RESUMO
OBJECTIVE: To explore the scavenging action of tenuigenin (TEN) on intracerebral amyloid ß protein (Aß) aggregation and the abnormal phosphorylated tau protein and its mechanism in Alzheimer's disease (AD) rats' brain. METHODS: Aß1-40 was injected into the right CA1 region hippocampus to establish the AD model. Successfully modeled rats were divided into the model group, the low, middle, high TEN group. Rats were administered with TEN (18.5, 37.0, 74.0 mg/kg) by gastrogavage. Besides, a sham-operation group was set up. Expression levels of Aß1-40 and Tau p-Ser262 were detected by immunohistochemistry. Expression levels of ubiquitin (Ub) and Ub-protein ligase E3 were measured by Western blotting.The content of 26S proteasome was detected by ELISA. RESULTS: Immunohistochemical results showed that the number of Aß and Tau p-Ser262 positively reacted neurons significantly increased in model group, when compared with the sham-operation group (P < 0.01). Results of Western blot showed expression levels of ubiquitinated protein were up-regulated and those of Ub-protein ligase E3 were down-regulated in the model group (P < 0.01). ELISA results showed that the content of 26S proteasome significantly decreased in AD rats' brain (P < 0.01). Compared with the model group, expression levels of Aß1-40, Tau p-Ser262, and Ub significantly decreased; expression levels of Ub-protein ligase E3 apparently increased; the content of 26S proteasome significantly increased in each TEN treatment group (P < 0.05, P < 0.01). Best effect was shown in 37.0 mg/kg and 74.0 mg/kg TEN groups. CONCLUSIONS: Ub proteasome pathway (UPP) participated in the occurrence of AD. TEN could obviously reduce intracere- bral Aß1-40 accumulation and abnormal tau phosphorylation.
Assuntos
Doença de Alzheimer/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Neurônios/metabolismo , Peptídeos beta-Amiloides , Animais , Hipocampo/metabolismo , Fosforilação , Complexo de Endopeptidases do Proteassoma/metabolismo , Ratos , Ubiquitina-Proteína Ligases/metabolismo , UbiquitinasRESUMO
Wet spun microfibers have great potential in the design of multifunctional controlled release materials. Curcumin (Cur) and vitamin E acetate (Vit. E Ac) were used as a model drug system to evaluate the potential application of the drug-loaded microfiber system for enhanced delivery. The drugs and polyacrylonitrile (PAN) were blended together and spun to produce the target drug-loaded microfiber using an improved wet-spinning method and then the microfibers were successfully woven into fabrics. Morphological, mechanical properties, thermal behavior, drug release performance characteristics, and cytocompatibility were determined. The drug-loaded microfiber had a lobed "kidney" shape with a height of 50-100 µm and width of 100-200 µm. The addition of Cur and Vit. E Ac had a great influence on the surface and cross section structure of the microfiber, leading to a rough surface having microvoids. X-ray diffraction and Fourier transform infrared spectroscopy indicated that the drugs were successfully encapsulated and dispersed evenly in the microfilament fiber. After drug loading, the mechanical performance of the microfilament changed, with the breaking strength improved slightly, but the tensile elongation increased significantly. Thermogravimetric results showed that the drug load had no apparent adverse effect on the thermal properties of the microfibers. However, drug release from the fiber, as determined through in-vitro experiments, is relatively low and this property is maintained over time. Furthermore, in-vitro cytocompatibility testing showed that no cytotoxicity on the L929 cells was found up to 5% and 10% respectively of the theoretical drug loading content (TDLC) of curcumin and vitamin E acetate. This study provides reference data to aid the development of multifunctional textiles and to explore their use in the biomedical material field.