RESUMO
OBJECTIVE: To survey the status of current tamoxifen pharmacovigilance documentation reflecting tamoxifen use in an academic outpatient multispecialty practice in older adults. This data will help provide information to develop improved pharmacovigilance for a growing cohort of older adult users. The data will be utilized by an interdisciplinary team developing new methods of identifying factors for individualized pharmacovigilance in older adults. DESIGN: Retrospective chart review to gather descriptive and quantitative data on tamoxifen pharmacovigilance. SETTING: Multi-specialty clinic. PATIENTS: Ninety-three patients 60 years of age and older. MAIN OUTCOME MEASURES: Quantitative report of tamoxifen monitoring as well as descriptive analysis of individual cases. RESULTS: We found 19 cases of serious adverse events possibly related to tamoxifen (thrombi, uterine malignancies). There were 15 cases with no documentation of pharmacovigilance. All cases had incomplete pharmacovigilance documented. There were two cases of hypercalcemia. There was one case of tamoxifen discontinuation resulting from muscle pain and with chronic muscle pain complaints while receiving tamoxifen. We observed a correlation in older age or high comorbidity burden patients and adverse events patients. CONCLUSION: Some studies direct the important pharmacovigilance toward prevention of thrombi, uterine malignancies, and hypercalcemia; however, it is not easy to identify recommendations for frequency or focus of monitoring to prevent adverse events for individual older adults based on existing recommendations. The data collected and presented in this study serve to heighten awareness of tamoxifen pharmacovigilance and as a starting point for the application of machine learning techniques and modeling to identify high-risk patients and individualized pharmacovigilance recommendations.
Assuntos
Farmacovigilância , Tamoxifeno/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Hipercalcemia/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Trombose/induzido quimicamente , Neoplasias Uterinas/induzido quimicamenteRESUMO
In this study, we evaluated the gastric protective activities of mokdanpi in vitro. Further, we used experimental ulcer models to identify the active ingredients of mokdanpi. As a preliminary evaluation of mokdanpi ethanolic extract and its ingredients, we assessed its radical scavenging activities. In addition, its antimicrobial activity against Helicobacter pylori (H. pylori) was investigated. The antiulcerogenic activity of the active ingredients was evaluated in pylorus-ligated rats, an HCl/ethanol-induced and an absolute ethanol-induced ulcer model. We confirmed the scavenging effect of the ethanolic extract of mokdanpi and its ingredients against 2,2-diphenyl-1-picrylhydrazyl, nitric oxide and superoxide radicals, and we demonstrated that mokdanpi could inhibit the colonization of H. pylori. In an HCl-ethanol-induced ulcer model, gallic acid and catechin (100 mg/kg) inhibited 40.6% and 41.7% of gastric lesions, respectively. Catechin (100 mg/kg) significantly reduced (p<0.05) the gastric secretion induced by pylorus ligature in rats in comparison to the control group. Gallic acid (100 mg/kg) significantly increased (p<0.05) the mucus contents in an ethanol-induced ulcer model. The antioxidant ingredients (catechin and gallic acid) present in mokdanpi play a major role in antiulcerogenic activity, and demonstrate novel activity against H. pylori.
Assuntos
Anti-Infecciosos/uso terapêutico , Antiulcerosos/uso terapêutico , Antioxidantes/uso terapêutico , Helicobacter pylori/efeitos dos fármacos , Paeonia/química , Fitoterapia , Úlcera Gástrica/tratamento farmacológico , Animais , Anti-Infecciosos/farmacologia , Antiulcerosos/farmacologia , Antioxidantes/farmacologia , Compostos de Bifenilo/metabolismo , Catequina/farmacologia , Catequina/uso terapêutico , Etanol , Ácido Gálico/farmacologia , Ácido Gálico/uso terapêutico , Suco Gástrico/efeitos dos fármacos , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Mucosa Gástrica/microbiologia , Helicobacter pylori/crescimento & desenvolvimento , Ligadura , Muco/metabolismo , Óxido Nítrico/metabolismo , Picratos/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Raízes de Plantas , Ratos , Ratos Sprague-Dawley , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/metabolismo , Úlcera Gástrica/patologia , Superóxidos/metabolismoRESUMO
We isolated 18 polyphenols with neuraminidase inhibitory activity from methanol extracts of the roots of Glycyrrhiza uralensis. These polyphenols consisted of four chalcones (1-4), nine flavonoids (5-13), four coumarins (14-17), and one phenylbenzofuran (18). When we tested the effects of these individual compounds and analogs thereof on neuraminidase activation, we found that isoliquiritigenin (1, IC(50)=9.0 microM) and glycyrol (14, IC(50)=3.1 microM) had strong inhibitory activity. Structure-activity analysis showed that the furan rings of the polyphenols were essential for neuraminidase inhibitory activity, and that this activity was enhanced by the apioside group on the chalcone and flavanone backbone. In addition, the presence of a five-membered ring between C-4 and C-2' in coumestan was critical for neuraminidase inhibition. All neuraminidase inhibitors screened were found to be reversible noncompetitive inhibitors.
Assuntos
Flavonoides/farmacologia , Glycyrrhiza uralensis , Neuraminidase/antagonistas & inibidores , Fenóis/farmacologia , Extratos Vegetais/farmacologia , Raízes de Plantas , Ativação Enzimática/efeitos dos fármacos , Ativação Enzimática/fisiologia , Flavonoides/isolamento & purificação , Neuraminidase/metabolismo , Fenóis/isolamento & purificação , Extratos Vegetais/isolamento & purificação , Polifenóis , Relação Estrutura-AtividadeRESUMO
In the present study, we investigated the effect of 3alpha,23-isopropylidenedioxyolean-12-en-27-oic acid (IPA), an active compound isolated from Aceriphyllum rossii, on the apoptotic activity and the molecular mechanism of the action in human cervical cancer HeLa cells. Treatment with IPA significantly increased externalization of phosphatidylserine residues and apoptotic DNA fragmentation as shown by Annexin V staining and 4',6-diamidino-2-phenylindole-dihydrochloride (DAPI) staining, respectively. In addition, IPA induced the activations of caspase-8, -9, -3, and cleavage of poly(ADP ribose) polymerase (PARP-1) in HeLa cells. Pretreatment with a specific caspase-8, -9, or -3 inhibitor neutralized the pro-apoptotic activity of IPA in HeLa cells. Furthermore, IPA was found to induce the loss of mitochondrial membrane potential, the release of cytochrome c to the cytosol, and the increased ratio of mitochondrial Bax/Bcl-2. Moreover, we demonstrated that IPA triggered endoplasmic reticulum (ER) stress, as shown by changes in cytosol-calcium level, activation of mu-calpain and caspase-12, and up-regulation of glucose-regulated protein 78 (GRP78) and growth arrest DNA damage-inducible gene 153 (GADD153). IPA-induced apoptosis was substantially reduced in the presence of an intracellular calcium chelator BAPTA/AM. Taken together, these results suggest that both mitochondrial dysfunction and ER stress contribute to IPA-induced apoptosis of human cervical cancer HeLa cells.
Assuntos
Apoptose/efeitos dos fármacos , Retículo Endoplasmático/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Ácido Oleanólico/farmacologia , Saxifragaceae , Triterpenos/farmacologia , Apoptose/fisiologia , Relação Dose-Resposta a Droga , Retículo Endoplasmático/metabolismo , Chaperona BiP do Retículo Endoplasmático , Células HeLa , Humanos , Mitocôndrias/fisiologia , Ácido Oleanólico/isolamento & purificação , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Triterpenos/isolamento & purificaçãoRESUMO
In order to establish the antiallergic properties of Schisandra fructus and Magnolia flos, several compounds isolated from these plants were tested for 5-lipoxygenase (5-LOX) inhibitory activity in vitro, for the first time. The compounds including schizandrins, schisandrols, gomisins, fargesin, eudesmin and lirioresinol B dimethyl ether, inhibited 5-LOX-catalysed leukotriene production from A23187-treated rat basophilic leukemia (RBL-1) cells at concentrations of 1-100 microm. In particular, constituents such as schisandrol A and gomisins showed potent inhibitory activity (IC(50)s < 10 microm) on 5-LOX-catalysed leukotriene production, but were much less active on cyclooxygenase-2-catalysed prostaglandin E(2) and inducible nitric oxide-catalysed NO production. These compounds have the potential to be developed as novel antiallergic agents and may contribute to the antiallergic pharmacological use of these plant materials in Chinese medicine.
Assuntos
Antialérgicos/farmacologia , Inibidores de Lipoxigenase , Inibidores de Lipoxigenase/farmacologia , Magnolia/química , Extratos Vegetais/farmacologia , Schisandra/química , Animais , Antialérgicos/isolamento & purificação , Linhagem Celular Tumoral , Ciclo-Octanos/isolamento & purificação , Ciclo-Octanos/farmacologia , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/biossíntese , Flores , Frutas , Concentração Inibidora 50 , Leucotrienos/biossíntese , Lignanas/isolamento & purificação , Lignanas/farmacologia , Inibidores de Lipoxigenase/isolamento & purificação , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase Tipo II/metabolismo , Extratos Vegetais/química , RatosRESUMO
In the course of screening for the melanogenesis inhibitors, aspochalasin I was isolated from solid-state culture of Aspergillus sp. Fb020460. Its structure was determined by spectroscopic analysis including mass spectroscopy and NMR analysis. Aspochalasin I potently inhibited melanogenesis in Mel-Ab cells with an IC50 value of 22.4 microM without cytotoxicity.
Assuntos
Aspergillus/química , Citocalasinas/farmacologia , Melaninas , Melanócitos , Animais , Linhagem Celular Transformada , Sobrevivência Celular/efeitos dos fármacos , Citocalasinas/química , Citocalasinas/isolamento & purificação , Concentração Inibidora 50 , Espectrometria de Massas , Melaninas/antagonistas & inibidores , Melaninas/metabolismo , Melanócitos/efeitos dos fármacos , Melanócitos/metabolismo , Camundongos , Monofenol Mono-Oxigenase/antagonistas & inibidores , Monofenol Mono-Oxigenase/metabolismo , Ressonância Magnética Nuclear BiomolecularRESUMO
The need for Long-Term Care (LTC) arises in the elderly population, especially those reaching age 65 each year. This elderly population will grow tremendously in the United States over the next decade, resulting in short- and long-term challenges of matching resource capacity with uncertain demand for hospitals and other healthcare providers. This paper describes research involving the development of a simulation model of patient flow in order to understand the relationship between capacity and demand, and to investigate the impacts on performance measures such as average wait times for LTC patients. We propose an aggregate capacity model to consider patient flow among various types of care providers by integrating hospitals, nursing homes, assisted living facilities, and home health care. Using the data including patient demographics and service provider information, we forecast patient demand for LTC. The computational results demonstrate the efficacy of a simulation-based optimisation solution approach for capacity planning.
RESUMO
OBJECTIVE: We attempted to discover that Ankylosing spondylitis (AS) has a comprehensive relationship with congestive heart failure and death. METHODS: We used a nationwide database managed by the Korean National Health Insurance Service from 2010 to 2014. Twelve thousand nine hundred eighty-eight patients with a diagnosis of AS and 64940 age- and sex- stratified matching subjects without AS were enrolled in the AS and control groups. Incidence probabilities of 6 years congestive heart failure and death in each group were calculated. The Cox proportional hazard regression analysis was used to estimate the hazard ratio. We divided the AS and control groups into subgroups according to sex, age, income, and comorbidities. RESULTS: During the follow-up period, 102 patients (0.79%) in the AS group and 201 patients (0.32%) in the control group developed congestive heart failure (p<0.0001). In addition, 211 (1.62%) subjects in the AS group died during the follow-up period compared to 639 (0.98%) subjects in the control group (p<0.0001). The adjusted hazard ratio of congestive heart failure and death in the AS group was 2.28 (95% confidence interval [CI], 1.80-2.89) and 1.66 (95% CI, 1.42-1.95), respectively. The hazard ratios of congestive heart failure and death were significantly increased in all of the subgroups. CONCLUSION: The incidence rates of congestive heart failure and death were increased in AS patients.
RESUMO
Schisandrin is the main active ingredient isolated from the fruit of Schisandra chinensis Baill. Recent studies have demonstrated that schisandrin exhibits anti-oxidative effects in vivo. In the present study, the effect of schisandrin on plasma nitrite concentration in lipopolysaccharide (LPS)-treated mice was evaluated. It also significantly inhibited carrageenan-induced paw edema and acetic acid-induced vascular permeability in mice. Furthermore, schisandrin had a protective effect on lipopolysaccharide (LPS)-induced sepsis. In vitro, our results are the first that show that the anti-inflammatory properties of schisandrin result from the inhibition of nitric oxide (NO) production, prostaglandin E(2) (PGE(2)) release, cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression, which in turn results from the inhibition of nuclear factor-kappaB (NF-kappaB), c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) activities in a RAW 264.7 macrophage cell line.
Assuntos
Anti-Inflamatórios/farmacologia , Ciclo-Octanos/farmacologia , Inflamação/tratamento farmacológico , Lignanas/farmacologia , Compostos Policíclicos/farmacologia , Schisandra/química , Animais , Anti-Inflamatórios/isolamento & purificação , Permeabilidade Capilar/efeitos dos fármacos , Linhagem Celular , Ciclo-Octanos/isolamento & purificação , Ciclo-Oxigenase 2/efeitos dos fármacos , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/antagonistas & inibidores , Dinoprostona/metabolismo , Frutas , Regulação da Expressão Gênica/efeitos dos fármacos , Inflamação/etiologia , Inflamação/fisiopatologia , Lignanas/isolamento & purificação , Lipopolissacarídeos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase Tipo II/efeitos dos fármacos , Óxido Nítrico Sintase Tipo II/metabolismo , Nitritos/sangue , Compostos Policíclicos/isolamento & purificação , Sepse/prevenção & controleRESUMO
Magnolol, an active component extracted from Magnolia officinalis, has been reported to have protective effect on ischemia and reperfusion (I/R)-induced injury in experimental animals. The aim of the present investigation was to further evaluate the mechanism(s) by which magnolol reduces I/R-induced myocardial injury in rats in vivo. Under anesthesia, left anterior descending (LAD) coronary artery was occluded for 30 min followed by reperfusion for 24 h (for infarct size and cardiac function analysis). In some experiments, reperfusion was limited to 1 h or 6 h for analysis of biochemical and molecular events. Magnolol and DMSO solution (vehicle) were injected intra-peritoneally 1 h prior to I/R insult. The infarct size was measured by TTC technique and heart function was monitored by Millar Catheter. Apoptosis related events such as p-ERK, p-Bad, Bcl-xl and cytochrome c expression were evaluated by Western blot analysis and myocardial caspase-3 activity was also measured. Magnolol (10 mg/kg) reduced infarct size by 50% (P < 0.01 versus vehicle), and also improved I/R-induced myocardial dysfunction. Left ventricular systolic pressure and positive and negative maximal values of the first derivative of left ventricular pressure (dP/dt) were significantly improved in magnolol-treated rats. Magnolol increased the expression of phosphor ERK and Bad which resulted in inhibition of myocardial apoptosis as evidenced by TUNEL analysis and DNA laddering experiments. Application of PD 98059, a selective MEK1/2 inhibitor, strongly antagonized the effect of magnolol. Taken together, we concluded that magnolol inhibits apoptosis through enhancing the activation of ERK1/2 and modulation of the Bcl-xl proteins which brings about reduction of infarct size and improvement of cardiac function in I/R-induced injury.
Assuntos
Apoptose/efeitos dos fármacos , Compostos de Bifenilo/farmacologia , Lignanas/farmacologia , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Extratos Vegetais/farmacologia , Animais , Caspase 3/metabolismo , Modelos Animais de Doenças , Flavonoides/farmacologia , Coração/efeitos dos fármacos , Coração/fisiopatologia , Masculino , Proteína Quinase 1 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 3 Ativada por Mitógeno/antagonistas & inibidores , Infarto do Miocárdio/patologia , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacosRESUMO
Clitocybin A (1), a new antioxidant, was isolated from the culture broth of Clitocybe aurantiaca. This compound was purified by solvent extraction, silica gel column chromatography, Sephadex LH-20 column chromatography and preparative HPLC. Its structure was determined as 4,6-dihydroxy-2-p-hydroxyphenyl-isoindol1-one on the basis of the UV, NMR, and MS spectroscopic analysis. The compound 1 showed potent free radical scavenging activity against superoxide, ABTS, and DPPH radicals, and protective effect against cellular DNA damage induced by oxidative stress.
Assuntos
Agaricales/metabolismo , Antioxidantes/isolamento & purificação , Isoindóis/isolamento & purificação , Antioxidantes/química , Antioxidantes/farmacologia , Dano ao DNA/efeitos dos fármacos , Sequestradores de Radicais Livres/farmacologia , Isoindóis/química , Isoindóis/farmacologiaRESUMO
In this study, two daphnane diterpene esters isolated from the flower buds of Daphne genkwa, genkwadaphnin (1) and yuanhuacine (2), were assessed with regard to their apoptotic activity in human promyelocytic HL-60 cells. Both 1 and 2 were demonstrated to activate the apoptotic process, including DNA fragmentation, chromatin condensation, and sub-G1 hypodiploidy. In our immunoblotting analysis, treatment with compounds 1 and 2 resulted in the cleavage of procaspase-3 and poly(ADP-ribose)polymerase (PARP) into active forms, and the expression of Bcl-2 proteins was shifted toward apoptosis; the expression of the pro-apoptotic protein, Bax, was increased, and the expression of Bcl-2 and Bcl-XL, both anti-apoptotic proteins, were suppressed in a dose-dependent manner. The administration (ip) of the compounds to Lewis lung carcinoma (LLC)-inoculated mice evidenced a significant inhibition of tumor growth (volume), with reductions of 47.9% and 63.1% (1), and 24.2% and 45.8% (2) at concentrations of 0.1 mg/kg and 0.5 mg/kg, as compared with the control mice. These results indicate that compounds 1 and 2 are potent apoptotic constituents of Daphne genkwa, and might be potent as anti-tumoric agents.
Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma Pulmonar de Lewis/tratamento farmacológico , Daphne/química , Diterpenos/farmacologia , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/isolamento & purificação , Caspase 3/efeitos dos fármacos , Caspase 3/metabolismo , Processos de Crescimento Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Diterpenos/administração & dosagem , Diterpenos/isolamento & purificação , Relação Dose-Resposta a Droga , Citometria de Fluxo , Flores , Regulação da Expressão Gênica/efeitos dos fármacos , Células HL-60 , Humanos , Immunoblotting , Injeções Intraperitoneais , Neoplasias Pulmonares/tratamento farmacológico , Camundongos , Poli(ADP-Ribose) Polimerases/efeitos dos fármacos , Poli(ADP-Ribose) Polimerases/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Carga Tumoral/efeitos dos fármacosRESUMO
Acyl-coenzyme A: cholesterol acyltransferase (ACAT) esterifies free cholesterol in the liver and the intestine. It has relations with production of lipoproteins and accumulation of cholesteryl esters of the atheroma. Therefore, ACAT inhibitors may act as antihypercholesterolemic and antiatherosclerotic agents. One isoprenyl flavonoid was isolated from ethanol extract of licorice roots. On the basis of spectral evidences, the compound was identified as glabrol (1). Compound 1 inhibited rat liver microsomal ACAT activity with an IC(50) value of 24.6 microM and decreased cholesteryl ester formation with an IC(50) value of 26.0 microM in HepG2 cells. In addition, 1 showed a non-competitive type of inhibition against ACAT.
Assuntos
Anticolesterolemiantes/farmacologia , Flavonoides/farmacologia , Glycyrrhiza/química , Esterol O-Aciltransferase/efeitos dos fármacos , Animais , Anticolesterolemiantes/isolamento & purificação , Aterosclerose/tratamento farmacológico , Linhagem Celular Tumoral , Ésteres do Colesterol/metabolismo , Relação Dose-Resposta a Droga , Flavonoides/isolamento & purificação , Microssomos Hepáticos/efeitos dos fármacos , Microssomos Hepáticos/metabolismo , Fitoterapia , Raízes de Plantas , Plantas Medicinais/química , Ratos , Esterol O-Aciltransferase/metabolismoRESUMO
Gomisin A is a component of the fruits of Schizandra chinesis which are widely used as a tonic in traditional Chinese medicine. In the present study, we assessed the effect of gomisin A on the learning and memory impairments induced by scopolamine. The cognition-enhancing effect of gomisin A was investigated using a passive avoidance test, the Y-maze test, and the Morris water maze test in mice. Drug-induced amnesia was induced by treating animals with scopolamine (1 mg/kg, i.p.). Gomisin A (5 mg/kg, p.o.) administration significantly reversed scopolamine-induced cognitive impairments in mice by the passive avoidance test and the Y-maze test (P<0.05), and also improved escape latency in the Morris water maze test at 5 mg/kg (P<0.05). Moreover, in an in vitro study, gomisin A was found to inhibit acetylcholinesterase activity in a dose-dependent manner (IC50 value; 15.5 microM). These results suggest that gomisin A may be a useful cognitive impairment treatment, and its beneficial effects are mediated, in part, via enhancing the cholinergic nervous system.
Assuntos
Ciclo-Octanos/farmacologia , Dioxóis/farmacologia , Lignanas/farmacologia , Memória/efeitos dos fármacos , Escopolamina/toxicidade , Acetilcolinesterase/metabolismo , Amnésia/induzido quimicamente , Amnésia/fisiopatologia , Amnésia/prevenção & controle , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Inibidores da Colinesterase/farmacologia , Cognição/efeitos dos fármacos , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/farmacologia , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos ICRRESUMO
Acanthoic acid (AA) is a pimaradiene diterpene isolated from the Korean medicinal plant, Acanthopanax koreanum (Araliaceae). In the present study, we examined whether AA has the inhibitory effect on the production of inflammatory mediators and activating signals induced in trypsin-treated human leukemic mast cell-1 (HMC-1). HMC-1 cells were stimulated with trypsin (100 nM) in the presence or absence of AA (1, 10, and 100 microg/ml). We assessed the production of TNF-alpha and tryptase by enzyme-linked immunosorbent assay (ELISA) or reverse transcription-PCR, ERK activation by Western blot, and NF-kappaB activation by gel shift assay. AA (10 and 100 microg/ml) significantly inhibited production of both TNF-alpha and tryptase in a dose-dependent manner in trypsin-stimulated HMC-1. Furthermore, AA inhibited ERK phosphorylation and NF-kappaB activation induced by trypsin treatment without blocking of trypsin activity even with 100 microg/ml. These results suggest that AA may inhibit the production of inflammatory mediators through inhibition of ERK phosphorylation and NF-kappaB activation pathway in human mast cells. It supports the evidence that AA may be used to blocks the development of inflammation caused from mast cells.
Assuntos
Diterpenos/farmacologia , Mastócitos/efeitos dos fármacos , Inibidores da Tripsina/farmacologia , Células Cultivadas , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , NF-kappa B/metabolismo , Fosforilação , RNA Mensageiro/análise , Triptases/genética , Fator de Necrose Tumoral alfa/biossíntese , Fator de Necrose Tumoral alfa/genéticaRESUMO
Two isoflavone C-glucosides, puerarin (1) and PG-3 (2), a but-2-enolide, (+/-)-puerol B (3), two isoflavone O-glucosides, daidzin (4) and genistin (5), and three pterocarpans, (-)-medicarpin (6), (-)-glycinol (7) and (-)-tuberosin (8), were isolated from a MeOH extract of the roots of Pueraria lobata, using an in vitro bioassay based on the inhibition of the formation of advanced glycation end products (AGEs) to monitor chromatographic fractionation. The structures of 1-8 were determined by spectroscopic data interpretation, particularly by 1D- and 2D-NMR studies, and by comparison of these data with values in the literature. All of the isolates (1-8) were evaluated for their inhibitory activity on AGEs formation in vitro. Of these, puerarin (1), PG-3 (2), and (+/-)-puerol B (3) exhibited more potent inhibitory activity than the positive control aminoguanidine.
Assuntos
Produtos Finais de Glicação Avançada/antagonistas & inibidores , Extratos Vegetais/farmacologia , Raízes de Plantas/química , Pueraria/química , 4-Butirolactona/análogos & derivados , 4-Butirolactona/química , 4-Butirolactona/isolamento & purificação , 4-Butirolactona/farmacologia , Relação Dose-Resposta a Droga , Glucosídeos/química , Glucosídeos/isolamento & purificação , Glucosídeos/farmacologia , Produtos Finais de Glicação Avançada/metabolismo , Isoflavonas/química , Isoflavonas/isolamento & purificação , Isoflavonas/farmacologia , Estrutura Molecular , Fenóis/química , Fenóis/isolamento & purificação , Fenóis/farmacologia , Extratos Vegetais/química , Análise Espectral/métodosRESUMO
Interleukin (IL)-8 plays a central role in the initiation and maintenance of inflammatory responses in the inflammatory bowel disease. The proinflammatory cytokine-mediated production of IL-8 requires activation of various kinases, which leads to the I kappa B degradation and NF-kappa B activation. We investigated the role of 18 beta-glycyrrhetinic acid (GA), a saponin isolated from licorice roots, on TNF-alpha-induced IL-8 production in human colonic epithelial cells. HT29 cells were stimulated with TNF-alpha in the presence or absence of GA (1, 5 or 10 microM). IL-8 production was measured by enzyme-linked immunosorbent assay (ELISA) and reverse transcriptase-polymerase chain reaction analysis, and the mitogen-activated protein kinases (MAPKs) activation and I kappa B alpha degradation were determined by Western blot analysis. GA suppressed TNF-alpha-induced IL-8 production in a concentration-dependent manner. In addition, GA inhibited TNF-alpha-induced phosphorylation of p38 MAPK and extracellular-regulated kinases (ERK), I kappa B alpha degradation, and NF-kappa B activation. These results suggest that GA has the inhibitory effects on TNF-alpha-induced IL-8 production in the intestinal epithelial cells through blockade in the phosphorylation of MAPKs, following I kappa B alpha degradation and NF-kappa B activation.
Assuntos
Ácido Glicirretínico/análogos & derivados , Ácido Glicirretínico/farmacologia , Interleucina-8/antagonistas & inibidores , Western Blotting , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ativação Enzimática/efeitos dos fármacos , Ensaio de Imunoadsorção Enzimática , Células HT29 , Humanos , Proteínas I-kappa B/metabolismo , Interleucina-8/biossíntese , Proteína Quinase 1 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 3 Ativada por Mitógeno/antagonistas & inibidores , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Inibidor de NF-kappaB alfa , NF-kappa B/antagonistas & inibidores , Fosforilação/efeitos dos fármacos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Necrose Tumoral alfa/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidoresRESUMO
Scutellaria baicalensis Georgi (Labiatae) has been used in the treatment of inflammatory diseases. Drug processing (Poje) is the process of treating crude drugs by several methods before use. The aim of this study was to determine the effect of processed Scutellaria baicalensis on experimental ulcerative colitis induced by dextran sulfate sodium (DSS). The types of processed Scutellaria baicalensis used in this study were parched Scutellaria baicalensis (PS) and rice wine-baked Scutellaria baicalensis (RWBS). Experimental colitis was induced in mice using a daily treatment of 5% DSS in the drinking water for 7 days. The water extracts of processed Scutellaria baicalensis (1 g/kg) were administered orally once a day for 7 days. The mice were divided in four groups: i) water plus DSS group, ii) crude Scutellaria baicalensis (CS) plus DSS group, iii) PS plus DSS group, and iv) RWBS plus DSS group. RWBS ameliorated all of the inflammatory symptoms, such as body weight loss, rectal bleeding and histological damage, compared to CS. Furthermore, RWBS significantly reduced the mucosal myeloperoxidase activity, and TNF-alpha (tumor necrosis factor-alpha), COX-2 (cyclooxygenase-2), NF-kappaB (nuclear factor-kappa B) and chymase expression more than CS. But these effects were not shown in the PS plus DSS group. Efficacy of Scutellaria baicalensis was increased after rice wine baking, but not after parching. The findings in this study suggest that RWBS may be a useful therapeutic agent for ulcerative colitis.
Assuntos
Colite/prevenção & controle , Extratos Vegetais/farmacologia , Scutellaria baicalensis/química , Animais , Western Blotting , Colite/induzido quimicamente , Colo/efeitos dos fármacos , Colo/metabolismo , Colo/patologia , Sulfato de Dextrana/administração & dosagem , Sulfato de Dextrana/toxicidade , Feminino , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/metabolismo , Peroxidase/metabolismo , Fitoterapia , Extratos Vegetais/química , Raízes de Plantas/química , Água , VinhoRESUMO
Leukocyte adhesion to the vascular endothelium is a critical initiating step in inflammation and atherosclerosis. We have herein studied the effect of manassantin A (1) and B (2), dineolignans, on interaction of THP-1 monocytic cells and human umbilical vein endothelial cells (HUVEC) and expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin in HUVEC. When HUVEC were pretreated with 1 and 2 followed by stimulation with TNF-alpha, adhesion of THP-1 cells to HUVEC decreased in dose-dependent manner with IC50 values of 5 ng/mL and 7 ng/mL, respectively, without cytotoxicity. Also, 1 and 2 inhibited TNF-alpha-induced up-regulation of ICAM-1, VCAM-1 and E-selectin. The present findings suggest that 1 and 2 prevent monocyte adhesion to HUVEC through the inhibition of ICAM-1, VCAM-1 and E-selectin expression stimulated by TNF-alpha, and may imply their usefulness for the prevention of atherosclerosis relevant to endothelial activation.
Assuntos
Moléculas de Adesão Celular/antagonistas & inibidores , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/imunologia , Furanos/farmacologia , Saururaceae , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Veias Umbilicais/efeitos dos fármacos , Veias Umbilicais/imunologia , Moléculas de Adesão Celular/biossíntese , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/imunologia , Células Cultivadas , Relação Dose-Resposta Imunológica , Células Endoteliais/metabolismo , Furanos/química , Furanos/isolamento & purificação , Humanos , Lignanas , Fator de Necrose Tumoral alfa/farmacologia , Veias Umbilicais/citologia , Veias Umbilicais/metabolismoRESUMO
In the course of screening anti-dementia agents from natural products, two beta-secretase (BACE1) inhibitors were isolated from the ethyl acetate soluble fraction of Sanguisorbae Radix by the activity-guided purification using silica gel, Sephadex LH-20, and RP-HPLC. They were identified as 1,2,3-trigalloyl-4,6-hexahydroxydiphenoyl-beta-D-glucopyranoside (Tellimagrandin II, 1) and 1,2,3,4,6-pentagalloyl-beta-D-glucopyranoside (2) and were shown to non-competitively inhibit beta-secretase (BACE1) with the IC50 values of 3.10x10(-6) M and 3.76x10(-6) M, respectively. The Ki values of 1 and 2 were 6.84x10(-6) M and 5.13x10(-6) M. They were less inhibitory to alphasecretase (TACE) and other serine proteases such as chymotrypsin, trypsin, and elastase, suggesting that they were relatively specific inhibitors of BACE1.