RESUMEN
Alzheimer's disease (AD) is the most common cause of dementia among elderly population. Deranged ß-amyloid (Aß) trafficking across the blood-brain barrier is known to be a critical element in the pathogenesis of AD. In the vascular endothelial cells of hippocampus, Aß transport is mainly mediated by low-density lipoprotein-associated protein 1 (LRP1) and the receptor for advanced glycation end (RAGE) products; therefore, LRP1 and RAGE endothelial cells are potential therapeutic targets for AD. In this study, we explored the effects of Formononetin (FMN) on learning and memory improvement in APP/PS1 mice and the related mechanisms. We found that FMN significantly improved learning and memory ability by suppressing Aß production from APP processing, RAGE-dependent inflammatory signaling and promoted LRP1-dependent cerebral Aß clearance pathway. Moreover, FMN treatment alleviated ultrastructural changes in hippocampal vascular endothelial cells. In conclusion, we believe that FMN may be an efficacious and promising treatment for AD.
Asunto(s)
Enfermedad de Alzheimer/tratamiento farmacológico , Sistemas de Liberación de Medicamentos , Isoflavonas/uso terapéutico , Fármacos Neuroprotectores , Animales , Humanos , Proteína 1 Relacionada con Receptor de Lipoproteína de Baja Densidad , Ratones , Fármacos Neuroprotectores/uso terapéutico , Receptor para Productos Finales de Glicación Avanzada/efectos de los fármacos , Receptores de LDL/efectos de los fármacos , Proteínas Supresoras de Tumor/efectos de los fármacosRESUMEN
Alzheimer's disease (AD) is one of the most common age-related neurodegenerative disorders that have been studied for more than 100 years. Although an increased level of amyloid precursor protein is considered a key contributor to the development of AD, the exact pathogenic mechanism remains known. Multiple factors are related to AD, such as genetic factors, aging, lifestyle, and nutrients. Both epidemiological and clinical evidence has shown that the levels of micronutrients, such as copper, zinc, and iron, are closely related to the development of AD. In this review, we summarize the roles of eight micronutrients, including copper, zinc, iron, selenium, silicon, manganese, arsenic, and vitamin D in AD based on recently published studies.
RESUMEN
Pancreatic cancer is a highly malignant cancer associated with high expression levels of sonic hedgehog signaling molecule (Shh), patched 1 (Ptch1), smoothened frizzled class receptor (Smo) and glioma-associated oncogene family zinc finger 1 (Gli1) in the hedgehog (Hh) signaling pathway. Inhibition of the Hh signaling pathway is a potential therapeutic target for pancreatic cancer. The aim of the present study was to investigate the effects of dauricine in a pancreatic cancer BxPC-3 ×enograft animal model and examine the underlying molecular mechanisms through Hh signaling pathway. High-and low-dose dauricine treatment significantly suppressed tumor growth with no concomitant effect on the spleen index. In addition, dauricine induced apoptosis and cell cycle arrest in pancreatic cancer BxPC-3 cells. The inhibitory effects of dauricine on pancreatic cancer may be mediated by the suppression of the Hh signaling pathway, as indicated by the decreases in the gene and protein expression levels of Shh, Ptch1, Smo and Gli1. The effects of dauricine were similar to those of 5-fluorouracil. Dauricine, a naturally occurring alkaloid, may be a potential anticancer agent for the treatment of pancreatic cancer.
RESUMEN
OBJECTIVE: To prepare resveratrol chitosan nanoparticles with free amine groups on the surface so as to conjugate ligands, which will actively target to special tissues or organs. METHOD: The chitosan nanoparticles with free amine on the surface was prepared by sodium chloride precipitation. Nanoparticles with different solidification degrees were studied on turbidity, in vitro release, encapsulation efficiency, drug loading and diameter. RESULT: The turbidity of nanoparticles with various solidification degrees decreased at different rates after ultrasonic or water bath heating treatment. All nanoparticles mentioned above obviously shew sustained release. The rate of release was slowed down with the increase of solidification agents. Solidification had no obvious effects on the encapsulation efficiency and drug loading. The diameter of chitosan nanoparticles with 200 microL solidification agents was 487 nm. The polydispersion was 0.144. CONCLUSION: The diameter of the prepared nanoparticles was relatively small. The amine on the surface was free, which offered the possibility of designing the acive target drug delivery system.
Asunto(s)
Quitosano/química , Composición de Medicamentos/métodos , Nanoestructuras , Estilbenos/administración & dosificación , Sistemas de Liberación de Medicamentos , Tamaño de la Partícula , Resveratrol , Estilbenos/químicaRESUMEN
BACKGROUND: The Hedgehog (Hh) signaling pathway plays an important role in pancreatic cancer (PC) cells. Phenolic alkaloids from Menispermum dauricum (PAMD), a traditional Chinese medicine used for the treatment of immune disorders, have been reported to have antitumor activity recently. OBJECTIVE: To investigate the efficacy and mechanism of PAMD against PC cell BxPC-3. MATERIALS AND METHODS: F assay was used to assess cell proliferation inhibition of PAMD; the apoptotic induction and cell cycle arrest was detected by flow cytometry; the BxPC-3 xenograft was established to evaluate the tumor growth inhibition of PAMD; hematoxylin-eosin staining was applied to analyze the pathological morphology of tumor tissues; immunohistochemistry (IHC) and Western blot was adopted to detect the protein levels; quantitative real-time polymerase chain reaction was used to determine the mRNA expressions. RESULTS: PAMD shows time-and dose-dependent proliferation inhibition on the BxPC-3 cell, induced G0/G1 phase arrest and cell apoptosis in vitro. PAMD also showed better inhibition of tumor growth and a preferable safety profile compared with chemotherapeutic regimen 5-fluoro-2, 4 (1 H, 3 H) pyrimidinedione in BxPC-3 xenograft in vivo. Furthermore, PAMD directly decreases the protein and mRNA levels of Sonic Hedgehog (Shh) and its downstream transcription factor Gli-1 in the BxPC-3 tumor tissues. CONCLUSION: The treatment of PAMD displayed Hh signaling pathway blockade through decreasing the protein and mRNA levels of Shh and its downstream transcription factor Gli-1, suggesting a promising strategy in treating human PC.