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1.
ACS Chem Neurosci ; 14(24): 4298-4310, 2023 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-38048522

RESUMO

Alzheimer's disease (AD) is a neurodegenerative disorder caused by accumulation of amyloid-ß oligomers (AßO) in the brain, neuroinflammation, oxidative stress, and cognitive decline. Grandisin, a tetrahydrofuran neolignan, exhibits relevant anti-inflammatory and antioxidant properties. Interestingly, grandisin-based compounds were shown to prevent AßO-induced neuronal death in vitro. However, no study has assessed the effect of these compounds on the AD animal model. This study focuses on a triazole grandisin analogue (TGA) synthesized using simplification and bioisosteric drug design, which resulted in improved potency and solubility compared with the parent compound. This study aimed to investigate the possible in vivo effects of TGA against AßO-induced AD. Male C57/Bl6 mice underwent stereotaxic intracerebroventricular AßO (90 µM) or vehicle injections. 24 h after surgery, animals received intraperitoneal treatment with TGA (1 mg/kg) or vehicle, administered on a 14 day schedule. One day after treatment completion, a novel object recognition task (NORT) was performed. Memantine (10 mg/kg) was administered as a positive control. NORT retention sessions were performed on days 8 and 16 after AßO injection. Immediately after retention sessions, animals were euthanized for cortex and hippocampus collection. Specimens were subjected to oxidative stress and cytokine analyses. TGA reduced the level of cortex/hippocampus lipoperoxidation and prevented cognitive impairment in AßO-injected mice. Additionally, TGA reduced tumor necrosis factor (TNF) and interferon-γ (IFN-γ) levels in the hippocampus. By contrast, memantine failed to prevent cortex/hippocampus lipid peroxidation, recognition memory decline, and AßO-induced increases in TNF and IFN-γ levels in the hippocampus. Thus, memantine was unable to avoid the AßO-induced persistent cognitive impairment. The results showed that TGA may prevent memory impairment by exerting antioxidant and anti-inflammatory effects in AßO-injected mice. Moreover, TGA exhibited a persistent neuroprotective effect compared to memantine, reflecting an innovative profile of this promising agent against neurodegenerative diseases, such as AD.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Lignanas , Fármacos Neuroprotetores , Camundongos , Masculino , Animais , Peptídeos beta-Amiloides/metabolismo , Memantina/farmacologia , Antioxidantes/farmacologia , Doença de Alzheimer/patologia , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/tratamento farmacológico , Lignanas/farmacologia , Furanos/farmacologia , Anti-Inflamatórios/farmacologia , Fármacos Neuroprotetores/farmacologia , Hipocampo/metabolismo
2.
Bioresour Technol ; 342: 125949, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34592614

RESUMO

Large-scale microalgae cultivation is often associated with high costs, and nutrients account for a significant part. However, the use of cheaper nutrients, carbon, and water sources could reduce expenses. This study aims to produce Chlorella vulgaris and Desmodesmus sp. cultivated in sugarcane biorefinery residues bagasse and vinasse. A biofertilizer from bagasse biochar was produced and characterized, and a pre-treatment by filtration was performed on vinasse. The effects of varying growth conditions (antibiotic, vinasse, and biofertilizer concentrations; air flowrate; pH; light intensity; and photoperiod) were discussed based on the results of a Plackett-Burman design. The highest cell density was achieved by Desmodesmus sp. (46·106 cells mL-1 from an initial 6.5·106 cells mL-1) using vinasse (20%) and biofertilizer (1 g L-1). Specific metabolite accumulation was also observed. Under stress conditions, 21.3% lipids and 51.0% carbohydrates were obtained for two different cultivations. Using 1 g L-1 of biofertilizer, biomass composition had 74.8% proteins.


Assuntos
Chlorella vulgaris , Microalgas , Saccharum , Biomassa , Lipídeos
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