Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 27
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Front Nutr ; 8: 737521, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34676235

RESUMO

The fruit of Lycium ruthenicum (LRF), known as black wolfberry, is a medicinal and edible fruit. The fresh LRF is perishable and has only about 3 days of shelf life. Drying could prolong the shelf life of LRF. However, it could imply physical changes and chemical modification. This study evaluated the effect of sun drying (SD), hot air drying (HD), and freeze drying (FD) on the appearance characteristics, moisture content, bioactive compounds, amino acid composition, and antioxidant activity of LRF. The results showed that LRF dried by FD was round, expansive, fragile, and maintained the largest amount of appearance traits among the three drying methods. Drying methods had a significant effect on phytochemical content and antioxidant activity of LRF (P < 0.05). Principal component analysis (PCA) showed that procyanidin content (PAC), asparagine (Asn), total phenolic content (TPC), total anthocyanin content (TAC), and moisture content were the main sources of the difference in LRF dried by different methods. The characteristic of LRF in FD was low moisture content, and high TPC, Asn, PAC, and TAC. Sun drying was opposite to FD. Hot air drying was high TPC and low TAC content. The quality of LRF was in the order of FD > HD > SD based on comprehensive evaluation of the phytochemical component content and antioxidant capacity. Additionally, the water temperature and soaking time had different antioxidant activity effect on LRF dried by different methods. These findings will provide useful information for production and utilization of LRF.

2.
Molecules ; 26(17)2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34500814

RESUMO

The investigation of the constituents of the rhizomes of Dioscorea collettii afforded one new dihydroisocoumarin, named (-)-montroumarin (1a), along with five known compounds-montroumarin (1b), 1,1'-oxybis(2,4-di-tert-butylbenzene) (2), (3R)-3'-O-methylviolanone (3a), (3S)-3'-O-methylviolanone (3b), and (RS)-sativanone (4). Their structures were elucidated using extensive spectroscopic methods. To the best of our knowledge, compound 1a is a new enantiomer of compound 1b. The NMR data of compound 2 had been reported but its structure was erroneous. The structure of compound 2 was revised on the basis of a reinterpretation of its NMR data (1D and 2D) and the assignment of the 1H and 13C NMR data was given rightly for the first time. Compounds 3a-4, three dihydroisoflavones, were reported from the Dioscoreaceae family for the first time. The cytotoxic activities of all the compounds were tested against the NCI-H460 cell line. Two dihydroisocoumarins, compounds 1a and 1b, displayed moderate cytotoxic activities, while the other compounds showed no cytotoxicity.

3.
Food Chem Toxicol ; 157: 112581, 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34562529

RESUMO

Lung cancer caused one-quarter of all cancer deaths that was more than other cancers. Chemoprevention is a potential strategy to reducing lung cancer incidence and death, and the effective chemopreventive agents are needed. We investigated the efficacy and mechanism of garlic oil (GO), the garlic product, in the chemoprevention of tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung cancer in A/J mice and MRC-5 cell models in the present study. As a result, it was demonstrated that GO significantly inhibited the NNK-induced lung cancer in vivo and protected MRC-5 cells from NNK-induced cell damage. GO could induce the expressions of the phase II drug-metabolizing enzymes, including NAD(P)H: quinone oxidoreductase 1 (NQO-1), glutathione S-transferase alpha 1 (GSTA1), and antioxidative enzymes heme oxygenase-1 (HO-1). These results supported the potential of GO as a novel candidate agent for the chemoprevention of tobacco carcinogens induced lung cancer.

4.
Eur J Med Chem ; 222: 113599, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34119834

RESUMO

Blocking the Kelch-like epichlorohydrin-related protein 1 (Keap1)-nuclear factor-erythroid 2 related factor 2 (Nrf2) pathway represents as a promising strategy to reduce oxidative stress and related-inflammation, including acute lung injury (ALI). NXPZ-2, a naphthalensulfonamide derivative, was previously reported to effectively inhibit the Keap1-Nrf2 protein-protein interaction (PPI) by our group. In the present work, a series of novel isothiocyanate-containing naphthalensulfonamides with the thioether, sulfoxide and sulfone moieties were designed by a structure-based molecular hybridization strategy using NXPZ-2 and the Nrf2 activator sulforaphane. They possessed good Keap1-Nrf2 PPI inhibitory activity and low cytotoxicity. The molecular docking study was performed to further explain the different activity of the thioether-, sulfoxide- and sulfone-containing naphthalensulfonamides. Among these new derivatives, 2-((N-(4-((N-(2-amino-2-oxoethyl)-4-((3-isothiocyanatopropyl)sulfinyl)phenyl)sulfonamido) naphthalen-1-yl)-4-methoxyphenyl)sulfonamido)acetamide (SCN-16) showed a good KD2 value of 0.455 µM to disrupt the PPI. In an LPS-induced peritoneal macrophage cell model, this compound could cause a significant increase in the nuclear Nrf2 protein, decrease in the cytosolic Nrf2 protein, and further elevate the downstream protective enzymes HO-1 and NQO-1, which were better than the lead compound NXPZ-2 and sulforaphane. What's more, the production of ROS and NO and the expression of pro-inflammatory cytokine TNF-α were also suppressed. In the LPS-induced ALI model, SCN-16 could significantly reduce LPS-induced inflammations and alleviate lung injuries by triggering Nrf2 nuclear translocation. Collectively, our results suggested that SCN-16 could be a novel lead compound targeting Keap1-Nrf2 protective pathway for clinical treatment of ALI.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Proteína 1 Associada a ECH Semelhante a Kelch/antagonistas & inibidores , Fator 2 Relacionado a NF-E2/antagonistas & inibidores , Naftalenos/farmacologia , Substâncias Protetoras/farmacologia , Sulfonamidas/farmacologia , Lesão Pulmonar Aguda/metabolismo , Animais , Relação Dose-Resposta a Droga , Desenho de Fármacos , Feminino , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Estrutura Molecular , Fator 2 Relacionado a NF-E2/metabolismo , Naftalenos/síntese química , Naftalenos/química , Substâncias Protetoras/síntese química , Substâncias Protetoras/química , Relação Estrutura-Atividade , Sulfonamidas/síntese química , Sulfonamidas/química
5.
Chem Biol Interact ; 344: 109496, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-33939976

RESUMO

An increased risk of developing lung cancer has been associated with exposure to cigarette smoke carcinogens and alteration in the gut microbiota. However, there is limited understanding about the impact of exposure to NNK and BaP, the two important components of cigarette smoke carcinogens, on gut microbiota in lung cancer. The present study characterized the influence of exposure to a mixture of NNK plus BaP on lung cancer, feces metabolite composition, and gut microbiota in the A/J mice. The A/J mice were administered NNK plus BaP, and the changes in gut microbiota and feces metabolic profiles were characterized using 16S rRNA gene sequencing and metabolomics, respectively. Results presented here illustrated that a mixture of NNK plus BaP exposure triggered lung carcinogenesis as shown by light microscopy and histopathological evaluation. 16S rRNA sequencing of gut microbiota indicated that exposure to NNK plus BaP could modified fecal bacterial composition. Elevated levels of Actinobacteria, Bifidobacterium, and Intestinimonas and reduced levels of Alistipes, Odoribacter, and Acetatifactor are associated with NNK plus BaP triggered lung cancer. In addition, metabolomics profile revealed the regulation of metabolism including purine metabolism, phenylalanine metabolism, primary bile acid biosynthesis, steroid hormone biosynthesis, biosynthesis of unsaturated fatty acids, linoleic acid metabolism, and others. In conclusion, the results provide some guidance for using gut microbes as biomarkers to assess the progression of lung cancer, and lead to interventional targets to control the development of the disease in the future.


Assuntos
Adenocarcinoma de Pulmão/metabolismo , Benzo(a)pireno/farmacologia , Carcinógenos/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Metaboloma/efeitos dos fármacos , Nitrosaminas/farmacologia , Adenocarcinoma de Pulmão/complicações , Adenocarcinoma de Pulmão/patologia , Animais , Bactérias/metabolismo , Disbiose/etiologia , Disbiose/metabolismo , Fezes/química , Fezes/microbiologia , Feminino , Pulmão/patologia , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Metabolômica , Camundongos Endogâmicos
6.
Bioorg Med Chem Lett ; 43: 128084, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33964444

RESUMO

Necroptosis is a form of programmed cell death that contributes to the pathophysiology of multiple diseases. Development of small-molecule anti-necroptosis agents has great promising clinical therapeutic relevance. The benzothiazole compounds were discovered by our group from an in-house fluorine-containing compound library as potent necroptosis inhibitors. Herein, a chiral dimethylcyclopropyl benzothiazole necroptosis inhibitor was developed and the enantiomeric profiling resulted that the (S) form was generally more potent than the (R) counterpart in 2 ~ 4-fold toward cell necroptosis, receptor-interacting protein (RIP) kinases 1 and 3. The chiral compounds could significantly inhibit the expression of the phosphorylation of RIPK1, RIPK3 and MLKL in necroptotic cells. The molecular modelling studies predicted the binding modes of the enantiomers with RIP and explained their activity differences, guiding further rational design of the chiral necroptosis inhibitors.

7.
Free Radic Biol Med ; 159: 87-102, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-32730855

RESUMO

Oxidative stress is considered as one of the pathogenesis of Alzheimer's disease (AD) and plays an important role in the occurrence and development of AD. Nuclear factor erythroid 2 related factor 2 (NRF2) is a key regulatory of oxidative stress defence. There is growing evidence indicating the relationship between NRF2 and AD. NRF2 activation mitigates multiple pathogenic processes involved in AD by upregulating antioxidative defense, inhibiting neuroinflammation, improving mitochondrial function, maintaining proteostasis, and inhibiting ferroptosis. In addition, several NRF2 activators are currently being evaluated as AD therapeutic agents in clinical trials. Thus, targeting NRF2 has been the focus of a new strategy for prevention and treatment of AD. In this review, the role of NRF2 in AD and the NRF2 activators advanced into clinical and preclinical studies will be summarized.


Assuntos
Doença de Alzheimer , Fator 2 Relacionado a NF-E2 , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/genética , Antioxidantes/uso terapêutico , Regulação da Expressão Gênica , Humanos , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo
8.
Nanoscale Res Lett ; 15(1): 10, 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31933217

RESUMO

Point-of-care testing (POCT) is widely used for early diagnosis and monitoring of diseases. Lateral flow assay (LFA) is a successfully commercial tool for POCT. However, LFA often suffers from a lack of quantification and analytical sensitivity. To solve these drawbacks, we have previously developed a thermal LFA using plasmonic gold nanoparticles for thermal contrast into a portable device. Although this methodology significantly improves the analytical sensitivity compared with conventional visual detection, quantification problems are still remaining. In this study, we optimized the operating conditions for the device using conduction and radiation thermal sensing modes allowing the quantification of LFA. The limit of detection of the strips merely containing nanoparticles was decreased by 5-fold (conduction mode) and 12-fold (radiation mode) compared to traditional visual detection. The effect of the ambient temperature was studied for both methods of detection showing that the radiation mode was more affected by the ambient temperature than the conduction mode. To validate the thermal sensing method, human chorionic gonadotropin (HCG) biomarker was quantified using our LFA strips, obtaining a detection limit of 2.8 mIU/mL when using the radiation method of detection.

9.
Phytomedicine ; 53: 124-133, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30668391

RESUMO

BACKGROUND: Lung cancer is the leading cause of global cancer-related mortality. Dioscin-6'-O-acetate (DA), a novel natural steroidal saponin, was firstly isolated from the rhizomes of Dioscorea althaeoides R. Knuth. Until now, there were no studies on its pharmacological activities. PURPOSE: Here, we investigated the growth inhibitory effect and explored the underlying molecular mechanisms of DA against lung cancer cells. METHODS/STUDY DESIGNS: NSCLC H460, H1299, H520 cells and SCLC H446 cells were treated with DA. To display the cytotoxic effects and possible mechanism of DA on these cells, MTT assay, flow cytometry and western blot analysis were carried out. RESULTS: Our results showed that DA exerted strong anti-proliferative activity against lung cancer cells in a concentration- and time-dependent manner. Flow cytometry demonstrated DA induced the cell cycle arrest at S-phase (NCI-H460, NCI-H1299, NCI-H520) or G1-phase (NCI-H446), caused cellular apoptosis, generation of reactive oxygen species (ROS) and loss of mitochondrial membrane potential. Western blotting analysis showed DA treatment increased the levels of caspase 3, 8, 9, Bax, p21, p53, phosphorylated JNK and p38 MAPK and markedly decreased the expression of Bcl-2, p-ERK, p-PI3K, p-AKT and NF-κB. Blockade of caspases with Z-VAD-FMK converted apoptosis-related proteins. Suppression of p53 with pifithrin-α (PFT) attenuated cell cycle-related protein. Inhibition of ROS with N-acetyl-cysteine (NAC) adjusted apoptosis-related proteins and phosphorylated MAPK and PI3K, as well as NF-κB. CONCLUSION: Overall, our study indicated that DA suppressed lung cancer cells proliferation via inducing cell-cycle arrest and enhancing caspase-dependent apoptosis, at least partly, through ROS-mediated PI3K/AKT, MAPK and NF-κB signaling pathways.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Neoplasias Pulmonares/tratamento farmacológico , Saponinas/farmacologia , Espirostanos/farmacologia , Antineoplásicos Fitogênicos/química , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/metabolismo , Caspases/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Potencial da Membrana Mitocondrial/efeitos dos fármacos , NF-kappa B/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Saponinas/química , Transdução de Sinais/efeitos dos fármacos , Espirostanos/química , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
10.
J Med Chem ; 62(12): 5750-5772, 2019 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-30676015

RESUMO

Apoptosis, an important form of programmed cell death (PCD), is a tightly regulated cellular process to eliminate unwanted or damaged cells. Resistance of apoptosis is a hallmark of cancer cells. Inhibitor of apoptosis proteins (IAPs) is a class of key apoptosis regulators that promote cancer cell resistant to apoptosis, particularly in cancer treatment. Disrupting the binding of IAPs with their functional partners therefore is a promising strategy to restore the apoptotic response to proapoptotic stimuli, particularly those introduced by standard cancer therapies. The most successful example is the use of small molecules to mimic the IAP-binding motif of an endogenous IAP antagonist, second mitochondria-derived activator of caspase (SMAC). Here we will review the functions of IAPs, the structural interactions of IAPs with SMAC, four generations of SMAC-mimetic IAP antagonists, and representative antagonists in clinical evaluations, focusing on research articles over the past 15 years. Outlooks and perspectives on the associated challenges are provided as well.


Assuntos
Antineoplásicos/farmacologia , Descoberta de Drogas/métodos , Proteínas Inibidoras de Apoptose/antagonistas & inibidores , Animais , Antineoplásicos/química , Humanos , Proteínas Inibidoras de Apoptose/química , Proteínas Inibidoras de Apoptose/metabolismo
11.
Int J Biol Macromol ; 121: 381-389, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30315881

RESUMO

Polysaccharides (ASP) were extracted from Angelica Sinensis Radix (ASR) and were subjected to freeze drying (ASP-FD), vacuum drying (ASP-VD), and hot air drying (ASP-HD). Structural characteristics, rheological and emulsifying properties, antioxidant, anticoagulant and alkaline phosphatase inhibitory activities of ASPs were firstly investigated. ASP-FD owned higher thermostability, unique morphological structure, uniform and the lowest molecular weight, which is suitable for using as a raw material for polysaccharide derivatives. Smaller viscosity of ASP-FD supplied a better appearance that consumers preferred and the smallest particle size was benefit to manufacture instant soluble products. ASP-VD behaved the highest neutral sugar content, protein content, intrinsic viscosities, and the best emulsifying activity, being a candidate for cosmetics additive. ASP-HD exhibited the highest apparent viscosities, higher thermostability, loose structure, and better bioactivities. Drying conditions had significant effect on the physicochemical properties and bioactivities of ASPs. ASPs with specific characteristics may meet the requirements for diverse applications.


Assuntos
Angelica sinensis/química , Fenômenos Químicos , Dessecação/métodos , Raízes de Plantas/química , Polissacarídeos/química , Polissacarídeos/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Peso Molecular , Monossacarídeos/análise , Trombina/antagonistas & inibidores , Viscosidade
12.
Fitoterapia ; 127: 42-46, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29698682

RESUMO

Two novel 18,19-seco-ursane triterpenoid saponins, ilexasprellanosides J-K (1-2, resp.), 3-O-α-l-Rhamnopyranosyl-(1 → 2)-ß-d-xylopyrannosyl-19-O-ß-d-glucopyranosyl-16-ß-hydroxyl-18,19-seco-13(18)-urs-ene-21, 28-lactone (1), 3-O-ß-d-Xylopyrannosyl-19-O-α-l-rhamnopyran osyl-(1 → 2)-α-l-arabinopyranoside-16, 21-epoxy-18, 19-seco-13(18)-urs-ene-28-oic acid (2), five known compounds (3-7) were isolated from the leaves of Ilex asprella (Hook. et Arn.) Champ. ex Benth. (Gangmeiye). The chemical structures of these compounds were elucidated through UV, IR, ESI-MS, 1H NMR and 13C NMR analyses. In MTT and SRB assays, compounds 1-4 presented cytotoxic activities against several human cancer cell lines, namely, the HL-60 human acute promyelocytic leukaemia, Bel 7402 liver cancer, BGC-823 gastric cancer and KB human nasopharyngeal carcinoma cell lines. Compound 1 exhibited weak cytotoxic activities against the human tumour cell lines HL-60, Bel 7402 and KB with inhibition rates of 27.97%, 21.00% and 25.60%, respectively. Compound 2 exhibited weak cytotoxic activities against the human tumour cell lines HL-60, Bel 7402 and BGC-823 with inhibition rates of 19.34%, 7.50% and 4.26%. Respectively, the compounds exerted no statistically different effects on mast cell degranulation in rats. This result indicates that the compounds do not affect mast cell degranulation.


Assuntos
Ilex/química , Saponinas/isolamento & purificação , Triterpenos/isolamento & purificação , Animais , Degranulação Celular , Linhagem Celular Tumoral , Humanos , Mastócitos/efeitos dos fármacos , Estrutura Molecular , Folhas de Planta/química , Ratos
13.
ACS Nano ; 11(12): 12446-12452, 2017 12 26.
Artigo em Inglês | MEDLINE | ID: mdl-29195042

RESUMO

Polymer-based fluorescent nanomaterials have proven to universally image various tumors based on their extremely sharp responsiveness to pH change. Such a property has never been realized in supramolecular systems. We herein design a small molecule (DPP-thiophene-4) that is composed of a diketopyrrolopyrrole (DPP) core and two alkyl chains terminated with quaternary ammonium. DPP-thiophene-4 can self-assemble into a nonfluorescent nanoassembly when the pH is >7.0 but reversibly disassembles back to fluorescent monomers when the pH is <6.8. Meanwhile, its fluorescence emission increases by 10-fold within a 0.2 pH unit change. Such a fluorogenic nanoassembly can precisely differentiate a number of malignant tumors among normal tissues in vivo due to the slight acidity within tumor microenvironments. Further the nanoassembly shows satisfactory biocompatibility and an effective clearance from the body. Overall, this supramolecular fluorogenic nanoassembly exhibits an immense potential for realizing broad range tumor diagnosis.


Assuntos
Antineoplásicos/química , Cetonas/química , Nanopartículas/química , Neoplasias/diagnóstico por imagem , Pirróis/química , Tiofenos/química , Animais , Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Ensaios de Seleção de Medicamentos Antitumorais , Células HeLa , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Concentração de Íons de Hidrogênio , Cetonas/farmacologia , Células MCF-7 , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias/tratamento farmacológico , Neoplasias Experimentais/diagnóstico por imagem , Neoplasias Experimentais/tratamento farmacológico , Pirróis/farmacologia , Tiofenos/farmacologia , Microambiente Tumoral/efeitos dos fármacos
14.
Food Chem ; 224: 224-232, 2017 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-28159260

RESUMO

The effects of five different drying processes, air drying (AD), sulphur fumigation drying (SFD), hot air drying (HAD), freeze drying (FD) and microwave drying (MWD) for yams in terms of starch-related properties and antioxidant activity were studied. From the results of scanning electron microscopy (SEM), polarized optical microscopy (POM), X-ray diffraction (XRD), and Fourier transform infrared (FT-IR), the MWD sample was found to contain gelatinized starch granules. The FD yam had more slow digestible (SDS) and resistant starches (RS) compared with those processed with other modern drying methods. The bioactive components and the reducing power of the dried yams, were lower than those of fresh yam. When five dried samples were compared by principal component analysis, the HAD and SFD samples were observed to have the highest comprehensive principal component values. Based on our results, HAD would be a better method for yam drying than the more traditional SFD.


Assuntos
Antioxidantes/farmacologia , Dioscorea/química , Farinha/análise , Amido/química , Dessecação , Liofilização , Fumigação , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X
15.
J Agric Food Chem ; 65(2): 291-300, 2017 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-28001065

RESUMO

Prunella vulgaris L. is as a major plant in the Chinese traditional functional beverage Guangdong herbal tea for the treatment of fevers, diarrhea, and sore mouth. In this study, ethyl acetate parts of aqueous extracts from P. vulgaris L. (EtOAc-APV) were found to demonstrate potent acetylcholinesterase (AChE) inhibition in vitro. Therefore, this study was designed to further investigate the effects of EtOAc-APV on scopolamine (SCOP)-induced aging rats. Male Wistar rats were randomly divided into four groups (n = 12) and given orally by gavage EtOAc-APV (100 mg/kg) for 3 weeks. SCOP (1 mg/kg, ip) was administered to rats 30 min before starting behavioral tests consecutively for 3 days. EtOAc-APV could attenuate SCOP-induced brain senescence in rats by improving behavioral performance and decreasing brain cell damage, which was associated with a notable reduction in AChE activity and MDA level, as well as an increase in SOD and GPx activities. Additionally, EtOAc-APV administration could reduce the expression of NF-κB and GFAP, which showed an anti-neuroinflammatory effect on the SCOP-treated rat. Overall, the current study highlights P. vulgaris L. as an antidementia dietary supplement.


Assuntos
Transtornos da Memória/tratamento farmacológico , Extratos Vegetais/farmacologia , Prunella/química , Escopolamina/efeitos adversos , Animais , Apoptose/efeitos dos fármacos , Ácidos Cafeicos/análise , Inibidores da Colinesterase/farmacologia , Cinamatos/análise , Depsídeos/análise , Flavonoides/análise , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Transtornos da Memória/induzido quimicamente , NF-kappa B/metabolismo , Fármacos Neuroprotetores/farmacologia , Plantas Medicinais/química , Ratos Wistar
16.
Int J Food Sci Nutr ; 67(7): 806-17, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27345860

RESUMO

Ferulic acid (FA) acts as a powerful antioxidant against various age-related diseases. To investigate the effect and underlying mechanism of FA against d-galactose(d-gal)-induced memory deficit, mice were injected with d-gal to induce memory impairment and simultaneously treated with FA and donepezil. The behavioral results revealed that chronic FA treatment reversed d-gal-induced memory impairment. Further, FA treatment inhibited d-gal-induced AChE activity and oxidative stress via increase of superoxide dismutase activity and reduced glutathione content, as well as decrease of malondialdehyde and nitric oxide levels. We also observed that FA significantly inhibits inflammation in the brain through reduction of NF-κB and IL-1ß by enzyme-linked immunosorbent assay. Additionally, FA treatment significantly reduces the caspase-3 level in the hippocampus of d-gal-treated mice. Hematoxylin and eosin and Nissl staining showed that FA prevents neurodegeneration induced by d-gal. These findings showed that FA inhibits d-gal-induced AChE activity, oxidative stress, neuroinflammation and neurodegeneration, and consequently ameliorates memory impairment.


Assuntos
Envelhecimento/efeitos dos fármacos , Ácidos Cumáricos/farmacologia , Galactose/toxicidade , Transtornos da Memória/tratamento farmacológico , Acetilcolinesterase/metabolismo , Animais , Antioxidantes/farmacologia , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Caspase 3/metabolismo , Modelos Animais de Doenças , Donepezila , Glutationa/metabolismo , Hipocampo/efeitos dos fármacos , Indanos/farmacologia , Interleucina-1beta/metabolismo , Masculino , Malondialdeído/metabolismo , Transtornos da Memória/induzido quimicamente , Camundongos , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Piperidinas/farmacologia , Superóxido Dismutase/metabolismo
17.
Pharm Biol ; 54(11): 2742-2752, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27251608

RESUMO

CONTEXT: Folium Eriobotryae (FE), the dry leaf of Eriobotrya japonica (Thunb.) Lindl. (Rosaceae), has been widely used to treat respiratory disorders. OBJECTIVE: To examine the bronchodilatory activity of FE and the potential mechanisms involved. MATERIALS AND METHODS: The effects of ethyl acetate fraction of FE (EFE) (0.05-0.3 mg/mL) on the isolated tracheal strips, and ursolic acid (UA) (5-30 µg/mL) that was the main constituent of EFE, were tested in vitro. Meanwhile, acetylcholine (Ach) and histamine (His)-induced bronchospasm were conducted in vivo in guinea pig. Furthermore, mechanisms of relaxant effects of EFE and UA were evaluated in the absence and presence of specific inhibitors. RESULTS: With in vitro studies, the contractile response evoked by Ach or His (EC50 = 0.21 and 0.16 mg/mL) was decreased by EFE, and UA caused a concentration-dependent relaxation precontracted by His (EC50 = 23.2 µg/mL). With in vivo studies, EFE strongly prolonged preconvulsive time similar to isoprenalin. The bronchodilator effects of EFE could be blocked by propranolol (1 µM), NG-nitro-l-arginine methyl ester (l-NAME) (100 µM) and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one (ODQ) (1 µM). EFE also inhibited the contraction in Ca2+-free medium and produced rightward parallel displacement of CaCl2 curves. In addition, the relaxant effects of UA could only be blocked by l-NAME and ODQ. DISCUSSION AND CONCLUSION: These results suggest that bronchodilator activities of EFE were related to activation of ß-adrenoceptor and NO/cGMP pathway. Blockage of Ca2+ channels and inhibition of IP3R-mediated internal Ca2+ release were also involved. Additionally, UA produced relaxant effects by the NO/cGMP pathway.


Assuntos
Broncodilatadores/farmacologia , Eriobotrya , Extratos Vegetais/farmacologia , Traqueia/efeitos dos fármacos , Triterpenos/farmacologia , Animais , Cálcio/metabolismo , AMP Cíclico/fisiologia , Eriobotrya/química , Cobaias , Técnicas In Vitro , Masculino , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico/fisiologia , Oxidiazóis/farmacologia , Quinoxalinas/farmacologia , Traqueia/fisiologia
18.
Neurochem Res ; 41(9): 2199-214, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27161371

RESUMO

Cerebralcare granule(®) (CG) is a preparation of Traditional Chinese Medicine that widely used in China. It was approved by the China State Food and Drug Administration for treatment of headache and dizziness associated with cerebrovascular diseases. In the present study, we aimed to investigate whether CG had protective effect against D-galactose (gal)-induced memory impairment and to explore the mechanism of its action. D-gal was administered (100 mg/kg, subcutaneously) once daily for 8 weeks to induced memory deficit and neurotoxicity in the brain of aging mouse and CG (7.5, 15, and 30 g/kg) were simultaneously administered orally. The present study demonstrates that CG can alleviate aging in the mouse brain induced by D-gal through improving behavioral performance and reducing brain cell damage in the hippocampus. CG prevents aging mainly via suppression of oxidative stress response, such as decreasing NO and MDA levels, renewing activities of SOD, CAT, and GPx, as well as decreasing AChE activity in the brain of D-gal-treated mice. In addition, CG prevents aging through inhibiting NF-κB-mediated inflammatory response and caspase-3-medicated neurodegeneration in the brain of D-gal treated mice. Taken together, these data clearly demonstrates that subcutaneous injection of D-gal produced memory deficit, meanwhile CG can protect neuron from D-gal insults and improve memory ability.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Transtornos da Memória/tratamento farmacológico , Memória/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Envelhecimento/efeitos dos fármacos , Animais , Transtornos Cognitivos/tratamento farmacológico , Modelos Animais de Doenças , Galactose/farmacologia , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Neurônios/metabolismo , Estresse Oxidativo/efeitos dos fármacos
19.
Environ Toxicol Pharmacol ; 41: 22-31, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26650795

RESUMO

Cerebralcare granule(®) (CG) has been reported to have hypotensive effect. However, several pathways involved in the mechanism of hypotension are still unclear. This study was designed to verify the antihypertensive effect of CG and to characterize its mechanism of action, especially from the perspective of gasotrasmmiter NO/cGMP, CO/HO and H2S/CSE systems. By using the widely used in vitro model of rat isolated thoracic aortic rings, the vasorelaxant effect of CG were studied. Furthermore, we assessed the chronic hypotensive effect of CG on spontaneously hypertensive rats (SHRs) and further to explore the potential mechanisms of its antihypertensive activity. Data in the present study demonstrated that oral treatment with CG could induce a potent antihypertensive effect. CG could reduce the intima-media thickness (IMT) of thoracic aorta significantly and increase the serum NO and H2S levels. In addition, the present results indicated that CG played a critical protective role against pressure overload-induced cardiac hypertrophy. CG not only inhibited the development of cardiac hypertrophy but also improved ventricular function. In vitro, the results showed that CG induced relaxation in rat aortic rings through an endothelium-dependent pathway mediated by NO/cGMP, CO/HO and H2S/CSE systems. Taken together, the present study demonstrated that CG could induce a potent antihypertensive effect that was partly due to the improvement of endothelial function. Also CG played a critical protective role against pressure overload-induced cardiac hypertrophy. In addition, CG could induce relaxation in rat aortic rings.


Assuntos
Anti-Hipertensivos/administração & dosagem , Medicamentos de Ervas Chinesas/administração & dosagem , Testes de Função Cardíaca/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Vasodilatadores/administração & dosagem , Administração Oral , Animais , Anti-Hipertensivos/farmacologia , Aorta Torácica/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Sulfeto de Hidrogênio/sangue , Hipertensão/sangue , Hipertensão/fisiopatologia , Masculino , Óxido Nítrico/sangue , Ratos , Ratos Endogâmicos SHR , Túnica Íntima/efeitos dos fármacos , Vasodilatadores/farmacologia
20.
Physiol Behav ; 154: 114-25, 2016 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-26592138

RESUMO

Aging is associated with Alzheimer's disease (AD), cardiovascular disease and cancer. Oxidative stress is considered as a major factor that accelerates the aging process. d-galactose (d-gal), a reducing sugar, induces oxidative stress resulting in alteration in mitochondrial dynamics and apoptosis of neurons. To understand the ability of tetrahydropalmatine (THP) to ameliorate memory impairment caused by aging, we investigated the effect of THP on d-gal induced memory impairment in rats. Subcutaneous injection of d-gal (100mg/kg/d) for 8weeks caused memory loss as detected by the Morris water maze and morphologic abnormalities of neurons in the hippocampus regions and cortex of rat brain. THP treatment ameliorated d-gal induced memory impairment associated with the decrease of malondialdehyde (MDA) and nitric oxide (NO) contents, as well as the increase of glutathione (GSH) levels, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities. THP treatment was also found to reverse the abnormality of acetylcholine (ACh) levels and acetylcholinesterase (AChE) activities. In addition, treatment with THP could decrease the expression of nuclear factor κ (NF-κB) and glial fibrillary acidic protein (GFAP) which prevented the neuroinflammation and memory impairment in the d-gal treated rats. Taken together, these results clearly demonstrated that subcutaneous injection of d-gal produced memory deficits, meanwhile THP could protect neuron from d-gal insults and improve cognition. This study provided an experimental basis for clinical application of THP in AD therapy.


Assuntos
Alcaloides de Berberina/uso terapêutico , Galactose/toxicidade , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Análise de Variância , Animais , Alcaloides de Berberina/química , Alcaloides de Berberina/farmacologia , Peso Corporal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Comportamento Exploratório/efeitos dos fármacos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Transtornos da Memória/patologia , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/farmacologia , Ratos , Ratos Wistar , Fatores de Tempo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...