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1.
Food Chem ; 308: 125601, 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-31670190

RESUMO

The aim of this work was to analyse the hypotensive effect of amaranth protein/peptides on spontaneously hypertensive rats (SHR). The mechanism of action of these peptides was studied in vivo and ex vivo. We also tested the effect of protection against gastrointestinal digestion (GID) exerted by an O:W emulsion on the integrity of the antihypertensive peptides. All samples tested produced a decrease in blood pressure (SBP). The animals treated with emulsion (GE) and emulsion + peptide (GE+VIKP) showed the most significant reduction in the SBP (42 ±â€¯2 mmHg and 35 ±â€¯2 mmHg, respectively). The results presented suggest that after GID, a variety of peptides with biological activities were released or were resistant to this process. These peptides play a role in the regulation of the SBP by acting on plasma ACE, plasma renin and the vascular system. These results support the use of amaranth protein/peptides in the elaboration of functional foods for hypertensive individuals.


Assuntos
Amaranthus/química , Anti-Hipertensivos/farmacologia , Hipertensão/tratamento farmacológico , Peptídeos/farmacologia , Sistema Renina-Angiotensina/efeitos dos fármacos , Animais , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Masculino , Peptídeos/uso terapêutico , Proteínas de Plantas/farmacologia , Proteínas de Plantas/uso terapêutico , Ratos , Ratos Endogâmicos SHR
2.
World J Gastroenterol ; 25(25): 3196-3206, 2019 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-31333311

RESUMO

BACKGROUND: Colorectal cancer (CRC) is the third most common malignancy of the digestive tract and the fifth leading cause of cancer-related mortality in China. Sporamin, a Kunitz-type trypsin inhibitor isolated from sweet potato, is a potential anti-cancer agent with activities against a number of malignant tumor cells in vitro. The liver secretes a myriad of endocrine factors that may facilitate the growth and transformation of tumors in the development of CRC. AIM: To investigate the effects of sporamin on liver morphology and biomarkers of xenografted CRC in the liver of athymic BALB/c mice. METHODS: Twenty-seven male BALB/c nude mice were randomly divided into control, vehicle, and sporamin groups. Mice in the latter two groups were intraperitoneally xenografted with LoVo colorectal carcinoma cells and intragastrically infused with saline or sporamin (0.5 g/kg body weight/d), respectively, for 3 wk. Hematoxylin and eosin (HE) staining of the sections was performed to observe morphological changes in hepatic tissue and real-time fluorescent quantitative PCR (qPCR) and enzyme-linked immunosorbent assay (ELISA) were used to measure the expression of ß-catenin and vascular endothelial growth factor (VEGF) in the liver. RESULTS: Sporamin significantly reduced the number and weight of tumor nodules formed in the abdominal cavity. Compared with the vehicle group, the mean tumor weight (± SD) in the sporamin group was significantly reduced (0.44 ± 0.10 g vs 0.26 ± 0.15 g) and the total number of tumors decreased from 93 to 55. HE staining showed that enlargement of the nucleus and synthesis of proteins within hepatocytes, as well as infiltration of inflammatory cells into the liver, were attenuated by sporamin. Immunohistochemical staining and ELISA showed that the concentrations of ß-catenin and VEGF in the liver were significantly reduced by sporamin. Compared with the vehicle group, the expression of ß-catenin measured in integrated optical density units per area was reduced in the sporamin group (47.29 ± 9.10 vs 26.14 ± 1.72; P = 0.003). Expression of VEGF was also reduced after sporamin intervention from 20.78 ± 2.06 in the vehicle group to 15.80 ± 1.09 in the sporamin group (P = 0.021). Compared with the vehicle group, the concentration of ß-catenin decreased from 134.42 ± 22.04 pg/mL to 109.07 ± 9.65 pg/mL after sporamin intervention (P = 0.00002). qPCR indicated that compared to the vehicle group, relative mRNA expression of ß-catenin and VEGF in the liver of mice in the sporamin-treated group was significantly reduced to 71% ± 1% (P = 0.000001) and 23% ± 7% (P = 0.00002), respectively, of the vehicle group levels. CONCLUSION: Sporamin down-regulates the expression and secretion of ß-catenin and VEGF in the liver, which subsequently inhibits the transcription of downstream genes involved in cancer progression and angiogenesis.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Neovascularização Patológica/tratamento farmacológico , Peptídeos/farmacologia , Proteínas de Plantas/farmacologia , Animais , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Neoplasias Colorretais/irrigação sanguínea , Neoplasias Colorretais/patologia , Progressão da Doença , Regulação para Baixo/efeitos dos fármacos , Humanos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neovascularização Patológica/patologia , Peptídeos/uso terapêutico , Proteínas de Plantas/uso terapêutico , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , beta Catenina/metabolismo
3.
Nutrients ; 11(1)2019 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-30669313

RESUMO

Quality protein maize (QPM) varieties are biofortified, or nutritionally improved, to have higher lysine and tryptophan levels to increase quality protein intakes particularly among young children. This study assesses adequacy of children's protein intakes in Ethiopia, where QPM is being promoted, accounting for protein quality and seasonal dietary changes, and estimates potential increases in intakes if QPM replaced conventional maize in diets. Diets of randomly sampled children aged 12⁻36 months in rural southern Ethiopia (n = 218) were assessed after harvest during relative food security and 3⁻4 months later during relative food insecurity using 24-h weighed food records. Diets were analyzed for protein adequacy, accounting for protein quality using the protein digestibility corrected amino acid score (PDCAAS) method, and potential improvements from QPM substitution were estimated. Stunting was prevalent (38%) at the first assessment. Across seasons, 95⁻96% of children consumed maize, which provided 59⁻61% of energy and 51⁻55% of total protein in 24 h. Dietary intakes decreased in the food insecure season, though children were older. Among children no longer breastfeeding, QPM was estimated to reduce inadequacy of utilizable protein intakes from 17% to 13% in the food secure season and from 34% to 19% in the food insecure season. However, breastfed children had only 4⁻6% inadequate intakes of utilizable protein, limiting QPM's potential impact. Due to small farm sizes, maize stores from home production lasted a median of three months. Young Ethiopian children are at risk of inadequate quality protein intakes, particularly after breastfeeding has ceased and during food insecurity. QPM could reduce this risk; however, reliance on access through home production may result in only short-term benefits given the limited quantities of maize produced and stored.


Assuntos
Deficiências Nutricionais/prevenção & controle , Dieta , Proteínas na Dieta/administração & dosagem , Grão Comestível , Melhoramento Vegetal , Proteínas de Plantas/administração & dosagem , Zea mays/química , Aminoácidos/análise , Pré-Escolar , Deficiências Nutricionais/complicações , Proteínas na Dieta/análise , Proteínas na Dieta/normas , Proteínas na Dieta/uso terapêutico , Ingestão de Energia , Etiópia , Comportamento Alimentar , Feminino , Abastecimento de Alimentos , Jardinagem , Transtornos do Crescimento/epidemiologia , Transtornos do Crescimento/etiologia , Transtornos do Crescimento/prevenção & controle , Humanos , Lactente , Fenômenos Fisiológicos da Nutrição do Lactente , Masculino , Estado Nutricional , Proteínas de Plantas/análise , Proteínas de Plantas/uso terapêutico , Avaliação de Programas e Projetos de Saúde , População Rural , Estações do Ano , Zea mays/classificação
4.
FASEB J ; 33(4): 4836-4850, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30601695

RESUMO

Oxidative stress-induced vascular endothelial cell (VEC) injury is a major mechanism in the initiation and development of atherosclerosis. Lunasin, a soybean-derived 43-aa peptide, has been previously shown to possess potent antioxidant and anti-inflammatory activities other than its established anticancer activities. This study investigated the effects of lunasin on protecting VECs from oxidative damage and inhibiting atherosclerotic plaque progression in apolipoprotein E-deficient (ApoE-/-) mice and explored its underlying mechanism. Biochemical and histologic analyses were performed by using EA.hy926 human VECs and a high-fat diet (HFD) ApoE-/- mouse atherosclerosis model. Our data indicated that lunasin attenuated H2O2-induced, mitochondria-dependent endothelial apoptosis via down-regulating Bax and up-regulating Bcl-2, inhibiting the mitochondrial depolarization, and reducing the release of cytochrome c, as well as decreasing the activation of caspase-9 and caspase-3 in vitro and in vivo. Mechanic studies showed that lunasin significantly up-regulated heme oxygenase-1 via the PI3K/Akt/nuclear factor erythroid 2-related factor 2/antioxidant response element pathway, and reduced H2O2-induced ROS production in VECs, thereby attenuating oxidant-induced endothelial injury and inhibiting atherosclerotic plaque progression in ApoE-/- mice. In conclusion, our in vitro and in vivo data suggest that lunasin protects VECs from oxidative damage by enhancing heme oxygenase-1 expression via activation of the PI3K/Akt/nuclear factor erythroid 2-related factor 2/antioxidant response element pathway and inhibiting mitochondria-dependent apoptosis, thereby effectively attenuating atherosclerosis in HFD-fed ApoE-/- mice. Lunasin may act as a potential therapeutic agent for the prevention and treatment of atherosclerosis.-Gu, L., Ye, P., Li, H., Wang, Y., Xu, Y., Tian, Q., Lei, G., Zhao, C., Gao, Z., Zhao, W., Tan, S. Lunasin attenuates oxidant-induced endothelial injury and inhibits atherosclerotic plaque progression in ApoE-/- mice by up-regulating heme oxygenase-1 via PI3K/Akt/Nrf2/ARE pathway.


Assuntos
Apolipoproteínas E/metabolismo , Heme Oxigenase-1/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas de Plantas/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Apolipoproteínas E/genética , Apoptose/efeitos dos fármacos , Peróxido de Hidrogênio/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Estresse Oxidativo/efeitos dos fármacos
5.
Arch Oral Biol ; 98: 132-139, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30485826

RESUMO

OBJECTIVE: Food-derived peptides have been reported to exhibit antibacterial activity against periodontal pathogenic bacteria. However, no effect has been shown on inflammation and bone resorption in periodontal pathology. The overall objective of the current study was to investigate how rice peptides influence biological defense mechanisms against periodontitis-induced inflammatory bone loss, and identify their novel functions as a potential anti-inflammatory drug. DESIGN: The expression of inflammatory and osteoclast-related molecules was examined in mouse macrophage-derived RAW 264.7 cell cultures using qPCR. Subsequently, the effect of these peptides on inflammatory bone loss in mouse periodontitis was examined using a mouse model of tooth ligation. Briefly, periodontal bone loss was induced for 7 days in mice by ligating the maxillary second molar and leaving the contralateral tooth un-ligated (baseline control). The mice were microinjected daily with the peptide in the gingiva until the day before euthanization. One week after the ligation, TRAP-positive multinucleated cells (MNCs) were enumerated from five random coronal sections of the ligated sites in each mouse. RESULTS: Rice peptides REP9 and REP11 significantly inhibited transcription activity of inflammatory and osteoclast-related molecules. Local treatment with the rice peptides, in mice subjected to ligature-induced periodontitis, inhibited inflammatory bone loss, explaining the decreased numbers of osteoclasts in bone tissue sections. CONCLUSION: Therefore, these data suggested that the rice peptides possess a protective effect against periodontitis.


Assuntos
Perda do Osso Alveolar/tratamento farmacológico , Antibacterianos/farmacologia , Endosperma/química , Oryza/química , Peptídeos/antagonistas & inibidores , Periodontite/tratamento farmacológico , Extratos Vegetais/farmacologia , Perda do Osso Alveolar/diagnóstico por imagem , Perda do Osso Alveolar/patologia , Animais , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Reabsorção Óssea/diagnóstico por imagem , Reabsorção Óssea/tratamento farmacológico , Reabsorção Óssea/patologia , Sobrevivência Celular/efeitos dos fármacos , Citocinas/metabolismo , Modelos Animais de Doenças , Gengiva/efeitos dos fármacos , Inflamação , Ligadura , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Dente Molar , Osteoclastos/efeitos dos fármacos , Peptídeos/administração & dosagem , Peptídeos/uso terapêutico , Periodontite/diagnóstico por imagem , Periodontite/patologia , Extratos Vegetais/uso terapêutico , Proteínas de Plantas/administração & dosagem , Proteínas de Plantas/antagonistas & inibidores , Proteínas de Plantas/uso terapêutico , Células RAW 264.7 , Microtomografia por Raio-X/métodos
6.
Mol Pharm ; 16(1): 371-381, 2019 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-30543441

RESUMO

Rapeseed protein hydrolysates have recently shown in vitro antioxidant and anti-inflammatory activities. However, scant data exist about their in vivo activities. Here, we report that the peptide DHNNPQIR (hereinafter referred to as RAP-8), a bioactive peptide originated from rapeseed protein, exhibits excellent in vivo efficacy in mouse models of nonalcoholic steatohepatitis (NASH) and hepatic fibrosis. We demonstrated that RAP-8 significantly reduced hepatic steatosis and improved insulin resistance and lipid metabolism. Furthermore, RAP-8 showed markedly reduced hepatic inflammation, fibrosis, liver injury, and metabolic deterioration. In particular, RAP-8 directly suppressed fibrosis-associated gene expression, including α-smooth muscle actin (α-Sma) and collagen type I (Col-1α) in the liver of mice in vivo. In addtion, RAP-8 significantly decreased macrophage infiltration and reduced pro-inflammatory cytokines secretion. Finally, we found that RAP-8 administration significantly decreased oxidative stress-induced apoptosis in liver injury induced by CCl4. Therefore, our results suggest that RAP-8 could be available for treatment of NASH and NASH-related metabolic disorders as a potential therapeutic candidate.


Assuntos
Antioxidantes/uso terapêutico , Doenças Metabólicas/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Proteínas de Plantas/uso terapêutico , Animais , Brassica rapa/química , Tetracloreto de Carbono/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/metabolismo , Masculino , Doenças Metabólicas/metabolismo , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Fragmentos de Peptídeos/uso terapêutico , Proteínas S100/uso terapêutico
7.
Mar Drugs ; 16(12)2018 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-30544821

RESUMO

Glucocorticoids (GCs), which are endocrine hormones released under stress conditions, can cause skeletal muscle atrophy. This study investigated whether Pyropia yezoensis crude protein (PYCP) inhibits synthetic GCs dexamethasone (DEX)-induced myotube atrophy associated with proteolytic systems. Mouse skeletal muscle C2C12 myotubes were treated with DEX in the presence or absence of PYCP. DEX exposure (100 µM) for 24 h significantly decreased myotube diameter and myogenin expression, which were all increased by treatment with 20 and 40 µg/mL PYCP. Additionally, PYCP significantly reduced the nuclear expression of the forkhead box transcription factors, FoxO1 and FoxO3a, and ubiquitin-proteasome pathway activation. Further mechanistic research revealed that PYCP inhibited the autophagy-lysosome pathway in DEX-induced C2C12 myotubes. These findings indicate that PYCP prevents DEX-induced myotube atrophy through the regulation of FoxO transcription factors, followed by the inhibition of the ubiquitin-proteasome and autophagy-lysosome pathways. Therefore, we suggest that inhibiting these two proteolytic processes with FoxO transcription factors is a promising strategy for preventing DEX-related myotube atrophy.


Assuntos
Glucocorticoides/efeitos adversos , Atrofia Muscular/prevenção & controle , Extratos Vegetais/farmacologia , Proteínas de Plantas/farmacologia , Rodófitas/química , Animais , Autofagia/efeitos dos fármacos , Linhagem Celular , Dexametasona/efeitos adversos , Fatores de Transcrição Forkhead/metabolismo , Lisossomos/efeitos dos fármacos , Lisossomos/metabolismo , Camundongos , Fibras Musculares Esqueléticas/efeitos dos fármacos , Fibras Musculares Esqueléticas/patologia , Músculo Esquelético/citologia , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/patologia , Atrofia Muscular/induzido quimicamente , Atrofia Muscular/patologia , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/uso terapêutico , Proteínas de Plantas/isolamento & purificação , Proteínas de Plantas/uso terapêutico , Complexo de Endopeptidases do Proteassoma/efeitos dos fármacos , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteólise/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Resultado do Tratamento
8.
Pak J Pharm Sci ; 31(6 (Supplementary): 2597-2605, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30587467

RESUMO

Many clinical-pathogens have developed resistance against known antibiotics and there is an urgent need for the discovery of novel antibiotics. In this study, low molecular weight peptides were isolated from seeds/leaves of 20 medicinal plants and tested for their antibacterial activity against laboratory strains of S. aureusand P. aeruginosa. Peptides isolated from Peganum harmala (PhAMP) exhibited maximum activity against laboratory strains. As clinical-isolates are more virulent and resistant to antibiotics, we tested the potential of PhAMP on these bacterial strains isolated from infected wounds. Pathogens isolated from burn-wounds (S. aureus, P. aeruginosa and K. pneumoniae) and surgical-wounds (P. aeruginosa and K. pneumoniae) exhibited zones of inhibition against PhAMP when tested by disc diffusion method. Biofilm formation of wound pathogens in the presence/absence of PhAMP was analyzed to check its effect. Surgical-wound pathogens and K. pneumoniae from burn-wound showed significant reduction in biofilm formation and planktonic bacteria. While biofilms of S. aureus and P. aeruginosa from burn-wound showed resistance against PhAMP. An effective antibiotic treatment should not only inhibit but should also disrupt already developed biofilms. PhAMP was very effective in the disruption of developed biofilm of all pathogens after 36 hours. This data unravels the potential of PhAMP as a novel, natural antibiotic against clinical-pathogens.


Assuntos
Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Queimaduras/microbiologia , Peganum , Extratos Vegetais/farmacologia , Ferida Cirúrgica/microbiologia , Antibacterianos/isolamento & purificação , Antibacterianos/uso terapêutico , Biofilmes/crescimento & desenvolvimento , Queimaduras/tratamento farmacológico , Humanos , Testes de Sensibilidade Microbiana , Fragmentos de Peptídeos/isolamento & purificação , Fragmentos de Peptídeos/farmacologia , Fragmentos de Peptídeos/uso terapêutico , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/uso terapêutico , Proteínas de Plantas/isolamento & purificação , Proteínas de Plantas/farmacologia , Proteínas de Plantas/uso terapêutico , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/isolamento & purificação , Pseudomonas aeruginosa/fisiologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/isolamento & purificação , Staphylococcus aureus/fisiologia , Ferida Cirúrgica/tratamento farmacológico
9.
Molecules ; 23(9)2018 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-30201912

RESUMO

In recent years, with an increase in the aging population, neurodegenerative diseases have attracted more and more attention. This study aimed to investigate the potential neuroprotective effect of defatted walnut meal protein hydrolysates (DWMPH) on neurotoxicity induced by d-galactose (d-gal) and aluminum chloride (AlCl3) in mice. The animal models were established by combining treatments with d-gal (200 mg/kg/day, subcutaneously) and AlCl3 (100 mg/kg in drinking water) for 90 days. During the 90 days, 1 g/kg of DWMPH was administrated orally every day. The results indicated that DWMPH treatment alleviated oxidative stress, reversed cholinergic dysfunction, and suppressed the release of proinflammatory cytokines in the brains of d-gal + AlCl3-treated mice, and thus improving the learning and memory functions of these mice, which was closely correlated with the strong antioxidant activity of DWMPH. This finding suggests that DWMPH might be a promising dietary supplement in improving neuronal dysfunctions of the brain.


Assuntos
Fármacos Neuroprotetores/uso terapêutico , Síndromes Neurotóxicas/tratamento farmacológico , Proteínas de Plantas/uso terapêutico , Hidrolisados de Proteína/uso terapêutico , Cloreto de Alumínio , Aminoácidos/análise , Animais , Antioxidantes/farmacologia , Comportamento Animal , Peso Corporal/efeitos dos fármacos , Colina/metabolismo , Comportamento Alimentar , Galactose , Inflamação/patologia , Interleucina-1beta/metabolismo , Juglans , Masculino , Camundongos , Neurônios/efeitos dos fármacos , Neurônios/patologia , Síndromes Neurotóxicas/patologia , Estresse Oxidativo/efeitos dos fármacos , Proteínas de Plantas/química , Proteínas de Plantas/farmacologia , Hidrolisados de Proteína/química , Hidrolisados de Proteína/farmacologia , Fator de Necrose Tumoral alfa/metabolismo
10.
Int J Oncol ; 53(3): 1027-1042, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30015835

RESUMO

Fordin, which is derived from Vernicia fordii, is a novel type I ribosome inactivating protein (RIP) with RNA N-glycosidase activity. In the present study, fordin was expressed by Escherichia coli and purified using nickel affinity chromatography. Previous studies have demonstrated RIP toxicity in a variety of cancer cell lines. To understand the therapeutic potential of fordin on tumors, the present study investigated the effects of fordin on the viability of several tumor and normal cell lines. The results demonstrated that fordin induced significant cytotoxicity in four cancer cell lines, compared with the normal cell line. Specifically, profound apoptosis and inhibition of cell invasion were observed following fordin exposure in U-2 OS and HepG2 cells; however, the molecular mechanism underlying the action of RIP remains to be fully elucidated. In the present study, it was found that the anticancer effects of fordin were associated with suppression of the nuclear factor (NF)-κB signaling pathway. In U-2 OS and HepG2 cells, fordin inhibited the expression of inhibitor of NF-κB (IκB) kinase, leading to downregulation of the phosphorylation level of IκB, which quelled the nuclear translocation of NF-κB. Fordin also reduced the mRNA and protein levels of NF-κB downstream targets associated with cell apoptosis and metastasis, particularly B-cell lymphoma­2-related protein A1 (Blf-1) and matrix metalloproteinase (MMP)-9. The inactivation of NF-κB and the reduction in the expression levels of Blf-1 and MMP-9 mediated by fordin were also confirmed by co-treatment with lipopolysaccharide or p65 small interfering RNA. These findings suggested a possible mechanism for the fordin-induced effect on tumor cell death and metastasis. The results of the present study demonstrated the multiple anticancer effects of fordin in U-2 OS and HepG2 cells, in part by inhibiting activation of the NF-κB signaling pathway.


Assuntos
Euphorbiaceae/metabolismo , Neoplasias/tratamento farmacológico , Proteínas de Plantas/farmacologia , Proteínas Inativadoras de Ribossomos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Regulação para Baixo , Ensaios de Seleção de Medicamentos Antitumorais , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Quinase I-kappa B/metabolismo , Concentração Inibidora 50 , Metaloproteinase 9 da Matriz/metabolismo , Antígenos de Histocompatibilidade Menor/metabolismo , NF-kappa B/metabolismo , Invasividade Neoplásica/prevenção & controle , Neoplasias/patologia , Fosforilação/efeitos dos fármacos , Proteínas de Plantas/isolamento & purificação , Proteínas de Plantas/uso terapêutico , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/metabolismo , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/farmacologia , Proteínas Recombinantes/uso terapêutico , Proteínas Inativadoras de Ribossomos/uso terapêutico , Regulação para Cima
11.
Int Arch Allergy Immunol ; 177(3): 245-254, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30021201

RESUMO

BACKGROUND: The severity of symptoms of pollen-induced allergic rhinitis is affected by the amount of scattered pollen. However, the relationships between the pollen dispersal pattern, symptom severity, and treatment efficacy are not clear. METHODS: Between 2007 and 2012, we performed 4 randomized, placebo-controlled studies of sublingual immunotherapy (SLIT) on patients with Japanese cedar-induced allergic rhinitis who lived in or around Chiba, Japan. The participants were asked to avoid using rescue medicines during the cedar pollen season as much as possible and to record their nasal symptoms in allergy diaries. The amount of pollen dispersed daily was quantified using the Durham method, and the season was divided into early and late periods based on the pollen count. RESULTS: A total of 721 patients were enrolled in the 4 studies during the 6-year study period. In the placebo group (n = 349), a correlation was observed between the amount of pollen dispersed and the severity of symptoms in the early but not late period of pollen dispersal. Treatment with SLIT (n = 372) significantly improved symptom severity in the late but not early period. CONCLUSION: For patients with Japanese cedar pollen-induced allergic rhinitis, the fluctuation of daily pollen dispersal had a minimal effect on the severity of symptoms during the late period. SLIT was remarkably effective in alleviating symptoms during this period but not in the early period.


Assuntos
Antígenos de Plantas/uso terapêutico , Dessensibilização Imunológica/métodos , Proteínas de Plantas/uso terapêutico , Rinite Alérgica Sazonal/patologia , Rinite Alérgica Sazonal/terapia , Imunoterapia Sublingual/métodos , Administração Sublingual , Adolescente , Adulto , Idoso , Antígenos de Plantas/administração & dosagem , Antígenos de Plantas/imunologia , Criança , Cryptomeria/imunologia , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Proteínas de Plantas/administração & dosagem , Proteínas de Plantas/imunologia , Pólen/imunologia , Rinite Alérgica Sazonal/imunologia , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto Jovem
12.
J Nutr ; 148(8): 1229-1235, 2018 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-29939292

RESUMO

Background: Iron deficiency is an enduring global health problem that requires new remedial approaches. Iron absorption from soybean-derived ferritin, an ∼550-kDa iron storage protein, is comparable to bioavailable ferrous sulfate (FeSO4). However, the absorption of ferritin is reported to involve an endocytic mechanism, independent of divalent metal ion transporter 1 (DMT-1), the transporter for nonheme iron. Objective: Our overall aim was to examine the potential of purified ferritin from peas (Pisum sativum) as a food supplement by measuring its stability under gastric pH treatment and the mechanisms of iron uptake into Caco-2 cells. Methods: Caco-2 cells were treated with native or gastric pH-treated pea ferritin in combination with dietary modulators of nonheme iron uptake, small interfering RNA targeting DMT-1, or chemical inhibitors of endocytosis. Cellular ferritin formation, a surrogate measure of iron uptake, and internalization of pea ferritin with the use of specific antibodies were measured. The production of reactive oxygen species (ROS) in response to equimolar concentrations of native pea ferritin and FeSO4 was also compared. Results: Pea ferritin exposed to gastric pH treatment was degraded, and the released iron was transported into Caco-2 cells by DMT-1. Inhibitors of DMT-1 and nonheme iron absorption reduced iron uptake by 26-40%. Conversely, in the absence of gastric pH treatment, the iron uptake of native pea ferritin was unaffected by inhibitors of nonheme iron absorption, and the protein was observed to be internalized in Caco-2 cells. Chlorpromazine (clathrin-mediated endocytosis inhibitor) reduced the native pea ferritin content within cells by ∼30%, which confirmed that the native pea ferritin was transported into cells via a clathrin-mediated endocytic pathway. In addition, 60% less ROS production resulted from native pea ferritin in comparison to FeSO4. Conclusion: With consideration that nonheme dietary inhibitors display no effect on iron uptake and the low oxidative potential relative to FeSO4, intact pea ferritin appears to be a promising iron supplement.


Assuntos
Endocitose , Ferritinas/farmacocinética , Ácido Gástrico , Ferro/metabolismo , Ervilhas/química , Proteínas de Plantas/farmacocinética , Estômago/química , Anemia Ferropriva/tratamento farmacológico , Disponibilidade Biológica , Transporte Biológico , Células CACO-2 , Proteínas de Transporte de Cátions/metabolismo , Dieta , Proteínas na Dieta/isolamento & purificação , Proteínas na Dieta/metabolismo , Proteínas na Dieta/farmacocinética , Proteínas na Dieta/uso terapêutico , Suplementos Nutricionais , Ferritinas/isolamento & purificação , Ferritinas/metabolismo , Ferritinas/uso terapêutico , Humanos , Concentração de Íons de Hidrogênio , Absorção Intestinal , Proteínas de Plantas/isolamento & purificação , Proteínas de Plantas/metabolismo , Proteínas de Plantas/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Soja/química
13.
Int J Biol Macromol ; 114: 556-564, 2018 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-29578020

RESUMO

Therapeutic value of allelochemicals in inflammatory disorders and the potential drug targets need to be elucidated to alleviate tissue and vascular injury. Natural anti-inflammatory agents are known to cause minimal adverse effects. Presence of different secondary metabolites (allelochemicals), protease inhibitors like soap nut trypsin inhibitor (SNTI) from Sapindus trifoliatus and allied compounds from natural sources cannot be blithely ignored as natural therapeutics. In the present study, SNTI, a prospective protease inhibitor isolated from the seeds of Sapindus trifoliatus were subjected to docking against three isoforms of Phospholipase A2 (PLA2) molecules of the inflammatory pathways which are localized in the membrane, cytosol and pancreas. Eleven ligand molecules were selected from Sapindus trifoliatus and docked against membrane, cytosolic and pancreatic PLA2. Cytosolic PLA2 showed a strong inhibition by Kampferol, a secondary metabolite from seed endosperm of Sapindus trifoliatus. SNTI showed best interaction with membrane PLA2 in both in silico as well as in in vitro studies. SNTI showed IC50 value of 29.02 µM in in vitro assay. Docking interaction profiles and in vitro studies validate selected molecules from Sapindus trifoliatus as immunomodulators and can mollify inflammatory responses.


Assuntos
Fatores Imunológicos , Simulação de Acoplamento Molecular , Fosfolipases A2/química , Proteínas de Plantas , Sapindus/química , Inibidores da Tripsina , Animais , Humanos , Fatores Imunológicos/química , Fatores Imunológicos/isolamento & purificação , Fatores Imunológicos/uso terapêutico , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Isoenzimas/química , Isoenzimas/metabolismo , Camundongos , Fosfolipases A2/metabolismo , Proteínas de Plantas/química , Proteínas de Plantas/isolamento & purificação , Proteínas de Plantas/uso terapêutico , Inibidores da Tripsina/química , Inibidores da Tripsina/isolamento & purificação , Inibidores da Tripsina/uso terapêutico
14.
Food Chem Toxicol ; 119: 296-301, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29481895

RESUMO

As one of low-digestible proteins, tartary buckwheat protein (BWP) revealed a cholesterol-lowering activity. The relationship between the prevention of BWP on dyslipidemia and changes in the numbers of gut microbiota was investigated. The male C57BL/6 mice were separately fed on normal diet, high-fat diet (HFD) with casein, and HFD with BWP extract for 6 weeks. Quantitative PCR assay was applied to quantify the microbiota composition in feces. The levels of plasma total cholesterol (TC) and triglyceride (TG) in the mice fed on HFD with BWP were significantly lower than those on HFD with casein. BWP promoted the growth of Lactobacillus, Bifidobacterium and Enterococcus and inhibited the growth of Escherichia coli in HFD-fed mice. Moreover, Bifidobacterium population was closely related to contents of plasma lipids. Further, BWP significantly decreased the levels of plasma inflammation factors as induced by HFD, including lipopolysaccharide, tumor necrosis factor α and interleukin 6. BWP significantly increased the excretion of total bile acids and short-chain fatty acids in feces. In conlusion, BWP benefited cholesterol metabolism, which could be attributed to regulating composition of gut microbiota.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Fagopyrum/química , Microbioma Gastrointestinal , Proteínas de Plantas/uso terapêutico , Animais , Bactérias/isolamento & purificação , Citocinas/metabolismo , Ácidos Graxos Voláteis/análise , Fezes/química , Hiperlipidemias/prevenção & controle , Inflamação/prevenção & controle , Mediadores da Inflamação/metabolismo , Lipídeos/sangue , Masculino , Camundongos Endogâmicos C57BL
15.
Inflammopharmacology ; 26(3): 769-778, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29197932

RESUMO

The present study was designed to explore the anti-inflammatory activity of an anti-platelet agent crinumin, by various in vitro and in vivo inflammation models. Firstly, crinumin protein was purified through cation exchange chromatography; then, in vitro activity was estimated by albumin denaturation assay and HRBC membrane stabilization assay. Carrageenan-induced paw oedema and cotton pellet-induced granuloma models were used for in vivo anti-inflammatory activity assessment in rats. In both models, rats were pre-treated for 7 days with crinumin (25-50 µg/ml) and diclofenac sodium (50 µg/ml). Expression of P-selectin (in serum and plasma) through ELISA and NF-κB (in paw and granulomatous tissues) through western blotting was checked. Our results showed that crinumin at both doses (25 or 50 µg/kg of b.w.) significantly (p < 0.05) reduced the paw oedema formation in a dose-dependent manner in the second phase of inflammation and significant (p < 0.05) reduction of wet and dry weight of granuloma was observed indicating the anti-inflammatory potential of crinumin. Crinumin decreased the expression of P-selectin and NF-κB indicating its potential role in decreasing platelet activation and healing inflammation. Histopathological studies additionally proved the efficacy of drug in treating inflammation. The results of the study suggest that the crinumin might have an inhibitory role in atherosclerosis as platelet aggregation and inflammation are the key processes involved in atherosclerotic disorders.


Assuntos
Anti-Inflamatórios/uso terapêutico , Carragenina/toxicidade , Edema/tratamento farmacológico , Granuloma/tratamento farmacológico , Proteínas de Plantas/uso terapêutico , Inibidores da Agregação de Plaquetas/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Anticoagulantes/farmacologia , Anticoagulantes/uso terapêutico , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos/métodos , Edema/induzido quimicamente , Edema/patologia , Granuloma/induzido quimicamente , Granuloma/metabolismo , Masculino , Proteínas de Plantas/farmacologia , Inibidores da Agregação de Plaquetas/farmacologia , Ratos , Ratos Wistar
16.
Arq Bras Cir Dig ; 30(2): 93-97, 2017.
Artigo em Inglês, Português | MEDLINE | ID: mdl-29257842

RESUMO

BACKGROUND: Sepsis is a potentially life-threatening complication of an infection that occurs when chemicals released into the bloodstream to fight the infection trigger inflammatory responses throughout the body, especially in the acute phase of the disease, producing excessive pro-inflammatory cytokines, leading to multiple organ injury and death. The Hev b 13 fraction has demonstrated biological activity capable of inducing IL-10 production and shrinking inflammatory disease lesions. AIM: To investigate the immunomodulating effects of the Hev b 13 fraction on septic rats. METHODS: Acinetobacter baumannii was injected into the peritoneal cavity of the animals after sustaining a lesion in the pancreas, with the stomach as an entry point. After 10 h of infection, they were euthanized for blood and lung collection, followed by total and differential leukocyte count, determination of cytokine level and histopathological analysis. RESULTS: Administering a single dose of the Hev b 13 fraction 2 h after sepsis induction significantly decreased total leukocyte count. Higher IL-10 and IL-4 and lower IL-6 production shrank the lung tissue lesions compared to the control groups. CONCLUSION: The Hev b 13 fraction exhibits an anti-inflammatory tendency, with potential for sepsis treatment.


Assuntos
Antígenos de Plantas/uso terapêutico , Imunomodulação , Fitoterapia , Proteínas de Plantas/uso terapêutico , Sepse/terapia , Animais , Masculino , Ratos , Ratos Wistar , Sepse/imunologia
17.
Immunotherapy ; 9(15): 1271-1278, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-29130794

RESUMO

Apple allergy is common in patients allergic to birch pollen, and this is defined as 'birch-apple syndrome'. Allergens responsible for cross-reactivity belong to the pathogenesis-related-10 family, and high homology in the amino acid sequences of the major allergens Bet v 1 from birch and Mal d 1 from apple has been demonstrated. Here we review the literature on the treatment of birch-apple syndrome by allergen immunotherapy. The only allergen immunotherapy method available thus far is based on the administration of birch-pollen extracts, through the subcutaneous or sublingual route, to induce tolerance to Bet v1 and to the homologous allergen Mal d 1. However, the studies performed thus far show modest efficacy, and thus other methods of immunotherapy should be investigated.


Assuntos
Antígenos de Plantas/imunologia , Antígenos de Plantas/uso terapêutico , Dessensibilização Imunológica/métodos , Hipersensibilidade Alimentar/terapia , Proteínas de Plantas/uso terapêutico , Rinite Alérgica Sazonal/terapia , Betula/imunologia , Reações Cruzadas , Hipersensibilidade Alimentar/imunologia , Humanos , Tolerância Imunológica , Malus/imunologia , Proteínas de Plantas/imunologia , Pólen/imunologia , Síndrome , Resultado do Tratamento
18.
Nanoscale ; 9(43): 16887-16899, 2017 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-29076508

RESUMO

Metastatic breast cancer is a very serious life threatening condition that poses many challenges for the pharmaceutical development of effective chemotherapeutics. As the therapeutics targeted to the localized masses in breast improve, metastatic lesions in the brain slowly increase in their incidence compromising successful treatment outcomes overall. The blood-brain-barrier (BBB) is one important obstacle for the management of breast cancer brain metastases. New therapeutic approaches are in demand for overcoming the BBB's breaching by breast tumor cells. In this work we demonstrate the potential dual role of a natural antimicrobial plant defensin, PvD1: it interferes with the formation of solid tumors in the breast and concomitantly controls adhesion of breast cancer cells to human brain endothelial cells. We have used a combination of techniques that probe PvD1's effect at the single cell level and reveal that this peptide can effectively damage breast tumor cells, leaving healthy breast and brain cells unaffected. Results suggest that PvD1 quickly internalizes in cancer cells but remains located in the membrane of normal cells with no significant damage to its structure and biomechanical properties. These interactions in turn modulate cell adhesiveness between tumor and BBB cells. PvD1 is a potential template for the design of innovative pharmacological approaches for metastatic breast cancer treatment: the manipulation of the biomechanical properties of tumor cells that ultimately prevent their attachment to the BBB.


Assuntos
Barreira Hematoencefálica , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/terapia , Neoplasias da Mama/patologia , Defensinas/uso terapêutico , Proteínas de Plantas/uso terapêutico , Encéfalo/citologia , Mama/citologia , Linhagem Celular Tumoral , Humanos , Microscopia de Força Atômica , Phaseolus , Análise de Célula Única
19.
Biomed Res Int ; 2017: 5046451, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28875151

RESUMO

A thaumatin-like protein gene from Basrai banana was cloned and expressed in Escherichia coli. Amplified gene product was cloned into pTZ57R/T vector and subcloned into expression vector pET22b(+) and resulting pET22b-basrai TLP construct was introduced into E. coli BL21. Maximum protein expression was obtained at 0.7 mM IPTG concentration after 6 hours at 37°C. Western blot analysis showed the presence of approximately 20 kDa protein in induced cells. Basrai antifungal TLP was tried as pharmacological agent against fungal disease. Independently Basrai antifungal protein and amphotericin B exhibited their antifungal activity against A. fumigatus; however combined effect of both agents maximized activity against the pathogen. Docking studies were performed to evaluate the antimicrobial potential of TLP against A. fumigatus by probing binding pattern of antifungal protein with plasma membrane ergosterol of targeted fungal strain. Ice crystallization primarily damages frozen food items; however addition of antifreeze proteins limits the growth of ice crystal in frozen foods. The potential of Basrai TLP protein, as an antifreezing agent, in controlling the ice crystal formation in frozen yogurt was also studied. The scope of this study ranges from cost effective production of pharmaceutics to antifreezing and food preserving agent as well as other real life applications.


Assuntos
Musa/genética , Micoses/tratamento farmacológico , Proteínas de Plantas/genética , Sequência de Aminoácidos , Antifúngicos/química , Antifúngicos/uso terapêutico , Fungos/efeitos dos fármacos , Fungos/patogenicidade , Regulação da Expressão Gênica de Plantas , Humanos , Simulação de Acoplamento Molecular , Musa/química , Micoses/microbiologia , Proteínas de Plantas/química , Proteínas de Plantas/uso terapêutico , Conformação Proteica , Homologia de Sequência de Aminoácidos
20.
Int J Biol Macromol ; 103: 1121-1129, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28559184

RESUMO

Previous reports have demonstrated that a thermostable lipid transfer protein isolated from noni seeds (McLTP1; 9.4kDa) displays anti-nociceptive and anti-inflammatory activities. This work aimed to investigate the underlying mechanisms of the anti-inflammatory activity of McLTP1 in mice. The protein was solubilised in sterile saline (0.9% NaCl) immediately before the treatment of mice by oral or intraperitoneal routes at doses of 8mg/kg. Given orally or intraperitoneally, McLTP1 significantly inhibited (p<0.05) cell migration in experimental models of carrageenan-induced peritonitis and the formation of paw oedema induced by carrageenan and dextran. Additionally, McLTP1 demonstrated the ability to significantly inhibit the production of the cytokines IL-1ß, IL-6, and TNF-α (p<0.05) and to promote an increase in the production of the anti-inflammatory cytokine IL-10. The treatment of mice with McLTP1 by the oral or i.p route reduced pancreatic injury and activities of amylase, lipase, and pancreatitis-associated lung injury. This study suggested that the observed anti-inflammatory effects of McLTP1 can be related to modulation of pro- and anti-inflammatory cytokine levels.


Assuntos
Anti-Inflamatórios/farmacologia , Proteínas de Transporte/farmacologia , Citocinas/metabolismo , Morinda/química , Proteínas de Plantas/farmacologia , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/uso terapêutico , Proteínas de Transporte/química , Proteínas de Transporte/uso terapêutico , Movimento Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Masculino , Camundongos , Peritonite/tratamento farmacológico , Peritonite/metabolismo , Peritonite/patologia , Proteínas de Plantas/química , Proteínas de Plantas/uso terapêutico , Solubilidade
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