Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 5.766
Filtrar
1.
Zhongguo Zhong Yao Za Zhi ; 44(16): 3582-3587, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31602926

RESUMO

Terpenoids are main bioactive components in Tripterygium wilfordii,but the contents of some terpenoids are relatively low. In order to provide scientific evidence for the regulation of terpenoids in T. wilfordii,this research explored the effect of GR24 on accumulations of four diterpenoids( triptolide,tripterifordin,triptophenolide,and triptinin B) in T. wilfordii suspension cells by biological technology and UPLC-QQQ-MS/MS. The results indicated that 100 µmol·L-1 GR24 inhibited the accumulations of triptolide,tripterifordin,triptophenolide,and triptinin B to different degrees. Compared with the control group,the contents of 4 diterpenoids( in the induced group) were down to 96.59%,63.80%,61.02% and 33.59% in 240 h,respectively. Among them,the accumulation of triptinin B iswas significantly inhibited. In addition,the key time point of inhibitory effect was 120 h after induction with GR24 in some diterpenoids. This is the first systematic study focusing on the effect of GR24 on the accumulations of diterpenoids in T. wilfordii suspension cells. The dynamic accumulation ruleregularity of four diterpenoids after induced by GR24 was summarized,which laid a foundation for further study on the chemical response mechanism of terpenoids to GR24.


Assuntos
Diterpenos/farmacocinética , Lactonas/farmacologia , Tripterygium/química , Células Cultivadas , Humanos , Espectrometria de Massas em Tandem , Terpenos
2.
J Med Life ; 12(2): 150-155, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31406516

RESUMO

Pain control during and after any surgical procedure, is extremely essential for the comfort of patients. Pain killers used routinely act by inhibiting cyclooxygenase to control pain and inflammation. Cox-1 is constitutively expressed in most cell types, including platelets, whereas Cox-2 is absent from most healthy tissues but is induced by pro-inflammatory or proliferative stimuli. Cox-1 plays a role in the production of prostaglandins involved in protection of the gastric mucosal layer and thromboxanes (TX) in platelets. Cox-2 generally mediates elevations of prostaglandins associated with inflammation, pain, and pyresis. Nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin and ibuprofen are generally nonselective inhibitors of Coxs. This lack of selectivity has been linked to their propensity to cause gastrointestinal side effects. The new Cox-2 selective inhibitors, or coxibs, show the same anti-inflammatory, analgesic, and antipyretic effects as nonselective NSAIDs but are supposed to have reduced side-effect profiles. This study evaluates whether rofecoxib (50 mg) given one hour pre-operatively or the same drug given one hour post-operatively is more effective in controlling the pain and swelling in mandibular third molar surgery.


Assuntos
Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Mandíbula/cirurgia , Dente Serotino/cirurgia , Adolescente , Adulto , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/uso terapêutico , Proteína C-Reativa/metabolismo , Feminino , Humanos , Lactonas/farmacologia , Masculino , Cuidados Pós-Operatórios , Sulfonas/farmacologia , Adulto Jovem
3.
Vet Parasitol ; 272: 79-82, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31395209

RESUMO

The astigmatid mite Psoroptes ovis (Acari: Proroptidae) causes the highly contagious and debilitating ovine disease, sheep scab. This ectoparasitic infection has a high economic and animal welfare impact on British sheep farming. Following recent work demonstrating resistance of Psoroptes mites to moxidectin, a widely used macrocyclic lactone (ML) treatment for scab, the current study compared the toxicity of three of the commonly administered macrocylic lactone therapeutic treatments (moxidectin, ivermectin and doramectin) to P. ovis from outbreak populations that had appeared unresponsive to treatment. These outbreak populations were from Wales and south west England. The data presented demonstrate that there is resistance to all three available ML compounds in populations of Psoroptes mites. However, considerable variation in response suggested that resistance alone was not responsible for the reported lack of efficacy in all of the submitted cases; lack of response in others may be associated with inappropriate treatment application or management. These data highlight the importance of the appropriate use of these compounds to manage national scab incidence at levels that are consistent with acceptable animal welfare standards, while attempting to reduce the development and spread of resistance.


Assuntos
Resistência a Múltiplos Medicamentos , Lactonas/administração & dosagem , Lactonas/farmacologia , Infestações por Ácaros/veterinária , Psoroptidae/efeitos dos fármacos , Criação de Animais Domésticos/normas , Animais , Antiparasitários/administração & dosagem , Antiparasitários/farmacologia , Inglaterra , Infestações por Ácaros/tratamento farmacológico , Infestações por Ácaros/epidemiologia , Infestações por Ácaros/prevenção & controle , Ovinos , Doenças dos Ovinos/tratamento farmacológico , Doenças dos Ovinos/epidemiologia , Doenças dos Ovinos/prevenção & controle , País de Gales
4.
Fitoterapia ; 137: 104274, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31344394

RESUMO

We have previously demonstrated that out of the butyrolactones series synthesized based on the natural lichen metabolite lichesterinic acid, compound (B-13) was the most effective against oral bacteria. However, its antibacterial mechanism is still unknown. In this study, we have investigated its bacterial localization by synthesizing a fluorescently labeled B-13 with NBD while maintaining its antibacterial activity. We showed that this compound binds to Streptococcus gordonii cell surface, as demonstrated by HPLC analysis. By adhering to cell surface, B-13 induced cell wall disruption leading to the release of bacterial constituents and consequently, the death of S. gordonii, a Gram-positive bacterium. A Gram-negative counterpart, Porphyromanas gingivalis, showed also cracked and ruptured cells in the presence of B-13. Besides, we also demonstrated that the analog of B-13, B-12, has also induced disruption of P. gingivalis and S. gordonii. This study revealed that butyrolactones can be considered as potent antibacterial compounds against oral pathogens causing medical complications.


Assuntos
Antibacterianos/farmacologia , Lactonas/farmacologia , Líquens/química , Porphyromonas gingivalis/efeitos dos fármacos , Streptococcus gordonii/efeitos dos fármacos , Membrana Celular/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Estrutura Molecular
5.
Parasit Vectors ; 12(1): 345, 2019 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-31300011

RESUMO

BACKGROUND: The poultry red mite (PRM), Dermanyssus gallinae, is one of the most economically deleterious threats to laying-hen industry worldwide. Macrocyclic lactones (MLs) have been widely used in control of mites in mammals, but the effects of MLs on PRMs are not well studied. The main objective of the present study was to systematically evaluate the effects of three MLs, i.e. eprinomectin (EPR), moxidectin (MOX) or ivermectin (IVM), on PRMs fed on chicks following oral administration. METHODS: Chicks in treatment groups were orally administrated with EPR, MOX or IVM at a dose of 5.0 mg/kg bodyweight. Chicks in the control group received the carrier solvent without drug. Chicks in each cage were then infested with 200 starved adult D. gallinae. After infestation and feeding for 12 h, engorged mites were collected to evaluate the acaricidal efficacy of the MLs, and its impacts on the reproduction and blood-meal digestion of D. gallinae. RESULTS: MOX, IVM and EPR demonstrated higher acaricidal efficacies post-treatment compared with the control, i.e. 45.60% for MOX, 71.32% for IVM and 100% for EPR on Day 10. MLs did not have significant effects on the blood-meal ingestion of PRMs, but significantly slowed down blood digestion (P < 0.0001). The oviposition rate, egg hatching rate and fecundity of PRMs in treatment groups were remarkably reduced. Among the three MLs, EPR exhibited the highest performance against PRMs, with an oviposition rate of 1.04%, fecundity of 0.33 eggs per mite and a zero egg hatching rate in EPR treated groups. CONCLUSIONS: EPR, MOX or IVM administrated orally to chicks increased the mortality of D. gallinae, significantly slowed down their blood-meal digestion and significantly reduced their reproductive capability which included the oviposition rate, fecundity and egg hatching rate. The present study highlights the potential of MLs in the control of PRMs.


Assuntos
Acaricidas/uso terapêutico , Fertilidade/efeitos dos fármacos , Compostos Macrocíclicos/uso terapêutico , Infestações por Ácaros/veterinária , Ácaros/efeitos dos fármacos , Doenças das Aves Domésticas/tratamento farmacológico , Acaricidas/administração & dosagem , Administração Oral , Animais , Galinhas/parasitologia , Feminino , Lactonas/farmacologia , Compostos Macrocíclicos/administração & dosagem , Infestações por Ácaros/tratamento farmacológico , Ácaros/fisiologia , Doenças das Aves Domésticas/parasitologia
6.
Phytochemistry ; 165: 112047, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31203102

RESUMO

Four undescribed lignans and two undescribed sesquiterpenic acids, together with three known compounds (hypochoeroside C, hypochoeroside D, and 5-O-caffeoylshikimic acid) were isolated from the roots of Hypochaeris radicata subsp. neapolitana (Asteraceae, Cichorieae). The lignans were identified as 4-(3,4-dihydroxybenzyl)-2-(3,4-dihydroxyphenyl)tetrahydrofuran-3-carboxy-O-ß-D-glucopyranoside, 4-(3,4-dihydroxybenzyl)-2-(3,4-dihydroxyphenyl)tetrahydrofuran-3-carboxy-O-ß-D-glucopyranosyl-2'-O-methacrylate, (7S,8R,8'R)-7-(3,4-dihydroxyphenyl)-3',4'-dihydroxy-7,8,7',8'-tetrahydronaphtho [8,8'-c]furan-1(3H)-one, and (7S,8R,8'R)-7-(3,4-dihydroxyphenyl)-3',4'-dihydroxy-8'-(hydroxymethyl)-7,8,7',8'-tetrahydronaphthalen-8-carboxylic acid. The two sesquiterpenic acids were identified as the ring open precursors of hypochoerosides C and D. Structures were elucidated using NMR and HRMS. Absolute configurations of (7S,8R,8'R)-7-(3,4-dihydroxyphenyl)-3',4'-dihydroxy-7,8,7',8'-tetrahydronaphtho [8,8'-c]furan-1(3H)-one and (7S,8R,8'R)-7-(3,4-dihydroxyphenyl)-3',4'-dihydroxy-8'-(hydroxymethyl)-7,8,7',8'-tetrahydronaphthalen-8-carboxylic acid were determined using electronic circular dichroism (ECD) spectroscopy. 4-(3,4-dihydroxybenzyl)-2-(3,4-dihydroxyphenyl)tetrahydrofuran-3-carboxy-O-ß-D-glucopyranoside was evaluated for its anti-proliferative activity against myeloma cell lines MM1S, U266, and NCI-H929 and showed cytotoxicity at 100 mM against MM1S strain. No neurotoxicity was observed for major compounds 4-(3,4-dihydroxybenzyl)-2-(3,4-dihydroxyphenyl)tetrahydrofuran-3-carboxy-O-ß-D-glucopyranoside, hypochoeroside C, and hypochoeroside D in a fluorescence assay measuring neurite outgrowth in dorsal root ganglion (DRG) neurons. Additionally, compounds 4-(3,4-dihydroxybenzyl)-2-(3,4-dihydroxyphenyl)tetrahydrofuran-3-carboxy-O-ß-D-glucopyranoside, hypochoeroside C, hypochoeroside D, and hypochoerosidic acid D were quantified in unstressed and drought-stressed plants using HPLC-DAD. Drought-stressed plants were found to contain lower concentrations of the lignan 4-(3,4-dihydroxybenzyl)-2-(3,4-dihydroxyphenyl)tetrahydrofuran-3-carboxy-O-ß-D-glucopyranoside and sesquiterpene lactone hypochoeroside C.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Asteraceae/química , Lactonas/farmacologia , Lignanas/farmacologia , Mieloma Múltiplo/tratamento farmacológico , Sesquiterpenos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Lactonas/química , Lactonas/isolamento & purificação , Lignanas/química , Lignanas/isolamento & purificação , Estrutura Molecular , Mieloma Múltiplo/patologia , Sesquiterpenos/química , Sesquiterpenos/isolamento & purificação , Relação Estrutura-Atividade
7.
Chin J Nat Med ; 17(4): 264-274, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31076130

RESUMO

Atractylenolide III (ATL-III), a sesquiterpene compound isolated from Rhizoma Atractylodis Macrocephalae, has revealed a number of pharmacological properties including anti-inflammatory, anti-cancer activity, and neuroprotective effect. This study aimed to evaluate the cytoprotective efficiency and potential mechanisms of ATL-III on corticosterone injured rat phaeochromocytoma (PC12) cells. Our results demonstrate that ATL-III increases cell viability and reduces the release of lactate dehydrogenase (LDH). The results suggest that ATL-III protects PC12 cells from corticosterone-induced injury by inhibiting the intracellular Ca2+ overloading, inhibiting the mitochondrial apoptotic pathway and modulating the MAPK/NF-ΚB inflammatory pathways. These findings provide a novel insight into the molecular mechanism by which ATL-III protected the PC12 cells against corticosterone-induced injury for the first time. Our results provide the evidence that ATL-III may serve as a therapeutic agent in the treatment of depression.


Assuntos
Apoptose/efeitos dos fármacos , Corticosterona/toxicidade , Lactonas/farmacologia , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Fármacos Neuroprotetores/farmacologia , Sesquiterpenos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Animais , Cálcio/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Mediadores da Inflamação/metabolismo , L-Lactato Desidrogenase/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Células PC12 , Fosforilação/efeitos dos fármacos , Ratos
8.
Mar Drugs ; 17(5)2019 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-31060304

RESUMO

Six new depsidones, curdepsidones B-G (1-6), were obtained from the marine-derived fungus Curvularia sp. IFB-Z10. Their planar structures were determined by comprehensive analysis of HRESIMS and 1D/2D-NMR data. The absolute configuration of curdepsidones B-C (1-2) were established by synergistic use of DFT/NMR (density functional theory/nuclear magnetic resonance) and TDDFT/ECD (time-dependent density functional theory/electronic circular dichroism) calculations. Partial isolated compounds were tested for their anti-inflammatory activities in Propionibacterium acnes-induced THP-1 cells. Curdepsidone C (2) displayed significant anti-inflammatory properties with an IC50 value of 7.47 ± 0.35 µM, and reduced the P. acnes-induced phosphorylation levels of JNK and ERK in a dose-dependent mechanism. The possible anti-inflammatory mechanism of 2 was also investigated by molecular docking.


Assuntos
Anti-Inflamatórios/farmacologia , Depsídeos/química , Depsídeos/farmacologia , Lactonas/química , Lactonas/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Depsídeos/isolamento & purificação , Fungos , Humanos , Concentração Inibidora 50 , Lactonas/isolamento & purificação , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Simulação de Acoplamento Molecular , Estrutura Molecular , Propionibacterium acnes , Células THP-1/efeitos dos fármacos
9.
Mol Med Rep ; 19(6): 5291-5300, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31059055

RESUMO

Atherosclerosis (AS) is an inflammatory disease that occurs in the arterial wall and is characterized by progressive lipid accumulation within the intima of large arteries, leading to the dysfunction of endothelial cells and further destruction of the endothelial barrier and vascular tone. Arterial intima injury accelerates the adhesion and activation of platelets at the injury site. The activation of platelets results in the secretion of growth factors, leading to the migration and proliferation of vascular smooth muscle cells (VSMCs), promoting the formation of plaque, resulting in the formation of thrombus. The present study found that vorapaxar could alleviate the inflammatory response induced by a high concentration of cholesterol stimulation and increase the release of nitric oxide (NO) via the protein kinase B (AKT) signaling pathway and regulation of the intracellular concentration of Ca2+ ([Ca2+]i). We also found that vorapaxar could reduce the damage of DNA caused by cholesterol stimulation and regulate the cell cycle via the AKT/JNK signaling pathway and its downstream molecules glycogen synthase kinase 3ß (GSK­3ß) and connexin 43, maintaining the integrity of the endothelial barrier and proliferation of endothelial cells, serving a protective role in endothelial cells.


Assuntos
Lactonas/farmacologia , Piridinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Cálcio/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Colesterol/farmacologia , Conexina 43/metabolismo , Citocinas/genética , Citocinas/metabolismo , Células Endoteliais/citologia , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Permeabilidade/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Regulação para Cima/efeitos dos fármacos
10.
Phytochemistry ; 164: 122-129, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31125862

RESUMO

A phytochemical study on the fruits of Rubus idaeus L. (Rosaceae) yielded eight pairs of enantiomeric lignans, including one undescribed furolactone named (-)-idaeusinol A and six undescribed furofuran derivatives named (+/-)-idaeusinol B-D. The structures of these isolated compounds were elucidated by spectroscopic analyses and a combination of computational techniques including gauge-independent atomic orbital (GIAO) calculation of 1D NMR data and TD-DFT calculation of electronic circular dichroism (ECD) spectra. Bioactivity screenings suggested that (+)-idaeusinol D exhibited the most significant protective effect against H2O2-induced neurotoxicity at the concentration of 25 µM. In contrast, (-)-idaeusinol D, as the enantiomer of (+)-idaeusinol D, showed no effect against H2O2-induced neurotoxicity at both 25 and 50 µM concentration.


Assuntos
Furanos/farmacologia , Lactonas/farmacologia , Fármacos Neuroprotetores/farmacologia , Rubus/química , Sobrevivência Celular/efeitos dos fármacos , Teoria da Densidade Funcional , Relação Dose-Resposta a Droga , Furanos/química , Furanos/isolamento & purificação , Humanos , Peróxido de Hidrogênio/antagonistas & inibidores , Peróxido de Hidrogênio/farmacologia , Lactonas/química , Lactonas/isolamento & purificação , Conformação Molecular , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/isolamento & purificação , Estereoisomerismo , Relação Estrutura-Atividade , Células Tumorais Cultivadas
11.
Int J Mol Sci ; 20(9)2019 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-31083629

RESUMO

Alternariol (AOH) is a mycotoxin produced by Alternaria species. In vitro studies suggest the genotoxic, mutagenic, and endocrine disruptor effects of AOH, and an increased incidence of esophageal cancer has been reported related to higher AOH exposure. Human serum albumin (HSA) is the most abundant plasma protein in the circulation, it is able to affect toxicokinetic properties of numerous xenobiotics. HSA forms stable complexes with several mycotoxins, however, the interaction of AOH with albumin has not been examined. In this study, the complex formation of AOH with HSA was tested, employing fluorescence spectroscopy, ultrafiltration, and molecular modeling. Each spectroscopic measurement shows the formation of stable AOH-HSA complexes (K = 4 × 105 L/mol). Investigations with site markers (in spectroscopic and ultrafiltration models) as well as modeling studies suggest that AOH occupies Sudlow's site I as a high-affinity binding site in HSA. The binding affinity of AOH towards bovine, porcine, and rat albumins was also tested, suggesting that AOH binds to rat albumin with considerably higher affinity than other albumins tested. Our results demonstrate the strong interaction of AOH with serum albumins, suggesting the potential in vivo importance of these interactions.


Assuntos
Lactonas/farmacologia , Simulação de Acoplamento Molecular , Micotoxinas/farmacologia , Albumina Sérica/química , Sítios de Ligação , Humanos , Lactonas/química , Micotoxinas/química , Ligação Proteica , Albumina Sérica/metabolismo
12.
Fitoterapia ; 136: 104167, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31071435

RESUMO

Three new arylalkenyl α,ß-unsaturated δ-lactones, cryptobrachytones A-C (1-3), together with one known analogue kurzilactone (4), were isolated from the leaves and twigs of Cryptocarya brachythyrsa. Their structures were elucidated based on extensive spectroscopic data and electronic circular dichroism (ECD) analysis. All the isolates were evaluated in vitro for anti-proliferative activity against a panel of five human cancer cell lines and one human normal cell, respectively, and the results showed 1, 2 and 4 possessing significant selective cytotoxicity toward the human cancer cell lines with IC50 values from 5.41 to 15.43 µM. This is the first study for C. brachythyrsa.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Cryptocarya/química , Lactonas/farmacologia , Folhas de Planta/química , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular Tumoral , China , Humanos , Lactonas/isolamento & purificação , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia
13.
Life Sci ; 227: 153-165, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-31004657

RESUMO

AIMS: Alantolactone (ALT) is active component of natural product Inula helenium with a lot of pharmacological effects, including anti-tumor effect. The present work aimed to explore the antitumor effect of ALT in B cell acute lymphoblastic leukemia (B-ALL). MAIN METHODS: B-ALL cells were treated with various concentrations of ALT, and then trypan blue assay, Annexin V/PI staining assay, PI staining assay, western blot analysis were employed to measure the effect of ALT on viability, apoptosis and cell cycle in B-ALL cells. In addition, a synthetic bioinformatics method was used to predict the underlying mechanism of antitumor effect of ALT. Then Reactive Oxygen Species (ROS) probe Dihydroethidium (DHE) and 2',7'-Dichlorodihydrofluorescein diacetate (DCFH-DA) were used to detect accumulation of cellular ROS. Meanwhile, DNA damage was identified by 8-oxoG, p-ATM1987, γ-H2AX and comet assay. In addition, activity of glutathione reductase (GR), thioredoxin reductase (TrxR) and catalase were measured and overexpressed in SEM and RS4;11 cells to study the inhibition on these enzymes. Finally, B-ALL NOD-SCID mouse model was used to test its performance in vivo. KEY FINDINGS: ALT showed good antitumor effect in B-ALL in vivo and in vitro through inducing ROS overload, which led to DNA damage. In addition, we found ROS overload caused by ALT was due to its direct inhibition on reductase. SIGNIFICANCE: We found that ALT, a natural product, showing a promising tactic in the therapy of B-ALL by targeting ROS pathway.


Assuntos
Lactonas/farmacologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Sesquiterpenos de Eudesmano/farmacologia , Animais , Apoptose/efeitos dos fármacos , Linfócitos B/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Humanos , Lactonas/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Mitocôndrias/efeitos dos fármacos , Cultura Primária de Células , Espécies Reativas de Oxigênio/metabolismo , Sesquiterpenos de Eudesmano/metabolismo
14.
Exp Parasitol ; 200: 61-66, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30946841

RESUMO

Anthelmintic and in particular macrocyclic lactone (ML) resistance is a widespread problem in trichostrongyloid parasitic nematodes, yet mechanisms of ML resistance are still poorly understood. In the absence of target-site changes in resistant parasite field populations, increased drug extrusion and xenobiotic metabolism have been implicated in modification of susceptibility to MLs. In addition to P-glycoproteins, cytochrome P450 monooxygenases (CYPs) were considered to be involved in ML resistance. CYPs are highly divergent in nematodes with about 80 genes in the model organism Caenorhabditis elegans. Using larval development assays in the C. elegans model, piperonyl butoxide (PBO) and a temperature-sensitive variant of the emb-8 cytochrome reductase were used for chemical and genetic ablation of CYP activity. Additionally, a loss-of-function variant of cyp-14A5 was characterized to determine whether increased expression of this CYP in an ivermectin (IVM)-tolerant C. elegans line might be related to the phenotype. In a preliminary experiment with PBO, susceptibility to 5 nM IVM was synergistically increased by PBO. However, effects of genetic ablation of CYP activity on the EC50 values were small (1.5-fold decrease) for IVM and not significant for moxidectin (MOX). However, due to the steep concentration-response-curves, there were again strong differences between the wild-type and the CYP deficient genotype at individual IVM but not MOX concentrations. Although these results suggest small but significant effects on the susceptibility level of C. elegans to IVM, the cyp14A5 gene proposed by a previous study as candidate was ruled out since it was neither IVM/MOX inducible nor did a strain with a loss-of-function allele show increased susceptibility to either drug. In conclusion, the effect of the CYP system on IVM susceptibility in C. elegans is at best low while effects on MOX susceptibility were not detected. The previously suggested candidate cyp14A5 could be excluded to be involved in ML metabolism.


Assuntos
Anti-Helmínticos/farmacologia , Caenorhabditis elegans/efeitos dos fármacos , Inibidores das Enzimas do Citocromo P-450/farmacologia , Sistema Enzimático do Citocromo P-450/efeitos dos fármacos , Lactamas Macrocíclicas/farmacologia , Lactonas/farmacologia , Animais , Caenorhabditis elegans/enzimologia , Caenorhabditis elegans/genética , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/farmacologia , Relação Dose-Resposta a Droga , Ivermectina/farmacologia , Modelos Logísticos , Macrolídeos/farmacologia , Butóxido de Piperonila/farmacologia , Reação em Cadeia da Polimerase em Tempo Real
15.
J Chem Ecol ; 45(5-6): 440-446, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30941560

RESUMO

The elytra of females of the white-spotted longhorn beetle, Anoplophora malasiaca (Coleoptera: Cerambycidae), are coated with a contact sex pheromone, which was previously shown to be composed of at least three chemical groups. Individually, the chemical groups had little pheromonal activity, but a blend of all three exhibited activity equal to that of the crude female extract. Two groups are female-specific aliphatic hydrocarbons and ketones, which were previously synthesized and confirmed to elicit mating behavior. The third group consists of three lactones, gomadalactones A, B, and C, whose chemical structures were previously identified. These have now been synthesized, and the contact sex pheromone activities of synthetic gomadalactones A, B, and C, and the diastereomer of gomadalactone C, were tested in bioassays in this study. When tested in combination with synthetic hydrocarbons and ketones at the same doses as found in female elytra extract, the individual gomadalactones and a blend showed potent pheromonal activity equivalent to that of the crude extract of the elytra of female beetles. This completes the identification of the essential components of the contact sex pheromone of A. malasiaca. Redundancy of components in the hydrocarbon and ketone groups required to elicit mating behavior was observed previously, and this was also true for the gomadalactones.


Assuntos
Besouros/fisiologia , Lactonas/síntese química , Atrativos Sexuais/química , Animais , Cromatografia Líquida de Alta Pressão , Feminino , Lactonas/isolamento & purificação , Lactonas/farmacologia , Masculino , Atrativos Sexuais/isolamento & purificação , Atrativos Sexuais/farmacologia , Comportamento Sexual Animal/efeitos dos fármacos
16.
Molecules ; 24(7)2019 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-30974765

RESUMO

Seven resorcylic acid lactones (RALs) including five new analog rhinoclactones, A-E (1, 2, 4-6), were isolated from an endophytic fungus Rhinocladiella similis in the plant Agriophyllum squarrosum collected from the Tengger Desert of the Ningxia Province, China. The structures of these new compounds were determined by HR-ESI-MS (High Resolution Electrospray Ionization Mass Spectrometry), NMR data, modified Mosher's method, and X-ray diffraction experiments. All compounds isolated from this fungus possessed the 16-OMe/14-OH, not the common 16-OH/14-OH or 16-OH/14-OMe groups on the aromatic ring, which are rarely found in nature. Compound 7 displayed cytotoxic activities against HCT116 and HeLa cancer cell lines. The possible biosynthesis of 1-7 is suggested, and the potential ecological roles of these fungal secondary metabolites is discussed.


Assuntos
Ascomicetos/química , Chenopodiaceae/microbiologia , Citotoxinas , Endófitos/química , Lactonas , Citotoxinas/química , Citotoxinas/isolamento & purificação , Citotoxinas/farmacologia , Células HCT116 , Células HeLa , Humanos , Lactonas/química , Lactonas/isolamento & purificação , Lactonas/farmacologia
17.
Org Lett ; 21(9): 3193-3197, 2019 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-30995050

RESUMO

An asymmetric synthesis of C14-desmethylene corialactone D is described on the basis of strategic application of a metallacycle-mediated annulative cross-coupling reaction, a Still [2,3]-Wittig rearrangement, and Morken's hydroxyl-directed diboration reaction. While representing a convenient approach to access novel compositions of matter inspired by the sesquiterpenoid natural product class (including classic natural product synthesis targets including the picrotaxanes and dendrobine), these studies have led to the discovery of natural product-inspired agents that inhibit nerve growth factor (NGF)-mediated neurite outgrowth in PC-12 cells.


Assuntos
Alcaloides/síntese química , Lactonas/síntese química , Fator de Crescimento Neural/antagonistas & inibidores , Crescimento Neuronal/efeitos dos fármacos , Sesquiterpenos/síntese química , Alcaloides/farmacologia , Animais , Lactonas/farmacologia , Células PC12 , Ratos , Sesquiterpenos/farmacologia , Relação Estrutura-Atividade
18.
Molecules ; 24(7)2019 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-30934890

RESUMO

Catalpa ovata (Bignoniaceae) is widely distributed throughout Korea, China, and Japan. This study investigated the anti-inflammatory effects of catalpalactone isolated from C. ovata in lipopolysaccharide (LPS)-induced RAW264.7 cells. Catalpalactone significantly inhibited nitric oxide (NO) production and inducible NO synthase (iNOS) expression in LPS-induced RAW264.7 cells. The levels of cytokines such as interleukin-6 and tumor necrosis factor-α were reduced under catalpalactone exposure in LPS-induced RAW264.7 cells. Additionally, catalpalactone suppressed signal transducer and activator of transcription 1 (STAT-1) protein expression and interferon-ß (IFN-ß) production. Treatment with catalpalactone prevented interferon regulatory factor 3 (IRF3) and nuclear factor-κB (NF-κB) activation. Taken together, these results suggest that the anti-inflammatory effects of catalpalactone are associated with the suppression of NO production and iNOS expression through the inhibition of IRF3, NF-κB, and IFN-ß/STAT-1 activation.


Assuntos
Anti-Inflamatórios/farmacologia , Bignoniaceae/química , Lactonas/farmacologia , Macrófagos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Citocinas/genética , Citocinas/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Mediadores da Inflamação/metabolismo , Lactonas/química , Lactonas/isolamento & purificação , Lipopolissacarídeos/imunologia , Ativação de Macrófagos/efeitos dos fármacos , Ativação de Macrófagos/imunologia , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Células RAW 264.7
19.
Int J Mol Sci ; 20(8)2019 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-31013928

RESUMO

Strigolactones (SLs) have recently been shown to play roles in modulating plant architecture and improving plant tolerance to multiple stresses, but the underlying mechanisms for SLs regulating leaf elongation and the influence by air temperature are still unknown. This study aimed to investigate the effects of SLs on leaf elongation in tall fescue (Festuca arundinacea, cv. 'Kentucky-31') under different temperature regimes, and to determine the interactions of SLs and auxin in the regulation of leaf growth. Tall fescue plants were treated with GR24 (synthetic analog of SLs), naphthaleneacetic acid (NAA, synthetic analog), or N-1-naphthylphthalamic acid (NPA, auxin transport inhibitor) (individually and combined) under normal temperature (22/18 °C) and high-temperature conditions (35/30 °C) in controlled-environment growth chambers. Exogenous application of GR24 stimulated leaf elongation and mitigated the heat inhibition of leaf growth in tall fescue. GR24-induced leaf elongation was associated with an increase in cell numbers, upregulated expression of cell-cycle-related genes, and downregulated expression of auxin transport-related genes in elongating leaves. The results suggest that SLs enhance leaf elongation by stimulating cell division and interference with auxin transport in tall fescue.


Assuntos
Festuca/efeitos dos fármacos , Festuca/fisiologia , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Genes cdc , Lactonas/farmacologia , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/fisiologia , Transporte Biológico , Resposta ao Choque Térmico/efeitos dos fármacos , Resposta ao Choque Térmico/genética , Ácidos Indolacéticos/metabolismo , Lactonas/química , Temperatura Ambiente
20.
Molecules ; 24(8)2019 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-30999647

RESUMO

Acute lung injury (ALI) is a severe clinical disease marked by dysregulated inflammation response and has a high rate of morbidity and mortality. Macrophages, which play diverse roles in the inflammatory response, are becoming therapeutic targets in ALI. In this study we investigated the effects of dehydrocostus lactone (DHL), a natural sesquiterpene, on macrophage activation and LPS-induced ALI. The macrophage cell line RAW264.7 and primary lung macrophages were incubated with DHL (0, 3, 5, 10 and 30 µmol/L) for 0.5 h and then challenged with LPS (100 ng/mL) for up to 8 hours. C57BL/6 mice were intratracheally injected with LPS (5 mg/kg) to induce acute lung injury (ALI) and then treated with a range of DHL doses intraperitoneally (5 to 20 mg/kg). The results showed that DHL inhibited LPS-induced production of proinflammatory mediators such as iNOS, NO, and cytokines including TNF-α, IL-6, IL-1ß, and IL-12 p35 by suppressing the activity of NF-κB via p38 MAPK/MK2 and Akt signaling pathway in macrophages. The in vivo results revealed that DHL significantly attenuated LPS-induced pathological injury and reduced cytokines expression in the lung. NF-κB, p38 MAPK/MK2 and Akt signaling molecules were also involved in the anti-inflammatory effect. Collectively, our findings suggested that DHL is a promising agent for alleviating LPS-induced ALI.


Assuntos
Lesão Pulmonar Aguda , Anti-Inflamatórios/farmacologia , Lactonas/farmacologia , Lipopolissacarídeos/toxicidade , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Sesquiterpenos/farmacologia , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/patologia , Lesão Pulmonar Aguda/prevenção & controle , Animais , Células Cultivadas , Relação Dose-Resposta a Droga , Macrófagos/patologia , Masculino , Camundongos , NF-kappa B/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA