RESUMEN
Ellagic acid (EA) is a phenolic phytochemical found in many plants and their fruits. Vaginal epithelial cells are the first line of defense against pathogen invasion in the female reproductive tract and express antimicrobial peptides, including hBD2 and SLPI. This study investigated the in vitro effects of EA (1) on vaginal innate immunity using human vaginal epithelial cells, and (2) on HPV16 pseudovirus infection. Vaginal cells were cultured in the presence or absence of EA, and the expression of hBD2 and SLPI was determined at both transcriptional and translational levels. In addition, secretion of various cytokines and chemokines was measured. Cytotoxicity of EA was determined by CellTiter-blue and MTT assays. To investigate the ability of EA to inhibit HPV16 infection, EA was used to treat HEK-293FT cells in pre-attachment and adsorption steps. We found significant increases in both hBD2 mRNA (mean 2.9-fold at 12.5 µM EA, p < 0.001) and protein (mean 7.1-fold at 12.5 µM EA, p = 0.002) in response to EA. SLPI mRNA also increased significantly (mean 1.4-fold at 25 µM EA, p = 0.01), but SLPI protein did not. Secretion of IL-2 but not of other cytokines/chemokines was induced by EA in a dose-dependent manner. EA was not cytotoxic. At the pre-attachment step, EA at CC20 and CC50 showed a slight trend towards inhibiting HPV16 pseudovirus, but this was not significant. In summary, vaginal epithelial cells can respond to EA by producing innate immune factors, and at tested concentrations, EA is not cytotoxic. Thus, plant-derived EA could be useful as an immunomodulatory agent to improve vaginal health.
Asunto(s)
Ácido Elágico , Papillomavirus Humano 16 , Inmunidad Innata , Infecciones por Papillomavirus , Vagina , Humanos , Femenino , Ácido Elágico/farmacología , Inmunidad Innata/efectos de los fármacos , Vagina/virología , Vagina/inmunología , Vagina/efectos de los fármacos , Infecciones por Papillomavirus/inmunología , Infecciones por Papillomavirus/virología , Infecciones por Papillomavirus/tratamiento farmacológico , Citocinas/metabolismo , Células Epiteliales/efectos de los fármacos , Células Epiteliales/virología , Células Epiteliales/metabolismo , Células Epiteliales/inmunología , beta-Defensinas/metabolismo , Células HEK293RESUMEN
Photothermal therapy (PTT) of tumor would ineluctably cause oxidative stress and related inflammation in adjacent normal tissues, leading to a discounted therapeutic outcome. To address this issue, herein an innovative therapeutic strategy that integrates photothermal anticancer and normal cell protection is developed. A new type of nitrogen-doped carbon dot (ET-CD) has been synthesized in one step by hydrothermal method using ellagic acid and L-tyrosine as reaction precursors. The as-prepared ET-CD exhibits high photothermal conversion efficiency and good photothermal stability. After intravenous injection, ET-CD can accumulate at the tumor site and the hyperthermia generated under near infrared laser irradiation effectively ablates tumor tissues, thereby significantly inhibiting tumor growth. Importantly, owing to the inherited antioxidant activity from ellagic acid, ET-CD can remove reactive oxygen and nitrogen species produced in the body and reduce the levels of inflammatory factors induced by oxidative stress, so as to alleviate the damage caused by heat-induced inflammation to normal cells and tissues while photothermal anticancer. These attractive features of ET-CD may open the exploration of innovative therapeutic strategies to promote the clinical application of PTT.
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Carbono , Ácido Elágico , Nitrógeno , Terapia Fototérmica , Tirosina , Carbono/química , Carbono/farmacología , Nitrógeno/química , Ácido Elágico/farmacología , Ácido Elágico/química , Ácido Elágico/uso terapéutico , Animales , Tirosina/química , Humanos , Ratones , Terapia Fototérmica/métodos , Antiinflamatorios/farmacología , Antiinflamatorios/química , Puntos Cuánticos/química , Línea Celular Tumoral , Inflamación/tratamiento farmacológico , Antineoplásicos/farmacología , Antineoplásicos/química , Estrés Oxidativo/efectos de los fármacos , Neoplasias/tratamiento farmacológico , Neoplasias/terapia , Neoplasias/patologíaRESUMEN
Geraniin (GE), an ellagitannin (ET) renowned for its promising health advantages, faces challenges in its practical applications due to its limited bioavailability. This innovative and novel formulation of GE and soy-phosphatidylcholine (GE-PL) complex has the potential to increase oral bioavailability, exhibiting high entrapment efficiency of 100.2 ± 0.8 %, and complexation efficiency of 94.6 ± 1.1 %. The small particle size (1.04 ± 0.11 µm), low polydispersity index (0.26 ± 0.02), and adequate zeta potential (-26.1 ± 0.12 mV), indicate its uniformity and stability. Moreover, the formulation also demonstrates improved lipophilicity, reduced aqueous and buffer solubilities, and better partition coefficient. It has been validated by various analytical techniques, including Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and X-ray diffraction (XRD) studies. Oral bioavailability and pharmacokinetics of free GE and GE-PL complex investigated in rabbits demonstrated enhanced plasma concentration of ellagic acid (EA) compared to free GE. Significantly, GE, whether in its free form or as part of the GE-PL complex, was not found in the circulatory system. However, EA levels were observed at 0.5 h after administration, displaying two distinct peaks at 2 ± 0.03 h (T1max) and 24 ± 0.06 h (T2max). These peaks corresponded to peak plasma concentrations (C1max and C2max) of 588.82 ng/mL and 711.13 ng/mL respectively, signifying substantial 11-fold and 5-fold enhancements when compared to free GE. Additionally, it showed an increased area under the curve (AUC), the elimination half-life (t1/2, el) and the elimination rate constant (Kel). The formulation of the GE-PL complex prolonged the presence of EA in the bloodstream and improved its absorption, ultimately leading to a higher oral bioavailability. In summary, the study highlights the significance of the GE-PL complex in overcoming the bioavailability limitations of GE, paving the way for enhanced therapeutic outcomes and potential applications in drug delivery and healthcare.
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Disponibilidad Biológica , Glucósidos , Taninos Hidrolizables , Animales , Conejos , Taninos Hidrolizables/farmacocinética , Taninos Hidrolizables/química , Taninos Hidrolizables/administración & dosificación , Glucósidos/farmacocinética , Glucósidos/química , Glucósidos/administración & dosificación , Glucósidos/sangre , Administración Oral , Masculino , Tamaño de la Partícula , Fosfatidilcolinas/química , Solubilidad , Química Farmacéutica/métodos , Ácido Elágico/farmacocinética , Ácido Elágico/química , Ácido Elágico/administración & dosificación , Ácido Elágico/sangre , Taninos/química , Taninos/farmacocinética , Taninos/administración & dosificaciónRESUMEN
The aim of this experiment was to investigate the effect of storage temperature and pH on phenolic compounds of Phyllanthus emblica juice. Juice was stored at different temperatures and pH for 15 days and sampled on 2-day intervals. The browning index (BI, ABS420 nm), pH, centrifugal precipitation rate (CPR), and phenolic compounds were evaluated. The results showed 4°C and pH 2.5 could effectively inhibit browning and slow down pH drop of P. emblica juice. The result of orthogonal partial least square-discriminant analysis showed P. emblica juice stored at 4°C and pH 2.5 still had a similar phenolic composition, but at 20°C, 37°C, and pH 3.5, the score plots were concentrated only in the first 3 days. Additionally, gallic acid (GA) and ellagic acid (EA) were screened out to be the differential compounds for browning of P. emblica juice. The contents of GA, epigallocatechin (EGC), corilagin (CL), gallocatechin gallate (GCG), chebulagic acid (CA), 1,2,3,4,6-O-galloyl-d-glucose (PGG), and EA were more stable at 4°C and pH 2.5. Overall, during storage at 4°C and pH 2.5, it could inhibit the increase of GA and EA and decrease of CL, GCG, CA, and PGG, whereas EGC did not show significant difference between storage conditions. The CPR was higher at 4°C, while pH 2.5 could reduce the CPR. In conclusion, in order to maintain stability of phenolic compounds and extended storage period, the P. emblica juice could be stored at low temperature and adjust the pH to increase the stability of juice system.
Asunto(s)
Almacenamiento de Alimentos , Jugos de Frutas y Vegetales , Fenoles , Phyllanthus emblica , Temperatura , Phyllanthus emblica/química , Concentración de Iones de Hidrógeno , Almacenamiento de Alimentos/métodos , Fenoles/análisis , Jugos de Frutas y Vegetales/análisis , Ácido Elágico/análisis , Ácido Gálico/análisis , Frutas/química , Taninos Hidrolizables/análisisRESUMEN
The aim of this work was to develop and characterize a thin films composed of hyaluronic acid/ellagic acid for potential medical application. Its principal novelty, distinct from the prior literature in terms of hyaluronic acid films supplemented with phenolic acids, resides in the predominant incorporation of ellagic acid-a distinguished compound-as the primary constituent of the films. Herein, ellagic acid was dissolved in two different solvents, i.e., acetic acid (AcOH) or sodium hydroxide (NaOH), and the surface properties of the resultant films were assessed using atomic force microscopy and contact angle measurements. Additionally, various physicochemical parameters were evaluated including moisture content, antioxidant activity, and release of ellagic acid in phosphate buffered saline. Furthermore, the evaluation of films' biocompatibility was conducted using human epidermal keratinocytes, dermal fibroblasts, and human amelanotic melanoma cells (A375 and G361), and the antimicrobial activity was elucidated accordingly against Staphylococcus aureus ATCC 6538 and Pseudomonas aeruginosa ATCC 15442. Our results showed that the films exhibited prominent antibacterial properties particularly against Staphylococcus aureus, with the 80HA/20EA/AcOH film indicating the strong biocidal activity against this strain leading to a significant reduction in viable cells. Comparatively, the 50HA/50EA/AcOH film also displayed biocidal activity against Staphylococcus aureus. This experimental approach could be a promising technique for future applications in regenerative dermatology or novel strategies in terms of bioengineering.
Asunto(s)
Materiales Biocompatibles , Ácido Elágico , Ácido Hialurónico , Staphylococcus aureus , Ácido Hialurónico/química , Ácido Hialurónico/farmacología , Humanos , Staphylococcus aureus/efectos de los fármacos , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Ácido Elágico/farmacología , Ácido Elágico/química , Pseudomonas aeruginosa/efectos de los fármacos , Antibacterianos/farmacología , Antibacterianos/química , Antioxidantes/farmacología , Antioxidantes/química , Fibroblastos/efectos de los fármacos , Queratinocitos/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Línea Celular Tumoral , Propiedades de SuperficieRESUMEN
The pomegranate processing industry generates worldwide enormous amounts of by-products, such as pomegranate peels (PPs), which constitute a rich source of phenolic compounds. In this view, PPs could be exploited as a sustainable source of ellagic acid, which is a compound that possesses various biological actions. The present study aimed at the liberation of ellagic acid from its bound forms via ultrasound-assisted alkaline hydrolysis, which was optimized using response surface methodology. The effects of duration of sonication, solvent:solid ratio, and NaOH concentration on total phenol content (TPC), antioxidant activity, and punicalagin and ellagic acid content were investigated. Using the optimum hydrolysis conditions (i.e., 32 min, 1:48 v/w, 1.5 mol/L NaOH), the experimental responses were found to be TCP: 4230 ± 190 mg GAE/100 g dry PPs; AABTS: 32,398 ± 1817 µmol Trolox/100 g dry PPs; ACUPRAC: 29,816 ± 1955 µmol Trolox/100 g dry PPs; 59 ± 3 mg punicalagin/100 g dry PPs; and 1457 ± 71 mg ellagic acid/100 g dry PPs. LC-QTOF-MS and GC-MS analysis of the obtained PP extract revealed the presence of various phenolic compounds (e.g., ellagic acid), organic acids (e.g., citric acid), sugars (e.g., fructose) and amino acids (e.g., glycine). The proposed methodology could be of use for food, pharmaceutical, and cosmetics applications, thus reinforcing local economies.
Asunto(s)
Antioxidantes , Ácido Elágico , Granada (Fruta) , Ácido Elágico/química , Granada (Fruta)/química , Hidrólisis , Antioxidantes/química , Fenoles/química , Fenoles/análisis , Extractos Vegetales/química , Taninos Hidrolizables/química , Frutas/químicaRESUMEN
Oxidative stress (OS) plays an important role in the emergence and prevention of neurodegenerative diseases, such as Alzheimer's disease (AD). Excess reactive oxygen species (ROS) accumulated in a neuronal cell can lead to OS, producing cell injury and death. Seeking nanoantioxidants against AD-related oxidative stress has attracted a lot of attention, especially those potential antioxidant agents derived from natural polyphenols. However, the transformation of abundant plant polyphenols to antioxidative biomaterials against OS is still challenging. In this work, we report a new method to transform amorphous tannic acid (TA) into tailorable shaped ellagic acid (EA) crystalline particles without using an organic solvent. EA crystalline particles were generated from TA, which underwent a chemical transformation, in situ metal phenolic coordination and acid-induced assembly process, and the size and shape could be controlled by varying the amount of acid. As-prepared EA crystalline particles showed excellent stability in water and lysosomal mimicking fluid and possess unique fluorescence properties and a strong response in mass spectrometry, which is beneficial for their imaging analysis in cells and tissues. More importantly, EA particles have shown significant H2O2-related ROS scavenging ability, a high cellular uptake capacity, an excellent neuroprotective effect in PC12 cells, a high drug loading capacity and BBB permeability to enter the brain. Our study suggested that the EA crystalline particles show great potential for OS-mediated AD treatment.
Asunto(s)
Ácido Elágico , Fármacos Neuroprotectores , Estrés Oxidativo , Especies Reactivas de Oxígeno , Taninos , Ácido Elágico/farmacología , Ácido Elágico/química , Taninos/farmacología , Taninos/química , Estrés Oxidativo/efectos de los fármacos , Células PC12 , Animales , Ratas , Especies Reactivas de Oxígeno/metabolismo , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/química , Fármacos Neuroprotectores/síntesis química , Antioxidantes/farmacología , Antioxidantes/química , Antioxidantes/síntesis química , Barrera Hematoencefálica/metabolismo , Barrera Hematoencefálica/efectos de los fármacos , Peróxido de Hidrógeno/farmacología , Peróxido de Hidrógeno/química , Neuroprotección/efectos de los fármacos , Tecnología Química Verde , PolifenolesRESUMEN
Tormentilla erecta (L.) Raeusch is a widespread plant in Europe and Western Asia. Its rhizomes (Tormentilae rhizoma) are the main ingredient of herbal alcoholic beverages and can be used as a natural preservative in beer production. Apart from its unique taste qualities, therapeutic properties in gastrointestinal tract ailments are attributed to the tincture obtained from Tormentillae rhizoma. The presented research aimed to determine the mutual relationship between the components of Tormentillae tincture, present in popular alcoholic beverages, and intestinal epithelium (Caco-2 cell monolayers). A comprehensive qualitative and quantitative analysis of the tincture was performed, including the determination of condensed and hydrolyzable tannins as well as triterpenoids (UHPLC-DAD-MS/MS). Incubation of the tincture with Caco-2 monolayers has shown that only triterpenes pass through the monolayer, while condensed tannins are mainly bound to the monolayer surface. Ellagic acid derivatives were the only components of the Tormentillae tinctura being metabolized by cell monolayers to the compounds not previously described in the literature, which may be crucial in the treatment of intestinal diseases with inflammatory background.
Asunto(s)
Mucosa Intestinal , Rizoma , Humanos , Células CACO-2 , Rizoma/química , Mucosa Intestinal/metabolismo , Triterpenos/metabolismo , Extractos Vegetales/metabolismo , Extractos Vegetales/farmacología , Espectrometría de Masas en Tándem , Transporte Biológico , Cromatografía Líquida de Alta Presión , Bebidas Alcohólicas/análisis , Proantocianidinas/metabolismo , Taninos Hidrolizables/metabolismo , Ácido Elágico/metabolismoRESUMEN
Ellagic acid (EA) is a natural polyphenol and possesses excellent in vivo bioactivity and antioxidant behaviors, which play an important role in the treatment of oxidative stress-related diseases, such as cancer. Additionally, EA is also known as a skin-whitening ingredient. The content of EA would determine its efficacy. Therefore, the accurate analysis of EA content can provide more information for the scientific consumption of EA-rich foods and cosmetics. Nevertheless, the analysis of EA in these samples is challenging due to the low concentration level and the presence of interfering components with high abundance. Molecularly imprinted polymers are highly efficient pretreatment materials in achieving specific recognition of target molecules. However, the traditional template molecule (EA) could not be absolutely removed. Hence, template leakage continues to occur during the sample preparation process, leading to a lack of accuracy in the quantification of EA in actual samples, particularly for trace analytes. In addition, another drawback of EA as an imprinting template is that EA possesses poor solubility and a high price. Gallic acid (GA), called dummy templates, was employed for the synthesis of MIPs as a solution to these challenges. The approach used in this study was boronate affinity-based oriented surface imprinting. The prepared dummy-imprinted nanoparticles exhibited several significant advantages, such as good specificity, high binding affinity ((4.89 ± 0.46) × 10-5 M), high binding capacity (6.56 ± 0.35 mg/g), fast kinetics (6 min), and low binding pH (pH 5.0) toward EA. The reproducibility of the dummy-imprinted nanoparticles was satisfactory. The dummy-imprinted nanoparticles could still be reused even after six adsorption-desorption cycles. In addition, the recoveries of the proposed method for EA at three spiked levels of analysis in strawberry and pineapple were 91.0-106.8% and 93.8-104.0%, respectively, which indicated the successful application to real samples.
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Ácido Elágico , Impresión Molecular , Extracción en Fase Sólida , Ácido Elágico/química , Extracción en Fase Sólida/métodos , Impresión Molecular/métodos , Ácidos Borónicos/química , Polímeros Impresos Molecularmente/química , Análisis de los Alimentos/métodos , Nanoestructuras/químicaRESUMEN
BACKGROUND: Mediterranean diet rich in polyphenolic compounds holds great promise to prevent and alleviate multiple sclerosis (MS), a central nervous system autoimmune disease associated with gut microbiome dysbiosis. Health-promoting effects of natural polyphenols with low bioavailability could be attributed to gut microbiota reconstruction. However, its underlying mechanism of action remains elusive, resulting in rare therapies have proposed for polyphenol-targeted modulation of gut microbiota for the treatment of MS. RESULTS: We found that oral ellagic acid (EA), a natural polyphenol rich in the Mediterranean diet, effectively halted the progression of experimental autoimmune encephalomyelitis (EAE), the animal model of MS, via regulating a microbiota-metabolites-immunity axis. EA remodeled the gut microbiome composition and particularly increased the relative abundances of short-chain fatty acids -producing bacteria like Alloprevotella. Propionate (C3) was most significantly up-regulated by EA, and integrative modeling revealed a strong negative correlation between Alloprevotella or C3 and the pathological symptoms of EAE. Gut microbiota depletion negated the alleviating effects of EA on EAE, whereas oral administration of Alloprevotella rava mimicked the beneficial effects of EA on EAE. Moreover, EA directly promoted Alloprevotella rava (DSM 22548) growth and C3 production in vitro. The cell-free supernatants of Alloprevotella rava co-culture with EA suppressed Th17 differentiation by modulating acetylation in cell models. C3 can alleviate EAE development, and the mechanism may be through inhibiting HDAC activity and up-regulating acetylation thereby reducing inflammatory cytokines secreted by pathogenic Th17 cells. CONCLUSIONS: Our study identifies EA as a novel and potentially effective prebiotic for improving MS and other autoimmune diseases via the microbiota-metabolites-immunity axis. Video Abstract.
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Ácido Elágico , Encefalomielitis Autoinmune Experimental , Microbioma Gastrointestinal , Esclerosis Múltiple , Propionatos , Ácido Elágico/farmacología , Animales , Microbioma Gastrointestinal/efectos de los fármacos , Encefalomielitis Autoinmune Experimental/inmunología , Encefalomielitis Autoinmune Experimental/tratamiento farmacológico , Encefalomielitis Autoinmune Experimental/microbiología , Propionatos/metabolismo , Ratones , Esclerosis Múltiple/tratamiento farmacológico , Esclerosis Múltiple/microbiología , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad , Femenino , Autoinmunidad/efectos de los fármacos , Disbiosis/microbiología , Sistema Nervioso Central/efectos de los fármacos , Sistema Nervioso Central/inmunología , Humanos , Administración OralRESUMEN
In this study, a sensitive high-performance liquid chromatography detector was established and validated for the simultaneous determination of geniposide, ellagic acid, piperine, costunolide and dehydrocostuslactone in Liuwei Muxiang Capsules. The analysis was achieved on CHANIN 100-5-C18-H column (5µm, 250 mm×4.6 mm) with the temperature of 30oC. Gradient elution was applied using 0.1% phosphoric acid solution-methanol-acetonitrile (50:50) as mobile phase at the flow rate of 1.0 mL/min. The determination was performed at the wavelength of 225 nm (detecting geniposide), 254 nm (detecting ellagic acid), 343 nm (detecting piperine) and 225 nm (detecting costunolide and dehydrocostuslactone) along with the sample volume of 10µL. The linear ranges of geniposide, ellagic acid, piperine, costunolide and dehydrocostuslactone demonstrated good linear relationships within their respective determination ranges. The average recoveries were 100.04%, 99.86%, 99.79%, 100.17% and 100.41%, respectively. RSD% was 1.3%, 1.2%, 1.2%, 1.2%, 1.5%, respectively. The developed method was proved to be simple, accurate and sensitive, which can provide a quantitative analysis method for the content determination of geniposide, ellagic acid, piperine, costunolide and dehydrocostuslactone in Liuwei Muxiang capsules.
Asunto(s)
Alcaloides , Benzodioxoles , Cápsulas , Medicamentos Herbarios Chinos , Ácido Elágico , Iridoides , Lactonas , Piperidinas , Alcamidas Poliinsaturadas , Cromatografía Líquida de Alta Presión/métodos , Benzodioxoles/análisis , Alcamidas Poliinsaturadas/análisis , Piperidinas/análisis , Piperidinas/química , Alcaloides/análisis , Lactonas/análisis , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/análisis , Iridoides/análisis , Ácido Elágico/análisis , Reproducibilidad de los Resultados , Sesquiterpenos/análisisRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Androgenic alopecia (AGA) is the most prevalent form of hair loss in clinical practice and affects the physical and psychological well-being of adolescents. Paeonia lactiflora Pallas (PL), which is widely used in traditional Chinese medicine, enhances blood function and promotes hair growth, and ellagic acid (EA), a polyphenol in PL extract, shows strong antioxidant, anti-aging, and anti-inflammatory properties and also plays a role in the treatment of various skin conditions. However, its role and mechanism of action in AGA remain unclear. AIM OF THE STUDY: To determine whether EA can rescue slow hair regeneration by regulating dihydrotestosterone (DHT)-induced ferroptosis in AGA mice and clarify the effect of EA on DHT-induced ferroptosis in dermal papilla cells (DPCs). MATERIALS AND METHODS: Male C57BL/6 mice were used to establish a DHT-induced AGA mouse model, whereas DPCs were used to establish a DHT-induced cellular model. Thereafter, we investigated the therapeutic mechanism of action of EA via immunofluorescence, western blot analysis, immunohistochemistry, electron microscopy, and molecular docking. RESULTS: EA stimulated hair regeneration in mice and reversed DHT-induced increases in iron content, lipid peroxidation, and DHT-induced mitochondrial dysfunction by activating the Wnt/ß-catenin signaling pathway. Further, ß-catenin knockdown suppressed the inhibitory effect of EA on DHT-induced ferroptosis in DPCs. CONCLUSION: EA inhibits DHT-induced ferroptosis and promotes hair regrowth in mice by activating the Wnt/ß-catenin signaling pathway. Thus, it has potential for use as a treatment option for AGA.
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Alopecia , Dihidrotestosterona , Ácido Elágico , Cabello , Regeneración , Vía de Señalización Wnt , Animales , Masculino , Ratones , Alopecia/tratamiento farmacológico , Alopecia/inducido químicamente , beta Catenina/metabolismo , Dihidrotestosterona/farmacología , Ácido Elágico/farmacología , Ferroptosis/efectos de los fármacos , Cabello/efectos de los fármacos , Cabello/crecimiento & desarrollo , Ratones Endogámicos C57BL , Regeneración/efectos de los fármacos , Vía de Señalización Wnt/efectos de los fármacosAsunto(s)
Demencia , Ácido Elágico , Óxido Nítrico Sintasa de Tipo III , Fosfatidilinositol 3-Quinasas , Transducción de Señal , Estreptozocina , Animales , Transducción de Señal/efectos de los fármacos , Óxido Nítrico Sintasa de Tipo III/metabolismo , Ratas , Ácido Elágico/farmacología , Demencia/tratamiento farmacológico , Demencia/prevención & control , Fosfatidilinositol 3-Quinasas/metabolismo , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismoRESUMEN
The aim of this research was to explore the effects of ellagic acid (EA) on growth performance, meat quality, and metabolomics profile of broiler chickens. 240 healthy yellow-feathered broilers were randomly divided into 4 groups (6 replicates/group and 10 broilers /replicate): 1) a standard diet (CON); 2) CON+0.01% EA; 3) CON+0.02% EA; 4) CON+0.04% EA. Compared with the CON group, dietary 0.02% EA increased linearly and quadratically the ADG and lowered F/G ratio from 29 to 56 d and from 1 to 56 d of age (P < 0.05). The EA groups had higher spleen index and showed linear and quadratic improve thymus index (P < 0.05). A total of 0.02% EA linearly and quadratically increased the leg muscle percentage and quadratically increased the breast muscle percentage (P < 0.05). Compared to the control diet, 0.02% EA decreased quadratically the L* and increased a* of breast muscle at 45 min postslaughter (P < 0.05), and quadratically decreased (P < 0.05) the b* and increased linearly and quadratically (P < 0.05) drip loss. Additionally, EA improved linearly and quadratically (P < 0.05) serum total protein concentration and reduced linearly and quadratically (P < 0.05) serum blood urea nitrogen concentration. A total of 0.02% EA quadratically increased catalase activity and decreased malondialdehyde concentration in breast muscle compared with the control diet (P < 0.05). 0.02% and 0.04% EA could linearly and quadratically increase (P < 0.05) the concentrations of histidine, leucine and essential amino acids (EAA), 0.02% EA could linearly and quadratically increase (P < 0.05) the concentrations of threonine, glutamate, and flavored amino acids in breast muscle. 0.02% EA linearly and quadratically improved the C20:3n6, C22:6n3, polyunsaturated fatty acid (PUFA) concentrations, and the ratio of PUFA to saturated fatty acids (SFA), but reduced the C16:0 and the SFA concentrations in breast muscle than the CON group (P < 0.05). The EA diet linearly increased (P = 0.035) and quadratically tended (P = 0.068) to regulate the C18:2n6c concentration of breast muscle. Metabolomics showed that alanine metabolism, aspartate and glutamate metabolism, arginine and proline metabolism, taurine and hypotaurine metabolism, and glycerophospholipid metabolism were the most differentially abundant. These results showed that EA supported moderate positive effects on growth performance, meat quality, and metabolomics profile of broilers.
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Alimentación Animal , Pollos , Dieta , Suplementos Dietéticos , Ácido Elágico , Carne , Animales , Pollos/crecimiento & desarrollo , Pollos/fisiología , Pollos/metabolismo , Alimentación Animal/análisis , Dieta/veterinaria , Suplementos Dietéticos/análisis , Carne/análisis , Ácido Elágico/administración & dosificación , Ácido Elágico/farmacología , Metabolómica , Distribución Aleatoria , Masculino , Metaboloma/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Fenómenos Fisiológicos Nutricionales de los Animales/efectos de los fármacosRESUMEN
PURPOSE: To investigate the effect of ellagic acid (EA) in gingival tissues injury in rats. METHODS: Twenty rats were categorized into two groups. In burn group, an excisional wound area was created by removing a 4-mm diameter flap from the left molar region in the mucoperiosteal region of the gingiva. In burn + ellagic acid group, 1.2 mg/mL EA was administered as irrigation for one week. Animals was sacrificed under anesthesia at the end of experiment. Malondialdehyde (MDA), myeloperoxidase (MPO) and glutathione (GSH) level were measured. Hematoxylin and eosin, fibroblast growth factor (FGF) and epidermal growth factor (EGF) immunostainings were applied to tissues. RESULTS: MDA, MPO, inflammation and leukocyte infiltration were high in burn group. Degeneration epithelium, edema and inflammatory cell infiltration in connective tissue areas, and dilatation and congestion in blood vessels were observed in burn group. In burn + EA group, the gingival epithelium improved, collagen fiber production increased and organized dermis were observed. After burn injury, FGF and EGF activity was increased in EA treated groups. CONCLUSIONS: We suggest that EA have the potential for better healing outcomes in oral wounds. EA seems to have promising therapeutic efficacy to enhance oral wound healing.
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Anestesia , Factor de Crecimiento Epidérmico , Animales , Ratas , Encía , Ácido Elágico , Fibroblastos , GlutatiónRESUMEN
The target and mechanism of ellagic acid (EA) against rotavirus (RV) were investigated by network pharmacology, computational biology, and surface plasmon resonance verification. The target of EA was obtained from 11 databases such as HIT and TCMSP, and RV-related targets were obtained from the Gene Cards database. The relevant targets were imported into the Venny platform to draw a Venn diagram, and their intersections were visualized. The protein-protein interaction networks (PPI) were constructed using STRING, DAVID database, and Cytoscape software, and key targets were screened. The target was enriched by Gene Ontology (GO) and KEGG pathway, and the 'EA anti-RV target-pathway network' was constructed. Schrodinger Maestro 13.5 software was used for molecular docking to determine the binding free energy and binding mode of ellagic acid and target protein. The Desmond program was used for molecular dynamics simulation. Saturation mutagenesis analysis was performed using Schrodinger's Maestro 13.5 software. Finally, the affinity between ellagic acid and TLR4 protein was investigated by surface plasmon resonance (SPR) experiments. The results of network pharmacological analysis showed that there were 35 intersection proteins, among which Interleukin-1ß (IL-1ß), Albumin (ALB), Nuclear factor kappa-B1 (NF-κB1), Toll-Like Receptor 4 (TLR4), Tumor necrosis factor alpha (TNF-α), Tumor protein p53 (TP53), Recombinant SMAD family member 3 (SAMD3), Epidermal growth factor (EGF) and Interleukin-4 (IL-4) were potential core targets of EA anti-RV. The GO analysis consists of biological processes (BP), cellular components (CC), and molecular functions (MF). The KEGG pathways with the highest gene count were mainly related to enteritis, cancer, IL-17 signaling pathway, and MAPK signaling pathway. Based on the crystal structure of key targets, the complex structure models of TP53-EA, TLR4-EA, TNF-EA, IL-1ß-EA, ALB-EA, NF-κB1-EA, SAMD3-EA, EGF-EA, and IL-4-EA were constructed by molecular docking (XP mode of flexible docking). The MMGBS analysis and molecular dynamics simulation were also studied. The Δaffinity of TP53 was highest in 220 (CYS â TRP), 220 (CYS â TYR), and 220 (CYS â PHE), respectively. The Δaffinity of TLR4 was highest in 136 (THR â TYR), 136 (THR â PHE), and 136 (THR â TRP). The Δaffinity of TNF-α was highest in 150 (VAL â TRP), 18 (ALA â GLU), and 144 (PHE â GLY). SPR results showed that ellagic acid could bind TLR4 protein specifically. TP53, TLR4, and TNF-α are potential targets for EA to exert anti-RV effects, which may ultimately provide theoretical basis and clues for EA to be used as anti-RV drugs by regulating TLR4/NF-κB related pathways.
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Medicamentos Herbarios Chinos , Rotavirus , Factor de Necrosis Tumoral alfa , Ácido Elágico/farmacología , Interleucina-4 , Resonancia por Plasmón de Superficie , Receptor Toll-Like 4 , Factor de Crecimiento Epidérmico , Farmacología en Red , Simulación del Acoplamiento Molecular , Biología Computacional , AlbúminasRESUMEN
Streptococcus thermophilus FUA329 converts ellagic acid (EA) to urolithin A (Uro-A), which is not autonomously converted by the gut microbiota to produce highly bioavailable and multibiologically active Uro-A in urolithin metabotype 0 (UM-0) populations. We consider that Streptococcus thermophilus FUA329 has the potential to be developed as a probiotic. Therefore, we utilized S. thermophilus FUA329 for in vitro cofermentation with gut microbiota. The results revealed that strain FUA329 increased the production of EA-converted Uro-A during in vitro cofermentation with the human gut microbiota of different urolithin metabotypes (UMs), with a significant increase in the production of Uro-A in the experimental group of UM-0. In addition, changes in the in vitro cofermentation microbial community were determined using high-throughput sequencing. Strain FUA329 modulated the structure and composition of the gut microbiota in different UMs, thereby significantly increasing the abundance of beneficial microbiota in the gut microbiota while decreasing the abundance of harmful microbiota. Of greatest interest was the significant increase in the abundance of Actinobacteria phylum after the cofermentation of strain FUA329 with UM-0 gut microbiota, which might be related to the significant increase in the production of Uro-A.
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Microbioma Gastrointestinal , Microbiota , Humanos , Streptococcus thermophilus , Cumarinas/química , Ácido ElágicoRESUMEN
Ellagic acid, known for its various biological activities, is widely used. Ellagic acid from pomegranate peels is safe for consumption, while that from gallnuts is only suitable for external use. However, there is currently no effective method to confirm the source of ellagic acid. Therefore, this study establishes an analysis method using ultra-high-performance liquid chromatography-electrospray ionization-high-resolution mass spectrometry (UHPLC-ESI-HR-MS) to identify the components of crude ellagic acid extracts from pomegranate peels and gallnuts. The analysis revealed that there was a mix of components in the crude extracts, such as ellagic acid, palmitic acid, oleic acid, stearic acid, and 9(10)-EpODE. Furthermore, it could be observed that ellagic acid extracted from gallnuts contained toxic substances such as anacardic acid and ginkgolic acid (15:1). These components could be used to effectively distinguish the origin of ellagic acid from pomegranate peels or gallnuts. Additionally, a rapid quantitative analysis method using UHPLC-ESI-MS with multiple reaction monitoring (MRM) mode was developed for the quality control of ellagic acid products, by quantifying anacardic acid and ginkgolic acid (15:1). It was found that one of three ellagic acid health care products contained ginkgolic acid (C15:1) and anacardic acid at more than 1 ppm.
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Ácidos Anacárdicos , Granada (Fruta) , Salicilatos , Espectrometría de Masa por Ionización de Electrospray/métodos , Extractos Vegetales/química , Ácido Elágico/química , Cromatografía Líquida de Alta Presión/métodosRESUMEN
The metabolite urolithin A, a metabolite of the dietary polyphenol ellagic acid (EA), has significant health benefits for humans. However, studies on the gut microbiota involved in ellagic acid metabolism are limited. In this study, we conducted in vitro fermentation of EA using human intestinal microbiome combined with antibiotics (vancomycin, polymyxin B sulfate, and amphotericin B). Liquid chromatography-mass spectrometry (LC-MS/MS) analysis demonstrated that the production capacity of urolithin A by gut microbiota co-treated with polymyxin B sulfate and amphotericin B (22.39 µM) was similar to that of untreated gut microbiota (24.26 µM). Macrogenomics (high-throughput sequencing) was used to analyze the composition and structure of the gut microbiota. The results showed that the abundance of Bifidobacterium longum, Bifidobacterium adolescentis, and Bifidobacterium bifidum in the gut microbiota without antibiotic treatment or co-treated with polymyxin B sulfate and amphotericin B during EA fermentation was higher than that in other antibiotic treatment gut microbiota. Therefore, B. longum, B. adolescentis, and B. bifidum may be new genera involved in the conversion of EA to urolithin A. In conclusion, the study revealed unique interactions between polyphenols and gut microbiota, deepening our understanding of the relationship between phenolic compounds like EA and the gut microbiota. These findings may contribute to the development of gut bacteria as potential probiotics for further development. KEY POINTS: ⢠Intestinal microbiome involved in ellagic acid metabolism. ⢠Gram-positive bacteria in the intestinal microbiome are crucial for ellagic acid metabolism. ⢠Bifidobacterium longum, Bifidobacterium adolescentis, and Bifidobacterium bifidum participate in ellagic acid metabolism.
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Bifidobacterium longum , Cumarinas , Microbioma Gastrointestinal , Humanos , Ácido Elágico/metabolismo , Cromatografía Liquida , Polimixina B , Anfotericina B , Espectrometría de Masas en Tándem , Bifidobacterium longum/metabolismo , AntibacterianosRESUMEN
A Gram-stain-positive, anaerobic, motile, and short rod-shaped bacterium, designated KGMB12511T, was isolated from the feces of healthy Koreansubjects. Phylogenetic analysis based on the 16S rRNA gene sequence showed that strain KGMB12511T was closely related to Gordonibacter pamelaeae 7-10-1-bT (95.2%). The draft genome of KGMB12511T comprised 33 contigs and 2,744 protein-coding genes. The DNA G + C content was 59.9% based on whole-genome sequences. The major cellular fatty acids (>10%) of strain KGMB12511T were C18:1 cis9, C18:1 cis9 DMA (dimethylacetal), and C16:0 DMA. The predominant polar lipids included a diphosphatydilglycerol, four glycolipids, and an unidentified phospholipid. The major respiratory quinones were menaquinone 6 (MK-6) and monomethylmenaquinone 6 (MMK-6). Furthermore, HPLC analysis demonstrated the ability of strain KGMB12511T to convert ellagic acid into urolithin. Based on a comprehensive analysis of phenotypic, chemotaxonomic, and phylogenetic data, strain KGMB12511T represents a novel species in the genus Gordonibacter. The type strain is KGMB12511T (= KCTC 25343T = NBRC 116190T).