款冬花炮制前后总生物碱含量比较

目的:建立款冬花总生物碱含量测定方法,并对款冬花生品和炮制品的含量进行比较研究。方法:采用酸性染料比色法,检测波长:417.5 nm。结果:款冬花总生物碱在6.75~135.00μg范围内呈良好的线性关系,回归方程:y=85.228x-0.0401(r=0.9995)。款冬花生品样品中总生物碱平均含量为0.1070mg·g-1,蜜炙品样品中总生物碱平均含量为0.1633 mg·g-1,甘草炙品样品中总生物碱平均含量为0.0861 mg·g-1。结论:该方法经方法学验证可用于款冬花中总生物碱含量的测定。款冬花生品经炮制后,总生物碱含量发生变化,且炮制方法不同,总生物碱含量变化不同。蜜炙品的总生物碱含量最高,生品次之,甘草炙品最低。     

Increased brain uptake of venlafaxine loaded solid lipid nanoparticles by overcoming the efflux function and expression of P-gp

Venlafaxine (VLX) could be pumped out of the brain by P-glycoprotein (P-gp). Moreover, the expression of P-gp distributed in blood–brain barrier could be significantly induced by VLX. Thus, P-gp could be considered as the nature barrier for delivering of VLX to the brain. The aim of this study was to investigate whether the efflux function and increased expression of P-gp could be reversed by utilizing solid lipid nanoparticles (SLN). VLX solid lipid nanoparticles (VLX ? SLN) were prepared and evaluated. Pharmacokinetics and brain distribution of VLX in different formulations were conducted after oral or intravenous administration. P-gp efflux function to VLX was evaluated by the brain uptake amount of VLX, while P-gp expression was investigated by Western blotting. Results indicated that the entrapment, mean size and zata potential of VLX ? SLN was 74.9 ± 3.0 %, 186.3 ± 69.26 nm and ?22.8 ± 7.78 mv, respectively. After vein injection of VLX formulations, the brain uptake amount of VLX from VLX ? SLN was significantly higher than that of VLX solution, VLX solution with empty SLN (VLX+ empty SLN) and VLX solution with Verapamil (VLX + Ver), respectively. Furthermore, the protein mass of P-gp in VLX ? SLN treated group was the lowest among all the investigated groups. These results indicated that SLN could overcome P-gp and achieve brain target by intravenous administration.     

Curcumin alleviates lung injury in diabetic rats by inhibiting nuclear factor‐κB pathway

Curcumin is a polyphenolic compound that is extracted from Curcuma longa. It has broad anti‐inflammation and anti‐tumor activities. Curcumin was previously reported to exert beneficial effects on diabetes. However, the effect of curcumin on diabetes‐induced lung injury is not yet clear. In this study, the effects of curcumin on lung injury induced by diabetes was explored using quantitative real time polymerase chain reaction (PCR), enzyme‐linked immunosorbent assay (ELISA), immunohistochemistry and electrophoretic mobility shift assay. The results of this study showed that curcumin reduced oxidative stress level, inhibited the synthesis of nitric oxide and prostaglandin E2, and reduced inflammatory responses in the lungs of diabetic rats, thereby alleviating diabetes‐induced lung injury. Further study of the mechanism revealed that curcumin inhibited the activation of nuclear factor (NF)‐κB which is a key player in inflammatory responses. In summary, our study demonstrated that curcumin inhibited the activation of NF‐κB in the lungs of diabetic rats, thus reducing pulmonary inflammatory responses and oxidative stress, and ultimately relieving diabetes‐induced lung injury. This study suggests that curcumin may be a promising agent to alleviate diabetic lung injury and also provides theoretical foundation for the development of diabetes therapy.     

Comparative metabolism and pharmacokinetics of diisobutyl ketone and diisobutyl carbinol in male SD rats

Diisobutyl ketone (DIBK) and diisobutyl carbinol (DIBC) are important organic solvents widely used as industrial intermediates. It was hypothesized that DIBC and DIBK have common metabolic pathways and metabolites, and as such, toxicological data on DIBK could be used to characterize the hazards of DIBC. To confirm or refute this hypothesis a comparative metabolism and pharmacokinetics assessment of DIBK and DIBC was conducted. Dosing was via single oral gavage dosing in male SD rats, followed by blood collection, metabolite identification, major biomarker quantitation, and pharmacokinetics analysis. Overall, the major metabolites of both DIBC and DIBK in blood were their corresponding monohydroxylated metabolites (DIBC alcohol and DIBK alcohol) with the site of hydroxylation at the σ and σ-1 positions, respectively. Quantitative analysis of DIBC, DIBK, DIBC-alcohol, and DIBK-alcohol in blood samples collected from 5 min to 120 h after single dosing indicated the following: (1) DIBC and DIBK are both well absorbed following oral gavage with substantial evidence of enterohepatic recirculation of DIBK, DIBC, DIBK-alcohol, and DIBC-alcohol; (2) DIBK and DIBC are interconverted metabolically in rats; (3) DIBC and DIBK have similar bioavailability after oral administration; (4) higher systemic exposure was found for DIBK-alcohol than DIBC-alcohol, implying that DIBC-alcohol may be more easily conjugated and eliminated in bile. In summary, the metabolic similarities and the difference in systemic exposure to metabolites between these substances observed in the current study support the hypothesis that DIBC might have a lower potential toxicity than that of DIBK. The current study results support that toxicological data on DIBK could be used to characterize the hazards of DIBC