RESUMO
In this study, we present the isolation and characterization of the structure of six gallotannins (1-6), three ellagitannins (7-9), a neolignan glucoside (10), and three related polyphenolic compounds (gallic acid, 11 and 12) from Trapa bispinosa Roxb. pericarp extract (TBE). Among the isolates, the structure of compound 10 possessing a previously unclear absolute configuration was unambiguously determined through nuclear magnetic resonance and circular dichroism analyses. The α-glucosidase activity and glycation inhibitory effects of the isolates were evaluated. Decarboxylated rugosin A (8) showed an α-glucosidase inhibitory activity, while hydrolyzable tannins revealed stronger antiglycation activity than that of the positive control. Furthermore, the identification and quantification of the TBE polyphenols were investigated by high-performance liquid chromatography coupled to ultraviolet detection and electrospray ionization mass spectrometry analysis, indicating the predominance of gallic acid, ellagic acid, and galloyl glucoses showing marked antiglycation properties. These findings suggest that there is a potential food industry application of polyphenols in TBE as a functional food with antidiabetic and antiglycation activities.
Assuntos
Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Lythraceae/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Dicroísmo Circular , Ácido Elágico/isolamento & purificação , Indústria Alimentícia , Alimento Funcional/análise , Ácido Gálico/análogos & derivados , Ácido Gálico/isolamento & purificação , Glucosídeos/isolamento & purificação , Taninos Hidrolisáveis/isolamento & purificação , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Extratos Vegetais/química , Polifenóis/química , Polifenóis/isolamento & purificação , Espectrometria de Massas por Ionização por ElectrosprayRESUMO
The aim of the study was to investigate changes in the content of biologically active compounds during the fermentation and aging of natural meads with the addition of three Cornelian cherry juices from three cultivars: 'Koralovyi', 'Podolski' and 'Yantarnyi', in the amount of 10% v/v. After the fermentation process the content of gallic and ellagic acids significantly increased, in relation to wort. Whereas the greatest losses were observed among unstable anthocyanins. The three-month aging process also reduced the content of the analyzed compounds except for ellagic acid, the content of which increased by up to 90%. The content of biologically active compounds, including iridoids and antioxidant phenolics, are constantly changing in the process of fermentation and aging of fruit meads. The studies proved that the addition of Cornelian cherry juice allows significantly enriched classic meads with new biologically active compounds, such as: exceptional iridoids (loganic acid, cornuside, loganine, sweroside), flavonols, phenolic acids and anthocyanins.
Assuntos
Bebidas Alcoólicas/análise , Tecnologia de Alimentos/métodos , Mel/análise , Iridoides/química , Fenóis/química , Saccharomyces/metabolismo , Antocianinas/biossíntese , Antocianinas/química , Antocianinas/classificação , Antocianinas/isolamento & purificação , Antioxidantes/química , Antioxidantes/classificação , Antioxidantes/isolamento & purificação , Antioxidantes/metabolismo , Benzotiazóis/antagonistas & inibidores , Compostos de Bifenilo/antagonistas & inibidores , Ácido Elágico/química , Ácido Elágico/isolamento & purificação , Ácido Elágico/metabolismo , Fermentação , Flavonóis/química , Flavonóis/classificação , Flavonóis/isolamento & purificação , Flavonóis/metabolismo , Frutas/química , Sucos de Frutas e Vegetais/análise , Ácido Gálico/química , Ácido Gálico/isolamento & purificação , Ácido Gálico/metabolismo , Humanos , Iridoides/classificação , Iridoides/isolamento & purificação , Iridoides/metabolismo , Fenóis/classificação , Fenóis/isolamento & purificação , Fenóis/metabolismo , Picratos/antagonistas & inibidores , Prunus avium/química , Ácido Quínico/análogos & derivados , Ácido Quínico/química , Ácido Quínico/isolamento & purificação , Ácido Quínico/metabolismo , Ácidos Sulfônicos/antagonistas & inibidoresRESUMO
Among 276 herbal extracts, a methanol extract of Castanopsis cuspidata var. sieboldii stems was selected as an experimental source for novel acetylcholinesterase (AChE) inhibitors. Five compounds were isolated from the extract by activity-guided screening, and their inhibitory activities against butyrylcholinesterase (BChE), monoamine oxidases (MAOs), and ß-site amyloid precursor protein cleaving enzyme 1 (BACE-1) were also evaluated. Of these compounds, 4'-O-(α-L-rhamnopyranosyl)-3,3',4-tri-O-methylellagic acid (3) and 3,3',4-tri-O-methylellagic acid (4) effectively inhibited AChE with IC50 values of 10.1 and 10.7 µM, respectively. Ellagic acid (5) inhibited AChE (IC50 = 41.7 µM) less than 3 and 4. In addition, 3 effectively inhibited MAO-B (IC50 = 7.27 µM) followed by 5 (IC50 = 9.21 µM). All five compounds weakly inhibited BChE and BACE-1. Compounds 3, 4, and 5 reversibly and competitively inhibited AChE, and were slightly or non-toxic to MDCK cells. The binding energies of 3 and 4 (- 8.5 and - 9.2 kcal/mol, respectively) for AChE were greater than that of 5 (- 8.3 kcal/mol), and 3 and 4 formed a hydrogen bond with Tyr124 in AChE. These results suggest 3 is a dual-targeting inhibitor of AChE and MAO-B, and that these compounds should be viewed as potential therapeutics for the treatment of Alzheimer's disease.
Assuntos
Inibidores da Colinesterase/farmacologia , Ácido Elágico/isolamento & purificação , Ácido Elágico/farmacologia , Fagaceae/química , Inibidores da Monoaminoxidase/farmacologia , Monoaminoxidase/metabolismo , Animais , Bioensaio , Morte Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Fracionamento Químico , Inibidores da Colinesterase/farmacocinética , Diálise , Cães , Electrophorus , Ácido Elágico/farmacocinética , Células HL-60 , Humanos , Ligação de Hidrogênio , Cinética , Células Madin Darby de Rim Canino , Metanol , Simulação de Acoplamento Molecular , Inibidores da Monoaminoxidase/farmacocinética , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/químicaRESUMO
Polyphenols may be an effective therapy for both the prevention and treatment of cancer. Previous studies have found that these compounds may inactive Hela cells, which may even be converted into a normal cells post-treatment. The present study extracted phenolic compounds from pomegranate peel, with the polyphenols then purified using different solvents and identified by means of high-performance liquid chromatography-tandem mass spectrometry (HPLC/MS). Once the phenolic compounds had been purified, we evaluated their cytotoxic effects on both the Hela and NIH-3T3 cell lines, on which an apoptosis assay was also carried out. Additionally, apoptosis assay was carried out on Hela and NIH-3T3. Lastly, the proteome profile was analysed via two-dimensional gel electrophoresis (2-DE) and liquid chromatography-tandem mass spectrometry (LC/MS/MS). We isolated and then purified punicalagin and ellagic acid (EA) from pomegranate peel, with both compounds likely to have a cytotoxic effect on Hela and NIH-3T3. However, this effect depends on both concentration and exposure time. Results obtained using a Cayman commercial assay kit suggests that punicalin and EA regulate the apoptosis on the Hela and NIH-3T3 cell lines. Finally, we observed that polyphenols compounds regulate the expression of proteins related to apoptosis. In conclusion, punicalin and EA have a cytotoxic effect on Hela and, furthermore, reactive the apoptotic pathway in this cell.
Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Ácido Elágico/farmacologia , Taninos Hidrolisáveis/farmacologia , Extratos Vegetais/farmacologia , Punica granatum , Neoplasias do Colo do Útero/tratamento farmacológico , Animais , Antineoplásicos/isolamento & purificação , Proteínas Reguladoras de Apoptose/metabolismo , Ácido Elágico/isolamento & purificação , Feminino , Células HeLa , Humanos , Taninos Hidrolisáveis/isolamento & purificação , Camundongos , Células NIH 3T3 , Extratos Vegetais/isolamento & purificação , Punica granatum/química , Proteoma , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologiaRESUMO
Phytochemical investigation of the stem bark of Hopea parviflora resulted in the isolation of 9 compounds; which includes friedelin (1), friedelin-3ß-ol (2), (-)-ampelopsin A (3), (-)-É-viniferin (4), (-)-hopeaphenol (5), vaticaphenol A (6), 2,4,8-trihydroxyphenanthrene-2-O-glucoside (7), ellagic acid-3,3',4-trimethoxy-4'-O-α-L-rhamnopyranoside (8) and ß-sitosterol-ß-D-glucoside (9). Among them, compounds 1, 2, 6, 7, 8 and 9 are isolated for the first time from this species. Further, we evaluated the anti-inflammatory activity of compounds 4, 5, 6, 7 and 8. In this study, compound 8 inhibited the activity of proinflammatory mediators like NO, TNF-α, IL-6, 5-LOX and COX-2, also promoted the action of anti-inflammatory mediator like IL-10 via inhibition of the NF-κB pathway in LPS-stimulated RAW 264.7 macrophages.
Assuntos
Anti-Inflamatórios/farmacologia , Dipterocarpaceae , Ácido Elágico/farmacologia , Animais , Anti-Inflamatórios/isolamento & purificação , Dipterocarpaceae/química , Ácido Elágico/isolamento & purificação , Lipopolissacarídeos , Macrófagos/efeitos dos fármacos , Camundongos , NF-kappa B , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Casca de Planta/química , Células RAW 264.7RESUMO
Previously, we demonstrated that a 5% ethanol extract of unripe Rubus coreanus (5-uRCK) and ellagic acid has hypocholesterolemic and antiobesity activity, at least partially mediated by the downregulation of adipogenic and lipogenic gene expression in high-fat diet (HFD)-fed animals. The present study investigated the thermogenic and lipolytic antiobesity effects of 5-uRCK and ellagic acid in HFD-induced obese C57BL/6 mice and explored its mechanism of action. Mice fed an HFD received 5-uRCK or ellagic acid as a post-treatment or pretreatment. Both post-treated and pretreated mice showed significant reductions in body weight and adipose tissue mass compared to the HFD-fed mice. The protein levels of lipolysis-associated proteins, such as adipose triglyceride lipase (ATGL), phosphorylated hormone-sensitive lipase (p-HSL), and perilipin1 (PLIN1), were significantly increased in both the 5-uRCK- and ellagic acid-treated mouse epididymal white adipose tissue (eWAT). Additionally, thermogenesis-associated proteins, such as peroxisome proliferator-activated receptor α (PPARα), carnitine palmitoyl transferase-1 (CPT1), uncoupling protein 1 (UCP1), and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α), in inguinal white adipose tissue (ingWAT) were clearly increased in both the 5-uRCK- and ellagic acid-treated mice compared to HFD-fed mice. These results suggest that 5-uRCK and ellagic acid are effective for suppressing body weight gain and enhancing the lipid profile.
Assuntos
Ácido Elágico/química , Lipólise/efeitos dos fármacos , Extratos Vegetais/farmacologia , Rubus/química , Termogênese/efeitos dos fármacos , Adipogenia/genética , Tecido Adiposo Branco/efeitos dos fármacos , Tecido Adiposo Branco/metabolismo , Tecido Adiposo Branco/patologia , Animais , Biomarcadores/metabolismo , Peso Corporal/efeitos dos fármacos , Dieta Hiperlipídica , Regulação para Baixo/efeitos dos fármacos , Ácido Elágico/administração & dosagem , Ácido Elágico/isolamento & purificação , Ácido Elágico/farmacologia , Lipogênese/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/tratamento farmacológico , Obesidade/veterinária , PPAR alfa/genética , PPAR alfa/metabolismo , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Rubus/metabolismo , Proteína Desacopladora 1/genética , Proteína Desacopladora 1/metabolismoRESUMO
Inflammation is commonly characterized as a defensive and protective reaction of the body to various exogenous or endogenous stimuli, which aims to maintain the body health. Punica granatum (pomegranate) and its constituent ellagic acid (EA) are recently more taken into accounts since their promising pharmacological effects. Therefore, we aimed to obtain a comprehensive review regarding antiinflammatory, anticancer, and antioxidant activities of both pomegranate and EA and their possible involved mechanisms. In the procedure, scientific databases, including Web of Science, PubMed, Scopus, and Google Scholar, were searched in the English language, until the end of January 2019. Pomegranate belonging to the Punicaceae has been used for medical purposes from ancient and in different cultures. Several studies have also supported that EA is the major active compound of pomegranate and possesses antimutagenic, antiinflammatory, antifibrosis, anticancer, and antiaging properties. It has been suggested that pomegranate and EA possess promising immunomodulatory effects in preclinical models as well as human studies through regulation of the T-cell function and suppressing humoral immunity. Hopefully, we wish that this review and information could be helpful for designing further experiments to investigate the potential protective effects of pomegranate and EA.
Assuntos
Anti-Inflamatórios , Antineoplásicos , Ácido Elágico/farmacologia , Punica granatum/química , Animais , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Células Cultivadas , Estudos Clínicos como Assunto/métodos , Estudos Clínicos como Assunto/estatística & dados numéricos , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos/métodos , Avaliação Pré-Clínica de Medicamentos/estatística & dados numéricos , Ácido Elágico/isolamento & purificação , Ácido Elágico/uso terapêutico , Frutas/química , Humanos , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêuticoRESUMO
Fermentation in solid state culture (SSC) has been the focus of increasing interest because of its potential for industrial applications. In previous studies SSC of pomegranate wastes by Aspergillus niger has been extensively developed and optimized for the recovery of ellagic acid (EA), a high value bioactive. In this study we comparatively investigated the SSC of powdered pomegranate husks by A. niger and Saccharomyces cerevisiae and evaluated the recovery yields of EA by an ultrasound and microwave-assisted 7:3 water/ethanol extraction. Surprisingly enough, the yields obtained by S. cerevisiae fermentation (4% w/w) were found 5-fold higher than those of the A. niger fermented material, with a 10-fold increase with respect to the unfermented material. The EA origin was traced by HPLC analysis that showed a significant decrease in the levels of punicalagin isomers and granatin B and formation of punicalin following fermentation. Other extraction conditions that could warrant a complete solubilization of EA were evaluated. Using a 1:100 solid to solvent ratio and DMSO as the solvent, EA was obtained in 4% yields from S. cerevisiae fermented husks at a high purity degree. Hydrolytic treatment of S. cerevisiae fermented pomegranate husks afforded a material freed of the polysaccharides components that gave recovery yields of EA up to 12% w/w.
Assuntos
Ácido Elágico/química , Frutas/química , Punica granatum/química , Resíduos Sólidos , Aspergillus niger/química , Aspergillus niger/metabolismo , Ácido Elágico/isolamento & purificação , Etanol/química , Fermentação , Hidrólise , Taninos Hidrolisáveis/química , Taninos Hidrolisáveis/isolamento & purificação , Saccharomyces cerevisiae/química , Saccharomyces cerevisiae/metabolismoRESUMO
In Chinese medicine, herbal medicine is commonly used to treat individuals suffering from many types of diseases. We thus expected that some herbal medicines would contain promising compounds for cancer chemotherapy. Indeed, we found that Sanguisorba officinalis extracts strongly inhibit the growth of B16F10 melanoma cells, and we identified ellagic acid (EA) as the responsible ingredient. B16F10 cells treated with EA exhibited strong G1 arrest accompanied by accumulation of p53, followed by inactivation of AKT. Addition of a PTEN inhibitor, but not a p53 inhibitor, abrogated the EA-induced AKT inactivation and G1 arrest. The PTEN inhibitor also diminished EA-induced p53 accumulation. Furthermore, EA apparently increased the protein phosphatase activity of PTEN, as demonstrated by the reduced phosphorylation level of FAK, a protein substrate of PTEN. Furthermore, an in vitro PTEN phosphatase assay on PIP3 showed the direct modulation of PTEN activity by EA. These results suggest that EA functions as an allosteric modulator of PTEN, enhancing its protein phosphatase activity while inhibiting its lipid phosphatase activity. It is notable that a combination of EA and cisplatin, a widely used chemotherapy agent, dramatically enhanced cell death in B16F10 cells, suggesting a promising strategy in chemotherapy.
Assuntos
Antineoplásicos/farmacologia , Ácido Elágico/farmacologia , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Melanoma/tratamento farmacológico , PTEN Fosfo-Hidrolase/metabolismo , Extratos Vegetais/farmacologia , Sanguisorba/química , Antineoplásicos/química , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Cisplatino/farmacologia , Quimioterapia Combinada , Medicamentos de Ervas Chinesas/farmacologia , Ácido Elágico/química , Ácido Elágico/isolamento & purificação , Quinase 1 de Adesão Focal , Medicina Herbária , Humanos , PTEN Fosfo-Hidrolase/efeitos dos fármacos , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteína Supressora de Tumor p53/metabolismoRESUMO
Ellagic acid (EA) is a polyphenolic compound, naturally occurring in various fruits. It has antioxidant, anticancer and antimutagenic properties. Its low aqueous solubility and permeability in GIT, permanent binding to DNA and proteins of cells and first pass metabolism are considered as the reasons for its low oral bioavailability and consequently its low therapeutic potential. Cyclodextrin-based nanosponges (NS) have been utilized to improve the solubilization efficiency of Ellagic acid and to control its release. The scope of the work was to prepare EA nanosponges (EA-NS) using cyclodextrin (ß-CD) and cross-linked by dimethyl carbonate (DMC). It was found that the particle size of the prepared EA-NS was 423.2 nm with low polydispersity index (0.409) and high zeta potential (-34 mV) which manifests the construction of a stabilized colloidal nanoformulation. Moreover, high solubilization efficiency of the loaded EA-NS (49.79µg/ml) compared with the free EA (9.73µg/ml) was spotted. The prepared EA-NS was characterized by XRD, FTIR, and DSC studies and it elucidated a definite interaction of EA with NS. EA-NS successively improved its solubility and provided a controlled in vitro release for 24 hours. EA-NS produced about 69.17% drug content which indicates a good drug loading of the prepared nanosponges. Dissolution of EA-NS was higher than the drug alone. Animal study displayed an improvement in the oral bioavailability of EA indicated by an increase in AUC (1345.49 ng.hr.ml-1) of the EA -NS compared with (598.94 ng.hr.ml-1) for EA.
Assuntos
Ciclodextrinas/química , Sistemas de Liberação de Medicamentos/métodos , Ácido Elágico/química , Lythraceae , Nanoestruturas/química , Administração Oral , Animais , Disponibilidade Biológica , Ciclodextrinas/administração & dosagem , Ciclodextrinas/metabolismo , Ácido Elágico/administração & dosagem , Ácido Elágico/isolamento & purificação , Ácido Elágico/metabolismo , Masculino , Nanoestruturas/administração & dosagem , Coelhos , Solubilidade , Difração de Raios X/métodosRESUMO
Iron is a vital element required for normal cellular physiology in animal systems, but excess iron accumulation in the biological system accelerates oxidative stress, cellular toxicity, tissue injury and organ fibrosis, which ultimately leads to the generation of chronic liver diseases including cancer. A natural antioxidant, ellagic acid (EA) has been previously reported for its pharmacological properties; however, there is no significant evidence available that could illustrate its protective potential against iron-overload induced hepatotoxicity. In the present work, EA was evaluated for its in vitro free radical scavenging and iron chelation potentials. Further, EA was tested in vivo for its protective activity against iron overload-induced hepatotoxicity in Swiss albino mice by evaluating liver iron content, reactive oxygen species (ROS), liver antioxidant enzymes, serum marker levels, liver damage and fibrosis, histopathological study and finally western blotting analysis. EA treatment significantly decreased liver iron and serum ferritin levels. Elevated ROS levels, decreased antioxidant parameters and elevated serum markers were normalized upon treatment with EA. Cellular morphology, iron -overload and liver fibrosis were found to be effectively ameliorated. Finally, the protective effect of EA against iron overload-induced apoptosis was confirmed by western blotting when its treatment upregulated the expressions of caspase-3 and poly(ADP-ribose) polymerase (PARP) proteins. EA revealed hepatoprotective activity against iron overload-induced toxicity through scavenging free radicals, inhibiting excess ROS production, normalizing liver damage parameters and upregulating caspase-3, PARP expression. Collectively, our findings support the possible use of the natural antioxidant EA as a promising candidate against iron-overloaded diseases.
Assuntos
Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Clerodendrum , Ácido Elágico/farmacologia , Quelantes de Ferro/farmacologia , Sobrecarga de Ferro/tratamento farmacológico , Ferro/metabolismo , Cirrose Hepática Experimental/prevenção & controle , Fígado/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Folhas de Planta , Animais , Antioxidantes/isolamento & purificação , Proteínas Reguladoras de Apoptose/metabolismo , Clerodendrum/química , Citoproteção , Relação Dose-Resposta a Droga , Ácido Elágico/isolamento & purificação , Ferritinas/sangue , Quelantes de Ferro/isolamento & purificação , Sobrecarga de Ferro/metabolismo , Sobrecarga de Ferro/patologia , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática Experimental/metabolismo , Cirrose Hepática Experimental/patologia , Masculino , Camundongos , Fitoterapia , Extratos Vegetais/isolamento & purificação , Folhas de Planta/química , Plantas Medicinais , Espécies Reativas de Nitrogênio/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fatores de TempoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Pomegranate fruit is considered an antidiabetic medicine in certain systems of traditional medicine. In addition, pomegranate polyphenols are known as powerful antioxidants with beneficial effects such as the reduction of oxidative / inflammatory stress and the increase of protective signalling such as antioxidant enzymes, neurotrophic factors and cytoprotective proteins. AIM OF THE STUDY: This work evaluates the effects of pomegranate juice, its main polyphenols known as ellagic acid and punicalagin, as well as its main metabolite urolithin A, on physiological and pharmacological targets of metabolic diseases such as obesity and diabetes. MATERIALS AND METHODS: For this purpose, enzyme inhibition bioassays of lipase, α-glucosidase and dipeptidyl peptidase-4 were carried out in cell-free systems. Similarly, adipocytes derived from 3T3-L1 cells were employed to study the effects of ellagic acid, punicalagin and urolithin A on adipocyte differentiation and triglyceride (TG) accumulation. RESULTS: Pomegranate juice, ellagic acid, punicalagin and urolithin A were able to inhibit lipase, α-glucosidase and dipeptidyl peptidase-4. Furthermore, all tested compounds but significantly the metabolite urolithin A displayed anti-adipogenic properties in a dose-dependent manner as they significantly reduced TG accumulation and gene expression related to adipocyte formation such as adiponectin, PPARγ, GLUT4, and FABP4 in 3T3-L1 adipocytes. CONCLUSION: These results may explain from a molecular perspective the beneficial effects and traditional use of pomegranate in the prevention of metabolic-associated disorders such as obesity, diabetes and related complications.
Assuntos
Adipogenia/efeitos dos fármacos , Cumarínicos/farmacologia , Lythraceae/química , Polifenóis/farmacologia , Células 3T3-L1 , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Adipogenia/genética , Animais , Cumarínicos/administração & dosagem , Cumarínicos/isolamento & purificação , Dipeptidil Peptidase 4/efeitos dos fármacos , Dipeptidil Peptidase 4/metabolismo , Relação Dose-Resposta a Droga , Ácido Elágico/administração & dosagem , Ácido Elágico/isolamento & purificação , Ácido Elágico/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Taninos Hidrolisáveis/administração & dosagem , Taninos Hidrolisáveis/isolamento & purificação , Taninos Hidrolisáveis/farmacologia , Lipase/metabolismo , Camundongos , Polifenóis/administração & dosagem , Polifenóis/isolamento & purificação , Triglicerídeos/metabolismo , alfa-Glucosidases/efeitos dos fármacos , alfa-Glucosidases/metabolismoRESUMO
BACKGROUND: Chagas disease is caused by the protozoan parasite Trypanosoma cruzi. This illness is found mainly in 21 Latin American countries and an estimated 8 million people are infected worldwide. The unsatisfactory chemotherapy provokes severe toxicity and resistant strains. Medicinal plants constitute a promising source of new drugs and remedies against all kinds of disorders, mainly infectious diseases arousing interest worldwide. OBJECTIVE: The aim of this study is the isolation, structural identification and evaluation of the trypanocidal activity of samples present in the Excoecaria lucida Sw. leaves. METHODS: Total extract (TE) of E. lucida Sw. leaves was obtained by ethanol extract therefore fractionated sequentially with hexane, ethyl acetate and n-butanol, to obtain three phases: Hex, EA and But, respectively. Ellagic acid (EL1) was purified from both EA and But phases, while EL2; a 1:1 stigmasterol-3-O-ß-D-glucopyranoside plus sitosterol-3-O-ß-D-glucopyranoside mixture was obtained from the Hex phase. Activity assays were performed using bloodstream and intracellular forms of T. cruzi and cytotoxicity assays using L929 fibroblasts. RESULTS: The EL1 and EL2 samples were more active against bloodstream trypomastigote forms with EC50 of 53.0±3.6 and 58.2±29.0 µg/mL, respectively; at 100 µg/mL. These samples also showed 70% of inhibition of L929 cells infection. Toxicity assays demonstrated that after 96 h of treatment only the fractions Hex and EA presented detectable cytotoxicity. CONCLUSION: Ellagic acid, stigmasterol-3-O-ß-D-glucopyranoside and sitosterol-3-O-ß-Dglucopyranoside are reported for the first time in E. lucida Sw. leaves as well as their biological activity studies supporting further investigations for Chagas disease treatment.
Assuntos
Extratos Vegetais/farmacologia , Tripanossomicidas/farmacologia , 1-Butanol/química , Acetatos/química , Animais , Ácido Elágico/isolamento & purificação , Ácido Elágico/farmacologia , Ácido Elágico/toxicidade , Euphorbiaceae/química , Fibroblastos/efeitos dos fármacos , Fibroblastos/microbiologia , Glucosídeos/isolamento & purificação , Glucosídeos/farmacologia , Glucosídeos/toxicidade , Hexanos/química , Camundongos , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/toxicidade , Folhas de Planta/química , Sitosteroides/isolamento & purificação , Sitosteroides/farmacologia , Sitosteroides/toxicidade , Estigmasterol/análogos & derivados , Estigmasterol/isolamento & purificação , Estigmasterol/farmacologia , Estigmasterol/toxicidade , Tripanossomicidas/isolamento & purificação , Tripanossomicidas/toxicidade , Trypanosoma cruzi/efeitos dos fármacosRESUMO
Ellagic acid, a natural polyphenol, was isolated from pomegranate peel extract by hydrophobic interaction using graphene oxide grafted cotton fiber as a stationary adsorbent. The grafted graphene oxide moieties served as hydrophobic interaction-binding sites for ellagic acid adsorption. The graphene oxide grafted cotton fiber was made into a membrane-like sheet in order to complete ellagic acid purification by using a binding-elution mode. The effects of operational parameters, such as the composition of the binding buffer/elution buffer, buffer pH, and buffer concentration, on the isolation process were investigated. It was found that 5 mmol/L sodium carbonate aqueous solution is a proper-binding buffer, and sodium hydroxide aqueous solution ranging from 0.04 to 0.06 mol/L is a suitable elution solution for ellagic acid purification. Under the optimized condition, the purity of ellagic acid increased significantly from 7.5% in the crude extract to 75.0-80.0%. The pH value was found to be a key parameter that determines the adsorption and desorption of ellagic acid. No organic solvent is involved in the entire purification process. Thus, a simple and environmentally friendly method is established for ellagic acid purification using a graphene oxide-modified biodegradable and bio-sourced fibrous adsorbent.
Assuntos
Cromatografia , Ácido Elágico/isolamento & purificação , Grafite/química , Lythraceae/química , Óxidos/química , Adsorção , Soluções Tampão , Cromatografia Líquida de Alta Pressão , Fibra de Algodão , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Compostos Orgânicos , Fenol , Extratos Vegetais/química , Polifenóis/análise , Solubilidade , ÁguaRESUMO
A new coruleoellagic acid derivative, 3,3',4,4',5'-pentamethylcoruleoellagic acid (1) together with nine known compounds, hexamethylcoruleoellagic acid (2), 3,4,3'-tri-O-methylellagic acid (3), heptaphylline (4), 7-methoxymukonal (5), dentatin (6), sinapaldehyde (7), gallic acid (8), 2,6-dimethoxy-4H-pyran-4-one (9) and ß-sitosterol (10) were isolated from the stems of Rhodamnia dumetorum. Their structures were identified by physical and spectroscopic data (IR, 1D and 2D NMR, and MS). Compounds 1, 2 and 7-10 were tested for antibacterial activity against six pathogenic bacterial strains (Bacillus cereus, Escherichia coli, Pseudomonas aeruginosa, Salmonella enterica serovar Typhimurium, Staphylococcus aureus, and Methicillin resistant S. aureus (MRSA)).
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Antibacterianos/química , Ácido Elágico/análogos & derivados , Ácido Elágico/química , Myrtaceae/química , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Bacillus cereus/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos/métodos , Ácido Elágico/isolamento & purificação , Ácido Elágico/farmacologia , Escherichia coli/efeitos dos fármacos , Espectroscopia de Ressonância Magnética , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Caules de Planta/química , Pseudomonas aeruginosa/efeitos dos fármacos , Salmonella typhimurium/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacosRESUMO
Two new gallic acid glycosides, potentillanosides G (1) and H (2), were newly isolated from the methanol extract of the tuberous roots of Potentilla anserina (Rosaceae), together with a known compound, ellagic acid 3-O-α-L-rhamnopyranoside (3). Their structures were elucidated on the basis of chemical and physicochemical evidence. Among the constituents, potentillanoside H (2, IC50 = 99.5 µM) was found to show hepatoprotective activity.
Assuntos
Ácido Elágico/isolamento & purificação , Glicosídeos/isolamento & purificação , Hepatócitos/efeitos dos fármacos , Extratos Vegetais/isolamento & purificação , Potentilla/química , Acetatos/química , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Citoproteção , Ácido Elágico/farmacologia , Glicosídeos/farmacologia , Hepatócitos/fisiologia , Concentração Inibidora 50 , Medicina Tradicional Tibetana , Metanol/química , Camundongos , Estrutura Molecular , Extratos Vegetais/farmacologia , Raízes de Plantas/química , Solventes/químicaRESUMO
BACKGROUND: Alzheimer's disease (AD) is one of the common neurodegenerative disorders among elderly. The purpose of this study was to determine the neuroprotective effect and mechanisms of action underlying the Terminalia chebula extracts and ellagic acid by using beta-amyloid25-35 (Aß25-35)-induced cell toxicity in an undifferentiated pheochromocytoma (PC12) cell line. MATERIALS AND METHODS: The T. chebula extracts were prepared using the methanol, water, and 95% ethanol. Specifically, the ellagic acid was obtained in our laboratory. Assays including cell toxicity and changes in intracellular reactive oxygen species (ROS) and calcium level were evaluated to examine the neuroprotective effects and mechanisms of the T. chebula extracts and ellagic acid. RESULTS: The methanolic and water extracts of T. chebula and ellagic acid exhibited the strongest neuroprotective activity against Aß25-35-induced PC12 cell damages at 0.5-5.0 µg/ml. The ellagic acid also exhibited partial neuroprotective activity against H2O2-induced PC12 cell damages at 0.5-5.0 µg/ml. The methanolic and water extracts of T. chebula and ellagic acid protected PC12 cells from Aß25-35-mediated cell damages and enhanced cell viability thorough two key mechanisms by: (1) inhibiting ROS production and (2) reducing calcium ion influx. CONCLUSION: The T. chebula represents a promising plant-source as medicine in the application for the treatment of AD. Further investigation focusing on the active component of T. chebula extracts e.g., ellagic acid is crucial to verify the neuroprotective efficacy and mechanisms in vivo.
Assuntos
Ácido Elágico/farmacologia , Fármacos Neuroprotetores/farmacologia , Extratos Vegetais/farmacologia , Terminalia/química , Animais , Sobrevivência Celular/efeitos dos fármacos , Ácido Elágico/isolamento & purificação , Peróxido de Hidrogênio/toxicidade , Neurônios/citologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fármacos Neuroprotetores/isolamento & purificação , Células PC12 , Extratos Vegetais/isolamento & purificação , Ratos , Espécies Reativas de Oxigênio/metabolismoRESUMO
INTRODUCTION: Pomegranate-husk is the main by-product generated from the pomegranate industry. It is a potential source of compounds highly appreciated by different costumers. Punicalagin is the main compound present in pomegranate-husk. OBJECTIVE: To characterise the pomegranate-husk total polyphenols by HPLC-ESI-MS and to establish a method for the recovery of punicalagin using a medium pressure liquid chromatography (MPLC) system. MATERIALS AND METHODS: The characterisation of total pomegranate-husk polyphenols was carried out using liquid chromatography coupled to mass spectrometry. Thus, 200 mg of pomegranate-husk polyphenols were fractionated by MPLC. The isolated punicalagin was characterised by HPLC-MS and was tested as standard reagent for the measurement of its scavenging capacity reducing DPPH and ABTS radicals. RESULTS: Twenty peaks were identified by analytical HPLC-MS analysis from the pomegranate-husk polyphenols. The main compounds were the punicalagin anomers, punicalin and ellagic acid. The MPLC method allowed three fractions to be obtained. In fraction three 39.40 ± 8.06 mg of punicalagin anomers (purity > 97.9%) were recovered. The scavenging capacity of punicalagin showed an IC50 of 109.53 and 151.50 µg/mL for DPPH and ABTS radicals, respectively. CONCLUSION: The MPLC system was an excellent tool for the separation of the main ellagitannins from pomegranate husk and for the isolation of punicalagin anomers. Fraction three was rich in high purity punicalagin anomers. The IC50 was obtained for DPPH and ABTS radicals. Copyright © 2017 John Wiley & Sons, Ltd.
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Ácido Elágico/isolamento & purificação , Taninos Hidrolisáveis/isolamento & purificação , Lythraceae/química , Polifenóis/isolamento & purificação , Cromatografia Líquida de Alta Pressão , Espectrometria de MassasRESUMO
BACKGROUND: Punica granatum (pomegranate), an edible fruit originating in the Middle East, has been used as a traditional medicine for treatment of pain and inflammatory conditions such as peptic ulcer. The numerous risks associated with nonsteroidal anti-inflammatory drugs (NSAIDs) for treatment of pain and inflammation give rise to using medicinal herbs as alternative therapies. This study aimed to evaluate the anti-inflammatory effect of isolated compounds from the ethyl acetate (EtOAc) fraction of P. granatum by determination of their inhibitory effects on lipopolysaccharide (LPS), stimulated nitric oxide (NO), prostaglandin E2 (PGE-2), interleukin-6 (IL-6) and cyclooxxgenase-2 (COX-2) release from RAW264.7 cells. METHODS: The compounds ellagic acid, gallic acid and punicalagin A&B were isolated from EtOAc by high performance liquid chromatography (HPLC) and further identified by mass spectrometry (MS). The inhibitory effect of ellagic acid, gallic acid and punicalagin A&B were evaluated on the production of LPS-induced NO by Griess reagent, PGE-2 and IL-6 by immunoassay kit and prostaglandin E2 competitive ELISA kit, and COX-2 by Western blotting. RESULTS: Ellagic acid, gallic acid and punicalagin A&B potentially inhibited LPS-induced NO, PGE-2 and IL-6 production. CONCLUSION: The results indicate that ellagic acid, gallic acid and punicalagin may be the compounds responsible for the anti-inflammatory potential of P. granatum.
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Anti-Inflamatórios/farmacologia , Ácido Elágico/farmacologia , Ácido Gálico/farmacologia , Taninos Hidrolisáveis/farmacologia , Lythraceae/química , Extratos Vegetais/farmacologia , Animais , Anti-Inflamatórios/análise , Anti-Inflamatórios/isolamento & purificação , Dinoprostona/imunologia , Ácido Elágico/análise , Ácido Elágico/isolamento & purificação , Frutas/química , Ácido Gálico/análise , Ácido Gálico/isolamento & purificação , Taninos Hidrolisáveis/análise , Taninos Hidrolisáveis/isolamento & purificação , Interleucina-6/genética , Interleucina-6/imunologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Camundongos , Extratos Vegetais/análise , Extratos Vegetais/isolamento & purificação , Células RAW 264.7RESUMO
BACKGROUND: Some studies have reported that different parts of the pomegranate fruit, especially the peel, may act as potential antimicrobial agents and thus might be proposed as a safe natural alternative to synthetic antimicrobial agents. The high tannin content, especially punicalagin, found in pomegranate extracts, has been reported as the main compound responsible for such antimicrobial activity. Because the pomegranate peel chemical composition may vary with the type of cultivar (sweet, sour-sweet and sour), pomegranates may also differ with respect to their antimicrobial capacity. RESULTS: The extract from PTO8 pomegranate cultivar peel had the highest antimicrobial activity, as well as the highest punicalagins (α and ß) and ellagic acid concentrations. In the results obtained from both antibacterial and antifungal activity studies, the sour-sweet pomegranate cultivar PTO8 showed the best antimicrobial activity, and the highest ellagic acid concentrations. CONCLUSION: The results of the present study suggest that ellagic acid content has a significant influence on the antimicrobial activity of the pomegranate extracts investigated. The pomegranate peel of the PTO8 cultivar is a good source of antifungal and antibacterial compounds, and may represent an alternative to antimicrobial agents of synthetic origin. © 2016 Society of Chemical Industry.