The biotransformation of artemisinin by hairy root cultures ofRheum palmatum L. was investigated for the first time. The main product, deoxyartemisinin, was isolated and characterized on the basis of its spectral data.
OBJECTIVE To investigate the in vitro lethal effect of photo- dynamic therapy （PDT） using the photosensitizer hematoporphyrin on the human pancreatic cancer cell line Panc-1, the major influencing factors and the me...OBJECTIVE To investigate the in vitro lethal effect of photo- dynamic therapy （PDT） using the photosensitizer hematoporphyrin on the human pancreatic cancer cell line Panc-1, the major influencing factors and the mechanisms of treatment. METHODS Three factors--the time needed for photosensitizer and cell incubation, the photosensitizer concentration （PhoC） and the exposure dose （ExpD）--were examined with different levels of these factors. Optical density （OD） was used as a measure of CCK-8 in the experiment, and was converted to the rate of cell survival. The separate effect of each factor on the photodynamic action was studied, and the interactions were investigated. The effects of different incubation times and PhoC levels on the fluorescence intensity （FI） of the intracellular photosensitizer were determined, and the mechanisms of these factors leading to the therapeutic effects of PDT discussed. RESULTS An increase in the photosensitizer and cell incubation time, an increase of PhoC, and enhancement of the ExpD, produced a corresponding decrease in the rate of Panc-1 cell survival after PDT （P 〈 0.05）. PDT achieved its maximum lethal effects 16 h after starting the incubation, with a PhoC of 10 mg/L and an ExpD of 20 J/cm2; at these levels a synergistic interaction between PhoC and the ExpD occurred, decreasing the cell survival rate （P 〈 0.05）. Neither simple administration of photosensitizer without ExpD （0 J/cm2） or illumination in the absence of PhoC （0 mg/L） affected the rate of cell survival （P 〉 0.05）. With an increase of PhoC and lengthening of the incubation time, the FI of the intracellular photosensitizer accordingly increased （P 〈 0.05）, and attained its maximum value at a PhoC of 10 mg/L and 36 h after the incubation. With an increase of PhoC, the FI of the photosensitizer, hematoporphyrin, in the solution increased progressively at first and then decreased （fluorescence quenching）. CONCLUSION PDT with the photosensitizer hematoporphyrin has clear lethal effects on the human pancreatic cancer cell line Panc-1, but the presence of a photosensitizer and laser irradiation by themselves do not have independent lethal effects. The three influencing factors--the time for photosensitizer and cell incuba- tion, PhoC and ExpD--correlate positively with the PDT response, within certain limits. Beyond these limits, the PDT response does not significantly increase. The main mechanism of the PDT response lies in the effect of these factors on the level of the intracellular photosensitizer and the fluorescence quenching of the photosensitizer. A synergistic effect exists between PhoC and ExpD.展开更多
Microglial activation plays an important role in a panel of neurological disorders such as multiple sclerosis(MS) and Parkinson's disease(PD),and is a key target for developing therapeutic strategies for these dis...Microglial activation plays an important role in a panel of neurological disorders such as multiple sclerosis(MS) and Parkinson's disease(PD),and is a key target for developing therapeutic strategies for these diseases.Ketogenic diet (KD),which is able to inhibit microglial activation in substantia nigra pars compacta of mice,has been shown effective in a mouse model of PD,possibly through increasing D-β-hydroxybutyrate(D-β-HB),a major component of ketone bodies.To verify this,we developed an in vitro model of microglia activation with a microglia line,BV-2,and investigated how D-β-HB have an effect on the LPS-stimulated BV-2 cells.We found D-β-HB is able to recover the cell viability,and inhibit the production of inflammatory mediators and cytokines such as ROS,nitrite,IL-1β,TNF-α,and IL-6,which otherwise were increased in LPS-stimulated BV-2 cells.We conclude that the LPS induced BV-2 cells activation is a valid in vitro model of microglia activation.D-β-HB is able to suppress the activation of BV-2 cells, which might account for one of the possible reasons of KD therapy on the PD model.展开更多
文摘The biotransformation of artemisinin by hairy root cultures ofRheum palmatum L. was investigated for the first time. The main product, deoxyartemisinin, was isolated and characterized on the basis of its spectral data.
基金This work was supported by grants from Guangdong Provincial Natural Science Foundation （06021369） and Guangdong Medical Research Funds （B2006043）.
文摘OBJECTIVE To investigate the in vitro lethal effect of photo- dynamic therapy （PDT） using the photosensitizer hematoporphyrin on the human pancreatic cancer cell line Panc-1, the major influencing factors and the mechanisms of treatment. METHODS Three factors--the time needed for photosensitizer and cell incubation, the photosensitizer concentration （PhoC） and the exposure dose （ExpD）--were examined with different levels of these factors. Optical density （OD） was used as a measure of CCK-8 in the experiment, and was converted to the rate of cell survival. The separate effect of each factor on the photodynamic action was studied, and the interactions were investigated. The effects of different incubation times and PhoC levels on the fluorescence intensity （FI） of the intracellular photosensitizer were determined, and the mechanisms of these factors leading to the therapeutic effects of PDT discussed. RESULTS An increase in the photosensitizer and cell incubation time, an increase of PhoC, and enhancement of the ExpD, produced a corresponding decrease in the rate of Panc-1 cell survival after PDT （P 〈 0.05）. PDT achieved its maximum lethal effects 16 h after starting the incubation, with a PhoC of 10 mg/L and an ExpD of 20 J/cm2; at these levels a synergistic interaction between PhoC and the ExpD occurred, decreasing the cell survival rate （P 〈 0.05）. Neither simple administration of photosensitizer without ExpD （0 J/cm2） or illumination in the absence of PhoC （0 mg/L） affected the rate of cell survival （P 〉 0.05）. With an increase of PhoC and lengthening of the incubation time, the FI of the intracellular photosensitizer accordingly increased （P 〈 0.05）, and attained its maximum value at a PhoC of 10 mg/L and 36 h after the incubation. With an increase of PhoC, the FI of the photosensitizer, hematoporphyrin, in the solution increased progressively at first and then decreased （fluorescence quenching）. CONCLUSION PDT with the photosensitizer hematoporphyrin has clear lethal effects on the human pancreatic cancer cell line Panc-1, but the presence of a photosensitizer and laser irradiation by themselves do not have independent lethal effects. The three influencing factors--the time for photosensitizer and cell incuba- tion, PhoC and ExpD--correlate positively with the PDT response, within certain limits. Beyond these limits, the PDT response does not significantly increase. The main mechanism of the PDT response lies in the effect of these factors on the level of the intracellular photosensitizer and the fluorescence quenching of the photosensitizer. A synergistic effect exists between PhoC and ExpD.
文摘Microglial activation plays an important role in a panel of neurological disorders such as multiple sclerosis(MS) and Parkinson's disease(PD),and is a key target for developing therapeutic strategies for these diseases.Ketogenic diet (KD),which is able to inhibit microglial activation in substantia nigra pars compacta of mice,has been shown effective in a mouse model of PD,possibly through increasing D-β-hydroxybutyrate(D-β-HB),a major component of ketone bodies.To verify this,we developed an in vitro model of microglia activation with a microglia line,BV-2,and investigated how D-β-HB have an effect on the LPS-stimulated BV-2 cells.We found D-β-HB is able to recover the cell viability,and inhibit the production of inflammatory mediators and cytokines such as ROS,nitrite,IL-1β,TNF-α,and IL-6,which otherwise were increased in LPS-stimulated BV-2 cells.We conclude that the LPS induced BV-2 cells activation is a valid in vitro model of microglia activation.D-β-HB is able to suppress the activation of BV-2 cells, which might account for one of the possible reasons of KD therapy on the PD model.
