Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 24
Filtrar
Mais filtros

Métodos Terapêuticos e Terapias MTCI
Base de dados
País/Região como assunto
Tipo de documento
Intervalo de ano de publicação
1.
Phytomedicine ; 119: 154955, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37572567

RESUMO

BACKGROUND: The Chinese herbal compound Xinmaikang (XMK) is effective in treating atherosclerosis (AS), although the associated mechanisms of action remain unclear. We hypothesize that XMK increases mitophagy via the PINK1/Parkin signaling pathway and decreases reactive oxygen species (ROS), thus treating AS. PURPOSE: To explore the above-mentioned mechanisms of action of XMK in AS. MATERIALS AND METHODS: Ultra-performance liquid chromatography assay was performed to clarify the composition of XMK. A 16-week high-fat diet was fed to APOE-/- mice to form an AS model. Next, mice were given XMK(0.95 g/kg/d, 1.99 g/kg/d, 3.98 g/kg/d, i.g.) or Atorvastatin(3 mg/kg/d, i.g.) or Rapamycin(4 mg/kg/d, i.p.) or XMK with Mdivi-1(40 mg/kg/d, i.p.) or an equivalent amount of normal saline for 4 weeks. Then mice were examined for AS plaque area, lesion area, collagen fiber, pro-inflammatory cytokines, lipid level, ROS level and mitophagy level. We assessed AS using Oil Red O, hematoxylin and eosin, and Sirius red staining, as well as ROS measurements. Mitophagy was evaluated by transmission electron microscopy, real-time quantitative polymerase chain reaction (RT-qPCR), Western blot, single-cell Western blot, and immunofluorescence staining. In vitro, by oxidizing low-density lipoprotein, formation of RAW264.7 macrophage-derived foam cells induced. we induced foam cell formation in RAW264.7 macrophages. Then cells were incubated with XMK-medicated serum with or without Mdivi-1. We examined foam cell formation, ROS level, mitophagy level in cells. Finally, we knocked down the PINK1, and examined foam cell formation and PINK1/Parkin level in RAW264.7 macrophages. RESULTS: UPLC analysis revealed 102 main ingredients in XMK. In vivo, XMK at medium-dose or high-dose significantly reduced AS plaques, lipids, pro-inflammatory cytokines, and ROS and increased mitophagy. In further study, Single-cell western blot showed that mitophagy level in macrophages sorted from AS mice was lower than the control mice. While XMK improved mitophagy level. In vitro, XMK reduced foam cell formation and ROS and increased mitophagy. When PINK1 was knocked down, XMK's effects on foam cell formation and PINK1/Parkin pathway activation were reduced. CONCLUSION: The study shows that XMK is effective against AS by mediating macrophage mitophagy via the PINK1/Parkin signaling pathway. For the treatment of AS and drug discovery, it provides an experimental basis and target.


Assuntos
Aterosclerose , Placa Aterosclerótica , Camundongos , Animais , Mitofagia , Proteínas Quinases/metabolismo , Mitocôndrias , Espécies Reativas de Oxigênio/metabolismo , Aterosclerose/tratamento farmacológico , Aterosclerose/metabolismo , Placa Aterosclerótica/metabolismo , Transdução de Sinais , Ubiquitina-Proteína Ligases/metabolismo , Citocinas/metabolismo
2.
Artigo em Inglês | MEDLINE | ID: mdl-37011544

RESUMO

Xiexin Tang (XXT) is a classic prescription for treating diabetes in clinical practices for thousands of years in China, which has been also proved by a large number of modern pharmacological studies. However, due to its complex composition, the bioactive ingredients of XXT is still unclear. In present researches, spectrum-effect relationship analysis is widely used to explore the material basis of traditional medical herbs, so this method was adopted in this study. Firstly, the extract of XXT was separated and enriched into 5 fractions by macroporous adsorption resin. Then, UPLC-Q-TOF/MS method was used for qualitative identification of components in each eluting part, and efficacy of each fraction was assessed by the T2DM rat model. Based on grey relational analysis and pearson bivariate correlation analysis, it was found that the components such as berberine, gallic acid, catechin, epicatechin, acteoside, berberastine and 1-O-galloyl-ß-D-glucose might be the main effective basis of XXT to improve T2DM.


Assuntos
Diabetes Mellitus Tipo 2 , Medicamentos de Ervas Chinesas , Ratos , Animais , Diabetes Mellitus Tipo 2/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos de Ervas Chinesas/farmacologia , China , Cromatografia Líquida de Alta Pressão/métodos
3.
J Ginseng Res ; 46(6): 790-800, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36312732

RESUMO

Background: Panax ginseng Meyer is one of the most valuable medicinal plants which is enriched in anti-microbe secondary metabolites and widely used in traditional medicine. Botrytis cinerea is a necrotrophic fungus that causes gray mold disease in a broad range of hosts. B. cinerea could overcome the ginseng defense and cause serious leaf and root diseases with unknown mechanism. Methods: We conducted simultaneous transcriptomic and metabolomic analysis of the host to investigate the defense response of ginseng affected by B. cinerea. The gene deletion and replacement were then performed to study the pathogenic gene in B. cinerea during ginseng - fungi interaction. Results: Upon B. cinerea infection, ginseng defense responses were switched from the activation to repression, thus the expression of many defense genes decreased and the biosynthesis of antifungal metabolites were reduced. Particularly, ginseng metabolites like kaempferol, quercetin and luteolin which could inhibit fungi growth were decreased after B. cinerea infection. B. cinerea quercetin dioxygenase (Qdo) involved in catalyzing flavonoids degradation and △BcQdo mutants showed increased substrates accumulation and reduced disease development. Conclusion: This work indicates the flavonoids play a role in ginseng defense and BcQdo involves in B. cinerea virulence towards the P. ginseng. B. cinerea promotes disease development in ginseng by suppressing of defense related genes expression and reduction of antifungal metabolites biosynthesis.

4.
Nat Prod Res ; 36(4): 1009-1013, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33111556

RESUMO

The main targets of this work were to evaluate the antioxidative properties of flavonoids in Jerusalem artichoke (Helianthus tuberosus L.) leaves and quantitatively determine their contents. 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2-azino-bis (3-ethylbenzothiazoline)-6-sulphonic acid (ABTS) and hydroxyl free radicals scavenging assays were performed to determine their antioxidative capacities. The validated ultra high-performance liquid chromatography-quadrupole-time-of-flight/mass spectrometry (UHPLC-Q-TOF/MS) method was subsequently applied to the quality evaluation of eleven batches of Jerusalem artichoke leaves grown in different habitats at different harvesting time. Results indicated that two flavonoids isolated from Jerusalem artichoke leaves showed stronger antioxidant effects than the positive control, butylated hydroxytoluene (BHT). And the total contents of the two flavonoids in the Jerusalem artichoke leaves of flowering stage from Dalian, Liaoning Province, China, were the highest, their contents varied significantly depending on region and harvesting time. This study indicated that the leaves of Jerusalem artichoke possessed excellent antioxidant properties, highlighting their candidacy as natural antioxidants, which could be utilized therapeutically to protect the body from diseases caused by oxidative stress.


Assuntos
Helianthus , Antioxidantes/química , Flavonoides/química , Helianthus/química , Extratos Vegetais/química , Folhas de Planta/química
5.
Small ; 17(46): e2101780, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34611987

RESUMO

Although chemotherapy and photothermal therapy are widely used to combat cancer, their efficacy is often limited by multidrug resistance. Small interfering RNAs (siRNAs) have ability to suppress the expression of target genes, which has been extensively employed for combating the multidrug resistance to chemodrugs and hyperthermia in cancer therapy. However, efficient delivery of siRNAs along with chemo-photothermal agents in vivo is still an enormous challenge. Herein, octahedral DNA origami frameworks (OctDOFs) are constructed as a nanovehicle for precise organization and orchestrated delivery of siRNAs, chemodrugs (doxorubicin, Dox), and photothermal agents (gold nanorods, AuNRs) in combinatorial treatment of cancer. The inner cavity of the rigid OctDOFs structure is able to shield the encapsulated siRNAs during transportation by sterically hindering RNase degradation and protein binding, thus achieving effective downregulation of connective tissue growth factor (CTGF) and heat shock protein 72 (HSP72) for dual sensitization of cancer cells to chemodrugs and hyperthermia. By amplifying chemo-photothermal therapeutic potency with siRNAs, the proposed OctDOFs exhibited superior cytotoxicity and tumor inhibition efficacy in vitro and in vivo. This nanovehicle creates a promising siRNA delivery platform for precise medication and combination therapy.


Assuntos
Hipertermia Induzida , Fototerapia , Linhagem Celular Tumoral , DNA , Doxorrubicina , Terapia Fototérmica , RNA Interferente Pequeno
6.
Oxid Med Cell Longev ; 2020: 6059058, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32850001

RESUMO

This study assessed the molecular mechanism of selenium (Se) protecting against kidney injury induced by zearalenone (ZEA) in mice. The experimental mice were divided into 4 groups including the control group, the Se group, the ZEA group, and the Se+ZEA group; ZEA and Se were administered orally for 28 days. The changes in renal biochemical index (BUN, UA, and CRE), biochemical change of kidney damage such as BUN, UA, and CRE, and oxidative damage such as MDA, T-SOD, and GSH-Px were investigated. Pathological sections and TUNEL staining were used to analyze renal pathological changes and cell apoptosis. qRT-PCR and Western blot were employed to detect the expression of genes and proteins which were related with endoplasmic reticulum stress. The results showed that ZEA increased the concentration of BUN, UA, and CRE and the content of MDA and decreased the activities of T-SOD and GSH-Px in the mouse kidneys. However, Se reversed above changes of the biochemical and antioxidant indexes of renal injury. Moreover, the results also showed that ZEA can increase the expression of Bax, caspase-12, caspase-3, Bip, CHOP, JNK protein, and mRNA and decrease the expression of Bcl-2 protein and mRNA. But Se reversed these proteins and genes related to endoplasmic reticulum stress and apoptosis. It can be concluded that Se protected against the kidney damage induced by ZEA. Se may protect the kidney from ZEA-induced apoptosis and oxidative stress by inhibiting ERS.


Assuntos
Apoptose/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Rim/patologia , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Selênio/farmacologia , Zearalenona/toxicidade , Animais , Antioxidantes/farmacologia , Peso Corporal/efeitos dos fármacos , Estresse do Retículo Endoplasmático/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Rim/efeitos dos fármacos , Rim/metabolismo , Masculino , Camundongos , Tamanho do Órgão/efeitos dos fármacos , Especificidade de Órgãos/efeitos dos fármacos , Oxirredução , Estresse Oxidativo/genética , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética
7.
Brain Res Bull ; 162: 132-140, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32592805

RESUMO

Cerebral hypoperfusion is a common feature of cerebral small vascular disease (CSVD), which has been considered as one of the causes of cognitive decline in recent years. Epimedium flavonoids (EF) are the main ingredients extracted from Epimedium. The purpose of this study was to investigate the effects of EF on cognitive impairment, and the underlying mechanisms in rats with permanent occlusion of the bilateral common carotid artery (2VO). EF (50, 100, and 200 mg/kg) was intragastrically administered for 12 weeks starting 2 weeks after 2VO surgery. The results showed that EF treatment improved learning and memory impairment in 2VO rats evaluated by novel object recognition and Y-maze tests. NeuN immunohistochemical staining indicated that EF alleviated neuronal loss in the hippocampus and cerebral cortex of 2VO rats. MAP-2 immunofluorescence staining and western blotting showed that EF protected neuronal dendrites and increased the expression of cytoskeleton proteins MAP-2 and NF200 in the hippocampus of 2VO rats. Moreover, EF protected the synapse ultrastructure detected by transmission electron microscopy, and increased the expression of synaptic plasticity-related proteins, including synaptophysin, synaptotagmin-I, synapsin I, PSD-95, p-NMDA2B, and p-CaMKII-α in the hippocampus of 2VO rats. In addition, EF increased the expression of neuregulin-1 (NRG-1), p-ErbB4, brain-derived neurotrophic factor (BDNF), p-Fyn, PI3K, p-Akt, and p-CREB in the hippocampus of 2VO rats. These results suggest that EF may protect neurons and synapses by activating the NRG1/ErbB4, BDNF/Fyn, and P13 K/Akt/CREB pathways in the hippocampus and cerebral cortex, thus improving cognitive impairment induced by chronic cerebral hypoperfusion. EF may be a potential candidate drug for chronic cerebral hypoperfusion and CSVD therapy.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/metabolismo , Doenças de Pequenos Vasos Cerebrais/metabolismo , Epimedium , Flavonoides/uso terapêutico , Neuregulina-1/metabolismo , Proteínas Proto-Oncogênicas c-fyn/metabolismo , Receptor ErbB-4/metabolismo , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Doenças de Pequenos Vasos Cerebrais/tratamento farmacológico , Circulação Cerebrovascular/efeitos dos fármacos , Circulação Cerebrovascular/fisiologia , Relação Dose-Resposta a Droga , Flavonoides/farmacologia , Masculino , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Sinapses/efeitos dos fármacos , Sinapses/metabolismo
8.
Basic Clin Pharmacol Toxicol ; 127(5): 380-388, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32511877

RESUMO

Piper laetispicum C. DC is one of the Chinese herbal medicines used for alleviating depressive disorders. G11-5 [3-(3, 4-methylenedioxy-5-trifluoromethyl phenyl)-2E-propenoic acid isobutyl amide] is synthesized based on the chemical structure of an active integrant of Piper laetispicum C. DC. The present study assessed the antidepressant effect of G11-5 and investigated the underlying mechanism with learned helplessness (LH) and social defeat stress (SDS) mice model of depression. In the LH model, mice were exposed to 60 inescapable electric shocks once a day for three consecutive days followed by 2-week drug administration and helpless behaviour assessment. In the SDS model, mice were subjected to repeated social defeat by an aggressive CD-1 mouse once a day for consecutive 10 days. Following oral administration for 2 weeks, the mice were subjected to a series of behavioural tests including social interaction test. G11-5 significantly decreased the number of escape failures induced by LH paradigm, meanwhile increased the social interaction ratio and shortened the immobility time in forced swimming test for the SDS-exposed mice, suggesting remarkable antidepressant effect. Moreover, G11-5 ameliorated the changes in mitophagy-related proteins induced by two stress exposures and restored retrograde axonal transport and neurotransmitter release. Our findings suggested that G11-5 exhibited an obvious antidepressant through TSPO-mediated mitophagy pathway.


Assuntos
Amidas/farmacologia , Antidepressivos/farmacologia , Benzodioxóis/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Receptores de GABA/metabolismo , Estresse Psicológico/tratamento farmacológico , Animais , Depressão/tratamento farmacológico , Depressão/metabolismo , Depressão/patologia , Depressão/psicologia , Teste de Labirinto em Cruz Elevado , Desamparo Aprendido , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Mitofagia/efeitos dos fármacos , Piper/química , Distribuição Aleatória , Transdução de Sinais/efeitos dos fármacos , Derrota Social , Estresse Psicológico/metabolismo , Estresse Psicológico/patologia , Estresse Psicológico/psicologia , Natação
9.
Brain Res ; 1743: 146902, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32446949

RESUMO

Chronic cerebral hypoperfusion is a common cause of cerebral small vascular disease (CSVD). White matter (WM) lesions are the typical pathological manifestation of CSVD and contribute to cognitive decline. Epimedium flavonoids (EF) are the main component in Epimedium brevicornu Maxim., which is commonly used in traditional Chinese medicine. The purpose of this study was to investigate the effects of EF on cognitive impairment and the underlying mechanisms in a CSVD rat model induced with chronic cerebral hypoperfusion. The model was established by permanent bilateral common carotid artery occlusion (2VO) in rats. EF (50, 100, and 200 mg/kg) was intragastrically administered once a day for 12 weeks starting 2 weeks after 2VO surgery. The learning and memory capacity of the rats were measured using the Morris water maze and step-through tests. WM lesions were observed by MRI-diffusion tensor imaging, transmission electron microscopy, and LFB staining. Oligodendrocytes were detected by immunohistochemistry. Western blotting assay was used to determine the level of protein expression. The results showed that EF significantly improved learning and memory impairment, alleviated WM nerve fiber injuries and demyelination, and increased the number of mature oligodendrocytes in the corpus callosum, subcortical WM, and periventricular WM in 2VO rats. Mechanistically, EF reduced the expression of Lingo-1 and ROCK2 and increased the levels of phosphorylated (p-) Fyn, brain-derived neurotrophic factor (BDNF), TrkB, neuregulin-1 (NRG-1), p-ErbB4, PI3K p85 and p110α, p-Akt, and p-CREB in the corpus callosum of 2VO rats. These results suggest that EF may improve cognitive impairment and WM lesions induced by chronic cerebral hypoperfusion through inhibiting the Lingo-1/Fyn/ROCK pathway and activating the BDNF/TrkB, NRG-1/ErbB4, and the downstream PI3K/Akt/CREB pathways in WM. Thus, EF can be used as a potential neuroprotective agent in CSVD therapy.


Assuntos
Encéfalo/efeitos dos fármacos , Doenças de Pequenos Vasos Cerebrais/patologia , Disfunção Cognitiva/etiologia , Medicamentos de Ervas Chinesas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Substância Branca/efeitos dos fármacos , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Doenças de Pequenos Vasos Cerebrais/complicações , Doenças de Pequenos Vasos Cerebrais/metabolismo , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/patologia , Epimedium , Flavonoides/farmacologia , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Proteínas de Membrana/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Neuregulina-1/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-fyn/metabolismo , Ratos , Ratos Sprague-Dawley , Substância Branca/patologia , Quinases Associadas a rho/metabolismo
10.
J Enzyme Inhib Med Chem ; 35(1): 235-244, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31760818

RESUMO

Cyclin-dependent kinase 2 (CDK2) is the family of Ser/Thr protein kinases that has emerged as a highly selective with low toxic cancer therapy target. A multistage virtual screening method combined by SVM, protein-ligand interaction fingerprints (PLIF) pharmacophore and docking was utilised for screening the CDK2 inhibitors. The evaluation of the validation set indicated that this method can be used to screen large chemical databases because it has a high hit-rate and enrichment factor (80.1% and 332.83 respectively). Six compounds were screened out from NCI, Enamine and Pubchem database. After molecular dynamics and binding free energy calculation, two compounds had great potential as novel CDK2 inhibitors and they also showed selective inhibition against CDK2 in the kinase activity assay.


Assuntos
Antineoplásicos/análise , Antineoplásicos/farmacologia , Quinase 2 Dependente de Ciclina/antagonistas & inibidores , Simulação de Acoplamento Molecular , Inibidores de Proteínas Quinases/análise , Inibidores de Proteínas Quinases/farmacologia , Máquina de Vetores de Suporte , Células A549 , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Quinase 2 Dependente de Ciclina/metabolismo , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Ensaios de Seleção de Medicamentos Antitumorais , Células HCT116 , Humanos , Estrutura Molecular , Inibidores de Proteínas Quinases/química , Relação Estrutura-Atividade
11.
Sci Rep ; 9(1): 8109, 2019 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-31147584

RESUMO

The flower of Trollius chinensis Bunge was widely used for the treatment of inflammation-related diseases in traditional Chinese medicine (TCM). In order to clarify the anti-inflammatory mechanism of this Chinese herbs, a comprehensive network pharmacology strategy that consists of three sequential modules (pharmacophore matching, enrichment analysis and molecular docking.) was carried out. As a result, Apoptosis signal-regulating kinase 1 (ASK1), Janus kinase 1 (JAK1), c-Jun N-terminal kinases (JNKs), transforming protein p21 (HRas) and mitogen-activated protein kinase 14 (p38α) that related to the anti-inflammatory effect were filtered out. In further molecular dynamics (MD) simulation, the conformation of CID21578038 and CID20055288 were found stable in the protein ASK1 and JNKs respectively. The current investigation revealed that two effective compounds in the flower of Trollius chinensis Bunge played a crucial role in the process of inflammation by targeting ASK1 and JNKs, the comprehensive strategy can serve as a universal method to guide in illuminating the mechanism of the prescription of traditional Chinese medicine by identifying the pathways or targets.


Assuntos
Flores/química , Regulação da Expressão Gênica/genética , Inflamação/tratamento farmacológico , Ranunculaceae/química , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Biologia Computacional , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Flavonoides/química , Flavonoides/farmacologia , Flores/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Inflamação/genética , Inflamação/patologia , Proteínas Quinases JNK Ativadas por Mitógeno/genética , Janus Quinase 1/genética , MAP Quinase Quinase Quinase 5/genética , Proteína Quinase 14 Ativada por Mitógeno/genética , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Ranunculaceae/genética , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética
12.
Food Funct ; 9(8): 4493-4499, 2018 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-30083671

RESUMO

The production of Pleurotus eryngii by selenium (Se) biofortification is an effective way to improve the demand for Se in humans. In order to investigate the Se bioaccessibility and speciation of Se-enriched P. eryngii during the growing stage, the Se distribution in biochemical fractions, and the molecular weight and the Se species of Se-containing compounds derived from in vitro simulated gastrointestinal fluids were analyzed by size exclusion and anion exchange-high performance liquid chromatography and inductively coupled plasma mass spectrometry. The results showed that albumin had the highest Se content among biochemical fractions, approximately 34.40% of total Se, followed by glutelin, globulin and gliadins. Selenomethionine that was proved to be the major Se species would increase with P. eryngii growing from 45.85% to 59.32%, while selenocysteine would decrease from 40.68% to 15.17% of total Se. In conclusion, selenocysteine would gradually convert to selenomethionine, and thus the bioaccessibility of Se was greater in mature P. eryngii than in younger mushrooms.


Assuntos
Extratos Vegetais/análise , Pleurotus/química , Pleurotus/crescimento & desenvolvimento , Selenocisteína/análise , Selenometionina/análise , Cromatografia Líquida de Alta Pressão , Extratos Vegetais/metabolismo , Pleurotus/metabolismo , Selênio , Selenocisteína/metabolismo , Selenometionina/metabolismo , Verduras/química , Verduras/crescimento & desenvolvimento , Verduras/metabolismo
13.
Free Radic Res ; 51(5): 529-544, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28503972

RESUMO

Convallatoxin is widely used as a cardiac glycoside in acute and chronic congestive heart-failure and paroxysmal tachycardia, with many effects and underlying protective mechanisms on inflammation and cellular proliferation. However, convallatoxin has not been investigated in its antioxidant effects and lifespan extension in Caenorhabditis elegans. In this study, we found that convallatoxin (20 µM) could significantly prolong the lifespan of wild-type C. elegans up to 16.3% through daf-16, but not sir-2.1 signalling and increased thermotolerance and resistance to paraquat-induced oxidative stress. Convallatoxin also improved pharyngeal pumping, locomotion, reduced lipofuscin accumulation and reactive oxygen species levels in C. elegans, which were attributed to hormesis, free radical-scavenging effects in vivo, and up-regulation of stress resistance-related proteins, such as SOD-3 and HSP-16.1. Furthermore, aging-associated genes daf-16, sod-3, and ctl-2 also appeared to contribute to the stress-resistance effect of convallatoxin. In summary, this study demonstrates that convallatoxin can protect against heat and oxidative stress and extend the lifespan of C. elegans, pointing it as a potential novel drug for retarding the aging process in humans.


Assuntos
Envelhecimento/efeitos dos fármacos , Estrofantinas/farmacologia , Animais , Antioxidantes/farmacologia , Caenorhabditis elegans , Proteínas de Caenorhabditis elegans/metabolismo , Avaliação Pré-Clínica de Medicamentos , Fatores de Transcrição Forkhead/metabolismo , Estresse Oxidativo , Paraquat/toxicidade , Transporte Proteico , Espécies Reativas de Oxigênio/metabolismo
14.
Langenbecks Arch Surg ; 402(2): 203-211, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27807617

RESUMO

BACKGROUND: Postoperative weight loss and malnutrition are major issues in gastric cancer patients. The concept of oral nutritional supplements (ONS) is gaining widespread acceptance. We investigated the effects of ONS administration on postoperative body weight loss in patients with gastric cancer who had undergone total gastrectomy or distal gastrectomy. METHODS: Patients were randomized to either the treatment or the control group. In both groups, standard surgery for gastric cancer was performed. In the treatment group, intervention with ONS was performed until 12 weeks after discharge. In the control group, patients were fed the usual postoperative diet. Weight, body composition, quality of life, hematological parameters, and blood chemistry were evaluated. RESULTS: We analyzed 113 cases (73 distal gastrectomy, 40 total gastrectomy). Weight loss in the ONS group after total gastrectomy was significantly less than that in the control group. Weight loss and skeletal muscle mass loss after distal gastrectomy did not differ significantly between the ONS and control groups. CONCLUSION: This study showed ONS after total gastrectomy to significantly diminish postoperative weight loss.


Assuntos
Suplementos Nutricionais , Gastrectomia , Cuidados Pós-Operatórios , Neoplasias Gástricas/cirurgia , Redução de Peso , Administração Oral , Adulto , Idoso , Composição Corporal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida
15.
J Ethnopharmacol ; 186: 181-188, 2016 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-27063986

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Wuling powder (trade name: Wuling capsule), a traditional Chinese medicine (TCM), was extracted from mycelia of precious Xylaria Nigripes (Kl.) Sacc by modern fermentation technology, and has been claimed to be fully potent in improving the signs of insomnia and cognitive deficits. Moreover, Wuling capsule was effective in treating post-stroke and orther co-cormbid depression both in clinical and in basic research. In order to clarify the molecular mechanisms of the antidepressant effect of Wuling powder, we established learned helplessness (LH) depression animal model and focused on 18kDa translocator protein (TSPO) mediated-mitophagy pathway. MATERIALS AND METHODS: Mice were exposed to the inescapable e-shock (IS) once a day for three consecutive days to establish the LH model. Then mice were orally administered Wuling powder for 2 weeks. For the behavioral assessment, Shuttle box test, novelty suppressed feeding test (NSF) and forced swimming test (FST) were performed. Following the behavioral assessment, we assessed the protein expression level that were related to TSPO-mediated mitophagy signaling pathway by Western blotting analysis. Finally, immunohistochemistry method was used to assess the neuroprotective effects of Wuling powder. RESULTS: Compared with mice that were subjected to inescapable e-shock, Wuling powder exhibited antidepressant effect in the multiple behavioral tests. In addition, Wuling powder altered the expression level of multiple proteins related to TSPO-mediated mitophagy signaling pathway. CONCLUSIONS: Our results suggested that Wuling powder exhibited an obvious antidepressant effect, which could be due to the improvement of TSPO-mediated mitophagy signaling pathway.


Assuntos
Antidepressivos/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Desamparo Aprendido , Mitofagia/efeitos dos fármacos , Receptores de GABA/metabolismo , Animais , Medicamentos de Ervas Chinesas/administração & dosagem , Fluoxetina/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Mesencéfalo/efeitos dos fármacos , Mesencéfalo/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Distribuição Aleatória , Receptores de GABA/genética , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Transdução de Sinais/fisiologia
16.
Nutr J ; 14: 9, 2015 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-25609264

RESUMO

BACKGROUND: A lipid emulsion composed of soybean oil (long-chain triglycerides, LCT), medium-chain triglycerides (MCT) and n-3 poly-unsaturated fatty acids (PUFAs) was evaluated for immune-modulation efficacy, safety, and tolerance in patients undergoing major surgery for gastric and colorectal cancer. METHODS: In a prospective, randomized, double-blind study, 99 patients with gastric and colorectal cancer receiving elective surgery were recruited and randomly assigned to either the study group, receiving the n-3 PUFAs enriched intravenous fat emulsion (IVFE), or the control group, receiving a lipid emulsion comprised of soybean oil and MCTs (0.8 - 1.5 g · kg-1 · day-1) as part of total parenteral nutrition (TPN) regimen from surgery (day -1) up to post-operative day 7. Safety and efficacy parameters were assessed on day -1 and post-operative visits on day 1, 3, and 7. Adverse events were documented daily and compared between the groups. RESULTS: Pro-inflammatory markers, laboratory parameters, and adverse events did not differ prominently between the 2 groups, with the exception of net changes (day 7 minus day -1) of free fatty acids (FFAs), triglyceride, and high-density lipoprotein (HDL). Net decrease of FFAs was remarkably higher in the study group, while the net increase of triglyceride and decrease of HDL was significantly lower. CONCLUSIONS: The n-3 PUFA-enriched IVFE showed improvements in lipid metabolism. In respect of efficacy, safety and tolerance both IVFE were comparable. In patients with severe stress, there is an inflammation-attenuating effect of n-3 PUFAs. Further, adequately powered clinical trials will be necessary to address this question in postsurgical GI cancer patients. TRIAL REGISTRATION: US ClinicalTrials.gov NCT00798447.


Assuntos
Neoplasias Colorretais/cirurgia , Emulsões Gordurosas Intravenosas/administração & dosagem , Ácidos Graxos Ômega-3/administração & dosagem , Ácidos Graxos Ômega-3/efeitos adversos , Cuidados Pós-Operatórios/métodos , Neoplasias Gástricas/cirurgia , Idoso , Método Duplo-Cego , Feminino , Humanos , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
17.
Mediators Inflamm ; 2014: 837107, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24891768

RESUMO

BACKGROUND: Migration of T cells into the colon plays a major role in the pathogenesis in inflammatory bowel disease. This study investigated the effects of glutamine (Gln) supplementation on chemokine receptors and adhesion molecules expressed by T cells in mice with dextran sulfate sodium- (DSS-) induced colitis. METHODS: C57BL/6 mice were fed either a standard diet or a Gln diet replacing 25% of the total nitrogen. After being fed the diets for 5 days, half of the mice from both groups were given 1.5% DSS in drinking water to induce colitis. Mice were killed after 5 days of DSS exposure. RESULTS: DSS colitis resulted in higher expression levels of P-selectin glycoprotein ligand- (PSGL-) 1, leukocyte function-associated antigen- (LFA-) 1, and C-C chemokine receptor type 9 (CCR9) by T helper (Th) and cytotoxic T (Tc) cells, and mRNA levels of endothelial adhesion molecules in colons were upregulated. Gln supplementation decreased expressions of PSGL-1, LFA-1, and CCR9 by Th cells. Colonic gene expressions of endothelial adhesion molecules were also lower in Gln-colitis mice. Histological finding showed that colon infiltrating Th cells were less in the DSS group with Gln administration. CONCLUSIONS: Gln supplementation may ameliorate the inflammation of colitis possibly via suppression of T cell migration.


Assuntos
Moléculas de Adesão Celular/metabolismo , Colite/metabolismo , Suplementos Nutricionais , Glutamina/uso terapêutico , Receptores de Quimiocinas/metabolismo , Linfócitos T/metabolismo , Doença Aguda , Administração Oral , Animais , Peso Corporal , Movimento Celular , Colite/fisiopatologia , Colo/efeitos dos fármacos , Colo/patologia , Modelos Animais de Doenças , Heparina/química , Mucosa Intestinal/patologia , Leucócitos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microscopia de Fluorescência , Polissacarídeos/química , Receptores CCR/metabolismo , Linfócitos T/citologia
18.
JPEN J Parenter Enteral Nutr ; 38(7): 800-8, 2014 09.
Artigo em Inglês | MEDLINE | ID: mdl-24285251

RESUMO

BACKGROUND: SMOFlipid 20% is intravenous lipid emulsion (ILE) containing long-chain triglycerides (LCT), medium-chain triglycerides (MCT), olive oil, and fish oil as a mixed emulsion containing α-tocopherol. The aim was to assess the efficacy of this new ILE in gastrointestinal surgery compared with MCT/LCT. METHODS: In this prospective study, 40 patients were randomized to SMOFlipid 20% or MCT/LCT (Lipovenoes 20%) group. Clinical and biochemistry data were collected. Inflammatory markers (CRP, IL-6, IL-10, TNF-α, TGF-ß1) and oxidative stress (ROS and superoxide) were measured. RESULTS: Thirty-five patients (17 males and 18 females) with a mean age of 57 years completed the study. The patients' demographic characteristics (age, gender, height, body weight, and BMI) were similar without significant differences between groups. The increment of triglyceride on day 6 from baseline was significantly lower in SMOFlipid group than in Lipovenoes MCT/LCT group. Inflammatory markers, as well as superoxide radical and total oxygen radical were not different between groups. CONCLUSIONS: Despite the comparable effect on inflammatory response, because of its well-balanced fatty acid pattern, relatively low n-6:n-3 ratio, and high vitamin E content, SMOFlipid had a better triglyceride-lowering effect as compared with MCT/LCT in adult patients undergoing gastrointestinal surgery.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório , Emulsões Gordurosas Intravenosas/farmacologia , Ácidos Graxos/farmacologia , Mediadores da Inflamação/sangue , Estresse Oxidativo/efeitos dos fármacos , Cuidados Pós-Operatórios , Triglicerídeos/farmacologia , Idoso , Proteína C-Reativa/metabolismo , Citocinas/sangue , Emulsões Gordurosas Intravenosas/química , Ácidos Graxos/sangue , Feminino , Óleos de Peixe/química , Óleos de Peixe/farmacologia , Humanos , Lipídeos/sangue , Lipídeos/farmacologia , Masculino , Pessoa de Meia-Idade , Azeite de Oliva , Nutrição Parenteral , Óleos de Plantas/química , Óleos de Plantas/farmacologia , Estudos Prospectivos , Espécies Reativas de Oxigênio/sangue , Óleo de Soja/química , Óleo de Soja/farmacologia , Triglicerídeos/sangue , alfa-Tocoferol/farmacologia
19.
Zhonghua Yan Ke Za Zhi ; 48(4): 318-22, 2012 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-22800452

RESUMO

OBJECTIVE: To study the effects of transpupillary thermotherapy (TTT) on circumscribed choroidal hemangiomas (CCH). METHODS: It was a retrospective cases series study. One hundred and fourteen cases (114 eyes) in out-patient department were enrolled in the study with 80 male cases and 34 female cases. The age ranged from 16 to 71 yrs with an average at 44 years. Single eye was affected in all cases. Indirect ophthalmoscope, fundus fluorescein angiography (FFA), ultrasound (B) were used for the examination. Treatment was delivered via slit lamp by using an 810 nm diode laser (Irises) with spots or composed spots (larger tumor) covering the whole tumor. If the tumor was located or partly located in the fovea, laser spot should be avoided in the fovea and papillo-macular bundle. The laser power should be lesser (light gray color) in parafovea area. Routine laser spot (gray-white color) was used in perifovea area. A width of 200 µm out of disk border should not be placed by laser spot in paradisk tumor cases. RESULTS: The visual acuity (VA) ≥ 0.5 of pre-and post-treatment was 17 eyes (14.9%) and 27 eyes (23.7%), respectively. Pre-treatment, the retinal detachment extended in the inferior part in 27 cases (23.7%) except on the tumor surface. The tumor was located at macular area in 67 cases (58.8%), around the disc in 35 cases (30.7%), at the temporal arcuate in 12 cases (10.5%). In our cases, VA maintenance with fluid absorption was noted in 76 cases (66.7%) after the treatment. VA improvement with fluid absorption in 28 case (24.6%). Both VA maintenance and improvement (rate of efficiency) with fluid absorption were 91.2%. Fluid non-absorption or VA decline was regarded as unsuccessful in 10 cases (8.8%). The average thickness of 32 cases tumor pre- and post-treatment was (3.90 ± 1.15) mm and (2.41 ± 1.30) mm. Twenty seven cases were followed up for ≥ 1 year (mean 22.8 months) with rate of efficiency at 81.5%. The complications (9 eyes, 7.9%) contained minor macular hemorrhage in 2 eyes, macular pucker in 3 eyes, macular edema and cystoid macular edema in 2 eyes, retinal branch occlusion in 1 eye, and arcuate scotoma in 1 eye. CONCLUSIONS: The treatment of TTT on CCH, whether the tumor located around-disc or in foveal area with exudative fluid could get successful in the majority of cases. TTT is one of the treatments worth doing owing to fewer complications, less expenses and easy-doing with definite and persistent effect.


Assuntos
Neoplasias da Coroide/terapia , Hemangioma/terapia , Hipertermia Induzida/métodos , Adolescente , Adulto , Idoso , Neovascularização de Coroide/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
20.
Hepatogastroenterology ; 59(118): 1776-9, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22819900

RESUMO

BACKGROUND/AIMS: Exogenous glutamine supplement is known to improve morbidity and mortality of critically-ill patients. This study was conducted to elucidate the role of glutamine in minimally invasive surgery. METHODOLOGY: We retrospectively reviewed subtotal gastrectomy patients in National Taiwan University Hospital from Dec 2005 to Dec 2008. The patients were divided into three groups. Group 1 underwent subtotal gastrectomy by laparotomy without glutamine supplement, group 2 underwent subtotal gastrectomy by laparotomy with glutamine supplement and group 3 underwent gasless laparoscopy-assisted subtotal gastrectomy with parenteral glutamine supplement. RESULTS: There were 155 patients in total; 85 patients in group 1, 17 in group 2 and 53 in group 3. The mean flatus days after operation are 3.6, 3.1 and 2.8 for groups 1, 2 and 3, respectively (p=0.001). Oral intake after operation was commenced after 6.7, 5.0 and 4.7 days (p=0.006). The body temperature had borderline differences between groups 3 and 1. There were significant differences in postoperative systemic responses including heart rates (p<0.001) and tenderness (p=0.011) 5 days after operation for group 3 vs. group 1. Minimally invasive surgery was a negative factor for postoperative body temperature change. Glutamine was a significant factor for postoperative heart rate change and reduction of tenderness. CONCLUSIONS: Glutamine supplement may have synergic effects of rapid recovery in minimal invasive surgery for subtotal gastrectomy patients by minimizing the postoperative systemic response and accelerating recovery.


Assuntos
Suplementos Nutricionais , Gastrectomia/métodos , Glutamina/administração & dosagem , Laparoscopia , Nutrição Parenteral , Idoso , Regulação da Temperatura Corporal , Feminino , Gastrectomia/efeitos adversos , Frequência Cardíaca , Humanos , Laparoscopia/efeitos adversos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Recuperação de Função Fisiológica , Estudos Retrospectivos , Taiwan , Fatores de Tempo , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA