developed for their anticipated analgesic effects, there have been few successful reports because of adverse effects due to burn injuries and hyperthermia. Eugenol is a vanilloid that has been used as an analgesic in the dental treatment, and its TRPV1 activation ability has been reported. However, our knowledge about the underlying mechanisms of the antagonistic effects of eugenol on TRPV1 activation induced by three different modes is limited. Here, we show that eugenol dose-dependently inhibited the capsaicin-activated inward currents of mouse TRPV1 expressed in human embryonic kidney 293 (HEK293) cells. Under low pH conditions, low concentrations of eugenol only enhanced the proton-induced TRPV1 currents, whereas high eugenol concentrations initially potentiated but then immediately abrogated TRPV1 currents. Finally, eugenol had no modulatory effects on heat-activated TRPV1 in electrophysiological and Fura-2-based Ca2+ imaging experiments. Our results demonstrate that eugenol is a mode-selective antagonist of TRPV1 and can be evaluated as a lead compound of analgesics targeting TRPV1 without serious side effects.
Asunto(s)
Eugenol/farmacología , Calor , Protones , Canales Catiónicos TRPV/antagonistas & inhibidores , Canales Catiónicos TRPV/metabolismo , Animales , Unión Competitiva/efectos de los fármacos , Calcio/metabolismo , Capsaicina/antagonistas & inhibidores , Capsaicina/farmacología , Relación Dosis-Respuesta a Droga , Conductividad Eléctrica , Eugenol/administración & dosificación , Células HEK293 , Humanos , RatonesRESUMEN
The rodent uterotrophic and Hershberger assays evaluate potential estrogenic and (anti)-androgenic effects, respectively. Both US EPA and OECD guidelines specify that test substance is administered daily either by subcutaneous injection or oral gavage. However, dietary administration is a relevant exposure route for agrochemical regulatory toxicology studies due to potential human intake via crop residues. In this study, equivalent doses of positive control chemicals administered via dietary and gavage routes of administration were compared in the uterotrophic (17α-ethinyl estradiol) and Hershberger (flutamide, linuron, dichloro-2,2-bis(4-chlorophenyl) ethane; 4,4'-DDE) assays in ovariectomized and castrated rats, respectively. For all positive control chemicals tested, statistically significant changes in organ weights and decreases in food consumption were observed by both routes of test substance administration. Decreased body weight gain observed for dietary linuron and 4,4'-DDE indicated that the maximum tolerated dose was exceeded. Hershberger dietary administration resulted in a similar blood exposure (AUC24) for each positive control chemical when compared to gavage. Overall, the correlation in organ weight changes for both the uterotrophic and Hershberger assays suggest that dietary administration is an acceptable route of exposure with similar sensitivity to oral gavage dosing for evaluation of the endocrine potential of a test substance and represents a more appropriate route of test substance administration for most environmental exposure scenarios.
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Antagonistas de Andrógenos/administración & dosificación , Estrógenos/administración & dosificación , Etinilestradiol/administración & dosificación , Genitales Masculinos/efectos de los fármacos , Útero/efectos de los fármacos , Administración Oral , Antagonistas de Andrógenos/farmacocinética , Antagonistas de Andrógenos/toxicidad , Animales , Bioensayo/métodos , Dieta , Eugenol/administración & dosificación , Eugenol/análogos & derivados , Eugenol/farmacocinética , Eugenol/toxicidad , Femenino , Flutamida/administración & dosificación , Flutamida/farmacocinética , Flutamida/toxicidad , Genitales Masculinos/crecimiento & desarrollo , Linurona/administración & dosificación , Linurona/farmacocinética , Linurona/toxicidad , Masculino , Tamaño de los Órganos/efectos de los fármacos , Ratas , Útero/crecimiento & desarrolloRESUMEN
The use of anesthetics in fish farming is essential to reduce stress during management. The present study proposes to evaluate the effect of eugenol as an anesthetic for the management of curimatã (Prochilodus nigricans). Fifty specimens were used (221.34±9.0 g; 25.8 ±1.1 cm), submitted to five treatments with concentrations of 0, 25, 50, 100 and 200 mgL−1 eugenol for 10 min. The times required to reach each anesthetic stage and the recovery of each fish were recorded. To check bloodglucose levels individual blood samples were taken from the fish before immersion and after ten minutes of anesthetic exposure. Evaluation of the anesthetic effect ongills was performed by histopathological analysis. The concentration of 50 mgL−1 was within the ideal limit of three minutes recommended for surgical anesthesia induction and did not significantly increase glucose levels when compared to the control group (35.7±19.4 mg dL−1), besides not causing gill injuries. At this concentration the fish presented controlled blood glucose levels within the basal levels, besides not taking the risk to have later problems concernig mortality, because this concentration ensures the good health of the gills and good recovery of the animals.(AU)
O uso de anestésicos em pisciculturas é indispensável para reduzir o estresse durante o manejo. O presente trabalho propôs avaliar o efeito do eugenol como anestésico para manejo do curimatã (Prochilodus nigricans). Foram utilizados 50 espécimes (221,34±9,0 g; 25,8 ±1,1 cm), submetidos a cinco tratamentos com concentrações de 0, 25, 50, 100 e 200 mg L−1 de eugenol em exposição de 10 minutos. Foram registrados os tempos necessários para atingir cada estágio anestésico e a recuperação de cada peixe. Para verificação dos níveis de glicose sanguínea, foram realizadas coletas individuais de sangue dos peixes antes da imersão e após os 10 minutos de exposição ao anestésico. A avaliação do efeito do anestésico sobre as brânquias foi realizada por meio de análises histopatológicas. A concentração de 50 mg L−1 ficou dentro do limite ideal de três minutos preconizado para indução à anestesia cirúrgica e não elevou significativamente os níveis de glicose quando comparada ao grupo controle (35,7±19,4 mg dL−1), além de não provocar lesões branquiais. Nessa concentração, os peixes apresentaram níveis de glicose sanguínea controlada, dentro dos teores basais, além de não correrem o risco de apresentarem problemas posteriores em relação à mortalidade, pois essa concentração garante a boa saúde das brânquias e uma boa recuperação dos animais.(AU)
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Animales , Eugenol/administración & dosificación , Characiformes , Periodo de Recuperación de la Anestesia , Acuicultura/métodos , Anestésicos GeneralesRESUMEN
The aim of this study was to investigate the combination effect of exercise training and eugenol supplementation on the hippocampus apoptosis induced by CPF. 64 adult male albino rats were randomly selected and devided into eight groups of eight including: control, exercise (EXE), chlorpyrifos (CPF), Control + Oil (Co + Oil), Control + DMSO (Co + DMSO), chlorpyrifos + eugenol (CPF + Sup), chlorpyrifos + exercise (CPF + Exe) and, chlorpyrifos + exercise + eugenol (CPF + Exe + Eu). Four experimental groups received intraperitoneal injection (5 days a week) of 3.0 mg/kg body weight CPF in DMSO for 6 consecutive weeks. The exercise groups performed aerobic 5 days per week over 4 weeks. Eugenol were administered by gavage. Finally, the animals were sacrificed using CO2 gas (a half of the rats were anesthetized with ketamine and xylazine and then perfused) to evaluate hippocampus histology and parameters. The results of this study showed that CPF injection significantly decreased BDNF, AChE and ATP in CA1 area of the hippocampus (p Ë 0.05). Also, CA1 apoptosis by tunnel assay, it was found that CPF receiving groups with different dosage, showed a significant increase compared to other groups, which was confirmed by increasing cytochrome C and procaspase-3 in CPF groups (p Ë 0.05). The result of this study show that 4 weeks of exercise training and eugenol supplementation does not improve the destructive effects of CPF in CA1 area of the hippocampus. As a result, it is recommended that future studies longer periods for treatment with exercise and eugenol supplementation.
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Apoptosis/efectos de los fármacos , Cloropirifos/toxicidad , Eugenol/uso terapéutico , Terapia por Ejercicio , Hipocampo/efectos de los fármacos , Intoxicación por Organofosfatos/terapia , Condicionamiento Físico Animal , Acetilcolinesterasa/análisis , Adenosina Trifosfato/análisis , Animales , Reacción de Prevención/efectos de los fármacos , Factor Neurotrófico Derivado del Encéfalo/análisis , Caspasa 3/análisis , Terapia Combinada , Citocromos c/análisis , Modelos Animales de Enfermedad , Eugenol/administración & dosificación , Hipocampo/enzimología , Hipocampo/patología , Masculino , Trastornos de la Memoria/inducido químicamente , Trastornos de la Memoria/tratamiento farmacológico , Trastornos de la Memoria/patología , Trastornos de la Memoria/terapia , Proteínas del Tejido Nervioso/análisis , Intoxicación por Organofosfatos/tratamiento farmacológico , Distribución Aleatoria , Ratas , Ratas WistarRESUMEN
Chitosan Nanoparticles Eugenol recognizes as a potent antioxidant that can use the first therapeutic chemical to treat rheumatoid arthritis (RA) instead of Methotrexate. The purpose of this study was to investigate the effects of Chitosan Nanoparticles Eugenol as a potent Nano-herbal agent in the healing process of experimental neonatal RA compared to Methotrexate. The neonatal Wistar rats induced rheumatoid arthritis in both genders were divided into sham, control, the treatment receiving Methotrexate, and the second treatment receiving encapsulated Eugenol by Chitosan Nanoparticles groups. Afterward, Malondialdehyde, for assessment of lipid peroxidation as an oxidative stress biomarker by assay kit, FOXO3 protein as an antioxidant up-regulating by western blotting and expression of the TGF-ß and CCL2/MCP-1 genes by real-time PCR evaluation, supported by a cartilage histopathology analysis. Based on these results, Methotrexate and Eugenol encapsulated by Chitosan Nanoparticles, a significant decrease is observed in the serum level of MDA and FOXO3 protein expression in comparison to the control group. Additionally, Nanoparticle herbal agent and Methotrexate has a decreasing effect on the expression of TGF-ß and MCP-1 genes and a significant positive correlation was observed between MCP-1 and TGF-ß. Inflammation, synovial hyperplasia, and pannus formation were extreme in the Collagen Induced Arthritis rats. It can be concluded that Encapsulated Eugenol by Chitosan Nanoparticles and Methotrexate, probably by dint of their immunomodulatory, anti-inflammatory, and antioxidant potential has a protective effect against RA. Nano Eugenol is capable of delivering promising lines results to treat autoimmune diseases such as RA can also be suggested.