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1.
Chem Biol Interact ; 324: 109089, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32272095

RESUMO

Ulcerative colitis (UC) is a chronic, idiopathic and inflammatory disease of the rectal and colonic mucosa. Studies have shown that Toll-like receptors (TLR) 4 and Signal Transducer and Activator of Transcription 3 (STAT3)-mediated the decline in immune function and inflammatory infiltration are potential pathomechanism of UC occurrence and development. In this study, the anti-inflammation of Erianin, a natural bibenzyl compound with the antioxidant, antitumor, and anti-inflammatory activities, was investigated in a dextran sodium sulphate-induced UC mouse model. Three-week Erianin administration resulted in the increment on the body weight and colon length, and the reduction on the activity index score of UC mice. Liver, spleen, and renal organ indexes and pathological observations confirmed that Erianin was not cytotoxic and had an effect of improving immune organ function. The haematoxylin and eosin staining sections of colon tissue show Erianin's effect of reversing inflammation in the mucosal laye. Proteomic analysis and enzyme-linked immunosorbent assay indicated that Erianin regulated the levels of inflammatory and oxidative stress-related factors and immunochemokines in serum and colon tissues thereby reducing cell peroxidative damage and reducing immune inflammatory responses. Further data obtained by Western Blotting confirmed that Erianin's anti-UC activity was mediated by inhibiting the TLR4 and STAT3 signaling.


Assuntos
Anti-Inflamatórios/uso terapêutico , Bibenzilas/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Fator de Transcrição STAT3/metabolismo , Receptor 4 Toll-Like/metabolismo , Animais , Anti-Inflamatórios/toxicidade , Antioxidantes/uso terapêutico , Bibenzilas/toxicidade , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/patologia , Colo/patologia , Sulfato de Dextrana , Rim/patologia , Fígado/patologia , Masculino , Camundongos Endogâmicos C57BL , Transdução de Sinais/efeitos dos fármacos , Baço/patologia
2.
Carbohydr Polym ; 232: 115766, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31952583

RESUMO

Type 2 diabetes mellitus plagues many people in China and the world, and its nephritis complication is the leading cause of death for patients. Paecilomyces hepiali contained various functional components, especially polysaccharides, which possesses well pharmacological activities. In this study, polysaccharide purified from Paecilomyces hepiali fermented mycelium entitled PHEA was obtained, and its structure was systemically characterized using fourier transform infrared spectroscopy (FT-IR) and nuclear magnetic resonance (NMR). In C57BL/KsJ (BKS).Cg-Dock7m +/+ Leprdb/JNju mice (db/db mice), via detecting the alternations on biochemical criterions, pathological indicators and protein expressions related to nuclear factor-E2-related factor 2 (Nrf2) and nuclear factor-κB (NF-κB) signaling in serum and/or tissues including muscle, liver and kidney after 8-week PHEA administration, the hypoglycemic, hypolipidemic, and anti-diabetic nephropathic activities of PHEA were confirmed. The purified P. Hepiali polysaccharide with the anti-diabetic and -nephritic properties was first reported in this study via regulating Nrf2-meadited NF-κB signaling in db/db mice.

3.
Pak J Pharm Sci ; 32(3): 1011-1018, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31278714

RESUMO

Irpex lacteus is a white rot basidiomycete proposed for a wide spectrum of biotechnological applications. However, few studies examined its effects on exercise performance and physical fatigue. The present study evaluated the potential beneficial effects of I. lacteus extract (ILE) on physical fatigue in mice. Anti-fatigue activities of ILE were evaluated in Kunming mice using the forced swim test, rotating rod and forced running test. Serum and liver biochemical parameters were determined by an autoanalyzer and commercially available kits. Seven-day ILE administration at doses of 0.04, 0.2 and 1.0g/kg failed to influence mouse horizontal and vertical movement indicating its safety on the central nervous system. Compared with normal mice, ILE significantly increased persistent period during rotating rod and swimming tests, and reduced shock times in forced running test. Additionally, ILE resulted in 23.4% and 64.5% increments on adrenocorticotropic hormone and cortisol levels in serum. Compared with normal mice, and 209.0% increment on adenosine triphosphate level in liver (up to 2.5 mmol/gHb) were noted in ILE-treated mice. Moreover, ILE increased the level of super oxide dismutase and reduced the level of malondialdehyde in the liver suggesting its antioxidant activity. Data obtained from western bolt suggests that ILE-improved endurance capacity is mainly acquired through activating 5'-AMP-activated protein kinase (AMPK). ILE enhanced the endurance capacity of mouse by an elevation of antioxidant at least partially associated with AMPK pathway. Our data highlight the potential of I. lacteus as an antioxidant in the treatment of fatigue-related diseases.


Assuntos
Fadiga/tratamento farmacológico , Polissacarídeos Fúngicos/farmacologia , Polyporales/química , Proteínas Quinases Ativadas por AMP/metabolismo , Trifosfato de Adenosina/metabolismo , Hormônio Adrenocorticotrópico/metabolismo , Animais , Comportamento Animal/efeitos dos fármacos , Corticosterona/metabolismo , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Fadiga/metabolismo , Feminino , Polissacarídeos Fúngicos/química , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Malondialdeído/metabolismo , Camundongos , Resistência Física/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Teste de Desempenho do Rota-Rod , Superóxido Dismutase/metabolismo , Natação
4.
Int J Mol Med ; 43(2): 956-966, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30569175

RESUMO

Due to its complex pathogenesis, the prevention and therapization of Alzheimer's disease (AD) remains a serious challenge. Crocin, the main compound isolated from Crocus sativus L., demonstrates various pharmacological activities including anti­apoptotic properties. The present study investigated the neuroprotective effect of crocin and the underlying mechanisms. In l­glutamate­damaged HT22 cells, 3­h crocin pretreatment strongly enhanced the HT22 cell viability, reduced the apoptotic rate, mitigated mitochondrial dysfunction, suppressed intracellular reactive oxygen species (ROS) accumulation and Ca2+ overload compared with untreated cells. Additionally, crocin significantly decreased the expression levels of Bax, Bad and cleaved caspase­3 and increased the expression levels of B­cell lymphoma­extra large, phosphorylated (P­) protein kinase B and P­mammalian target of rapamycin compared with untreated cells. In mice with AD induced by d­galactose and aluminum trichloride, crocin substantially improved the cognition and memory abilities of the mice as measured by their coordination of movement in an open field test, and reduced their escape time in the Morris water maze test compared with untreated mice. Biochemical analysis confirmed that crocin was able to reduce the Aß1­42 content in the mouse brains, increase the levels of glutathione peroxidase, superoxide dismutase, acetylcholine and choline acetyltransferase, and reduce the levels of ROS and acetylcholinesterase in the serum, cerebral cortex and hypothalamus compared with untreated mice. Immunohistochemical analysis demonstrated that crocin reduced Aß1­42 deposition in the hippocampus of the brains of treated mice compared with untreated mice. In conclusion, crocin demonstrates good prospects in the treatment of AD through the oxidative stress­associated apoptosis signaling pathway.


Assuntos
Doença de Alzheimer/metabolismo , Antioxidantes/metabolismo , Carotenoides/farmacologia , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Doença de Alzheimer/patologia , Doença de Alzheimer/psicologia , Animais , Apoptose/efeitos dos fármacos , Cálcio/metabolismo , Carotenoides/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Cognição , Modelos Animais de Doenças , Ácido Glutâmico/farmacologia , Camundongos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Fármacos Neuroprotetores/química , Células Piramidais/efeitos dos fármacos , Células Piramidais/metabolismo , Espécies Reativas de Oxigênio/metabolismo
5.
Chem Biol Interact ; 283: 51-58, 2018 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-29408431

RESUMO

Aucubin, an iridoid glycoside found in several plants, such as Eucommia ulmoide and Rehmannia, has various pharmacological effects. Bone formation is a complex process in which osteoblast differentiation plays an important role. This study aimed to investigate the promotion effects of aucubin on osteoblast differentiation in MG63 cells, a human osteoblast-like cell line. Aucubin not only improved osteoblast differentiation, as shown by enhanced ALP (alkaline phosphatase) concentration and mineralization in cells, but increased the expression of various cytokines, including collagen I, osteocalcin, osteopontin, integrin ß1, and Osterix. Aucubin strongly enhanced the levels of BMP2 (bone morphogenetic proteins-2) in MG63 cells, which play a central role during osteoblast differentiation. Further data show that aucubin exposure after 1 day, 7 days, and 14 days enhanced the expression of Smad1, 5, and 8, and the phosphoresced levels of MAPKs (mitogen-activated protein kinases) family Erk (extracellular signal-regulated kinases), JNK (c-Jun-NH2-terminal kinases), P38, and Akt (serine/threonine protein kinase)/mTOR (mammalian target of rapamycin)/p70s6k in MG63 cells. This study shows the improved effects of aucubin on osteoblast differentiation in MG63 cells, related to the signaling of BMP2-mediated Smads (drosophila mothers against decapentaplegic proteins), MAPKs, and Akt/mTOR/p70S6K. This study indicates the potential of aucubin for osteoporosis treatment.


Assuntos
Proteína Morfogenética Óssea 2/metabolismo , Diferenciação Celular/efeitos dos fármacos , Glucosídeos Iridoides/farmacologia , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Colágeno Tipo I/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Glucosídeos Iridoides/química , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Osteoblastos/citologia , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Osteocalcina/metabolismo , Osteopontina/metabolismo , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteína Smad1/metabolismo , Proteína Smad5/metabolismo , Proteína Smad8/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
6.
PLoS One ; 12(6): e0180476, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28662169

RESUMO

This study evaluated the effects of Inonotus obliquus polysaccharides (IOs) on diabetes and other underlying mechanisms related to inflammatory factors and oxidative stress in a mouse model of streptozotocin (STZ)-induced diabetes. Four weeks administration of metformin (120 mg/kg) and IO1-4 (50%-80% alcohol precipitation), or IO5 (total 80% alcohol precipitation) at doses of 50 mg/kg reverses the abnormal changes of bodyweights and fasting blood glucose levels of diabetic mice. IOs significantly increased the insulin and pyruvate kinase levels in serum, and improved the synthesis of glycogen, especially for IO5. IOs restored the disturbed serum levels of superoxide dismutase, catalase, glutathione peroxidase, and malondialdehyde. The down-regulation of interleukin-2 receptor, matrix metalloproteinase-9, and the enhancement of interleukin-2 in serum of diabetic mice were significantly attenuated by IOs. Histologic and morphology examinations showed that IOs repaired the damage on kidney tissues, inhibited inflammatory infiltrate and extracellular matrix deposit injuries in diabetic mice. Compared with untreated diabetic mice, IOs decreased the expression of phosphor-NF-κB in the kidneys. These results show that IOs treatment attenuated diabetic and renal injure in STZ-induced diabetic mice, possibly through the modulation of oxidative stress and inflammatory factors. These results provide valuable evidences to support the use of I. obliquus as a hypoglycemic functional food and/or medicine.


Assuntos
Basidiomycota/química , Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Polissacarídeos/farmacologia , Animais , Hemoglobina A Glicada/metabolismo , Hipoglicemiantes/uso terapêutico , Insulina/sangue , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Polissacarídeos/uso terapêutico , Piruvato Quinase/sangue , Estreptozocina
7.
Oxid Med Cell Longev ; 2017: 7841823, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28337253

RESUMO

In the present study, the components of A. cinnamomea (AC) mycelia were systematically analyzed. Subsequently, its hepatoprotective effects and the underlying mechanisms were explored using a mouse model of acute alcohol-induced liver injury. AC contained 25 types of fatty acid, 16 types of amino acid, 3 types of nucleotide, and 8 types of mineral. The hepatoprotective effects were observed after 2 weeks of AC treatment at doses of 75 mg/kg, 225 mg/kg, and 675 mg/kg in the mouse model. These effects were indicated by the changes in the levels of aspartate aminotransferase, alanine aminotransferase, several oxidation-related factors, and inflammatory cytokines in serum and/or liver samples. AC reduced the incidence rate of necrosis, inflammatory infiltration, fatty droplets formation, and cell apoptosis in liver detecting via histological and TUNEL assay. In addition, AC reduced the expression of cleaved caspase-3, -8, and -9 and the levels of phosphor-protein kinase B (Akt) and phosphor-nuclear factor-κB (NF-κB) in the liver samples. Collectively, AC-mediated hepatoprotective effects in a mouse model of acute alcohol-induced liver injury are the result of reduction in oxidative stress. This may be associated with Akt/NF-κB signaling. These results provide valuable evidence to support the use of A. cinnamomea as a functional food and/or medicine.


Assuntos
Antrodia/química , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Transdução de Sinais/efeitos dos fármacos , Alanina Transaminase/sangue , Álcoois/toxicidade , Animais , Antioxidantes/metabolismo , Antrodia/metabolismo , Aspartato Aminotransferases/sangue , Caspase 3/metabolismo , Caspase 8/metabolismo , Caspase 9/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Citocinas/sangue , Citocinas/metabolismo , Modelos Animais de Doenças , Fígado/metabolismo , Fígado/patologia , Camundongos , NF-kappa B/metabolismo , Extratos Vegetais/química , Substâncias Protetoras/química , Proteínas Proto-Oncogênicas c-akt/metabolismo , Espécies Reativas de Oxigênio/metabolismo
8.
Int J Mol Sci ; 17(11)2016 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-27809277

RESUMO

Hericium erinaceus, an edible and medicinal mushroom, displays various pharmacological activities in the prevention of dementia in conditions such as Parkinson's and Alzheimer's disease. The present study explored the neuroprotective effects of H. erinaceus mycelium polysaccharide-enriched aqueous extract (HE) on an l-glutamic acid (l-Glu)-induced differentiated PC12 (DPC12) cellular apoptosis model and an AlCl3 combined with d-galactose-induced Alzheimer's disease mouse model. The data revealed that HE successfully induced PC12 cell differentiation. A 3 h HE incubation at doses of 50 and 100 µg/mL before 25 mM of l-Glu effectively reversed the reduction of cell viability and the enhancement of the nuclear apoptosis rate in DPC12 cells. Compared with l-Glu-damaged cells, in PC12 cells, HE suppressed intracellular reactive oxygen species accumulation, blocked Ca2+ overload and prevented mitochondrial membrane potential (MMP) depolarization. In the Alzheimer's disease mouse model, HE administration enhanced the horizontal and vertical movements in the autonomic activity test, improved the endurance time in the rotarod test, and decreased the escape latency time in the water maze test. It also improved the central cholinergic system function in the Alzheimer's mice, demonstrated by the fact that it dose-dependently enhanced the acetylcholine (Ach) and choline acetyltransferase (ChAT) concentrations in both the serum and the hypothalamus. Our findings provide experimental evidence that HE may provide neuroprotective candidates for treating or preventing neurodegenerative diseases.


Assuntos
Doença de Alzheimer/fisiopatologia , Basidiomycota/química , Diferenciação Celular/efeitos dos fármacos , Ácido Glutâmico/farmacologia , Fármacos Neuroprotetores/farmacologia , Acetilcolina/sangue , Acetilcolina/metabolismo , Cloreto de Alumínio , Compostos de Alumínio , Doença de Alzheimer/sangue , Doença de Alzheimer/induzido quimicamente , Animais , Apoptose/efeitos dos fármacos , Western Blotting , Cálcio/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Cloretos , Colina O-Acetiltransferase/sangue , Colina O-Acetiltransferase/metabolismo , Feminino , Galactose , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Aprendizagem em Labirinto/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Atividade Motora/efeitos dos fármacos , Micélio/química , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fármacos Neuroprotetores/isolamento & purificação , Células PC12 , Ratos , Espécies Reativas de Oxigênio/metabolismo
9.
J Diabetes Res ; 2016: 4368380, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27034961

RESUMO

Paecilomyces hepiali is a fungus widely used in Asian countries for various potential pharmacological activities. The present study aims to evaluate the antidiabetic and antinephritic effects of the Paecilomyces hepiali mycelium water extract (PHC) in diabetic rat, which is established by eight-week high-fat diet administration followed by one-week tail intravenous injection of 25 mg/kg streptozotocin (STZ). After four-week 0.12 g/kg metformin and PHC at doses of 0.08, 0.4, and 2.0 g/kg treatment, an increment of body weight, a decrement of plasma glucose, low levels of total cholesterol, and low density lipoprotein cholesterol in diabetic rats were observed. PHC promotes glucose metabolism by enhancing insulin, pyruvate kinase activity, and increasing the synthesis of glycogen. PHC normalized the disturbed levels of superoxide dismutase, methane dicarboxylic aldehyde, and glutathione peroxidase in kidney. The inhibitory effects on the levels of interleukin-2, interleukin-6, interleukin-10, and tumor necrosis factor-α in serum and kidney revealed the protection of PHC against diabetic nephropathy. Compared with nontreated diabetic rats, four-week PHC treatment resulted in a decrement on nuclear factor kappa B expression in kidney. These results show that Paecilomyces hepiali possesses antidiabetic and antinephritic effects which are related to the modulation of nuclear factor kappa B activity.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Nefropatias Diabéticas/prevenção & controle , Hipoglicemiantes/farmacologia , Solventes/química , Água/química , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Antioxidantes/química , Antioxidantes/isolamento & purificação , Biomarcadores/sangue , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/etiologia , Hipoglicemiantes/química , Hipoglicemiantes/isolamento & purificação , Mediadores da Inflamação/metabolismo , Rim/efeitos dos fármacos , Rim/metabolismo , Lipídeos/sangue , Masculino , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Paecilomyces , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos
10.
Chin J Nat Med ; 11(3): 296-301, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23725845

RESUMO

AIM: To synthesize three novel esterified-derivatives of mangiferin and evaluate their hypoglycemic activities. METHODS: Acetic, propionic, and butyric anhydride were reacted with mangiferin, respectively. The hypoglycemic activity of the derivatives was evaluated using a hyperglycemic mouse model induced by streptozotocin (STZ), and the islet cells were checked by biopsy inspection. RESULTS: 7, 2', 3', 4', 6'-penta-acetyl-mangiferin (PAM), 3, 6, 7, 2', 3', 4', 6'-hepta-propionyl-mangiferin (HPM) and 3, 6, 7, 2', 3', 4'-hexa-butyryl-mangiferin (HBM) were synthesized and their structures were identified by MS,(1)H, (13)C NMR, and 2D NMR. These three compounds were reported for the first time. PAM group (0.5, 0.25 mmol·kg(-1)), HPM group (0.5, 0.25 mmol·kg(-1)), and HBM group (0.5, 0.25, 0.125 mmol·kg(-1)) mice showed strong hypoglycemic activity (P < 0.01); mangiferin group (1, 0.5 mmol·kg(-1)), PAM group (0.125 mmol·kg(-1)) and HPM group (0.125 mmol·kg(-1)) showed marginal hypoglycemic activity (P < 0.05); mangiferin group (0.25 mmol·kg(-1)) had the potential for a hypoglycemic effect, although it did not demonstrate that statistically. In histological examination, the islet cells of the PAM, HPM, and HBM groups could recover from the STZ damage; islet cells of the mangiferin group could recover also, but less than the esterified-derivative groups. CONCLUSION: Derivatives could repair the damaged islet cells, and had higher lipid-solubility and stronger hypoglycemic activity than mangiferin itself. There existed a structure activity effect, and a solubility effect relationship: the larger esterification moieties, or the higher lipid-solubility, the stronger the hypoglycemic activity (no ester → acetyl → propionyl → butyryl). Esterified derivatives of mangiferin are potential compounds for new anti-diabetes drugs.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/síntese química , Xantonas/administração & dosagem , Xantonas/síntese química , Animais , Esterificação , Humanos , Hipoglicemiantes/química , Ilhotas Pancreáticas/efeitos dos fármacos , Masculino , Camundongos , Estrutura Molecular , Xantonas/química
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