RESUMO
Our previous work found that in the presence of nitrite, titanium dioxide nanoparticles can cause protein tyrosine nitration under UVA irradiation in vivo. In this paper, the human keratinocyte cells was used as a skin cell model to further study the photo-toxicity of titanium dioxide nanoparticles when nitrite was present. The results showed that nitrite increased the photo-toxicity of titanium dioxide in a dose-dependant manner, and generated protein tyrosine nitration in keratinocyte cells. Morphological study of keratinocyte cells suggested a specific apoptosis mediated by apoptosis inducing factor. It was also found the main target nitrated in cells was cystatin-A, which expressed abundantly in cytoplasm and functioned as a cysteine protease inhibitor. The stress induced by titanium dioxide with nitrite under UVA irradiation in human keratinocyte cells appeared to trigger the apoptosis inducing factor mediated cell death and lose the inhibition of active caspase by cystatin-A. We conclude that nitrite can bring new damage and stress to human keratinocyte cells with titanium dioxide nanoparticles under UVA irradiation.
Assuntos
Queratinócitos/efeitos dos fármacos , Nanopartículas/toxicidade , Nitritos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Pele/efeitos dos fármacos , Titânio/toxicidade , Apoptose/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Cistatina A/metabolismo , Dermatite Fototóxica , Humanos , Queratinócitos/metabolismo , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Nanopartículas/ultraestrutura , Estresse Oxidativo/efeitos da radiação , Pele/metabolismo , Espectrometria de Massas em Tandem , Tirosina/metabolismoRESUMO
Protein tyrosine nitration is a common post-translational modification occurring under conditions of nitrative/oxidative stress in a number of diseases. The major pathways of protein tyrosine nitration in vivo include peroxynitrite (ONOO(- )) and hemoglobin/[image omitted] /H(2)O(2)-dependent reaction. In this paper, several structural diversity flavonoids (quercetin, kaempferol, (+)-catechin, baicalein, apigenin, and naringenin) were chosen, to study their efficiencies against ONOO(- ) or hemoglobin/NaNO(2)/H(2)O(2)-mediated nitrative/oxidative damage to human plasma proteins in vitro. Protein nitration was efficiently inhibited by these flavonoids regardless of nitration pathways, and the inhibitory effects were consistent with their free radical scavenging activities. These flavonoids dose dependently inhibited ONOO(- )-induced protein oxidation, while they ineffectively suppressed hemoglobin/NaNO(2)/H(2)O(2)-triggered protein oxidation. These results mean that ONOO(- ) and hemoglobin/NaNO(2)/H(2)O(2) can cause plasma protein nitrative and oxidative damage in different pathways, and those flavonoids with strong antioxidant activities may contribute their protective effect partly through inhibiting protein nitration.
Assuntos
Proteínas Sanguíneas/efeitos dos fármacos , Flavonoides/farmacologia , Hemoglobinas/metabolismo , Nitratos/metabolismo , Ácido Peroxinitroso/farmacologia , Tirosina/análogos & derivados , Antioxidantes/química , Antioxidantes/farmacologia , Flavonoides/análise , Flavonoides/sangue , Flavonoides/química , Sequestradores de Radicais Livres/sangue , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/farmacologia , Humanos , Estrutura Molecular , Oxirredução , Tirosina/metabolismoRESUMO
OBJECTIVE: To study the anti-inflammations of the ethyl acetate extract of S. china on acute and chronic inflammations. METHOD: The rat paw edema induced by egg-albumin, the ear edema and the foot edema of mice induced by xylene and formaldehyde, the increased vascular permeability of capillary induced by intraperitoneal injection of 0.7% acetic acid in mice were used to study on the acute, early inflammations and chronic inflammation for the ethyl acetate extract of S. china. RESULT: The extract (50-100 g x kg(-1)) could significantly decrease the rat paw edema, and inhibit the ear edema, the increased vascular permeability and the foot edema of mice. CONCLUSION: The ethyl acetate extract of S. china possesses remarkable anti-inflammatory effects on acute inflammation, and also displays anti-inflammatory effects on the chronic inflammation at a certain extent.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Edema/patologia , Inflamação/patologia , Smilax , Animais , Anti-Inflamatórios não Esteroides/farmacocinética , Permeabilidade Capilar , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/farmacocinética , Edema/metabolismo , Inflamação/metabolismo , Masculino , Camundongos , Plantas Medicinais/química , Ratos , Ratos Sprague-Dawley , Smilax/químicaRESUMO
The aqueous extract of the tuber of Smilax china L., popularly known in China as "jin gang ten", was tested for its anti-inflammatory activities in rats by egg-albumin-induced edema and anti-nociceptive effects in mice using hot-plate test and acetic acid-induced abdominal constriction test, respectively. The aqueous extract in the dose of 1000 mg/kg (i.g.) had a significant anti-nociceptive and anti-inflammatory effect compared to physiological saline. The anti-inflammatory effects are similar to acetylsalicylic acid (200 mg/kg, i.g.). We also evaluated the aqueous extract for the inhibition of prostaglandin production (for COX-2 inhibitions) in lipopolysaccharide (LPS)-induced mouse macrophage cells. The result showed that both COX-2 activity and COX expression were inhibited by the extract. These active extracts suppressing activities warranted further studies of active principles and development of new anti-inflammatory and analgesic agents. Studies to determine correlation between chemical composition and pharmacological activity are underway.
Assuntos
Analgésicos/farmacologia , Anti-Inflamatórios/farmacologia , Inibidores de Ciclo-Oxigenase 2/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Smilax , Ácido Acético , Albuminas , Animais , Células Cultivadas , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/metabolismo , Relação Dose-Resposta a Droga , Edema/induzido quimicamente , Edema/prevenção & controle , Feminino , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/metabolismo , Camundongos , Dor/induzido quimicamente , Dor/prevenção & controle , Ratos , Ratos Sprague-Dawley , Fatores de TempoRESUMO
OBJECTIVE: To develop a with high efficiency and practicality for separating and purifying total steroidal saponins lax china. METHOD: Using adsorption capacity and desorption rate of total steroidal saponins as the primary screening index, surveyed, and the optimized conditions of adsorption and desorption of total steroidal saponins were studied. RESULT: The adsorption and desorption rate of total steroidal saponins reached 16 mg x mL(-1) and 90% respectively for macroporous resin HPD100 chosen. Macroporous resin HPD100 could be well used in separating and purifying total steroidal saponins from S. china.
Assuntos
Resinas de Troca Aniônica , Plantas Medicinais/química , Saponinas/isolamento & purificação , Smilax/química , Adsorção , Concentração de Íons de Hidrogênio , Rizoma/química , Espectrofotometria Ultravioleta/métodosRESUMO
Supercritical CO(2) fluid extraction (SFE-CO(2)) was used to extract the sapogenins after acid hydrolysis from Smilax china tubers. The influence of extraction variables, such as modifier, pressure, temperature and extraction time, were studied. SFE-CO(2) was found to produce higher yield than conventional solvent extraction. The highest yield (0.454%) of sapogenins, mostly containing diosgenin, was obtained using 35 MPa pressure, 65 degrees C and 95% EtOH as a modifier for 180 min, higher than that obtained with conventional extraction methods (0.385%).
Assuntos
Fitoterapia , Extratos Vegetais/química , Sapogeninas/química , Smilax , Cromatografia com Fluido Supercrítico , HumanosRESUMO
Transmucosal delivery is a suitable route for insulin non-injection administration. In this study, the hypoglycaemic effect of INSULIN BUCCAL SPRAY (IBS), a formulation with soybean lecithin and propanediol combined as absorption enhancer for insulin on diabetic rabbits and rats, were investigated. The hypoglycaemic rate was calculated and the pharmacodynamics and pharmacokinetics of the formulation in rabbits were studied. The results show that when the diabetic rabbits were administrated with IBS in dosages of 0.5, 1.5 and 4.5Ukg(-1), the blood glucose level decreased significantly compared with that of the control group and the hypoglycaemic effect lasted over 5h. The blood glucose decreasing rates are 22.4, 48.1 and 53.5%, respectively. The average bioavailability of IBS by buccal delivery versus subcutaneous injection is 29.2%. Meanwhile, the diabetic rats were administrated with IBS in dosages of 1.0, 3.0 and 9.0Ukg(-1), the blood glucose level decreased significantly compared with that of the control group and the hypoglycaemic effect lasted over 4h. The blood glucose decreasing rates are 24.6, 47.5 and 59.6%, respectively. Furthermore, the penetration of fluorescein isothiocyanate (FITC)-labelled insulin through rabbit buccal mucosa was investigated by scanning the distribution of the fluorescent probe in the epithelium using confocal laser scanning microscopy. The results revealed that FITC-insulin can pass through the buccal mucosa promoted by the enhancer and the passage of insulin across the epithelium includes both intracellular and paracellular routes. From the rabbit and rat experimental results showed that IBS is an effective buccal delivery system, which is promising for clinical trial and the future clinical application.