RESUMO
Microglia activation-mediated neuroinflammation plays an important role in the progression of Parkinson's disease (PD). However, effects of microglia activation on dopaminergic neuronal cell (DAC) fate are still poorly understood. The objective of this study was to explore the neurotoxic effects of microglia activation-mediated oxidative injury in DACs and its possible mechanisms. In the present study, microglia-DACs co-culture systems (murine BV-2 and MN9D cells, or primary microglia and mesencephalic neurons) were used to display the crosstalk between both cell types. The cytotoxicity of lipopolysaccharide-induced microglia activation led to the accumulation of intracellular reactive oxygen species, increased cell apoptosis rate, reduced number of DACs, concomitant to cell cycle arrest at G1 phase. Molecular mechanisms of apoptosis caused by microglia activation-induced oxidative injury included the increased opening of mitochondrial permeability transition pore and enhanced membrane potential depolarization in MN9D cells, down-regulation of Bcl-2 and up-regulation of Bax, caspase-3 expression in DACs. In addition, microglia activation made a significant reduction of SIRT3 and superoxide dismutase 2 gene expression in DACs. Taken together, these data imply that microglia activation promotes cell apoptosis through mitochondrial pathway and decreases SIRT3 expression in DACs, which may provide some support for PD progression promoted by neuroinflammation.
Assuntos
Neurônios Dopaminérgicos/metabolismo , Microglia/metabolismo , Estresse Oxidativo/fisiologia , Sirtuína 3/metabolismo , Animais , Apoptose/fisiologia , Linhagem Celular , Neurônios Dopaminérgicos/patologia , Inflamação/metabolismo , Inflamação/patologia , Camundongos , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Ratos , Ratos Sprague-DawleyRESUMO
Two new lignan compounds, 5'-allyl-2,2'-dihydroxy-[1,1'-biphenyl]-5-carboxylic acid (1) and 4,4'-diallyl-[1,1'-biphenyl]-2,2'-diol (2), together with four known compounds (3-6), were isolated from the barks of Sassafras tzumu. The new compounds were determined by NMR (1H and 13C NMR, HSQC, HMBC, 1H-1H COSY, NOESY/ROESY), and MS analysis. Compounds 1-3 showed potent AChE inhibitory activities, with IC50 values of 2.00, 1.81 and 1.91 µM, respectively.
Assuntos
Inibidores da Colinesterase/farmacologia , Lignanas/farmacologia , Sassafras/química , Inibidores da Colinesterase/química , Inibidores da Colinesterase/isolamento & purificação , Humanos , Lignanas/química , Lignanas/isolamento & purificação , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Casca de Planta/química , Extratos Vegetais/química , Relação Estrutura-AtividadeRESUMO
Objective: To study the chemical constituents of the stems from Altingia chinensis. Methods: The stems from Altingia chinensis were extracted with 95% ethanol for reflux,and the extract were evaporated. The chemical constituents were isolated by silica gel chromatography and Sephadex LH-20 column chromatography from petrol ether part and ethyl acetate part of extract. Their structures were identified on the basis of physico-chemical characters and spectroscopic analysis. Results: Eleven compounds were obtained from the stems from Altingia chinensis,which identified as myrsinene( 1),oleanonic aldehyde( 2),3ß,23,28-trihydroxyolean-12-ene( 3),ursolic acid-3ß-octadecanoate( 4),arjunglucoside â ¡( 5),ß-sitosterol( 6),daucosterol( 7),trans-resveratrol-3-O-ß-D-glucopyranoside( 8),ellagic acid 3,3'-dimethylether( 9),lyoniside( 10) and 3,3'-O-dimethylellagic acid-4'-O-α-L-rhamnoside( 11). Conclusion: All the compounds are isolated from Altingia chinensis for the first time.
Assuntos
Saxifragaceae , Ácido Elágico , Sitosteroides , Triterpenos , Ácido UrsólicoRESUMO
OBJECTIVE: To study the chemical constituents from the roots of Semiliquidambar cathayensis. METHODS: The roots of Semiliquidambar cathayensis were extracted with 80% ethanol for reflux. Chemical constituents were isolated by silica gel chromatography and Sephadex LH-20 column chromatography from petrol ether part and ethyl acetate part of extracts. Their structures were identified on the basis of physico-chemical characters and spectroscopic analysis. RESULTS: Eleven compounds were obtained from the roots of Semiliquidambar cathayensis, and identified as 3-acetyl-12-ene-oleanolic acid methyl ester (1), ß-sitosterol (2), 3-acetyl-12-ene-oleanol-ic acid (3), 2α,3ß-dihydroxy-lup-20(29)-en-28-oic acid (4), (24R)-5α-stignast-3,6-dione (5), betulonic acid (6), stearic acid (7), hexadecanoic acid (8), 3-oxo-olean-12-en-28-oic acid (9), arjunolic acid (10) and daucosterol (11). CONCLUSION: Compounds 1,3 - 6 and 8 are isolated from this genus for the first time.