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1.
Aquat Toxicol ; 227: 105591, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32853898

RESUMO

The effects of allelopathy and the potential harm of several isolated allelochemicals have been studied in detail. Microorganisms in the phycosphere play an important role in algal growth, decay and nutrient cycling. However, it is unknown and often neglected whether allelochemicals affect the phycosphere. The present study selected a phenolic acid protocatechuic acid (PA) - previously shown to be an allelochemical. We studied PA at a half maximal effective concentration of 0.20 mM (30 mg L-1) against Scrippsiella trochoidea to assess the effect of PA on its phycosphere in an acute time period (48 h). The results showed that: 1) OTUs (operational taxonomic units) in the treatment groups (31.4 ± 0.55) exceeded those of the control groups (28.2 ± 1.30) and the Shannon and Simpson indices were lower than the control groups (3.31 ± 0.08 and 0.84 ± 0.02, 3.45 ± 0.09 and 0.88 ± 0.01); 2) Gammaproteobacteria predominated in the treatment groups (44.71 ± 2.13 %) while Alphaproteobacteria dominated in the controls (67.17 ± 3.87 %); 3) Gammaproteobacteria and Alphaproteobacteria were important biomarkers in the treatment and control groups respectively (LDA > 4.0). PA improved the relative abundance of Alteromonas significantly and decreased the one of Rhodobacteraceae. PICRUSt analysis showed that the decrease of Rhodobacterceae was closely related with the decline of most functional genes in metabolism such as amino acid, carbohydrate, xenobiotics, cofactors and vitamins metabolism after PA-treated.


Assuntos
Alelopatia/efeitos dos fármacos , Dinoflagelados/efeitos dos fármacos , Proliferação Nociva de Algas/efeitos dos fármacos , Hidroxibenzoatos/farmacologia , Microbiota/efeitos dos fármacos , Feromônios/farmacologia , Alelopatia/genética , Bacteroidetes/efeitos dos fármacos , Bacteroidetes/genética , Bacteroidetes/isolamento & purificação , Dinoflagelados/genética , Dinoflagelados/crescimento & desenvolvimento , Microbiota/genética , Proteobactérias/efeitos dos fármacos , Proteobactérias/genética , Proteobactérias/isolamento & purificação
2.
Life Sci ; 256: 117907, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32504751

RESUMO

Acute lung injury (ALI) and the subsequent multi-system organ failure is a serious health problem with devastating impacts on the health care systems. Indeed, the world has been facing an un-preceded situation in the past couple of months following COVID-19 infestation and the associated high-mortality rates mainly attributed to sepsis and the associated multiple organ failures of particular concern; acute respiratory distress syndrome post lung injury. The current study provides evidence on the ameliorative impact of nifuroxazide, and FDA approved antidiarrheal drug in attenuation of lipopolysaccharide (LPS)-induced ALI and myocarditis when administrated either in prophylactic or curative regimens. Nifuroxazide administration was associated with a significant improvement in lung and heart histopathological characteristics and architecture with retraction of LPS-induced inflammatory-infiltration. This was associated with retraction in serum biomarkers of cellular injury of which; LDH, CK-MB, and ALP. Nifuroxazide administration was associated with a significant improvement in both lung and heart oxidative status. Such positive outcomes were underlined by a significant inhibitory effect of nifuroxazide on lung and heart contents of toll-like receptor (4) (TLR4)/the inflammasome NALPR3/interleukin- 1ß (IL-1ß). In conclusion: Nifuroxazide attenuates LPS-induced ALI and myocardial injury via interruption of TLR4/NALPR3/IL-1ß signaling. Thus it can offer a potential approach for attenuation of sepsis in critically ill patients.


Assuntos
Lesão Pulmonar Aguda/prevenção & controle , Infecções por Coronavirus/complicações , Hidroxibenzoatos/farmacologia , Miocardite/prevenção & controle , Nitrofuranos/farmacologia , Pneumonia Viral/complicações , Sepse/tratamento farmacológico , Lesão Pulmonar Aguda/etiologia , Animais , Infecções por Coronavirus/epidemiologia , Modelos Animais de Doenças , Interleucina-1beta/metabolismo , Lipopolissacarídeos/toxicidade , Masculino , Insuficiência de Múltiplos Órgãos/etiologia , Insuficiência de Múltiplos Órgãos/prevenção & controle , Miocardite/etiologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Pandemias , Pneumonia Viral/epidemiologia , Ratos , Ratos Sprague-Dawley , Sepse/complicações , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismo
3.
Int J Food Microbiol ; 328: 108664, 2020 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-32474229

RESUMO

To control Pseudomonas and Shewanella as important psychrotrophic spoilage bacteria in fish meat, we used ethanolic extracts of oregano (Origanum vulgare subsp. vulgare) and nettle (Urtica dioica), with phytochemical characterisation of the extracts and their bioactive compounds. Liquid chromatography coupled with photodiode array detection and electrospray ionisation-mass spectrometry was used for qualitative compositional determination of the extracts. Four main compounds were identified in the oregano extract, with rosmarinic acid the most abundant, followed by three glycosylated phenolics, one of which is reported for the first time in O. vulgare: 4'-O-ß-d-glucopyranosyl-3',4'-dihydroxybenzyl-4-hydroxybenzoate. Six main compounds were identified in the nettle extract, as caffeoylmalic acid and five flavonoid glycosides. These oregano and nettle ethanolic extracts showed in-vitro antimicrobial activities against selected Pseudomonas and Shewanella strains in broth and fish meat homogenate when evaluated at two inoculum concentrations. The antimicrobial activities were more pronounced for the nettle extract at the lower inoculum concentration, and for both the Shewanella strains. Growth inhibition in the fish meat homogenate was evaluated at 3.13 mg/mL and 1.56 mg/mL at 5 °C. Again, the nettle extract showed greater antimicrobial activity, which was seen as the lowest maximum growth rate, followed by the oregano extract, which was inhibitory only at 3.13 mg/mL. Finally, the extracts were applied to fish meat that was then stored at 5 °C for 9 days. Evaluation here was for the counts of the mesophilic, psychrotrophic, Pseudomonas and H2S producers. These confirmed the better antimicrobial effects of the nettle extract, especially against the H2S-producing bacteria, which included Shewanella. Both of the extracts were rich in glycosides of flavonoids and phenolic acids. The enzymatic activities of the Pseudomonas and Shewanella spoilage bacteria and their actions on the phenolic glycosides from natural sources will be further investigated.


Assuntos
Doenças dos Peixes/tratamento farmacológico , Origanum/química , Extratos Vegetais/farmacologia , Pseudomonas/efeitos dos fármacos , Shewanella/efeitos dos fármacos , Urtica dioica/química , Animais , Ácidos Cafeicos/farmacologia , Cinamatos/farmacologia , Depsídeos/farmacologia , Peixes/microbiologia , Flavonoides , Microbiologia de Alimentos , Hidroxibenzoatos/farmacologia , Malatos/farmacologia , Fenóis/química , Alimentos Marinhos/microbiologia , Espectrometria de Massas por Ionização por Electrospray
4.
J Pharmacol Sci ; 143(3): 165-175, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32387002

RESUMO

yeyachun and danshen exist as Chinese patent medicine, Xuemai Tong, and are clearly effective at alleviating liver fibrosis (LF). Previous studies have indicated that triterpenoids from yeyachun (EFT), and phenolic acids from danshen (SMP) are effective in the treatment of LF. The regulation of intestinal flora is an effective method for treating LF. The aim of this study was to investigate the effect of a mixture of EFT and SMP on carbon tetrachloride (CCl4) induced LF. Our results showed the mixture significantly decreased liver damage and fibrosis index, and maintained liver tissue composition, compared to the model group. Moreover, the imbalance of symptoms of intestinal flora was improved. The mixture also caused changes to metabolites of gut flora. Furthermore, the expression of CD68 in liver tissues from the treated groups was significantly decreased when compared to the model group. However, no significant difference was observed from microstructure of gut tissues and LPS concentrations in the serum between mixture treated mice and model mice. This study suggests that the mixture of EFT and SMP had a significant effect on CCl4 induced LF, and the mechanism of this action, at least in part, involved the regulation of intestinal flora and their metabolites.


Assuntos
Tetracloreto de Carbono/efeitos adversos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Microbioma Gastrointestinal/efeitos dos fármacos , Hidroxibenzoatos/farmacologia , Hidroxibenzoatos/uso terapêutico , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/microbiologia , Fitoterapia , Salvia miltiorrhiza/química , Triterpenos/farmacologia , Triterpenos/uso terapêutico , Animais , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/isolamento & purificação , Fígado/metabolismo , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/metabolismo , Masculino , Camundongos Endogâmicos ICR , Triterpenos/isolamento & purificação
5.
Int J Food Microbiol ; 324: 108613, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32224332

RESUMO

This study aimed to develop a pasteurization method against Salmonella enterica serovar Typhimurium in orange juice using low concentrations of naturally derived antimicrobials, ß-resorcylic acid and capric acid, under mild temperature conditions based on their synergistic bactericidal interactions. Response surface methodology was used to construct a model based on four variables, namely ß-resorcylic acid (1, 3, 5, 7, and 9 mM), capric acid (0.05, 0.10, 0.15, 0.20, and 0.25 mM), treatment temperature (35, 40, 45, 50, and 55 °C), and time (1, 2, 3, 4, and 5 min), and the resulting model was used to predict the reduction in the content of fastidious bacteria (S. Typhimurium) in orange juice and to identify the optimal treatment combination for juice pasteurization. A second-order quadratic model for Salmonella reduction showed a high regression coefficient (R2 = 0.9503), and the accuracy of the predictive model was also verified (R2 = 0.9317). The optimal conditions determined by ridge analysis were 8.43 mM ß-resorcylic acid combined with 0.10 mM capric acid at 43.46 °C for 3.03 min, and these yielded an estimated 7.41-log reduction. Treatment times <30 s under the optimal conditions also resulted in a >5.7-log reduction. The combined treatment did not affect either the pH or sugar concentration in brix, and average pH and sugar concentration values of 3.86 and 11.05% were observed, respectively. The distinct advantage of the developed method is its ability to effectively reduce the content of S. Typhimurium over a short time under low temperature conditions through the addition of consumer-preferred naturally derived antimicrobials. The predictive model could be used to determine the most cost-efficient amounts of antimicrobial agents and conditions (treatment temperature and time) for sterilizing orange juice.


Assuntos
Anti-Infecciosos/farmacologia , Citrus sinensis , Sucos de Frutas e Vegetais/microbiologia , Pasteurização/métodos , Salmonella typhimurium/isolamento & purificação , Contagem de Colônia Microbiana , Ácidos Decanoicos/farmacologia , Hidroxibenzoatos/farmacologia , Salmonella typhimurium/efeitos dos fármacos , Temperatura , Fatores de Tempo
6.
Life Sci ; 252: 117610, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32259601

RESUMO

Hyperammonemia is a serious metabolic disorder associating with hepatic encephalopathy (HE) which occurs secondary to several forms of liver injury ranging from simple acute liver failure (ALF) to its most serious form; cirrhosis. The resent study highlights the possible ameliorative effect of oral nifuroxazide (25 mg/kg) against experimentally induced ALF and the subsequent HE in a well-standardized rat model. ALF and HE were induced in a rat model by I.P. injection of thioacetamide (TAA) (200 mg/kg) for 1 week at alternative days. Nifuroxazide administration for 14 days prior to and for further 7 days alongside TAA injection successfully attenuated TAA-induced ALF and HE; as demonstrated by the significant retraction in both brain and serum hyperammonemia with significant improvement in liver function biomarkers; ALT, AST, ALP, GGT, albumin, and serum total protein. This was associated with a significant restoration of both hepatic and brain oxidative stress incidences; MDA, SOD and catalase activities and GSH concentration. The observed improvement was associated with a significant reduction in liver and brain contents of c-Jun N-terminal kinase (cJNK); as an anti-inflammatory biomarker and a modulator of various pro- and anti-apoptotic proteins, caspase-8, and tumor necrosis factor-related apoptosis ligand (TRAIL); as biomarkers of apoptosis. In conclusion; the modulatory effect of nifuroxazide on cJNK/caspase-8/TRAIL signaling appears to underly its hepatoprotective effect and its ameliorative effect on HE progression.


Assuntos
Encefalopatia Hepática/tratamento farmacológico , Hidroxibenzoatos/farmacologia , Hiperamonemia/prevenção & controle , Falência Hepática Aguda/tratamento farmacológico , Nitrofuranos/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Animais , Caspase 8/metabolismo , Modelos Animais de Doenças , Progressão da Doença , Encefalopatia Hepática/complicações , Encefalopatia Hepática/fisiopatologia , Hidroxibenzoatos/administração & dosagem , Hiperamonemia/etiologia , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Falência Hepática Aguda/complicações , Falência Hepática Aguda/fisiopatologia , Masculino , Nitrofuranos/administração & dosagem , Ratos , Ratos Sprague-Dawley , Ligante Indutor de Apoptose Relacionado a TNF/metabolismo
7.
Sci Rep ; 10(1): 3689, 2020 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-32111871

RESUMO

The root of Paeonia lactiflora Pall. (Chishao, CS) and Ligusticum chuanxiong Hort. (Chuanxiong, CX) were widely used as a drug pair in Chinese Medicine, and the combination of CS and CX showed a more significant inhibition on neuronal apoptosis in our previous study. In the present study, total paeony glycosides (TPGs) from CS and total ligustici phenolic acids (TLPAs) from CX were combined to evaluate the synergistic effects against focal cerebral ischemia both in vitro and in vivo. The combination of TPGs and TLPAs at 7:3 had the best anti-oxidative stress and anti-inflammatory effect on OGD-induced HUVEC. Additionally, the infarction area proportion and neuron apoptosis of rats by TPGs:TLPAs (7:3) was significantly lower than their alone in MCAO rats. Moreover, TPGs: TLPAs of 7:3 showed a more significant effect on decreasing the expression of MMP-2 and MMP-9, and increasing the protein expression or mRNA level of TIMP-1 than other combinations. The optimal ratio of TPGs and TLPAs at 7:3 could bring more remarkable protective effects against focal cerebral ischemia in MCAO rats by alleviating oxidative stress, inflammatory and neuronal apoptosis to protect the blood-brain barrier. Overall, the present study provided benefical evidence for clinical application of CS and CX as a "drug pair".


Assuntos
Isquemia Encefálica , Glicosídeos/farmacologia , Células Endoteliais da Veia Umbilical Humana/metabolismo , Hidroxibenzoatos/farmacologia , Ligusticum/química , Estresse Oxidativo/efeitos dos fármacos , Paeonia/química , Raízes de Plantas/química , Animais , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patologia , Glicosídeos/química , Células Endoteliais da Veia Umbilical Humana/patologia , Humanos , Hidroxibenzoatos/química , Masculino , Ratos , Ratos Sprague-Dawley
8.
Molecules ; 25(3)2020 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-32050498

RESUMO

Lonicera caerulea L., also known as haskap or honeysuckle berry, is a fruit commonly planted in eastern Europe, Canada and Asia. The fruit was registered as a traditional food from a third country under European Union regulations only on December 2018. It is resistant to cold, pests, various soil acidities and diseases. However, its attractiveness is associated mostly with its health properties. The fruit shows anticancer, anti-inflammatory, and antioxidant activity-important factors in improving health. These features result from the diverse content of phytochemicals in honeysuckle berries with high concentrations of phytocompounds, mainly hydroxycinnamic acids, hydroxybenzoic acids, flavanols, flavones, isoflavones, flavonols, flavanones and anthocyanins but also iridoids, present in the fruit in exceptional amounts. The content and health properties of the fruit were identified to be dependent on cultivar, genotype and the place of harvesting. Great potential benefits of this nutritious food are its ability to minimize the negative effects of UV radiation, diabetes mellitus and neurodegenerative diseases, and to exert hepato- and cardioprotective activity.


Assuntos
Antocianinas/isolamento & purificação , Ácidos Cumáricos/isolamento & purificação , Flavonoides/isolamento & purificação , Frutas/química , Hidroxibenzoatos/isolamento & purificação , Iridoides/isolamento & purificação , Lonicera/química , Antocianinas/química , Antocianinas/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Antioxidantes/química , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Ásia , Canadá , Cardiotônicos/química , Cardiotônicos/isolamento & purificação , Cardiotônicos/farmacologia , Ácidos Cumáricos/química , Ácidos Cumáricos/farmacologia , Europa (Continente) , Flavonoides/química , Flavonoides/farmacologia , Frutas/metabolismo , Hidroxibenzoatos/química , Hidroxibenzoatos/farmacologia , Hipoglicemiantes/química , Hipoglicemiantes/isolamento & purificação , Hipoglicemiantes/farmacologia , Iridoides/química , Iridoides/farmacologia , Lonicera/metabolismo , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/isolamento & purificação , Fármacos Neuroprotetores/farmacologia , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/química , Protetores Solares/química , Protetores Solares/isolamento & purificação , Protetores Solares/farmacologia
9.
Int J Mol Sci ; 21(3)2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32046095

RESUMO

The JAK-STAT signalling pathway regulates cellular processes like cell division, cell death and immune regulation. Dysregulation has been identified in solid tumours and STAT3 activation is a marker for poor outcome. The aim of this study was to explore potential therapeutic strategies by targeting this pathway in bladder cancer (BC). High STAT3 expression was detected in 51.3% from 149 patient specimens with invasive bladder cancer by immunohistochemistry. Protein expression of JAK, STAT and downstream targets were confirmed in 10 cell lines. Effects of the JAK inhibitors Ruxolitinib and BSK-805, and STAT3/5 inhibitors Stattic, Nifuroxazide and SH-4-54 were analysed by cell viability assays, immunoblotting, apoptosis and cell cycle progression. Treatment with STAT3/5 but not JAK1/2 inhibitors reduced survival, levels of phosphorylated STAT3 and Cyclin-D1 and increased apoptosis. Tumour xenografts, using the chicken chorioallantoic membrane (CAM) model responded to Stattic monotherapy. Combination of Stattic with Cisplatin, Docetaxel, Gemcitabine, Paclitaxel and CDK4/6 inhibitors showed additive effects. The combination of Stattic with the oncolytic adenovirus XVir-N-31 increased viral replication and cell lysis. Our results provide evidence that inhibitors against STAT3/5 are promising as novel mono- and combination therapy in bladder cancer.


Assuntos
Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Terapia Viral Oncolítica/métodos , Inibidores de Proteínas Quinases/farmacologia , Fator de Transcrição STAT3/antagonistas & inibidores , Fator de Transcrição STAT6/antagonistas & inibidores , Neoplasias da Bexiga Urinária/terapia , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Embrião de Galinha , Terapia Combinada/métodos , Óxidos S-Cíclicos/farmacologia , Quinase 4 Dependente de Ciclina/antagonistas & inibidores , Quinase 6 Dependente de Ciclina/antagonistas & inibidores , Humanos , Hidroxibenzoatos/farmacologia , Janus Quinases/antagonistas & inibidores , Nitrofuranos/farmacologia , Pirazóis/farmacologia , Quinoxalinas/farmacologia , Neoplasias da Bexiga Urinária/metabolismo
10.
Molecules ; 25(3)2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-32013151

RESUMO

To clarify whether flavonoids and phenols in Allium mongolicum Regel have the effect of improving gastrointestinal function and analyze its quality, this study was designed to isolate and identify them from the aerial parts of A. mongolicum by using various chromatographic and spectrophotometric methods, a bioassay on motility of mouse isolated intestine tissue, as well as qualitative analysis using liquid chromatography/mass spectrometry (LC-MS) analysis. As a result, 31 flavonoids and phenolic acids were obtained and identified, including six new flavonoid glycosides, mongoflavonosides A1 (1), A2 (2), A3 (3), A4 (4), B1 (5), B2 (6), and four new phenolic acid glycosides, mongophenosides A1 (7), A2 (8), A3 (9), B (10). Among them, eleven flavonoids and three phenolic acids showed significant increase in the height of mouse small intestinal muscle. It was a first systematic bioactive constituents' study for A. mongolicum on gastrointestinal tract. Furthermore, according to the retention time (tR) and the exact mass-to-charge ratio (m/z), thirty-one compounds were unambiguously identified by comparing to the standard references by using LC-MS. Then, on the basis of generalized rules of MS/MS fragmentation pattern, chromatographic behaviors, as well as biosynthetic laws of the 31 isolates, five flavonoid glycosides and one phenolic acid glycoside were tentatively speculated. On the basis of the study, a fast analysis method for flavonoids and phenolic acids in A. mongolicum was established.


Assuntos
Allium/química , Flavonoides/química , Hidroxibenzoatos/química , Compostos Fitoquímicos/química , Componentes Aéreos da Planta/química , Extratos Vegetais/química , Animais , Flavonoides/farmacologia , Motilidade Gastrointestinal/efeitos dos fármacos , Hidroxibenzoatos/farmacologia , Camundongos , Estrutura Molecular , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Análise Espectral
11.
Molecules ; 25(3)2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-32012913

RESUMO

Honey, propolis, bee pollen, bee bread, royal jelly, beeswax and bee venom are natural products which have been used in medicine since ancient times. Nowadays, studies indicate that natural bee products can be used for skin treatment and care. Biological properties of these products are related to flavonoids they contain like: chrysin, apigenin, kaempferol, quercetin, galangin, pinocembrin or naringenin. Several pharmacological activities of phenolic acids and flavonoids, and also 10-hydroxy-trans-2-decenoic acid, which is present in royal jelly, have been reported. Royal jelly has multitude of pharmacological activities: antibiotic, antiinflammatory, antiallergenic, tonic and antiaging. Honey, propolis and pollen are used to heal burn wounds, and they possess numerous functional properties such as: antibacterial, anti-inflammatory, antioxidant, disinfectant, antifungal and antiviral. Beeswax is used for production of cosmetics and ointments in pharmacy. Due to a large number of biological activities, bee products could be considered as important ingredients in medicines and cosmetics applied to skin.


Assuntos
Produtos Biológicos/farmacologia , Flavonoides/farmacologia , Hidroxibenzoatos/farmacologia , Animais , Abelhas , Produtos Biológicos/química , Dermatologia , Ácidos Graxos/química , Flavonoides/química , Mel/análise , Hidroxibenzoatos/química , Pólen/química , Própole/química , Higiene da Pele
12.
Molecules ; 25(3)2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32033190

RESUMO

Abstract: A main cellular functional module that becomes dysfunctional during aging is the proteostasis network. In the present study, we show that benzoic acid derivatives isolated from Bjerkandera adusta promote the activity of the two main protein degradation systems, namely the ubiquitin-proteasome (UPP) and especially the autophagy-lysosome pathway (ALP) in human foreskin fibroblasts. Our findings were further supported by in silico studies, where all compounds were found to be putative binders of both cathepsins B and L. Among them, compound 3 (3-chloro-4-methoxybenzoic acid) showed the most potent interaction with both enzymes, which justifies the strong activation of cathepsins B and L (467.3 ± 3.9%) on cell-based assays. Considering that the activity of both the UPP and ALP pathways decreases with aging, our results suggest that the hydroxybenzoic acid scaffold could be considered as a promising candidate for the development of novel modulators of the proteostasis network, and likely of anti-aging agents.


Assuntos
Autofagia/fisiologia , Coriolaceae/química , Hidroxibenzoatos/farmacologia , Lisossomos/fisiologia , Proteostase/efeitos dos fármacos , Ácido Benzoico/farmacologia , Catepsinas/metabolismo , Extratos Celulares/farmacologia , Linhagem Celular , Coriolaceae/metabolismo , Humanos , Hidroxibenzoatos/química , Simulação de Acoplamento Molecular , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteólise , Ubiquitina-Proteína Ligases/metabolismo
13.
J Neuroimmunol ; 341: 577164, 2020 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-32007785

RESUMO

SIRT1 exhibits inhibitory effects on microglial activation-induced neurodegeneration. Regulating SIRT1 may become a novel approach for curing neurodegenerative diseases. Protocatechuic acid (PA), a phenolic acid, has anti-neuroinflammatory effects. The effect of PA on SIRT1 in activated microglia remains unknown. Here, we examined whether PA has anti-inflammatory effects against microglial activation-induced neuronal cell death via regulating SIRT1 in microglia. We found that PA inhibited the release of inflammatory mediators in LPS-activated BV2 microglia via the SIRT1/NF-κB pathway and thereby attenuated microglial activation-induced PC12 cell apoptosis. This suggests that SIRT1 mediates the anti-neuroinflammatory effects of PA to ameliorate microglial activation-induced neuron death.


Assuntos
Anti-Inflamatórios/farmacologia , Hidroxibenzoatos/farmacologia , Microglia/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Animais , Apoptose/efeitos dos fármacos , Forma Celular/efeitos dos fármacos , Meios de Cultivo Condicionados/farmacologia , Mediadores da Inflamação/metabolismo , Lipopolissacarídeos/farmacologia , Camundongos , Microglia/metabolismo , Microglia/ultraestrutura , NF-kappa B/fisiologia , Doenças Neurodegenerativas/tratamento farmacológico , Doenças Neurodegenerativas/imunologia , Doenças Neurodegenerativas/patologia , Óxido Nítrico/metabolismo , Células PC12 , Ratos , Transdução de Sinais/efeitos dos fármacos , Sirtuína 1/fisiologia
14.
BMC Complement Med Ther ; 20(1): 28, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32020855

RESUMO

BACKGROUND: The tanshinones and phenolic acids in Salvia miltiorrhiza (also named Danshen) have been confirmed for the treatment of coronary heart disease (CHD), but the action mechanisms remain elusive. METHODS: In the current study, the co-expression protein interaction network (Ce-PIN) was used to illustrate the differences between the tanshinones and phenolic acids of Danshen in the treatment of CHD. By integrating the gene expression profile data and protein-protein interactions (PPIs) data, the Ce-PINs of tanshinones and phenolic acids were constructed. Then, the Ce-PINs were analyzed by gene ontology enrichment analyzed based on the optimal algorithm. RESULTS: It turned out that Danshen is able to treat CHD by regulating the blood circulation, immune response and lipid metabolism. However, phenolic acids may regulate the blood circulation by Extracellular calcium-sensing receptor (CaSR), Endothelin-1 receptor (EDNRA), Endothelin-1 receptor (EDNRB), Kininogen-1 (KNG1), tanshinones may regulate the blood circulation by Guanylate cyclase soluble subunit alpha-1 (GUCY1A3) and Guanylate cyclase soluble subunit beta-1 (GUCY1B3). In addition, both the phenolic acids and tanshinones may regulate the immune response or inflammation by T-cell surface glycoprotein CD4 (CD4), Receptor-type tyrosine-protein phosphatase C (PTPRC). CONCLUSION: Through the same targets of the same biological process and different targets of the same biological process, the tanshinones and phenolic acids synergistically treat coronary heart disease.


Assuntos
Abietanos/farmacologia , Doença das Coronárias/tratamento farmacológico , Hidroxibenzoatos/farmacologia , Mapas de Interação de Proteínas , Humanos , Salvia miltiorrhiza/química
15.
J Food Sci ; 85(3): 576-581, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32078759

RESUMO

Elevated free fatty acids may impair insulin-mediated signaling to eNOS that contributes to the pathophysiology of endothelial dysfunction. Previous studies have indicated the protective effect of ginseng and the regulatory potential of phenolic acid components from other plants on endothelial function. Therefore, this study investigated the protective effects of phenolic acid extract from ginseng (PG2) on endothelial cells against palmitate-induced damage. We found that PG2 increases cell viability, inhibits the palmitate-induced intracellular accumulation of lipids, and the overexpression of endothelin-1 (ET-1) through enhancing the phosphorylation of the phosphatidylinositol 3-kinase/Akt/endothelial nitric oxide synthase (PI3K/Akt/eNOS) signaling pathway. The results of this study may be valuable for the development of PG2 to combat the endothelial cell damage caused by hyperlipidemia. PRACTICAL APPLICATION: We proved that phenolic acid extract from ginseng has a protective effect on free fatty acid-induced endothelial dysfunction in vitro. This study provides experimental data for the application of ginseng-derived phenolic acids in treating cardiovascular disease.


Assuntos
Células Endoteliais/efeitos dos fármacos , Hidroxibenzoatos/farmacologia , Óxido Nítrico Sintase Tipo III/metabolismo , Panax/química , Fosfatidilinositol 3-Quinase/metabolismo , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Células Endoteliais/enzimologia , Endotelina-1/metabolismo , Humanos , Insulina/metabolismo , Palmitatos/toxicidade , Fosforilação/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
16.
Food Funct ; 11(2): 1425-1440, 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-31971191

RESUMO

Although Parkinson's disease (PD) is the second most common neurodegenerative disorder, the preventative or therapeutic agents for the treatment of PD are limited. Eucommia ulmoides Oliver (EuO) is widely used as a traditional herb to treat various diseases. EuO bark extracts have been reported to possess anti-PD activity. Here, we investigated whether extracts of EuO leaves (EEuOL) also have therapeutic effects on PD since similar components and clinical applications have been found between barks and leaves of this tree. We identified the chemical composition of EEuOL by HPLC-Q-TOF-MS and tested the anti-PD effect of EEuOL using the zebrafish PD model. As a result, 28 compounds including 3 phenolic acids, 7 flavonoids, and 9 iridoids were identified. EEuOL significantly reversed the loss of dopaminergic neurons and neural vasculature and reduced the number of apoptotic cells in zebrafish brain in a concentration-dependent manner. Moreover, EEuOL relieved locomotor impairments in MPTP-modeled PD zebrafish. We also investigated the underlying mechanism and found that EEuOL may activate autophagy, contributing to α-synuclein degradation, therefore alleviating PD-like symptoms. Molecular docking simulation implied the interaction between autophagy regulators (Pink1, Beclin1, Ulk2, and Atg5) and phenolic acids of EEuOL, affirming the involvement of autophagy in EEuOL-exerted anti-PD action. The overall results indicated the anti-PD effect of EEuOL, opening the possibility to use the extract in PD treatment.


Assuntos
Eucommiaceae , Hidroxibenzoatos/farmacologia , Atividade Motora/efeitos dos fármacos , Doença de Parkinson/tratamento farmacológico , Extratos Vegetais/farmacologia , Animais , Autofagia/efeitos dos fármacos , Modelos Animais de Doenças , Fitoterapia , Folhas de Planta , Peixe-Zebra
17.
Mol Med Rep ; 21(3): 1328-1335, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31894327

RESUMO

Okadaic acid (OA) can be used to induce an Alzheimer's disease (AD) model characterized by tau hyperphosphorylation, the formation of neurofibrillary tangles formation and ß­amyloid (Aß) deposition. Previous studies have shown that the upregulation of Beclin­1­dependent autophagy may contribute to the elimination of aggregated Aß. However, the effects of protocatechuic acid (PA) on the levels of Aß42, phosphorylated (p)­tau and ß­secretase in OA­induced cell injury are unclear, and little is known concerning the role of the PA signaling pathway in the regulation of autophagy. The present study aimed to determine whether PA protects cells from OA­induced cytotoxicity via the regulation of Beclin­1­dependent autophagy and its regulatory signaling pathway. PC12 cells were treated with OA with or without PA for 24 h. Enzymatic assays were performed to measure p­tau, Aß42 and ß­secretase activity. Western blotting was performed to detect p­Akt, p­glycogen synthase kinase­3ß (p­GSK­3ß), Akt, GSK­3ß, myocyte enhancer factor 2D (MEF2D) and Beclin­1 protein expression levels. Immunofluorescence and immunocytochemistry were used to measure Beclin­1 expression levels. The results from this study showed that PA could increase cell viability and significantly decrease the levels of Aß42, p­tau, ß­secretase and Beclin­1. PA can also promote the expression of p­Akt and MEF2D while suppressing the expression of p­GSK­3ß. These results indicated that PA protects PC12 cells from OA­induced cytotoxicity, and attenuates autophagy via regulation of the Akt/GSK­3ß/MEF2D pathway, therefore potentially contributing to the neuroprotective effects of PA against OA toxicity. These findings suggested that PA may have potential as a drug candidate in preventative AD therapy.


Assuntos
Secretases da Proteína Precursora do Amiloide/metabolismo , Autofagia/efeitos dos fármacos , Glicogênio Sintase Quinase 3 beta/metabolismo , Hidroxibenzoatos/farmacologia , Ácido Okadáico/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Fatores de Transcrição MEF2/metabolismo , Células PC12 , Ratos
18.
Molecules ; 25(1)2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31947799

RESUMO

Unlike its aerial parts, the underground parts of Mentha have so far been studied only marginally. By examining the polyphenolic fingerprint, the antioxidant efficacy and the mutual antioxidant behaviour of mixtures of mint rhizomes, our study presents a modest contribution to addressing this gap. Firstly, we examined the composition of the mint rhizomes: Mentha × piperita cv. 'Perpeta' (MPP), M. longifolia (ML), and M. × villosa cv. 'Snezna' (MVS). Our LC-MS-DAD analysis revealed the presence of ten compounds belonging to groups of phenolic acids and flavonoids, of which the rosmarinic acid (RA) and lithospermic were most strongly represented. Secondly, we evaluated the antioxidant activity of rhizome infusions by DPPH and ABTS and on NIH/3T3 cell lines by DCFH-DA. Thirdly, we determined, examined, and explained the mutual interactions of rhizome infusions mixtures. While most of the combinations acted additive, synergy was observed in ternary infusion mixtures. The synergic action was also detected in the combination of MPP rhizome infusion and RA in the DCFH-DA test. The combinations of mint rhizomes and rosmarinic acid displayed a high dose-reduction index. This leads to beneficial dose reduction at a given antioxidant effect level in mixtures, compared to the dose of the parts used alone. So far, the pharmaceutical and food industry has not used mint rhizomes in commercial products. Hence, our study draws attention to further applications of the Mentha rhizomes as a valuable alternative source of natural antioxidants.


Assuntos
Antioxidantes , Cinamatos , Depsídeos , Flavonoides , Hidroxibenzoatos , Mentha/química , Rizoma/química , Animais , Antioxidantes/química , Antioxidantes/farmacologia , Cinamatos/química , Cinamatos/farmacologia , Depsídeos/química , Depsídeos/farmacologia , Flavonoides/química , Flavonoides/farmacologia , Hidroxibenzoatos/química , Hidroxibenzoatos/farmacologia , Camundongos , Células NIH 3T3
19.
PLoS One ; 15(1): e0227549, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31986186

RESUMO

Over-expression of thymidine phosphorylase (TP) plays a key role in many pathological complications, including angiogenesis which leads to cancer cells proliferation. Thus in search of new anticancer agents, a series of 4-hydroxybenzohydrazides (1-29) was synthesized, and evaluated for in vitro thymidine phosphorylase inhibitory activity. Twenty compounds 1-3, 6-14, 16, 19, 22-24, and 27-29 showed potent to weak TP inhibitory activities with IC50 values in the range of 6.8 to 229.5 µM, in comparison to the standards i.e. tipiracil (IC50 = 0.014 ± 0.002 µM) and 7-deazaxanthine (IC50 = 41.0 ± 1.63 µM). Kinetic studies on selected inhibitors 3, 9, 14, 22, 27, and 29 revealed uncompetitive and non-competitive modes of inhibition. Molecular docking studies of these inhibitors indicated that they were able to interact with the amino acid residues present in allosteric site of TP, including Asp391, Arg388, and Leu389. Antiproliferative (cytotoxic) activities of active compounds were also evaluated against mouse fibroblast (3T3) and prostate cancer (PC3) cell lines. Compounds 1, 2, 19, and 22-24 exhibited anti-proliferative activities against PC3 cells with IC50 values between 6.5 to 10.5 µM, while they were largely non-cytotoxic to 3T3 (mouse fibroblast) cells proliferation. Present study thus identifies a new class of dual inhibitors of TP and cancer cell proliferation, which deserves to be further investigated for anti-cancer drug development.


Assuntos
Simulação por Computador , Inibidores Enzimáticos/farmacologia , Hidroxibenzoatos/farmacologia , Neoplasias da Próstata/patologia , Timidina Fosforilase/antagonistas & inibidores , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/metabolismo , Humanos , Hidroxibenzoatos/síntese química , Hidroxibenzoatos/metabolismo , Cinética , Masculino , Simulação de Acoplamento Molecular , Conformação Proteica , Timidina Fosforilase/química , Timidina Fosforilase/metabolismo
20.
J Photochem Photobiol B ; 203: 111771, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31911399

RESUMO

Ultraviolet B (UVB) radiation triggers the activation of many reactive oxygen species (ROS)-sensitive signaling pathways, resulting in the induction of skin damage that can progress to premature skin aging with long-term exposure. Even after the cessation of UVB radiation, the activated photosensitizers can still cause cellular injury. Thus, the use of photoprotectors that inhibit or prevent intracellular ROS production during or after UV exposure is one alternative to counteract UV-induced oxidative damage. The present study investigated the photoprotective activity of protocatechuic acid (P0) and its alkyl esters ethyl protocatechuate (P2) and heptyl protocatechuate (P7) against UVB-induced damage in L929 fibroblasts by evaluating biomarkers of oxidative stress and photoaging. P0, P2 and P7 markedly increased cell viability after UVB exposure. This protective effect was related to the ability of these compounds to absorb UVB and restore cellular redox balance even 24 h after UVB exposure. P0, P2 and P7 also decreased oxidative damage to membrane lipids, mitochondrial membrane potential, and DNA. They also inhibited the nuclear translocation of NF-κB p65 and downregulated the expression of the photoaging-related proteins matrix metalloproteinases-1 and -9 and cyclooxygenase-2. As the lipophilicity of the P0 derivatives increased, their antioxidant potency increased, but more pronounced cytotoxic effects were also detected. In summary, P0 and P2 may be promising candidates for the prevention and treatment of UVB-induced skin photodamage and photoaging.


Assuntos
Senescência Celular/efeitos dos fármacos , Ésteres/química , Hidroxibenzoatos/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Raios Ultravioleta , Animais , Antioxidantes/química , Antioxidantes/metabolismo , Linhagem Celular , Senescência Celular/efeitos da radiação , Ciclo-Oxigenase 2/metabolismo , Regulação para Baixo/efeitos dos fármacos , Fibroblastos/citologia , Hidroxibenzoatos/química , Peroxidação de Lipídeos/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos da radiação , Metaloproteinase 1 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , NADPH Oxidases/metabolismo , Oxirredução , Estresse Oxidativo/efeitos da radiação , Substâncias Protetoras/química , Substâncias Protetoras/farmacologia , Espécies Reativas de Oxigênio/metabolismo
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