RESUMO
Advanced glycation end-products (AGEs) have been regarded as an initial motivating factor in the pathogenesis of endothelial dysfunction in diabetic complications. 4,4'-Diphenylmethane-bis(methyl) carbamate (DMPC), a carbamate compound, was isolated from Cortex Mori and its prevention effects against AGEs-induced endothelial dysfunction were studied. 4,4'-Diphenylmethane-bis(methyl) carbamate significantly reduced cell apoptosis to normal level at 10â»9 mol/L concentration. Advanced glycation end-products up-regulated the expression of Bad and Bax and down-regulated Bcl-2 proteins, and pretreatment with DMPC significantly down-regulated Bad and Bax while up-regulating Bcl-2 expressions. In addition, ICAM (intercellular adhesion molecule)-1 and TGF (transforming growth factor)-ß1 expressions in human umbilical vein endothelial cell (HUVEC) were significantly enhanced by AGEs. More importantly, these increases of ICAM-1 and TGF-ß1 expressions were reduced meaningfully with the pretreatment of DMPC. All the results showed DMPC had prevention effects against the progression of AGE-induced endothelial dysfunction, and this compound might be a promising agent against endothelial dysfunction in diabetic vascular complications.
Assuntos
Carbamatos/farmacologia , Produtos Finais de Glicação Avançada/efeitos adversos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Morus/química , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Apoptose , Carbamatos/química , Carbamatos/isolamento & purificação , Sobrevivência Celular , Células Cultivadas , Células Endoteliais da Veia Umbilical Humana/patologia , Humanos , Imuno-Histoquímica , Molécula 1 de Adesão Intercelular/genética , Molécula 1 de Adesão Intercelular/metabolismo , Raízes de Plantas/química , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo , Proteína de Morte Celular Associada a bcl/genética , Proteína de Morte Celular Associada a bcl/metabolismoRESUMO
Prunella vulgaris L. (PV) has been used as a herb for chemoprevention of lung cancer. In this study, the main active compound, oleanolic acid (OA) was isolated from an ethanol extract and its chemical structure was identified according to the results of high performance liquid chromatography (HPLC), high performance thin layer chromatography (HPTLC) and liquid chromatography-mass spectrography (LC-MS). Results for cell viability indictated no notable differences between OA and ethanol extract of PV in lung adenocarcinoma SPC-A-1 cells measured by MTT assay. Consistent concentration-response curves. Fluorescence detection with acridine orange-ethidium bromide was used to evaluate apoptosis of SPC-A-1 cells. OA at 16 and 8 microM group increased significantly the apoptosis rate compared with normal and 1% DMSO groups (p<0.05). In addition, immunocytochemistry assays showed increase in Bax and Bad protein expression while Bcl-2 decreased. Moreover, the ratio of Bax/Bcl-2 was heightened by OA treatment. The results suggest OA induced apoptosis of lung adenocarcinoma cells through down-regulating Bcl-2 expression, and up-regulating Bax and Bad expression.