Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 4.589
Filtrar
1.
Mem Inst Oswaldo Cruz ; 115: e200207, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33027419

RESUMO

BACKGROUND: Since the World Health Organization (WHO) declared Coronavirus disease 2019 (COVID-19) to be a pandemic infection, important severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) non-structural proteins (nsp) have been analysed as promising targets in virtual screening approaches. Among these proteins, 3-chymotrypsin-like cysteine protease (3CLpro), also named main protease, and the RNA-dependent RNA polymerase (RdRp), have been identified as fundamental targets due to its importance in the viral replication stages. OBJECTIVES: To investigate, in silico, two of the most abundant flavonoid glycosides from Dysphania ambrosioides; a medicinal plant found in many regions of the world, along with some of the putative derivatives of these flavonoid glycosides in the human organism as potential inhibitors of the SARS-CoV-2 3CLpro and RdRp. METHODS: Using a molecular docking approach, the interactions and the binding affinity with SARS-CoV-2 3CLpro and RdRp were predicted for quercetin-3-O-rutinoside (rutin), kaempferol-3-O-rutinoside (nicotiflorin) and some of their glucuronide and sulfate derivatives. FINDINGS: Docking analysis, based on the crystal structure of 3CLpro and RdRp, indicated rutin, nicotiflorin, and their glucuronide and sulfate derivatives as potential inhibitors for both proteins. Also, the importance of the hydrogen bond and π-based interactions was evidenced for the presumed active sites. MAIN CONCLUSIONS: Overall, these results suggest that both flavonoid glycosides and their putative human metabolites can play a key role as inhibitors of the SARS-CoV-2 3CLpro and RdRp. Obviously, further researches, mainly in vitro and in vivo experiments, are necessary to certify the docking results reported here, as well as the adequate application of these substances. Furthermore, it is necessary to investigate the risks of D. ambrosioides as a phytomedicine for use against COVID-19.


Assuntos
Betacoronavirus/efeitos dos fármacos , Flavonoides/farmacologia , Glicosídeos/farmacologia , RNA Replicase/antagonistas & inibidores , Proteínas não Estruturais Virais/antagonistas & inibidores , Infecções por Coronavirus , Cisteína Endopeptidases , Humanos , Simulação de Acoplamento Molecular , Pandemias , Pneumonia Viral
2.
Cell Prolif ; 53(8): e12866, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32643284

RESUMO

OBJECTIVES: High glucose (HG)-mediated bone marrow mesenchymal stem cell (BMSC) dysfunction plays a key role in impaired bone formation induced by type 1 diabetes mellitus (T1DM). Morroniside is an iridoid glycoside derived from the Chinese herb Cornus officinalis, and it has abundant biological activities associated with cell metabolism and tissue regeneration. However, the effects and underlying mechanisms of morroniside on HG-induced BMSC dysfunction remain poorly understood. MATERIALS AND METHODS: Alkaline phosphatase (ALP) staining, ALP activity and Alizarin Red staining were performed to assess the osteogenesis of BMSCs. Quantitative real-time PCR and Western blot (WB) were used to investigate the osteo-specific markers, receptor for advanced glycation end product (RAGE) signalling and glyoxalase-1 (Glo1). Additionally, a T1DM rat model was used to assess the protective effect of morroniside in vivo. RESULTS: Morroniside treatment reverses the HG-impaired osteogenic differentiation of BMSCs in vitro. Morroniside suppressed advanced glycation end product (AGEs) formation and RAGE expression by triggering Glo1. Moreover, the enhanced osteogenesis due to morroniside treatment was partially blocked by the Glo1 inhibitor, BBGCP2. Furthermore, in vivo, morroniside attenuated bone loss and improved bone microarchitecture accompanied by Glo1 upregulation and RAGE downregulation. CONCLUSIONS: These findings suggest that morroniside attenuates HG-mediated BMSC dysfunction partly through the inhibition of AGE-RAGE signalling and activation of Glo1 and may be a potential treatment for diabetic osteoporosis.


Assuntos
Glicosídeos/farmacologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Receptor para Produtos Finais de Glicação Avançada/efeitos dos fármacos , Animais , Diferenciação Celular/efeitos dos fármacos , Produtos Finais de Glicação Avançada/efeitos dos fármacos , Osteoporose/tratamento farmacológico , Ratos Sprague-Dawley , Cicatrização/efeitos dos fármacos
3.
J Environ Pathol Toxicol Oncol ; 39(1): 89-99, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32479015

RESUMO

Oxidative stress and inflammation are regarded as prime reasons for the progression and development of diabetic retinopathy. Currently, nuclear factor erythroid-2-related factor 2 (Nrf2), thioredoxin interacting protein (TXNIP) and NLRP3 inflammasome pathways are under increasing focus in research on oxidative stress and inflammation-related diseases. On the other hand, tilianin (TN) has received much attention because of its various pharmacological properties. Based on results of these studies, this investigation was performed to inspect the therapeutic efficiency of TN on the retina in diabetic rats. Rats were arbitrarily assigned to three groups: control group, diabetic group, and diabetic plus TN (20 mg/ kg body weight for 42 days, orally) group. TN supplementation in diabetic rats, their food intake, fasting blood glucose status, glycosylated hemoglobin (HbA1c) levels were drastically reduced, and there was a marked augmentation in serum insulin status. TN treatment of diabetic rats increased mRNA expression of Nrf2 and its target gene, HO-1, and noticeably decreased the malondialdehyde status. Activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidases (GPX) were increased relative to diabetic rats. Furthermore, administering TN to the diabetic rats resulted in decreased expression of TXNIP, NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), caspase-1, and IL-1ß proteins and decreased distribution of TXNIP, NLRP3, ASC, and caspase-1 proteins in retinas. In addition, TN treatment ameliorated morphological and morphometric changes in the retinas of diabetic rats. Together, all of these findings provide clear evidence that TN treatment of diabetic rats attenuated diabetic retinal changes through its hypoglycemic, antioxidant, and anti-inflammatory properties. The antioxidant and anti-inflammatory effects in diabetic retinas occur at least in part through the modulation of Nrf2/TXNIP/NLRP3 inflammasome pathways, which may have remedial benefits in the healing of diabetic retinopathy.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Flavonoides/farmacologia , Glicosídeos/farmacologia , Inflamassomos/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Retina/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Ração Animal/análise , Animais , Dieta , Suplementos Nutricionais/análise , Masculino , Distribuição Aleatória , Ratos , Ratos Wistar , Retina/patologia
4.
Int J Biol Macromol ; 161: 936-938, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32534094

RESUMO

This short report is dedicated to the description of the wide antiviral and antibacterial activity of the immune-modulating agent Panavir®. Panavir® is a high-molecular-weight fraction of the polysaccharides extracted from the shoots of the Solanum tuberosum. It demonstrates activity against many types of viruses, including animal coronavirus and also against bacterial infections. These properties look very promising considering the COVID-19 epidemy and allow propose that Panavir® would be effective in the therapy of the SARS-CoV-2 infection.


Assuntos
Antivirais/farmacologia , Glicosídeos/farmacologia , Herpes Genital/tratamento farmacológico , Adulto , Animais , Antivirais/química , Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/virologia , Modelos Animais de Doenças , Disenteria Bacilar/tratamento farmacológico , Feminino , Glicosídeos/química , Glicosídeos/uso terapêutico , Humanos , Infecções por Klebsiella/tratamento farmacológico , Klebsiella pneumoniae/efeitos dos fármacos , Masculino , Camundongos , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/virologia , Shigella flexneri/efeitos dos fármacos , Adulto Jovem
5.
PLoS One ; 15(5): e0227844, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32470043

RESUMO

Morroniside is a biologically active polyphenol found in Cornus officinalis Sieb. et Zucc (CO) that exhibits a broad spectrum of pharmacological activities, such as protecting nerves, and preventing diabetic liver damage and renal damage. However, little data are available regarding the mechanism of its intestinal absorption. Here, an in vitro human intestinal epithelial cell model of cultured Caco-2 cells was applied to study the absorption and transport of morroniside. The effects of donor concentration, pH and inhibitors were investigated. The bidirectional permeability of morroniside from the apical (AP) to the basolateral (BL) side and in the reverse direction was studied. When administered at three tested concentrations (5, 25 and 100 µM), the apparent permeability coefficient (Papp) values in the AP-to-BL direction ranged from 1.59 × 10-6 to 2.66 × 10-6 cm/s. In the reverse direction, BL-to-AP, the value was ranged from 2.67 × 10-6 to 4.10 × 10-6 cm/s. The data indicated that morroniside transport was pH-dependent. The permeability of morroniside was affected by treatment with various inhibitors, such as multidrug resistance protein inhibitors MK571 and indomethacin, as well as the breast cancer resistance protein inhibitor apigenin. The mechanisms of the intestinal absorption of morroniside may involve multiple transport pathways, such as the passive diffusion and efflux protein-mediated active transport especially involving multidrug resistance protein 2 and breast cancer resistance protein. After the addition of CO, the Papp values in the AP-to-BL direction increased significantly, therefore, it can be assumed that some ingredients in the CO promote morroniside absorption in the small intestine.


Assuntos
Cornus/química , Glicosídeos/farmacologia , Absorção Intestinal/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Subfamília B de Transportador de Cassetes de Ligação de ATP/antagonistas & inibidores , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/antagonistas & inibidores , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/antagonistas & inibidores , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Células CACO-2 , Proliferação de Células/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Indometacina/farmacologia , Absorção Intestinal/genética , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/genética , Neoplasias/patologia , Permeabilidade/efeitos dos fármacos , Propionatos/farmacologia , Quinolinas/farmacologia
6.
Zhongguo Zhong Yao Za Zhi ; 45(4): 746-754, 2020 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-32237474

RESUMO

The aim of this paper was to compare different effects of Tripterygium Glycosides Tablets from 6 different manufacturers on multiple organ injuries in rats and to explore mechanism of hepatotoxicity preliminarily from the perspective of apoptosis and oxidative stress. Rats were randomly divided into the groups normal, Zhejiang, Hunan, Hubei, Shanghai, Jiangsu and Fujian(7 groups with 16 rats in each group, sex in half). Rats were given Tripterygium Glycosides Tablets at 144 mg·kg~(-1)·d~(-1)(16 times the clinical equivalent dose) once a day according to its corresponding group like rats in Zhejiang group was given Tripterygium Glycosides Tablets from Zhejiang manufactures continuously for 20 days with the life and death situation of mice to be observed, then rats were executed to detect various indicators. RESULTS:: showed that 8 female rats in Zhejiang group died after 15 days of administration, the serum NEUT of rats in Hubei, Fujian and Shanghai groups was significantly lower than that of normal rats. The serum AST, ALT and/or TBiL levels were increased in all rats, and serum BUN and/or CRE levels of rats were also increased in Hunan, Hubei, Fujian and Shanghai groups. In dosage groups, testicular and ovarian coefficients of rats were reduced, the number of sperm were significant decreased while the rate of sperm malformation increased and sperm dynamics parameters of normal, especially in Jiangsu and Zhejiang groups. Liver histopathology and apoptosis of liver cells were observed in dosage groups, especially in Jiangsu and Hubei groups. In liver, Nrf2, HO-1 and Bcl-2 were inhibited and the protein expression level of Bax were increased simultaneously in dosage groups. These results showed that all Tripterygium Glycosides Tablets from 6 manufacturers could lead to chronic multiple organ injuries with disparate specialties in rats, and Jiangsu and Zhejiang groups were more toxic. It could be the mechanism promoting mitochondrial mediated Bax/Bcl-2 cell apoptosis signaling pathway and negatively regulating Nrf2/HO-1 oxidative stress signaling pathway that Tripterygium Glycosides Tablets from 6 different manufacturers resulted in chronic liver injury, the results above were for reference only in subsequent study.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Glicosídeos/farmacologia , Tripterygium/química , Animais , Apoptose , China , Feminino , Masculino , Estresse Oxidativo , Distribuição Aleatória , Ratos , Transdução de Sinais , Comprimidos
7.
Z Naturforsch C J Biosci ; 75(3-4): 121-128, 2020 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-32267249

RESUMO

Plants of the Plantago genus are widely used in Turkish folk medicine especially for the treatment of wound, abscess, and inflammation. The aqueous extract and five phenylethanoid glycosides acteoside (1), arenarioside (2), echinacoside (3), isoacteoside (4), and leucosceptoside A (5) isolated from the aerial parts and roots of Plantago holosteum Scop. (Plantaginaceae) were tested for their possible inhibitory activity against hyaluronidase, elastase, and collagenase, related to wound pathogenesis. Even though the aqueous extract prepared from the aerial parts (36.26%) and roots (47.01%) and the isolated compounds acteoside (29.13%), echinacoside (28.73%), and isoacteoside (31.69%) exerted a notable inhibition, arenarioside and leucosceptoside A were found inactive in the hyaluronidase enzyme inhibition test. Similar results were obtained from the collagenase enzyme inhibition test. The aqueous extract prepared from the aerial parts (31.09%) and roots (35.17%), echinacoside (25.13%), and isoacteoside (23.85%) exerted a notable inhibition in this test. However, none of the extracts and isolated compounds displayed elastase enzyme inhibitory activity. The experimental data demonstrated that P. holosteum displayed a remarkable enzyme inhibitory activity against hyaluronidase and collagenase. This paper is the first report regarding the in vitro enzyme inhibitory activity of P. holosteum.


Assuntos
Colagenases/metabolismo , Glicosídeos/farmacologia , Hialuronoglucosaminidase/antagonistas & inibidores , Elastase Pancreática/antagonistas & inibidores , Plantago/química , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Glucosídeos/química , Glucosídeos/farmacologia , Glicosídeos/química , Humanos , Medicina Tradicional , Estrutura Molecular , Fenóis/química , Fenóis/farmacologia , Componentes Aéreos da Planta/química , Extratos Vegetais/química , Raízes de Plantas/química , Turquia
8.
Chem Pharm Bull (Tokyo) ; 68(3): 273-287, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32115535

RESUMO

Phytochemical analysis of the whole Helleborus foetidus plants identified 28 steroidal glycosides (1-28), including 20 novel spirostanol glycosides (1-20) and a novel furostanol glycoside (21). The structures of the newly identified compounds were elucidated by two-dimensional NMR spectroscopy and hydrolytic cleavage. Compounds 12, 13, and 15 were determined to be spirostanol trisdesmosides bearing sugar moieties at the C-1, -21, and -24 hydroxy groups of the aglycone unit. The isolated compounds were subsequently evaluated for cytotoxic activity against HL-60 human promyelocytic leukemia cells and A549 human lung carcinoma cells. In particular, 7 showed cytotoxic activity against the HL-60 and A549 cells, with IC50 values of 5.9 and 6.6 µM, respectively, whereas 19 was selectively cytotoxic to A549 cells with an IC50 value of 5.5 µM.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Glicosídeos/farmacologia , Helleborus/química , Compostos Fitoquímicos/farmacologia , Esteroides/farmacologia , Células A549 , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Glicosídeos/química , Glicosídeos/isolamento & purificação , Células HL-60 , Humanos , Conformação Molecular , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Esteroides/química , Esteroides/isolamento & purificação , Relação Estrutura-Atividade
9.
Carbohydr Res ; 488: 107905, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32004953

RESUMO

A series of 19 synthetic alkyl and thioalkyl glycosides derived from d-mannose, d-glucose and d-galactose and having C10-C16 aglycone were investigated for cytotoxic activity against 7 human cancer and 2 non-tumor cell lines as well as for antimicrobial potential on 12 bacterial and yeast strains. The most potent compounds were found to be tetradecyl and hexadecyl ß-d-galactopyranosides (18, 19), which showed the best cytotoxicity and therapeutic index against CCRF-CEM cancer cell line. Similar cytotoxic activity showed hexadecyl α-d-mannopyranoside (5) but it also inhibited non-tumor cell lines. Because these two galactosides (18, 19) were inactive against all tested bacteria and yeast strains, they could be a target-specific for eukaryotic cells. On the other hand, ß-D-glucopyranosides with tetradecyl (11) and hexadecyl (12) aglycone inhibited only Gram-positive bacterial strain Enterococcus faecalis. The studied glycosides induce changes in the lipid bilayer thickness and lateral phase separation at high concentration, as derived from SAXS experiments on POPC model membranes. In general, glucosides and galactosides exhibit more specific properties. Those with longer aglycone show high cytotoxicity and therefore, they are more promising candidates for cancer cell line targeted inhibition.


Assuntos
Antibacterianos/síntese química , Antineoplásicos/síntese química , Enterococcus faecalis/efeitos dos fármacos , Glicosídeos/síntese química , Bicamadas Lipídicas/química , Células A549 , Antibacterianos/química , Antibacterianos/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Sequência de Carboidratos , Linhagem Celular , Proliferação de Células , Sobrevivência Celular/efeitos dos fármacos , Galactose/síntese química , Galactose/química , Galactose/farmacologia , Glicosídeos/química , Glicosídeos/farmacologia , Células HCT116 , Humanos , Células K562 , Testes de Sensibilidade Microbiana , Estrutura Molecular , Espalhamento a Baixo Ângulo , Difração de Raios X
10.
Phytochemistry ; 171: 112232, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31911266

RESUMO

Corni Fructus, also known as the fruit of Cornus officinalis Sieb. et Zucc., has long been used as a traditional Chinese medicine and is widely consumed as a nutritional food in the form of function drink and wine. Recently, Corni Fructus has attracted considerable interest because of its anti-diabetic effects. A systematic phytochemical investigation of Corni Fructus was performed to find anti-diabetic components, which led to the isolation of 10 unreported iridoid glycosides, cornusdiglycosides A-J (1-8, 9a/9b and 10a/10b). Their chemical structures were determined through spectroscopic analysis (ultraviolet [UV], infrared [IR], high-resolution electrospray ionisation mass spectroscopy [HRESIMS], one-dimensional [1D] and two-dimensional [2D] nuclear magnetic resonance [NMR]). Such morroniside-type diglycosides were first reported from natural sources, and all isolates were evaluated for α-glucosidase inhibitory activity. The results showed that all compounds (1-10) exhibited α-glucosidase (from Saccharomyces cerevisiae) inhibitory activities with IC50 values ranging from 78.9 ± 4.09 to 162.2 ± 9.17 µM, whereas acarbose, the positive control, displayed α-glucosidase inhibitory activity with IC50 value of 118.9 ± 7.89 µM.


Assuntos
Cornus/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Glicosídeos/farmacologia , Glucosídeos Iridoides/farmacologia , Compostos Fitoquímicos/farmacologia , alfa-Glucosidases/metabolismo , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Glicosídeos/química , Glicosídeos/isolamento & purificação , Humanos , Glucosídeos Iridoides/química , Glucosídeos Iridoides/isolamento & purificação , Conformação Molecular , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação
11.
Toxicol Appl Pharmacol ; 389: 114880, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31945383

RESUMO

Metabolomics is a powerful tool for studying physiological state of the system. In this study, we proposed a single-injection targeted metabolomics method to identify reliable tripterygium glycosides efficacy and toxicity related biomarkers based on ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Through careful optimization of the UHPLC-MS/MS conditions, a total of 289 metabolites can be quantified in single-injection of 27 min using both positive and negative scanning modes with rapid polarity switching. Tripterygium glycosides is widely used in clinical for its excellent anti-inflammatory and immunosuppressive functions. However, it is the most common drug that can cause hepatotoxicity. In this study, the established metabolomics method was used for determination of biomarkers to reflect tripterygium glycosides efficacy and toxicity. Two different dosages were designed in the animal experiment, including therapeutic dosage and toxic dosage. Statistical analysis based on metabolite concentrations showed that the glutathione metabolism and pyrimidine metabolism were the obvious interfering pathways. This was highly consistent with previous studies. A total of 22 and 47 metabolites were screened as potential biomarkers related to the efficacy and hepatotoxicity of tripterygium glycosides, respectively. Receiver operating characteristic curve (ROC) analysis showed that ten metabolites, including cytosine, 5-methyluridine, deoxyuridine, 5-methylcytidine, deoxycytidine triphosphate (DCTP), keto-glutarate, d-ribose, dihydrofolate, nordeoxycholic acid and isodeoxycholic acid possessed area under the curve (AUC) of 1. The metabolites filtered here can better distinguish tripterygium glycosides treated rats from the control rats compared with the traditional blood indicators of liver function.


Assuntos
Biomarcadores/metabolismo , Glicosídeos/efeitos adversos , Glicosídeos/farmacologia , Tripterygium/efeitos adversos , Tripterygium/química , Animais , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Cromatografia Líquida de Alta Pressão/métodos , Glutationa/metabolismo , Injeções , Fígado/efeitos dos fármacos , Masculino , Metabolômica/métodos , Ratos , Ratos Wistar , Espectrometria de Massas em Tandem/métodos
12.
Carbohydr Res ; 488: 107908, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31927345

RESUMO

Three new triacetic acid lactone (TAL) glycosides, forsyphensides A-C (1-3) were isolated from the fruits of Forsythia suspensa. Their structures were elucidated by comprehensive spectroscopic techniques. The absolute configurations of their monosaccharides were determined by GC analysis. Notably, forsyphensides A-C were relatively rare TAL glycosides identified from plants. Compound 1 exhibited inhibitory activity against the lipopolysaccharide (LPS)-induced nitric oxide (NO) production in microglia BV2 cells with the inhibition rate of 69.40%.


Assuntos
Forsythia/química , Glicosídeos/química , Microglia/metabolismo , Pironas/química , Animais , Sequência de Carboidratos , Linhagem Celular , Glicosídeos/farmacologia , Lipopolissacarídeos/efeitos adversos , Camundongos , Microglia/citologia , Microglia/efeitos dos fármacos , Estrutura Molecular , Óxido Nítrico/metabolismo , Extratos Vegetais/química , Pironas/farmacologia
13.
Curr Med Chem ; 27(9): 1405-1419, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31333082

RESUMO

Antimicrobial Peptides (AMPs) are the key effectors of the innate immunity and represent promising molecules for the development of new antibacterial drugs. However, to achieve this goal, some problems need to be overcome: (i) the cytotoxic effects at high concentrations; (ii) the poor biostability and (iii) the difficulty in reaching the target site. Frog skin is one of the richest natural storehouses of AMPs, and over the years, many peptides have been isolated from it, characterized and classified into several families encompassing temporins, brevinins, nigrocins and esculentins. In this review, we summarized how the isolation/characterization of peptides belonging to the esculentin-1 family drove us to the design of an analogue, i.e. esculentin-1a(1-21)NH2, with a powerful antimicrobial action and immunomodulatory properties. The peptide had a wide spectrum of activity, especially against the opportunistic Gram-negative bacterium Pseudomonas aeruginosa. We described the structural features and the in vitro/in vivo biological characterization of this peptide as well as the strategies used to improve its biological properties. Among them: (i) the design of a diastereomer carrying Damino acids in order to reduce the peptide's cytotoxicity and improve its half-life; (ii) the covalent conjugation of the peptide to gold nanoparticles or its encapsulation into poly(lactide- co-glycolide) nanoparticles; and (iii) the peptide immobilization to biomedical devices (such as silicon hydrogel contact lenses) to obtain an antibacterial surface able to reduce microbial growth and attachment. Summing up the best results obtained so far, this review traces all the steps that led these frog-skin AMPs to the direction of peptide-based drugs for clinical use.


Assuntos
Glicosídeos/farmacologia , Nanopartículas Metálicas , Pregnenolona/análogos & derivados , Proteínas de Anfíbios , Animais , Ouro , Peptídeos , Pregnenolona/farmacologia , Pele
14.
Phytochemistry ; 170: 112181, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31727321

RESUMO

Gymnema sylvestre (Retz.) R. Br. ex Schult. has a long history to be used as an antidiabetic herbal medicine. Various varieties of G. sylvestre, have been studied intensively on their 3ß-hydroxy oleanane triterpenoid composition for hypoglycemic effects. It is also well-known that most species belonging to the same genus have similar chemical composition and biological activity. Thus, an extract of the Gymnema latifolium Wall. ex Wight, which showed considerable protein tyrosine phosphatase 1B (PTP1B) inhibitory activity (>70% inhibition at 30 µg/mL), was studied intensively. Extensive chemical investigation on the 70% EtOH of G. latifolium led to the isolation of four previously undescribed oleanane hemiacetal glycosides, gymlatinosides GL1-GL4, three previously undescribed oleanane glycosides, gymlatinosides GL5-GL7, and two known 3ß-hydroxy oleanane analogs. The structures of the previously undescribed compounds were elucidated using diverse spectroscopic methods. The hemiacetal structure of the glycoside portion was further elaborated precisely by HMBC and J resolved proton NMR. Gymlatinosides GL2 and GL3 showed considerable PTP1B inhibitory effect.


Assuntos
Inibidores Enzimáticos/farmacologia , Glicosídeos/farmacologia , Gymnema/química , Ácido Oleanólico/análogos & derivados , Compostos Fitoquímicos/farmacologia , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Glicosídeos/química , Glicosídeos/isolamento & purificação , Humanos , Estrutura Molecular , Ácido Oleanólico/química , Ácido Oleanólico/isolamento & purificação , Ácido Oleanólico/farmacologia , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Proteína Tirosina Fosfatase não Receptora Tipo 1/metabolismo , Proteínas Recombinantes/metabolismo , Relação Estrutura-Atividade
15.
Nat Prod Res ; 34(2): 311-316, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30404547

RESUMO

Development of a novel agent for control of schistosomiasis is a mandate. In-vitro anti-schistosomal activity of the aerial parts of Huernia saudi-arabica were examined. Chromatographic investigations of the ethanol extract (EE) were afforded three compounds. Pregnane glycoside (CI) 12-ß-p-hydroxy-benzoyl-20-O-acetyl-boucerin-3-O-ß-D-glucopyranosyl-(1→4)-ß-D-cymaropyranosyl-(1→4)-ß-D-cymaropyranoside, in addition to two flavonoids (CII) luteolin-4'-O-ß-D-neohesperidoside and (CIII)quercetin-3-rutinoside were recognized via spectral analysis. The schistosomicidal effects were evaluated using scanning electron microscope (SEM). In-vitro bioassays on the viability (mobility, morphological changes and mortality) of Schistosoma mansoni adults, cercariae, miracidia and eggs at different concentrations 2.5, 5, 12.5, 25 and 50 µg/ml of EE and 2.6, 5.2, 13, 26 and 52 µM of CI in incubation times 1,2,4,6,12hrs were carried out. EE and CI evidenced in-vitro anti-schistosomal activity with a dose and incubation time-dependent fashion. The effect of EE and CI was evident by the topography damage showed by SEM. EE proved moderate in-vitro cytotoxicity with IC50 of 8.48 µg/ml.


Assuntos
Apocynaceae/química , Glicosídeos/farmacologia , Pregnanos/farmacologia , Esquistossomicidas/isolamento & purificação , Animais , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Glicosídeos/isolamento & purificação , Extratos Vegetais/química , Pregnanos/isolamento & purificação , Schistosoma mansoni/efeitos dos fármacos , Esquistossomicidas/farmacologia
16.
Nat Prod Res ; 34(6): 816-822, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30398365

RESUMO

The chemical constituents of Cupressus macrocarpa were investigated. A new neolignan glycoside (1) in addition to nine known compounds were isolated. The acetylcholinesterase (AChE) inhibitory activity and antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) of different fractions and isolates of C. macrocarpa were evaluated. The light petroleum fraction showed the highest activity in both assays with IC50 value of 88.79 µg/ml and 152.58 µg/ml for the AChE inhibitory activity and MRSA antibacterial activities, respectively. Weak to moderate activity were detected for the isolated compounds.


Assuntos
Antibacterianos/isolamento & purificação , Inibidores da Colinesterase/isolamento & purificação , Cupressus/química , Antibacterianos/farmacologia , Inibidores da Colinesterase/farmacologia , Glicosídeos/isolamento & purificação , Glicosídeos/farmacologia , Lignanas/isolamento & purificação , Lignanas/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Extratos Vegetais/química , Folhas de Planta/química
17.
Nat Prod Res ; 34(7): 1041-1045, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30580603

RESUMO

The pollen of T. angustifolia, also known as Pu huang in Chinese, has been used for treatment of stranguria, hematuria, dysmenorrhea, metrorrhagia and injuries in China for a long time. Extensive efforts have been directed toward its phytochemical and biological aspects. However, little is known about its anti-nociceptive implication and material basis. This work presented the investigation of the anti-nociceptive effect of Typhae Pollen using an effect-directed fractionation strategy, thereby leading to identification of isorhamnetin-3-O-neohesperidin (1) and typhaneoside (2), together with other minor flavonoid glycoside congeners, as the main anti-nociceptive constituents. This work not only unveils the anti-nociceptive potential of Typhae Pollen, but also establishes a method to enrich and identify the anti-nociceptive constitutes of Typhae Pollen. Moreover, this work is a successful example of effect-directed fractionation strategy, which represents a powerful tool in TCM-based drug discovery and development.


Assuntos
Analgésicos/isolamento & purificação , Flavonoides/farmacologia , Pólen/química , Typhaceae/química , Analgésicos/química , Animais , Fracionamento Químico/métodos , China , Medicamentos de Ervas Chinesas , Flavonoides/química , Flavonoides/isolamento & purificação , Glicosídeos/química , Glicosídeos/isolamento & purificação , Glicosídeos/farmacologia
18.
Nat Prod Res ; 34(2): 284-289, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30580615

RESUMO

Baccharoides anthelmintica is the most popular traditional Uighur medicines used for vitiligo. The chemical investigation of the seeds of B. anthelmintica led to the isolation of three new flavonoid glycosides (Vernosides A-C). Their structures were determined by comprehensive analysis of spectroscopic data including 1D and 2D NMR and HRMS data. Vernosides A-C were evaluated for their effects on tyrosinase activity, Vernoside B can enhance tyrosinase activity.


Assuntos
Asteraceae/química , Flavonoides/isolamento & purificação , Glicosídeos/isolamento & purificação , Sementes/química , Flavonoides/química , Flavonoides/farmacologia , Glicosídeos/química , Glicosídeos/farmacologia , Estrutura Molecular , Monofenol Mono-Oxigenase/efeitos dos fármacos , Monofenol Mono-Oxigenase/metabolismo
19.
Nat Prod Res ; 34(6): 859-862, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30289000

RESUMO

The stem bark of Cussonia bancoensis is used traditionally for the treatment of different types of infection and pain. A bioassay guided fractionation of the methanol stem bark extract led to the isolation of five pentacyclic triterpenes and glycosides identified based on spectroscopic data as 23-hydroxyursolic acid (CB1), hederagenin (CB2), 3-O-α-L-arabinopyranosyl-echinocystic acid (CB3), 3-O-α-L-arabinopyranosyl- oleanolic acid (CB4) and 3-O-α-L-arabinopyranosyl-ursolic acid (CB5). CB2 - CB5 are being reported for the first time from this species. The compounds were evaluated for antimicrobial activity against ten microorganisms using the HT-SPOTi method. CB3 demonstrated remarkable antimicrobial activity against S. aureus, S. pyogens, E. faecalis, S. typhi and C. albicans at MICs between 3.12 and 12.5 µg/mL. Among the studied compounds, it was observed that hydroxylation of position C-16 of the oleanane skeleton may enhance antimicrobial activity. This study gives insight into the anti-infective constituents of the stem bark of C. bancoensis and justifies its use in ethnomedicine.[Formula: see text].


Assuntos
Anti-Infecciosos/isolamento & purificação , Araliaceae/química , Glicosídeos/farmacologia , Triterpenos Pentacíclicos/isolamento & purificação , Casca de Planta/química , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Bactérias/efeitos dos fármacos , Fungos/efeitos dos fármacos , Glicosídeos/química , Glicosídeos/isolamento & purificação , Ácido Oleanólico/análogos & derivados , Triterpenos Pentacíclicos/química , Triterpenos Pentacíclicos/farmacologia , Saponinas , Triterpenos
20.
Nat Prod Res ; 34(7): 943-949, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30760039

RESUMO

Saussurea involucrata, known for the abundant bioactive components, is a precious traditional Chinese medicine. In this study, a novel guaiane sesquiterpenoid glycoside named (1R, 5R, 6R, 7R, 8S, 11S)-11, 13-dihydrodehydrocostuslactone-8-O-6'-2''(E)-butenoyl-ß-D-glucopyranoside (1), together with seven known compounds (2-8) were isolated from the dried aerial part of S. involucrata. Their structures were elucidated by spectroscopic and physico-chemical analyses. The antioxidant and anti-inflammatory activities of compound 1 were investigated. And compound 1 showed weak radical scavenging activity and low inhibitory activity on nitric oxide (NO) production.


Assuntos
Glicosídeos/isolamento & purificação , Medicina Tradicional Chinesa , Saussurea/química , Sesquiterpenos/isolamento & purificação , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Antioxidantes/química , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Depuradores de Radicais Livres/química , Depuradores de Radicais Livres/isolamento & purificação , Depuradores de Radicais Livres/farmacologia , Glicosídeos/química , Glicosídeos/farmacologia , Óxido Nítrico/antagonistas & inibidores , Extratos Vegetais/química , Sesquiterpenos/química , Sesquiterpenos/farmacologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA