Echinococcosis is a worldwide anthropozoonosis which is highly endemic over large animal husbandry areas in northwestern China. The current clinical therapeutic medicine against echinococcosis is albendazole, although it caused serious side effects in patients. The component in traditional Chinese herb medicine, Sophora moorcroftiana alkaloids (SA), is thought to be a potential drug to treat echinococcosis. In order to explore the effect and mechanism of SA treatment against echinococcosis, we established animal echinococcosis model and treated rats with albendazole alone, alkaloids alone, and combined therapy. The combined treatment showed effective inhibition against parasite infection due to induction of host response and alleviated liver injury; meanwhile albendazole caused serious liver problem. The proteomics study revealed that the combined therapy might induce complement activation through C3, C4, C5, SERPINA1, and SERPINC1 proteins and cell adhesion by ANXA2, EZR, YWHAB, HSP90AN1, and PRKAR2A proteins, while albendazole treatment could induce liver injury through CRYAB, YWHAZ, SLC25A24, and HSPA1B proteins that were involved in cell death. In all, we consider that the combinational treatment displayed better therapeutic effects against liver echinococcosis as well as alleviated liver injury, which could be considered as an effective strategy to treat echinococcosis clinically.
Background: This study investigates the mediating effect of rumination on the associations between depressive symptoms and insomnia.Methods: This is a cross-sectional study. Insomnia Severity Index (ISI), Ruminant Response Scale (RRS) and Beck Depression Inventory (BDI) were determined in 12,178 college students in Qinghai province by a questionnaire network platform.Results: The prevalence of insomnia was 38.6% in the participants. Insomnia symptoms [interquartile range: 6 (3, 9)], depressive symptoms [interquartile range: 5 (1, 9)], and rumination [interquartile range: 22 (20, 26)] were positively correlated (r = 0.25–0.46, p < 0.01). Mediation effect analysis showed that the depressive symptoms affected insomnia directly and indirectly. The direct effect and the indirect effect through rumination account for 92.4 and 7.6% of the total effect, respectively.Conclusion: The study shows that insomnia, depressive symptoms, and rumination are related constructs in college students in Qinghai province. It demonstrates the direct effects and the rumination-mediated indirect effects between depressive symptoms and insomnia; the direct effects seem to be dominant.
The total alkaloids extracted from the seeds of Sophora moorcroftiana (TAs-SM) have the potential to treat alveolar echinococcosis, a disease included by the WHO in a list of 17 key neglected diseases world-wide. The aims of the current study were first to develop a supercritical fluid extraction (SFE) method for optimizing TAs-SM extraction, and second, to develop an optimized method for evaluating TAs-SM pharmacokinetics in vivo. The Box–Behnken response surface method was used to optimize the extraction process, and ultra-high liquid chromatography coupled with high resolution electrospray mass spectrometry (UPLC-HR-ESI-MS) was used to determine the pharmacokinetics of TAs-SM in SD rats. The results indicated the following optimal SFE extraction conditions: pressure = 31 MPa, temperature = 70 °C, time = 162.18 min. With these parameters, total alkaloids could be extracted from each gram of S. moorcroftiana, with the total content being 68.88 μg. The linear range of UPLC-HR-ESI-MS is 0.78–200.00 ng/ml, R2 > 0.99, and the sample recovery is 99–113%. The precision, accuracy, selectivity and stability of the method meet the requirements of US FDA guidelines. To our knowledge this study is the first to establish an SFE method for extracting TAs-SM and the first to employ UPLC-HR-ESI-MS for measuring TAs-SM in rats. These findings provide important contributions for using TAs-SM in further drug development and clinical applications.
Maximizing the pharmacodynamics of albendazole (ABZ), which is used to treat echinococcoses, is essential for the long-term treatment of echinococcosis patients. ABZ is a weak base whose solubility depends on the pH value of the solvent. After it has been orally administered, its solubility drops sharply from when it is in gastric juices (pH 1.4) to intestinal juices (pH 6.5) and is subsequently absorbed in the ileum and jejunum. This results in low solubility and poor bioavailability of the drug. In this study, we developed an orally administered albendazole-isethionate (ABZ-HES)/Hypromellose Acetate Succinate (HPMC-AS) complex tablet with improved solubility and bioavailability. Previous studies demonstrated that ABZ-HES has a higher intrinsic dissolution rate under pH 1.4 than the ABZ freebase used in the commercial product Albenda® and that HPMC-AS can effectively inhibit ABZ crystallization, which could be due to the hydrophobic interaction between ABZ and HPMC-AS in an aqueous environment. In this study, the dissolution behavior of ABZ-HES/HPMC-AS composite tablets (TABZ-HES-H) in vitro was studied by the two-step pH conversion method. Our results demonstrated that the oral bioavailability of TABZ-HES-H is approximately 2.6 times higher than that of ABZ. More importantly, in the rat model of secondary hepatic alveolar echinococcosis, the anti-hepatic alveolar echinococcosis effect of the TABZ-HES-H is 3.4 times higher than that of a commercial product. The improved preparation with salt and polymer has proven to be a feasible method of improving oral bioavailability and pharmacodynamics of ABZ.
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