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1.
Mol Cancer ; 18(1): 69, 2019 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-30927928

RESUMO

Drug resistance is of great concern in cancer treatment because most effective drugs are limited by the development of resistance following some periods of therapeutic administration. The tumor microenvironment (TME), which includes various types of cells and extracellular components, mediates tumor progression and affects treatment efficacy. TME-mediated drug resistance is associated with tumor cells and their pericellular matrix. Noninherent-adaptive drug resistance refers to a non-cell-autonomous mechanism in which the resistance lies in the treatment process rather than genetic or epigenetic changes, and this mechanism is closely related to the TME. A new concept is therefore proposed in which tumor cell resistance to targeted therapy may be due to non-cell-autonomous mechanisms. However, knowledge of non-cell-autonomous mechanisms of resistance to different treatments is not comprehensive. In this review, we outlined TME factors and molecular events involved in the regulation of non-cell-autonomous resistance of cancer, summarized how the TME contributes to non-cell-autonomous drug resistance in different types of antineoplastic treatment, and discussed the novel strategies to investigate and overcome the non-cell-autonomous mechanism of cancer non-cell-autonomous resistance.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Neoplasias/metabolismo , Microambiente Tumoral , Animais , Antineoplásicos/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Epigênese Genética , Humanos , Concentração de Íons de Hidrogênio , Neoplasias/tratamento farmacológico , Neoplasias/genética , Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacos
2.
Oxid Med Cell Longev ; 2018: 9140896, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30050662

RESUMO

Sarcodon imbricatus (SI), a precious edible fungus, contains 35.22% of total sugar, 18.33% of total protein, 24 types of fatty acid, 16 types of amino acid, and 8 types of minerals. Encouragingly, it is rich in potential antioxidants such as total polyphenols (0.41%), total sterols (3.16%), and vitamins (0.44%). In the present study, the antifatigue properties of SI and its potential mechanisms of action were explored by the experiments on acute excise-treated mice and chronic fatigue syndrome (CFS) mice. SI (0.25, 0.5, and 1 g/kg) significantly enhanced exercise tolerance in the weight-loaded forced swimming test (FST) and rota-rod test (RRT) and reduced the immobility in the tail suspension test on CFS mice. SI markedly increased the levels of glycogen in the liver and adenosine triphosphate (ATP) in the liver and muscle and decreased the lactic acid (LD) and blood urea nitrogen (BUN) content in both acute swimming-treated mice and CFS mice. SI improved the endogenous cellular antioxidant enzyme contents in the two mouse models by improving the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and reducing reactive oxygen species (ROS) and malondialdehyde (MDA) levels in serum, liver, and muscle, respectively. In CFS mice, the enhanced expression levels of nuclear factor erythroid-2-related factor 2 (Nrf2), SOD1, SOD2, heme oxygenase-1 (HO-1), and catalase (CAT) in the liver were observed after a 32-day SI administration. Our data indicated that SI possessed antifatigue activity, which may be related to its ability to normalize energy metabolism and Nrf2-mediated oxidative stress. Consequently, SI can be expected to serve as a novel natural antifatigue supplement in health foods.


Assuntos
Basidiomycota/fisiologia , Síndrome de Fadiga Crônica/dietoterapia , Síndrome de Fadiga Crônica/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/fisiologia , Animais , Western Blotting , Catalase/metabolismo , Suplementos Nutricionais , Glutationa Peroxidase/metabolismo , Heme Oxigenase-1/metabolismo , Masculino , Malondialdeído/metabolismo , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo
3.
Int J Biol Macromol ; 116: 8-15, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29730008

RESUMO

The objective of this study was to determine the ameliorative effects of Antrodia cinnamomea polysaccharide (ACPS) against cyclophosphamide (CTX)-induced immunosuppression in BALB/c mice. Four weeks of oral ACPS treatment successfully improved bodyweight and organ indexes and enhanced the function of T cells and the cytotoxicity of natural killer cells. CTX administration has been shown to notably decrease immunoglobulin A, G and M, interleukin 2, 6 and 12, and interferon α and γ levels in serum and in the spleen, and ACPS abolished these effects. Furthermore, ACPS effectively increased the total antioxidant capacity by stimulating superoxidase dismutase, catalase, and glutathione peroxidase activity in serum and in the spleen and by inhibiting the increases in reactive oxygen species and malondialdehyde levels. Notably, ACPS induced the activation of erythroid 2-related factor 2 (Nrf2) related to down-regulating Kelch-like ECH-associated protein 1 expression, which leads to enhanced levels of downstream antioxidative enzymes, including heme oxygenase-1 (HO-1), superoxide dismutase 2, and catalase in the spleen and thymus. Therefore, the protective effects of ACPS on CTX-induced immunosuppression in mice may be the result of a reduction in oxidative stress and involved in the Nrf2/HO-1 pathway. Our study suggests that ACPS has potential for development as an effective anti-immunosuppressive agent.


Assuntos
Ciclofosfamida/farmacologia , Heme Oxigenase-1/metabolismo , Imunossupressores/farmacologia , Proteínas de Membrana/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Polissacarídeos/farmacologia , Animais , Antioxidantes/metabolismo , Antrodia , Catalase/metabolismo , Glutationa Peroxidase/metabolismo , Imunossupressão/métodos , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Malondialdeído/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Baço/efeitos dos fármacos , Baço/metabolismo , Superóxido Dismutase/metabolismo
4.
Exp Ther Med ; 15(4): 3633-3638, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29545893

RESUMO

Gloeostereum incarnatum, a precious edible mushroom, displays anti-bacterial and anti-inflammatory activities; however, its immunomodulatory effect has not been studied yet. The present study aimed to investigate whether polysaccharide compositions of G. incarnatum polysaccharides (GIPS) possess immunomodulatory and immuno-enhancing effects in a Cyclophosphamide monohydrate (CTX)-induced BALB/c mice model. The 28-day GIPS administration at doses of 0.1, 0.3 and 0.9 g/kg remarkably reversed the bodyweight loss, increased the thymic index and promoted T lymphocyte proliferation in CTX-induced immunosuppressed mice. GIPS significantly raised the serum levels of immunoglobulin (Ig)A and IgG, promoted the production of interleukins (ILs), including IL-2, IL-3 and IL-6, interferons, including interferon (IFN)-α and IFN-γ, and monocyte chemotactic protein 1 in the spleen, which resulted in accelerating recovery of immunosuppression. Finally, GIPS showed anti-oxidative effects indicated by the increased superoxide dismutase levels in the serum and spleen, and the reduced level of reactive oxygen species in the spleen. The results of the current study demonstrated that GIPS positively adjusts the immune system, which may serve as a potential immunostimulatory agent.

5.
Braz J Med Biol Res ; 51(4): e7124, 2018 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-29513798

RESUMO

Marasmius androsaceus is a medicinal fungus mainly used to treat various forms of pain in China. This study investigated the analgesic effects of an ethanol extract of M. androsaceus (MAE) and its potential molecular mechanisms. Oral administration of MAE (50, 200, and 1000 mg/kg) had significant analgesic effects in an acid-induced writhing test, a formalin test, and a hot-plate test, with effectiveness similar to tramadol (the positive control drug). The autonomic activity test showed that MAE had no harmful effects on the central nervous system in mice. MAE resulted in significantly enhanced levels of noradrenalin and 5-hydroxytryptamine in serum but suppressed both of these neurotransmitters in the hypothalamus after 30 s of hot-plate stimulation. Co-administration with nimodipine (10 mg/kg; a Ca2+ channel blocker) strongly enhanced the analgesic effect in the hot-plate test compared to MAE alone. Moreover, MAE down-regulated the expression of calmodulin-dependent protein kinase II (CaMKII) in the hypothalamus after a 30-s thermal stimulus. These results suggested that the analgesic ability of MAE is related to the regulation of metabolism by monoamine neurotransmitters and Ca2+/CaMKII-mediated signaling, which can potentially aid the development of peripheral neuropathic pain treatments obtained from M. androsaceus.


Assuntos
Analgésicos/farmacologia , Marasmius/química , Dor/tratamento farmacológico , Extratos Vegetais/farmacologia , Tramadol/farmacologia , Animais , Modelos Animais de Doenças , Masculino , Camundongos , Medição da Dor/efeitos dos fármacos
6.
Mol Med Rep ; 17(3): 3599-3606, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29257339

RESUMO

Alzheimer's disease (AD) affects people worldwide and is caused by chronic and progressive damage to the central nervous system. Lycium barbarum (LB), a renowned functional food and medicinal plant in Southeast Asia, may possess protective effects against nerve injury. The present study aimed to investigate the neuroprotective effects of LB water extract in a differentiated (D)PC12 cellular apoptosis model induced by L­glutamic acid (L­Glu), and a mouse model of AD, induced by the combination of AlCl3 and D­galactose. LB markedly increased DPC12 cell survival against L­Glu induced damage by increasing cell viability, reducing the apoptosis rate and G1 phase arrest, suppressing intracellular reactive oxygen species accumulation, blocking Ca2+ overload and preventing mitochondrial membrane potential depolarization. LB additionally normalized the expression levels of apoptosis regulator Bcl­2, apoptosis regulator BAX, and cleaved caspase­3, ­8 and ­9 in L­Glu exposed cells. In the AD mouse model, LB increased the amount of horizontal and vertical movement in the autonomic activity test, improved endurance time in the rotarod test and decreased escape latency time in the Morris water maze test. Additionally, the levels of acetylcholine and choline acetyltransferase were significantly increased in the serum and hypothalamus in the LB­treated AD mice. These data suggested that LB may exert neuroprotective effects and may aid in preventing neurodegenerative disease.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Lycium/química , Fármacos Neuroprotetores/uso terapêutico , Extratos Vegetais/química , Acetilcolina/metabolismo , Doença de Alzheimer/patologia , Animais , Apoptose/efeitos dos fármacos , Cálcio/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Colina O-Acetiltransferase/sangue , Colina O-Acetiltransferase/metabolismo , Modelos Animais de Doenças , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Hipotálamo/metabolismo , Lycium/metabolismo , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/farmacologia , Células PC12 , Ratos , Espécies Reativas de Oxigênio/metabolismo
7.
Braz. j. med. biol. res ; 51(4): e7124, 2018. graf
Artigo em Inglês | LILACS | ID: biblio-889061

RESUMO

Marasmius androsaceus is a medicinal fungus mainly used to treat various forms of pain in China. This study investigated the analgesic effects of an ethanol extract of M. androsaceus (MAE) and its potential molecular mechanisms. Oral administration of MAE (50, 200, and 1000 mg/kg) had significant analgesic effects in an acid-induced writhing test, a formalin test, and a hot-plate test, with effectiveness similar to tramadol (the positive control drug). The autonomic activity test showed that MAE had no harmful effects on the central nervous system in mice. MAE resulted in significantly enhanced levels of noradrenalin and 5-hydroxytryptamine in serum but suppressed both of these neurotransmitters in the hypothalamus after 30 s of hot-plate stimulation. Co-administration with nimodipine (10 mg/kg; a Ca2+ channel blocker) strongly enhanced the analgesic effect in the hot-plate test compared to MAE alone. Moreover, MAE down-regulated the expression of calmodulin-dependent protein kinase II (CaMKII) in the hypothalamus after a 30-s thermal stimulus. These results suggested that the analgesic ability of MAE is related to the regulation of metabolism by monoamine neurotransmitters and Ca2+/CaMKII-mediated signaling, which can potentially aid the development of peripheral neuropathic pain treatments obtained from M. androsaceus.


Assuntos
Animais , Masculino , Camundongos , Dor/tratamento farmacológico , Tramadol/farmacologia , Extratos Vegetais/farmacologia , Marasmius/química , Analgésicos/farmacologia , Medição da Dor/efeitos dos fármacos , Modelos Animais de Doenças
8.
Biomed Res Int ; 2017: 5852076, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28929115

RESUMO

This study was performed to investigate the therapeutic effects and possible mechanisms of sunflower (Helianthus annuus) head extract (SHE) on gout. First, the components of sunflower head powder and SHE were analyzed systematically. SHE, especially SHEB (extracted with 20% ethanol and 80% double-distilled water), strongly suppressed the swelling of the ankles in rats with acute gout induced by monosodium urate (MSU) crystals and reduced the levels of uric acid and xanthine oxidase (XO) in mice with hyperuricemia induced by oteracil potassium and yeast extract powder. Hematoxylin and eosin staining indicated that SHEB reduced inflammation cells and increased the joint space in the ankle compared with the control rats with MSU-induced gout. In the rats with acute gout, among 13 detected inflammatory cytokines, SHEB significantly enhanced the serum levels of interleukin-10 and the monocyte chemoattractant protein 1α. In the mice with hyperuricemia, SHEB reduced the levels of glutathione peroxidase, superoxide dismutase, malondialdehyde, and nitrogen monoxide in liver tissues. The potential therapeutic effects of SHE on gout are probably due to the production of anti-inflammatory cytokines and the suppression of XO activity via the modulation of oxidative stress status.


Assuntos
Artrite Gotosa/tratamento farmacológico , Helianthus/química , Hiperuricemia/tratamento farmacológico , Extratos Vegetais/farmacologia , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Artrite Gotosa/induzido quimicamente , Modelos Animais de Doenças , Etanol , Flores/química , Humanos , Hiperuricemia/induzido quimicamente , Inflamação , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Estresse Oxidativo , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Ratos , Ratos Sprague-Dawley
9.
Mol Med Rep ; 16(4): 5043-5049, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28765907

RESUMO

Marasmius androsaceus (M. androsaceus), a medicinal fungus, has various pharmacological activities including antidepression. The present study investigated the effects of exopolysaccharides obtained during M. androsaceus submerged fermentation in a chronic unpredictable mild stress (CUMS)­induced depression rat model. Similar to fluoxetine (positive drug), 4­week administration of M. androsaceus exopolysaccharides (MEPS) at doses of 6, 30 and 150 mg/kg strongly enhanced bodyweight gain and sucrose consumption, and reduced the immobility time in forced swimming test and tail suspension test in CUMS rats. MEPS resulted in significant enhancement on the levels of noradrenalin, dopamine, 5­hydroxytryptamine (5­HT), and 5­hydroxyindoleacetic acid in the serum and hypothalamus of CUMS rats, as detected by ELISA. Western blotting results revealed that MEPS upregulated the protein expression levels of tyrosine hydroxylase in the hypothalamus of CUMS rats. In conclusion, these results confirmed the antidepressant­like effects of MEPS, and suggested that the monoamine neurotransmitter system is involved in its antidepressive effects in a CUMS rat model. The present study provided evidence for the clinical application of MEPS as an effective agent against depression.


Assuntos
Antidepressivos/farmacologia , Depressão/etiologia , Depressão/psicologia , Polissacarídeos Fúngicos/farmacologia , Marasmius/química , Estresse Psicológico , Animais , Comportamento Animal/efeitos dos fármacos , Depressão/tratamento farmacológico , Modelos Animais de Doenças , Polissacarídeos Fúngicos/química , Regulação da Expressão Gênica/efeitos dos fármacos , Ratos , Tirosina 3-Mono-Oxigenase/genética , Tirosina 3-Mono-Oxigenase/metabolismo
10.
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
11.
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
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