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1.
J Agric Food Chem ; 67(50): 13948-13959, 2019 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-31698901

RESUMO

The aim of this study was to investigate the protective effect of punicalagin (PU), which is a main component of pomegranate polyphenols, against liver injury induced by Type 2 diabetes mellitus (T2DM) and to explore the molecular mechanism based on autophagy in vivo and in vitro. In T2DM mice, we found that PU significantly improved liver histology, reversed serum biochemical abnormalities, and increased the autophagosome number in the liver. In HepG2 cells cultured in a high-glucose environment, PU upregulated the glucose uptake level. Both in vivo and in vitro, PU upregulated the expression of autophagy-related proteins, such as LC3b and p62, and reduced the phosphorylated Akt/total Akt and phosphorylated FoxO3a/total FoxO3a protein ratios, and these effects were enhanced by LY294002 (a PI3K/Akt inhibitor). In summary, our current findings suggest that PU protects against liver injury induced by T2DM by restoring autophagy through the Akt/FoxO3a signaling pathway.


Assuntos
Autofagia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/complicações , Proteína Forkhead Box O3/metabolismo , Taninos Hidrolisáveis/administração & dosagem , Hepatopatias/prevenção & controle , Fígado/lesões , Substâncias Protetoras/administração & dosagem , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Proteína Forkhead Box O3/genética , Humanos , Fígado/metabolismo , Hepatopatias/etiologia , Hepatopatias/metabolismo , Hepatopatias/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Proto-Oncogênicas c-akt/genética , Transdução de Sinais/efeitos dos fármacos
2.
J Agric Food Chem ; 67(36): 10079-10088, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31461286

RESUMO

Geraniin has been reported to possess potent anti-inflammatory properties and to modulate the macrophage polarization. This study sought to evaluate the protective effects and underlying mechanisms of geraniin on lipopolysaccharide (LPS)-induced neuroinflammation and neurobiological alternations as well as cognitive impairment. Daily intragastrical administration with geraniin (20 mg kg-1 day-1) for 14 days significantly prolonged the duration in the target quadrant (26.53 ± 2.03 versus 37.09 ± 3.27%; p < 0.05) and increased crossing-target number (1.93 ± 0.22 versus 3.08 ± 0.17; p < 0.01) in the probe test of LPS-treated mice. Geraniin also ameliorated LPS-elicited neural/synaptic impairments and decreased levels of LPS-induced Aß generation (p < 0.05), amyloid precursor protein (APP) (p < 0.05) and ß-site amyloid precursor protein cleavage enzyme 1 (BACE1) (p < 0.05). Furthermore, geraniin suppressed the production of pro-inflammatory cytokines, including tumor necrosis factor α (TNF-α) (9.85 ± 0.58 versus 5.20 ± 0.52 pg/mg of protein; p < 0.01), interleukin (IL)-1ß (16.31 ± 0.67 versus 8.62 ± 0.46 pg/mg of protein; p < 0.01), and IL-6 (12.12 ± 0.45 versus 7.43 ± 0.32 pg/mg of protein; p < 0.05), and inhibited glial cell activation. Moreover, geraniin effectively polarized the microglia toward an anti-inflammatory M2 phenotype. Further study revealed that geraniin targeted toll-like receptor 4 (TLR4)-mediated signaling and decreased the production of pro-inflammatory cytokines in BV-2 microglial cells. These results indicate that geraniin mitigates LPS-elicited neural/synaptic neurodegeneration, amyloidogenesis, neuroinflammation, and cognitive impairment and suggest geraniin as a therapeutic option for neuroinflammation-associated neurological disorders, such as Alzheimer's disease.


Assuntos
Disfunção Cognitiva/tratamento farmacológico , Glucosídeos/administração & dosagem , Taninos Hidrolisáveis/administração & dosagem , Receptor 4 Toll-Like/imunologia , Secretases da Proteína Precursora do Amiloide , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/imunologia , Animais , Ácido Aspártico Endopeptidases , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/genética , Disfunção Cognitiva/imunologia , Humanos , Interleucina-1beta/genética , Interleucina-1beta/imunologia , Lipopolissacarídeos/efeitos adversos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microglia/efeitos dos fármacos , Microglia/imunologia , NF-kappa B/genética , NF-kappa B/imunologia , Neuroglia/efeitos dos fármacos , Neuroglia/imunologia , Receptor 4 Toll-Like/genética , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia
3.
Trials ; 20(1): 327, 2019 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-31171016

RESUMO

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic condition characterized by recurrent episodes of intestinal inflammation and is thought to be related to an autoimmune reaction to genetic and environmental factors. Although evidence indicates that a polyphenolic-rich diet plays an important role in modulating aspects of chronic inflammation, few studies have focused on the effect of ellagitannin (ET)-rich food consumption on long-term remission maintenance in IBD patients with a high risk of clinical relapse. Therefore, we hypothesize that supplementation with a pomegranate juice, a naturally rich source of ETs, could significantly modulate the markers of mucosal and systemic inflammation relative to a control group receiving a placebo. METHODS/DESIGN: This double-blind, randomized controlled trial includes patients with IBD involving the colorectum who have been in stable therapy for at least the three previous months and have a high risk of clinical relapse. Participants are randomly allocated to one of two groups: active supplementation (125 mL of cv. Wonderful pomegranate juice) or placebo (125 mL) taken twice daily for 12 weeks. The primary outcome is changes in the fecal neutrophil-derived protein calprotectin, a surrogate marker of mucosal improvement, between the two groups from baseline to 12 weeks later. The secondary outcomes include transcriptomic changes in peripheral blood mononuclear cells and intestinal biopsies and changes in circulating inflammatory markers and trimethylamine-N-oxide levels. Pomegranate ET-derived metabolites are identified and quantified in plasma and urine samples. DISCUSSION: The results will provide information on the possible reduction of fecal calprotectin levels following the consumption of pomegranate juice. The findings will also show the in vivo metabolism of pomegranate ETs. Finally, the effect of 12-week pomegranate juice consumption on local and systemic inflammatory markers will be elucidated, which will likely provide additional insights into the maintenance of remission in IBD patients. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03000101 . Registered on 21 December 2016.


Assuntos
Anti-Inflamatórios/administração & dosagem , Fezes/química , Sucos de Frutas e Vegetais , Taninos Hidrolisáveis/administração & dosagem , Doenças Inflamatórias Intestinais/dietoterapia , Complexo Antígeno L1 Leucocitário/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Inflamatórios/efeitos adversos , Biomarcadores/metabolismo , Método Duplo-Cego , Regulação para Baixo , Feminino , Sucos de Frutas e Vegetais/efeitos adversos , Humanos , Taninos Hidrolisáveis/efeitos adversos , Mediadores da Inflamação/sangue , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/metabolismo , Itália , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Indução de Remissão , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
4.
Mol Biol Rep ; 46(4): 3701-3711, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31006095

RESUMO

Nowadays, medicinal plants have been widely used everywhere to provide essential care for many disorders including diabetes. Recent reports assumed that the antidiabetic activities of pomegranate aril juice (PAJ) may be ascribed to its punicalagin (PCG). Therefore, the present study evaluated and compared the antidiabetic activities of PAJ and its PCG, and monitored some mechanisms of their actions in streptozotocin-nicotinamide (STZ-NA) type 2 diabetic rats. STZ-NA diabetic rats were given, orally/daily, PAJ (100 or 300 mg/kg body weight, containing 2.6 and 7.8 mg of PCG/kg body weight, respectively), pure PCG (2.6 or 7.8 mg/kg body weight), or distilled water (vehicle) for 6 weeks. PAJ (especially at the high dose) alleviated significantly (P < 0.05-0.001) most signs of type 2 diabetes including body-weight loss, insulin resistance (IR) and hyperglycemia through decreasing serum tumor necrosis factor-α concentration and the expression of hepatic c-Jun N-terminal kinase, and increasing the skeletal muscle weight and the expression of hepatic insulin receptor substrate-1 in STZ-NA diabetic rats. Also, it decreased significantly (P < 0.001) the oxidative liver injury in STZ-NA diabetic rats through decreasing the hepatic lipid peroxidation and nitric oxide production, and improving the hepatic antioxidant defense system. Although the low dose of PCG induced some modulation in STZ-NA diabetic rats, the high dose of PCG did not show any valuable antidiabetic activity, but induced many side effects. In conclusion, PAJ was safer and more effective than pure PCG in alleviating IR and oxidative liver injury in STZ-NA diabetic rats.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Taninos Hidrolisáveis/administração & dosagem , Taninos Hidrolisáveis/uso terapêutico , Resistência à Insulina , Fígado/efeitos dos fármacos , Fígado/patologia , Niacinamida/administração & dosagem , Estreptozocina/administração & dosagem , Animais , Antioxidantes/metabolismo , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Taninos Hidrolisáveis/metabolismo , Hiperglicemia/tratamento farmacológico , Proteínas Substratos do Receptor de Insulina/efeitos dos fármacos , Proteínas Quinases JNK Ativadas por Mitógeno/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Masculino , Músculo Esquelético/efeitos dos fármacos , Niacinamida/metabolismo , Óxido Nítrico/metabolismo , Ratos , Estreptozocina/metabolismo , Fator de Necrose Tumoral alfa/efeitos dos fármacos
5.
Nutrients ; 11(3)2019 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-30884808

RESUMO

Hydroxytyrosol (HT) and Punicalagin (PC) exert cardioprotective and anti-atherosclerotic effects. This study evaluates the effect of oral supplementation with HT and PC (SAx) on early atherosclerosis markers in middle-aged, seemingly healthy adults. A randomized, double-blinded, placebo-controlled, crossover trial was performed for 20 weeks. There were two treatment sequences (Placebo/SAx, n = 41; SAx/Placebo, n = 43) for which the intervention periods (Placebo and SAx) were 8 weeks long, followed by a 4-week wash out period. The supplement was composed of 9.9 mg of HT and 195 mg of PC, and the placebo was composed of maltodextrin. SAx increased endothelial function (Flow-mediated dilatation [FMD]: 2.36%; p < 0.001) in the endothelial dysfunction subgroup compared to the placebo (2.36 ± 3.9 vs. 0.76 ± 3.5%, p < 0.05). SAx also reduced oxLDL by -28.74 ng/mL (p < 0.05) in subjects with higher levels of oxLDL, which was an improvement compared with the placebo (-28.74 ± 40.2 vs. 25.64 ± 93.8 ng/mL, p < 0.001). The prehypertension and hypertension subgroups exhibited decreased systolic (-15.75 ± 9.9 mmHg; p < 0.001) and diastolic (-6.36 ± 8.7 mmHg; p < 0.001) blood pressure after SAx consumption. Moreover, the systolic prehypertension and hypertension subgroups presented significant differences in systolic blood pressure compared to the placebo (-15.75 ± 9.9 vs. -2.67 ± 12.0 mmHg, p < 0.05). In conclusion, the supplement exerted anti-atherosclerotic effects by improving endothelial function, blood pressure, and levels of circulating oxLDL, especially for persons in whom these parameters were altered.


Assuntos
Aterosclerose/terapia , Cardiotônicos/administração & dosagem , Suplementos Nutricionais , Taninos Hidrolisáveis/administração & dosagem , Álcool Feniletílico/análogos & derivados , Idoso , Aterosclerose/etiologia , Aterosclerose/fisiopatologia , Biomarcadores/metabolismo , Pressão Sanguínea/fisiologia , Estudos Cross-Over , Método Duplo-Cego , Feminino , Humanos , Hipertensão/complicações , Hipertensão/fisiopatologia , Hipertensão/terapia , Masculino , Pessoa de Meia-Idade , Álcool Feniletílico/administração & dosagem , Pré-Hipertensão/complicações , Pré-Hipertensão/fisiopatologia , Pré-Hipertensão/terapia , Resultado do Tratamento
6.
Mol Nutr Food Res ; 63(9): e1800937, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30908878

RESUMO

SCOPE: Intestinal microbial metabolites from gallotannins (GT), including gallic acid (GA) and pyrogallol (PG), may possess potential anti-obesogenic properties. Lactobacillus plantarum (L. plantarum) found in the intestinal microbiome encodes for enzymatic activities that metabolize GT into GA and PG. Anti-obesogenic activities of orally administered GT in the presence or absence of L. plantarum is examined in gnotobiotic mice fed a high-fat diet (HFD). METHODS AND RESULTS: Germ-free (GF) C57BL/6J mice are divided into three groups, GF control, GF gavaged with GT, and mice colonized with L. plantarum and gavaged with GT. Compared to the control, GT decreases the expressions of lipogenic genes (e.g., fatty acid synthase (FAS)) in epididymal white adipose tissue and increases thermogenic genes (e.g., nuclear factor erythroid-2-like 1 (Nfe2l1)) in interscapular brown adipose tissue. Intestinal colonization with L. plantarum enhances these effects, and mice colonized with L. plantarum exhibit lower levels of tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), leptin and plasma insulin. CONCLUSIONS: Results indicate that GT and L. plantarum reduce HFD-induced inflammation, insulin resistance, and promote thermogenesis in adipose tissue potentially through the activity of GT-metabolizing bacterial enzymes yielding absorbable bioactive GT metabolites. These findings imply the potential role of prebiotic-probiotic interactions in the prevention of diet-induced metabolic disorders.


Assuntos
Tecido Adiposo/efeitos dos fármacos , Dieta Hiperlipídica/efeitos adversos , Taninos Hidrolisáveis/farmacologia , Lactobacillus plantarum , Probióticos/farmacologia , Termogênese/efeitos dos fármacos , Tecido Adiposo/metabolismo , Adiposidade/fisiologia , Administração Oral , Animais , Biomarcadores/metabolismo , Carboxiliases/metabolismo , Hidrolases de Éster Carboxílico/metabolismo , Citocinas/metabolismo , Vida Livre de Germes , Taninos Hidrolisáveis/administração & dosagem , Taninos Hidrolisáveis/química , Lactobacillus plantarum/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Paniculite/tratamento farmacológico , Paniculite/metabolismo , Termogênese/fisiologia
7.
Chem Biol Interact ; 298: 112-120, 2019 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-30452899

RESUMO

Oenothein B has a wide range of biological activities. The present study probed into the underlying mechanism on how Oenothein B inhibits the proliferation of a lung cancer line A549. Our results showed that Oenothein B effectively inhibited the proliferation of A549 cells by inducing apoptosis and arresting cells at G1 stage. Furthermore, Oenothein B not only increased the level of intracellular reactive oxygen species (ROS), but also induced the upregulation of intracellular apoptotic triggers (cleavage caspase-3, PARP, cytochrome c level in the cytosol, Bax). Moreover, ROS inhibitor (N-acetyl-L-cystein, NAC) and PI3K agonist (Insulin-like growth factor 1, IGF-1) could resist cell proliferation inhibition induced by Oenothein B, respectively. ROS inhibitor significantly abrogated the activation of caspase 3/7 and 9 in the presence of Oenothein B. Additionally, suppression of p-PI3K and p-Akt, p-NF-κB by Oenothein B could be compensated by treatment with ROS inhibitor. To summarize, these results demonstrated that Oenothein B was able to prevent cell proliferation probably via ROS-mediated PI3K/Akt/NF-κB signaling pathway.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Taninos Hidrolisáveis/farmacologia , NF-kappa B/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Células A549 , Acetilcisteína/farmacologia , Antineoplásicos Fitogênicos/administração & dosagem , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Caspases/metabolismo , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Humanos , Taninos Hidrolisáveis/administração & dosagem , Proteínas I-kappa B/metabolismo , Fosforilação/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos
8.
J Pharm Biomed Anal ; 165: 251-260, 2019 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-30562708

RESUMO

Corilagin is an Ellagitannin with favorable pharmacological activities. But there was no report regarding the metabolism of corilagin in vitro or in vivo. In this study, the metabolic profile of corilagin in rats as well as in rat intestinal bacteria and liver microsomes incubation system in vitro were investigated comprehensively for the first time. Consequently, with the aid of sensitive HPLC-Q-TOF-MS/MS, corilagin and its twenty-four metabolites (fourteen phase II conjugate metabolites of corilagin, three hydrolyzed metabolites EA, GA, M3 and their seven derived metabolites) were absolutely or tentatively identified in rat biological samples (urine, feces, plasma and tissues) after oral administration of corilagin. In vitro, the three hydrolyzed metabolites were identified in rat intestinal microflora and liver microsomes. These results demonstrated that corilagin itself not only could underwent extensive phase II metabolism in rats, but also could underwent hydrolysis reaction in rats as well as in rat intestinal bacteria and liver microsomes in vitro. This study is first report to identify phase II conjugate metabolites (except mono-methylate conjugated metabolites) of pure Ellagitannin and distribution of these metabolites in vivo. In addition, clear, detailed metabolic pathways of corilagin were shown to involve hydrolysis, methylation, glycosylation, reduction, glucuronidation and sulfation.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Glucosídeos/metabolismo , Taninos Hidrolisáveis/metabolismo , Espectrometria de Massas em Tandem/métodos , Administração Oral , Animais , Microbioma Gastrointestinal , Glucosídeos/administração & dosagem , Glucosídeos/análise , Taninos Hidrolisáveis/administração & dosagem , Taninos Hidrolisáveis/análise , Masculino , Microssomos Hepáticos/metabolismo , Ratos , Ratos Sprague-Dawley
9.
Minerva Pediatr ; 70(5): 425-429, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30302988

RESUMO

BACKGROUND: Infectious mononucleosis (IM) is a common disease of adolescents and young adults, characterized by a specific triad of symptoms represented by fever, sore throat and lymphadenopathy. IM may also affect older adults, with different, more intense signs and symptoms such as fatigue, general malaise, and diffuse body pain. The aim of this four-week-registry study was to evaluate the effects of Robuvit® supplementation on the main consequences of mononucleosis, particularly fatigue, in otherwise healthy adults. METHODS: All patients enrolled in this registry study experienced an episode of IM characterized by fatigue, a general feeling of unwellness, diffuse body and muscular pain, leukocytosis, and high levels of oxidative stress, at least 2 to 4 weeks prior to inclusion. Fever had already resolved at inclusion. All included patients were positively tested for the Epstein-Barr virus (EBV). Subjects were divided in two groups: those receiving the standard management (SM, N.=26; vitamin B, C, and D, balanced healthy diet, regular sleeping schedule, physical activity, 2 mg copper), and those treated with SM plus Robuvit® (N.=24) supplementation (300 mg/day). RESULTS: Supplementation with Robuvit® was safe, overall tolerability was good, and no side effects were reported. All patients completed the four-week treatment. After 4 weeks of treatment, a significant reduction in the rate of symptoms was evident in the Robuvit® group compared to the control group (P<0.05). CONCLUSIONS: Supplementation with Robuvit® is safe, well tolerated, and effective in controlling oxidative stress levels and improving fatigue and other symptoms related to IM episodes during the convalescence period.


Assuntos
Suplementos Nutricionais , Fadiga/terapia , Taninos Hidrolisáveis/administração & dosagem , Mononucleose Infecciosa/terapia , Extratos Vegetais/administração & dosagem , Adulto , Fadiga/etiologia , Feminino , Humanos , Mononucleose Infecciosa/fisiopatologia , Masculino , Estresse Oxidativo , Sistema de Registros , Resultado do Tratamento
10.
Meat Sci ; 146: 101-108, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30142506

RESUMO

The study investigated the effect of dietary inclusion of chestnut hydrolyzable tannin (CHT) in growing rabbit diets on nutrients digestibility, quality and oxidative status of meat, and content of tannin metabolites. At weaning, rabbits were assigned to 5 dietary groups (n = 72 rabbits/diet): control medication-free (Co), control with coccidiostat (Cc), and T200, T400 and T600 (diets supplemented with 200, 400 and 600 g/100 kg CHT extract). Sixteen carcasses/treatment were considered and hindleg meat and Longissimus thoracis et lumborum (LTL) muscle were used for analyses. L*a*b* color values, water holding capacity, Warner Bratzler shear force, haem iron content, oxidative status and nutritional quality were unaffected by dietary treatments. Saturated fatty acids (SFA) and monounsaturated FA (MUFA) in LTL meat were higher in T600 than Cc rabbits (P < .05), even though no differences were found for SFA and MUFA digestibility. Contrarily, polyunsaturated FA digestibility was lower in T400 and T600 than Co rabbits. No tannin metabolites traces were found in rabbit meat. Results of the present study showed that feeding CHT did not improve rabbit meat quality.


Assuntos
Suplementos Nutricionais , Fagaceae , Taninos Hidrolisáveis/farmacologia , Carne/análise , Coelhos , Ração Animal/análise , Animais , Coccidiostáticos/administração & dosagem , Dieta/veterinária , Ácidos Graxos/análise , Feminino , Taninos Hidrolisáveis/administração & dosagem , Masculino , Músculo Esquelético/química , Valor Nutritivo , Oxirredução , Robenidina/administração & dosagem
11.
J Agric Food Chem ; 66(27): 7054-7064, 2018 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-29920075

RESUMO

Worldwide, colorectal cancer (CRC) is a deleterious disease causing millions of death annually. 5-Fluorouracil (5-FU) is a first-line chemotherapy for CRC, but chemoresistance and gastrointestinal mucositis limit its efficacy. Polyphenol-rich foods are increasingly popular due to their potential beneficial roles in preventing and treating cancer. Ellagitannins are a group of phenolic compounds commonly found in pomegranate, strawberries, raspberries, etc. The objective of this study was to explore whether ellagitannins from pomegranate (PETs) could ameliorate 5-FU-induced intestinal mucositis and enhance the drug's efficacy against CRC. The results showed that PETs (100 mg/kg) counteracted 5-FU-induced intestinal mucositis in rats. The number of apoptotic cells per crypt was reduced from 1.50 ± 0.21 to 0.85 ± 0.18 ( P < 0.05). Moreover, PETs induced HT-29 CRC cell death through intrinsic apoptosis, as demonstrated by dissipation of mitochondrial membrane potential, increased Bax-to-Bcl-2 ratio, and cleavage of caspase 9 and caspase 3. PETs and 5-FU combination treatments exhibited synergistic cytotoxicity against HT-29 cells with a weighted combination index of 0.3494. PETs (80 µg/mL) and 5-FU (40 µg/mL) treatments for 48 h induced 14.03 ± 0.76% and 16.42 ± 1.15% of HT-29 cells to undergo apoptosis, while the combination treatment further increased apoptosis of cells to 34.00 ± 1.54% ( P < 0.05). Combination treatment of the cells also enhanced S phase cell cycle arrest as compared with PETs or 5-FU monotherapy ( P < 0.05). These results suggest that dietary ellagitannins from pomegranate could alleviate intestinal mucositis in rats induced by 5-FU while enhancing its toxicity against HT-29 cells through potentiation of apoptosis and cell cycle arrest.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Fluoruracila/efeitos adversos , Taninos Hidrolisáveis/farmacologia , Lythraceae/química , Mucosite/tratamento farmacológico , Animais , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Feminino , Fluoruracila/administração & dosagem , Células HT29 , Humanos , Taninos Hidrolisáveis/administração & dosagem , Taninos Hidrolisáveis/química , Metaloproteinases da Matriz/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mucosite/induzido quimicamente , Mucosite/metabolismo , Ratos , Espécies Reativas de Oxigênio/metabolismo
12.
Am J Chin Med ; 46(4): 785-800, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29754505

RESUMO

Renal ischemia-reperfusion injury (IRI), an important cause of acute kidney injury (AKI), causes increased renal tubular injury and microvascular inflammation. 1,[Formula: see text]2,[Formula: see text]3,[Formula: see text]4,[Formula: see text]6-penta-O-galloyl-[Formula: see text]-D-glucose (PGG) from Galla rhois has anticancer, anti-oxidation and angiogenesis effects. We examined protective effects of PGG on IRI-induced acute AKI. Clamping both renal arteries for 45[Formula: see text]min induced isechemia and then reperfusion. Treatment with PGG (10[Formula: see text]mg/kg/day and 50[Formula: see text]mg/kg/day for four days) significantly ameliorated urine volume, urine osmolality, creatinine clearance (Ccr) and blood urea nitrogen (BUN). In addition, PGG increased aquaporine 1/2/3, Na[Formula: see text]-K[Formula: see text]-ATPase and urea transporter (UT-B) and decreased ICAM-1, MCP-1, and HMGB-1 expression. In this histopathologic study, PGG improved glomerular and tubular damage. Immunohistochemistry results showed that PGG increased aquaporine 1/2, and Na[Formula: see text]-K[Formula: see text] ATPase and decreased ICAM-1 expression. These findings suggest that PGG ameliorates tubular injury including tubular dysfunction and microvascular inflammation in IRI-induced AKI rats.


Assuntos
Lesão Renal Aguda/tratamento farmacológico , Produtos Biológicos/química , Taninos Hidrolisáveis/administração & dosagem , Túbulos Renais , Rim/irrigação sanguínea , Microvasos , Fitoterapia , Lesão Renal Aguda/etiologia , Lesão Renal Aguda/metabolismo , Lesão Renal Aguda/prevenção & controle , Animais , Aquaporinas/metabolismo , Nitrogênio da Ureia Sanguínea , Creatinina/metabolismo , Taninos Hidrolisáveis/isolamento & purificação , Inflamação , Molécula 1 de Adesão Intercelular/metabolismo , Masculino , Proteínas de Membrana Transportadoras/metabolismo , Taxa de Depuração Metabólica , Ratos Sprague-Dawley , Traumatismo por Reperfusão/complicações , ATPase Trocadora de Sódio-Potássio/metabolismo
13.
Food Chem Toxicol ; 119: 133-140, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29751073

RESUMO

Corilagin content from different parts of longan (Dimocarpus longan Lour.) was determined by ultra performance liquid chromatography (UPLC) method. Additionally, the potential synergistic effects of corilagin + ginsenoside Rh2 (Rh2), and corilagin + 5-fluorouracil (5-FU) on ovarian cancer cells, and cancer-preventing activities, including inhibition of tyrosinase, properties of antioxidant and nitrite-scavenging, and blocking of nitrosamine synthesis were investigated. The results showed the content of corilagin from different parts of longan varied widely, while corilagin content in longan seed was high with a value of 542.15 ± 10.30 µg/g. Then the corilagin from longan seed was chosen for further study, since longan seed was easily obtained from by-product of longan fruit processing with low cost. Furthermore, the combinations of corilagin + Rh2, and corilagin + 5-FU showed an increased synergistic cytotoxicity on SKOv3ip and Hey cells. Moreover, corilagin inhibited exhibited effects of inhibiting tyrosinase, antioxidation, scavenging nitrite and blocking nitrosamine synthesis.


Assuntos
Fluoruracila/farmacologia , Ginsenosídeos/farmacologia , Glucosídeos/química , Glucosídeos/farmacologia , Taninos Hidrolisáveis/química , Taninos Hidrolisáveis/farmacologia , Sapindaceae/química , Sementes/química , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Quimioterapia Combinada , Feminino , Fluoruracila/administração & dosagem , Depuradores de Radicais Livres , Ginsenosídeos/administração & dosagem , Glucosídeos/administração & dosagem , Humanos , Taninos Hidrolisáveis/administração & dosagem , Nitritos , Nitrosaminas , Neoplasias Ovarianas
14.
Viruses ; 10(4)2018 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-29673174

RESUMO

The compound 1,2,3,4,6-penta-O-galloyl-β-d-glucose (PGG), a gallotannin present in various plants such as Rhus chinensis Mill and Paeonia suffruticosa, has a broad spectrum of antiviral effects. The present study investigated its potency against infection of mice with rabies virus (RABV). Results demonstrated that PGG strongly inhibited virus titers (50-fold), viral mRNA expression (up to 90%), and protein synthesis in vitro. Importantly, we found that PGG not only suppressed viral adsorption and entry, but also directly inactivated RABV through suppression of autophagy by mediating activation of the mTOR-dependent autophagy signaling pathway. In vivo, PGG (10 mg/kg) alleviated the clinical symptoms and reduced the mortality of infected mice by 27.3%. Collectively, our results indicate that PGG has potent anti-RABV effect, and merits further investigation as an anti-RABV drug.


Assuntos
Antivirais/metabolismo , Taninos Hidrolisáveis/metabolismo , Vírus da Raiva/efeitos dos fármacos , Vírus da Raiva/crescimento & desenvolvimento , Replicação Viral/efeitos dos fármacos , Animais , Antivirais/administração & dosagem , Autofagia/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Taninos Hidrolisáveis/administração & dosagem , Camundongos , Raiva/tratamento farmacológico , Raiva/patologia , Raiva/virologia , Análise de Sobrevida , Edulcorantes , Serina-Treonina Quinases TOR/metabolismo
15.
J Ethnopharmacol ; 220: 67-74, 2018 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-29604377

RESUMO

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/metabolismo
16.
Curr Med Chem ; 25(37): 4946-4967, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-27655073

RESUMO

The popularity of food products and medicinal plant materials containing hydrolysable tannins (HT) is nowadays rapidly increasing. Among various health effects attributable to the products of plant origin rich in gallotannins and/or ellagitannins the most often underlined is the beneficial influence on diseases possessing inflammatory background. Results of clinical, interventional and animal in vivo studies clearly indicate the antiinflammatory potential of HT-containing products, as well as pure ellagitannins and gallotannins. In recent years a great emphasis has been put on the consideration of metabolism and bioavailability of natural products during examination of their biological effects. Conducted in vivo and in vitro studies of polyphenols metabolism put a new light on this issue and indicate the gut microbiota to play a crucial role in the health effects following their oral administration. The aim of the review is to summarize the knowledge about HT-containing products' phytochemistry and their anti-inflammatory effects together with discussion of the data about observed biological activities with regards to the current concepts on the HTs' bioavailability and metabolism. Orally administered HT-containing products due to the limited bioavailability of ellagitannins and gallotannins can influence immune response at the level of gastrointestinal tract as well as express modulating effects on the gut microbiota composition. However, due to the chemical changes being a result of their transit through gastrointestinal tract, comprising of hydrolysis and gut microbiota metabolism, the activity of produced metabolites has to be taken into consideration. Studies regarding biological effects of the HTs' metabolites, in particular urolithins, indicate their strong and structure-dependent anti-inflammatory activities, being observed at the concentrations, which fit the range of their established bioavailability. The impact of HTs on inflammatory processes has been well established on various in vivo and in vitro models, while influence of microbiota metabolites on silencing the immune response gives a new perspective on understanding anti-inflammatory effects attributed to HT containing products, especially their postulated effectiveness in inflammatory bowel diseases (IBD) and cardiovascular diseases.


Assuntos
Anti-Inflamatórios/farmacologia , Alimentos , Taninos Hidrolisáveis/metabolismo , Taninos Hidrolisáveis/farmacologia , Plantas Medicinais/metabolismo , Administração Oral , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/farmacocinética , Disponibilidade Biológica , Alimento Funcional , Microbioma Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/metabolismo , Trato Gastrointestinal/microbiologia , Humanos , Taninos Hidrolisáveis/administração & dosagem , Taninos Hidrolisáveis/farmacocinética
17.
Int J Mol Med ; 41(2): 739-748, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29207024

RESUMO

Administration of bone marrow­derived mesenchymal stem cells (MSCs) has emerged as a potential therapeutic approach for the treatment of myocardial infarction (MI). However, the increase in reactive oxygen species (ROS) in ischemic cardiac tissue compromises the survival of transplanted MSCs, thus resulting in limited therapeutic efficiency. Therefore, strategies that attenuate oxidative stress­induced damage and enhance MSC viability are required. Geraniin has been reported to possess potent antioxidative activity and exert protective effects on numerous cell types under certain conditions. Therefore, geraniin may be considered a potential drug used to modulate MSC­based therapy for MI. In the present study, MSCs were pretreated with geraniin for 24 h and were exposed to hydrogen peroxide (H2O2) for 4 h. Cell apoptosis, intracellular ROS levels and mitochondrial membrane potential were measured using Annexin V­fluorescein isothiocyanate/propidium iodide staining, the 2',7'­dichlorodihydrofluorescein diacetate fluorescent probe and the membrane permeable dye JC­1, respectively. Glutathione and malondialdehyde levels were also investigated. The expression levels of apoptosis­associated proteins and proteins of the phosphoinositide 3­kinase (PI3K)/protein kinase B (Akt) signaling pathway were analyzed by western blotting. The results demonstrated that geraniin could significantly attenuate H2O2­induced cell damage by promoting MSC survival, reducing cellular ROS production and maintaining mitochondrial function. Furthermore, geraniin modulated the expression levels of phosphorylated­Akt in a time­ and dose­dependent manner. The cytoprotective effects of geraniin were suppressed by LY294002, a specific PI3K inhibitor. In conclusion, the present study revealed that geraniin protects MSCs from H2O2­induced oxidative stress injury via the PI3K/Akt pathway. These findings indicated that cotreatment of MSCs with geraniin may optimize therapeutic efficacy for the clinical treatment of MI.


Assuntos
Células da Medula Óssea/efeitos dos fármacos , Glucosídeos/administração & dosagem , Taninos Hidrolisáveis/administração & dosagem , Células-Tronco Mesenquimais/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/genética , Cromonas/administração & dosagem , Regulação da Expressão Gênica/efeitos dos fármacos , Peróxido de Hidrogênio/toxicidade , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Morfolinas/administração & dosagem , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Ratos , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos
18.
Minerva Med ; 109(3): 211-217, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29164838

RESUMO

BACKGROUND: This supplement registry study evaluated the effect of supplementation with Robuvit® on the burnout syndrome (BOS) of patients with significant fatigue and high oxidative stress. Robuvit® (French oak wood extract) is a standardized supplement, effective in treating chronic fatigue syndrome (CFS), post-traumatic stress disorder (PTSD) and convalescence. METHODS: A group of 108 subjects with BOS, consisting of a subgroup of 42 young surgeons in training and a subgroup of 66 managers, were studied. Subjects followed a standard management (SM); one half of the subjects received 300 mg/day of Robuvit® for 4 weeks in addition to SM. RESULTS: Robuvit® was (P<0.05) more effective compared to SM in improving parameters evaluated with the aid of Maslach Burnout Inventory: dealing with patients problems, improving the relationship with patients, decreasing emotional drainage and intolerance (P<0.05). The feeling of a positive influence improved. The decrease in strain from interactions at work, the decrease in the lack of care feeling, the improved levels in interest were all positively affected with Robuvit (P<0.05) in comparison with SM. The need for giving up decreased, the level of satisfaction improved and the regrets for being in the profession decreased. BOS symptoms were positively affected by the supplement (P<0.05). Oxidative stress (388;24 Carr Units decreased to 344;22 with Robuvit®; P<0.05), SM had no influence on oxidative stress. Robuvit® was also more effective in professionals with burnout syndrome than the SM only in in decreasing emotional drainage, fatigue and intolerance (P<0.05). Robuvit® significantly improved the feeling of having a positive influence (P<0.05). Also, Robuvit® significantly decreased the strain resulting from interactions at work and improved the care for colleagues/customers (P<0.05). Interest and enthusiasm were significantly increased in subjects taking Robuvit® in comparison with controls with standard management alone (P<0.05). The mean score of the desire to give up was decreased with Robuvit® in comparison with SM (P<0.05) and job satisfaction was significantly improved (P<0.05). The feeling of regrets of being in the profession was significantly reduced with the supplement in comparison to SM (P<0.05). Robuvit® reduced oxidative stress (P<0.05) from 397;33 to 323;29 Carr Units in comparison with a low decrease with SM (from 396;19 vs. 378;27) at 4 weeks. CONCLUSIONS: In conclusion, in this registry study on BOS, Robuvit® by controlling fatigue (the primary symptom) and oxidative stress, relieves the most important 'symptoms' associated with BOS. The effects are comparable in young surgeons not accustomed to stress, as well as in professionals in management positions who are used to control stress.


Assuntos
Esgotamento Profissional/tratamento farmacológico , Esgotamento Profissional/metabolismo , Suplementos Nutricionais , Fadiga/tratamento farmacológico , Fadiga/metabolismo , Taninos Hidrolisáveis/administração & dosagem , Estresse Oxidativo , Fitoterapia , Extratos Vegetais/administração & dosagem , Adulto , Autoavaliação Diagnóstica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
19.
Food Funct ; 8(11): 4070-4080, 2017 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-28980690

RESUMO

Oenothein B (OeB), a dimeric macrocyclic ellagitannin isolated from eucalyptus leaves has been demonstrated as a promising natural bioactive compound for its remarkable antitumor, antioxidant, anti-inflammatory and immunomodulating effects. Unfortunately, early study indicates that OeB has quite low bioaccessibility for oral consumption due to their susceptibility to decomposition both in vitro and in vivo. Herein, we report the design and synthesis of food-grade polyelectrolyte complex coacervate using caseinophosphopeptides (CPPs) and chitosan (CS) to encapsulate OeB for enhanced protection through gastrointestinal (GI) tract. Turbidimetric titration, dynamic light scattering (DLS), ζ-potential and scanning electric microscopy (SEM), as well as theoretical calculations based on principle of charge neutralization, were conducted to provide tentative and quantitative description for phase behavior in formation and disassociation of the complex. The optimum fabrication conditions were found to be at pH 5.5, with CPP : CS at 1 : 1, using CS of high molecular weight (980 kDa). The genipin cross-linking protected the system from disassembling in harsh acidic environments. The best cross-linking conditions were found to be 0.6 mg ml-1 genipin addition at 4 h cross-linking reaction time. The particle size and zeta potential of the nanoparticles varied from 200 to 300 nm and +20 to +24.2 mV, respectively. Scanning electron microscopy (SEM) revealed a spherical coacervate phase. Results from in vitro release study proved that controlled release of OeB through GI tract using CPP-CS nanoparticles cross-linked with genipin was achievable.


Assuntos
Portadores de Fármacos/química , Composição de Medicamentos/métodos , Medicamentos de Ervas Chinesas/química , Taninos Hidrolisáveis/química , Polieletrólitos/química , Quitosana/química , Sistemas de Liberação de Medicamentos , Medicamentos de Ervas Chinesas/administração & dosagem , Taninos Hidrolisáveis/administração & dosagem , Iridoides/química , Nanopartículas/química , Tamanho da Partícula
20.
Antiviral Res ; 147: 19-28, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28923507

RESUMO

Approximately 142 million people worldwide are infected with hepatitis C virus (HCV). Although potent direct acting antivirals are available, high costs limit access to treatment. Chronic hepatitis C virus infection remains a major cause of orthotopic liver transplantation. Moreover, re-infection of the graft occurs regularly. Antivirals derived from natural sources might be an alternative and cost-effective option to complement therapy regimens for global control of hepatitis C virus infection. We tested the antiviral properties of a mixture of different Chinese herbs/roots named Zhi Bai Di Huang Wan (ZBDHW) and its individual components on HCV. One of the ZBDHW components, Penta-O-Galloyl-Glucose (PGG), was further analyzed for its mode of action in vitro, its antiviral activity in primary human hepatocytes as well as for its bioavailability and hepatotoxicity in mice. ZBDHW, its component Cortex Moutan and the compound PGG efficiently block entry of HCV of all major genotypes and also of the related flavivirus Zika virus. PGG does not disrupt HCV virion integrity and acts primarily during virus attachment. PGG shows an additive effect when combined with the well characterized HCV inhibitor Daclatasvir. Analysis of bioavailability in mice revealed plasma levels above tissue culture IC50 after a single intraperitoneal injection. In conclusion, PGG is a pangenotypic HCV entry inhibitor with high bioavailability. The low cost and wide availability of this compound make it a promising candidate for HCV combination therapies, and also emerging human pathogenic flaviviruses like ZIKV.


Assuntos
Antivirais/farmacologia , Medicamentos de Ervas Chinesas/química , Hepacivirus/efeitos dos fármacos , Taninos Hidrolisáveis/farmacologia , Paeonia/química , Ligação Viral/efeitos dos fármacos , Animais , Antivirais/administração & dosagem , Antivirais/farmacocinética , Disponibilidade Biológica , Linhagem Celular Tumoral , Células Cultivadas , Sinergismo Farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Hepacivirus/genética , Hepacivirus/fisiologia , Hepatite C/tratamento farmacológico , Hepatite C Crônica/tratamento farmacológico , Hepatócitos/efeitos dos fármacos , Humanos , Taninos Hidrolisáveis/administração & dosagem , Taninos Hidrolisáveis/farmacocinética , Imidazóis/farmacologia , Camundongos , Camundongos SCID , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Vírion/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos
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