Our previous studies demonstrated that Ce^4＋could induce reactive oxygen species （ROS） burst as a signal to promote pacilitaxel biosynthesis in suspension cultured Taxus cuspidate cells. To further understand the m...Our previous studies demonstrated that Ce^4＋could induce reactive oxygen species （ROS） burst as a signal to promote pacilitaxel biosynthesis in suspension cultured Taxus cuspidate cells. To further understand the mechanism of cerium ions inducing ROS burst, circular dichroism （CD）, synchronous fluorescence, and electron paramagnetic resonance （EPR） were used to detect them inducing conformational change of horseradish peroxidase （HRP）. Horseradish peroxidase activity was reduced by 78% by 0.1 mmol/L Ce^4＋, whereas it was only reduced by 28% by 0.1 mmol/L Ce^3＋. Circular dichroism spectra showed that the percentage of transition from helical content and other structure to β strands and flturns was 23.1 when induced by Ce^4＋, whereas it was only 13.2 when induced by Ce^3＋. In synchronous fluorescence spectra, Ce^4＋ led to red shift and intensity-elevation of tryptophan fluorescence emission maximum, whereas in the case of Ce^3＋, the results were a contrast to the above. Furthermore, g factor （gx and gy） in electron paramagnetic resonance （EPR） induced by Ce^4＋ and Ce^3＋ was significantly different. These results indicated that the different valence of cerium ion induced various conformations of HRP, and Ce^4＋ was more effective than Ce^3＋. This suggested that Ce^4＋ affected the burst of ROS through changing the conformation of oxidoreductase.展开更多
Danshensu [3-(3, 4-dihydroxyphenyl) lactic acid, DSS], one of the significant cardioprotective components, is extracted from the root of Salvia miltiorrhiza. In the present study, an ester prodrug of Danshensu(DSS), p...Danshensu [3-(3, 4-dihydroxyphenyl) lactic acid, DSS], one of the significant cardioprotective components, is extracted from the root of Salvia miltiorrhiza. In the present study, an ester prodrug of Danshensu(DSS), palmitoyl Danshensu(PDSS), was synthesized with the aim to improve its oral bioavailability and prolong its half-life. The in vitro experiments were carried out to evaluate the physicochemical properties and stability of PDSS. Although the solubility of PDSS in water was only 0.055 mg·mL^(-1), its solubility in Fa SSIF and Fe SSIF reached 4.68 and 9.08 mg·mL^(-1), respectively. Octanol-water partition coefficient(log P) was increased from-2.48 of DSS to 1.90 of PDSS. PDSS was relatively stable in the aqueous solution in pH range from 5.6 to 7.4. Furthermore, the pharmacokinetics in rats was evaluated after oral administration of PDSS and DSS. AUC and t1/2 of PDSS were enhanced up to 9.8-fold and 2.2-fold, respectively, compared to that of DSS. Cmax was 1.67 ± 0.11 μg·mL^(-1) for PDSS and 0.81 ± 0.06 μg·m L-1 for DSS. Thus, these results demonstrated that PDSS had much higher oral bioavailability and longer circulation time than its parent drug.展开更多
文摘Our previous studies demonstrated that Ce^4＋could induce reactive oxygen species （ROS） burst as a signal to promote pacilitaxel biosynthesis in suspension cultured Taxus cuspidate cells. To further understand the mechanism of cerium ions inducing ROS burst, circular dichroism （CD）, synchronous fluorescence, and electron paramagnetic resonance （EPR） were used to detect them inducing conformational change of horseradish peroxidase （HRP）. Horseradish peroxidase activity was reduced by 78% by 0.1 mmol/L Ce^4＋, whereas it was only reduced by 28% by 0.1 mmol/L Ce^3＋. Circular dichroism spectra showed that the percentage of transition from helical content and other structure to β strands and flturns was 23.1 when induced by Ce^4＋, whereas it was only 13.2 when induced by Ce^3＋. In synchronous fluorescence spectra, Ce^4＋ led to red shift and intensity-elevation of tryptophan fluorescence emission maximum, whereas in the case of Ce^3＋, the results were a contrast to the above. Furthermore, g factor （gx and gy） in electron paramagnetic resonance （EPR） induced by Ce^4＋ and Ce^3＋ was significantly different. These results indicated that the different valence of cerium ion induced various conformations of HRP, and Ce^4＋ was more effective than Ce^3＋. This suggested that Ce^4＋ affected the burst of ROS through changing the conformation of oxidoreductase.
基金supported by the National Natural Science Foundation of China(No.31371014)
文摘Danshensu [3-(3, 4-dihydroxyphenyl) lactic acid, DSS], one of the significant cardioprotective components, is extracted from the root of Salvia miltiorrhiza. In the present study, an ester prodrug of Danshensu(DSS), palmitoyl Danshensu(PDSS), was synthesized with the aim to improve its oral bioavailability and prolong its half-life. The in vitro experiments were carried out to evaluate the physicochemical properties and stability of PDSS. Although the solubility of PDSS in water was only 0.055 mg·mL^(-1), its solubility in Fa SSIF and Fe SSIF reached 4.68 and 9.08 mg·mL^(-1), respectively. Octanol-water partition coefficient(log P) was increased from-2.48 of DSS to 1.90 of PDSS. PDSS was relatively stable in the aqueous solution in pH range from 5.6 to 7.4. Furthermore, the pharmacokinetics in rats was evaluated after oral administration of PDSS and DSS. AUC and t1/2 of PDSS were enhanced up to 9.8-fold and 2.2-fold, respectively, compared to that of DSS. Cmax was 1.67 ± 0.11 μg·mL^(-1) for PDSS and 0.81 ± 0.06 μg·m L-1 for DSS. Thus, these results demonstrated that PDSS had much higher oral bioavailability and longer circulation time than its parent drug.
