ABSTRACT
Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor dysfunction. Recent studies have shown that curcumin (CUR) has neuroprotective effects in PD experimental models. However, its efficacy is limited due to low water solubility, bioavailability, and access to the central nervous system. In this study, we compared the effects of new curcumin-loaded nanoemulsions (NC) and free CUR in an experimental model of PD. Adult Swiss mice received NC or CUR (25 and 50 mg/kg) or vehicle orally for 30 days. Starting on the eighth day, they were administered rotenone (1 mg/kg) intraperitoneally until the 30th day. At the end of the treatment, motor assessment was evaluated by open field, pole test, and beam walking tests. Oxidative stress markers and mitochondrial complex I activity were measured in the brain tissue. Both NC and CUR treatment significantly improved motor impairment, reduced lipoperoxidation, modified antioxidant defenses, and prevented inhibition of complex I. However, NC was more effective in preventing motor impairment and inhibition of complex I when compared to CUR in the free form. In conclusion, our results suggest that NC effectively enhances the neuroprotective potential of CUR and is a promising nanomedical application for PD.
Subject(s)
Curcumin/administration & dosage , Emulsions/administration & dosage , Nanoparticles/administration & dosage , Neuroprotective Agents/administration & dosage , Parkinsonian Disorders/prevention & control , Rotenone/toxicity , Animals , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Curcumin/chemistry , Emulsions/chemistry , Male , Mice , Nanoparticles/chemistry , Neuroprotective Agents/chemistry , Parkinsonian Disorders/chemically induced , Parkinsonian Disorders/metabolismABSTRACT
In this study we provide new evidence that the columnar vesicles of the sea anemone Bunodosoma cangicum are toxic in vivo and contain at least two active polypeptides, a neurotoxic and an apoptosis inducing polypeptide. Here we show that it is also an effective inducer of apoptosis in vivo in the nematode Caenorhabditis elegans. In addition, the anemone peptides rapidly paralyze C. elegans, and set in motion a sequence of events that result in the complete dissolution of the internal organs in adult animals within 60 min. Nematodes that survive the toxin treatment exhibit a decreased reproductive capacity. Interestingly, adult animals appear to be much more susceptible to the effects of the toxins than larval stages, suggesting possible developmentally dependent targets of the toxins. Here we also provide chemical characterization of the compounds through chromatographic analysis and mass spectrometry. Gel filtration chromatography coupled with reverse phase HPLC shows that our partially purified extract contains at least two principle components. Additionally, MALDI-TOF mass spectrometry analysis of our extract shows three principal compounds at 814.6, 2914.1, and 4360.3 m/z plus three other minor components or fragments. Mass spectrometry analysis also indicates the presence of three disulfide bridges. Which is in agreement with other characterizations of anemone venoms.
Subject(s)
Caenorhabditis elegans/drug effects , Sea Anemones/metabolism , Sea Anemones/physiology , Amino Acid Sequence , Animals , Apoptosis/drug effects , Caenorhabditis elegans/physiology , Chromatography, Gel/methods , Chromatography, High Pressure Liquid/methods , Peptides , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods , Toxicological Phenomena/physiologyABSTRACT
We provide ultrastructural and cytological evidence that the tentacles of the sea anemone Bunodosoma cangicum does not contain cytotoxic venom. However, we show that the stimulated secretion of an apparent mixture of biomolecules containing polypeptides from the columnar vesicles of Bunodosoma cangicum is apparently a potent inducer of apoptosis in the zebrafish cell line, ZF-L. Microscopic fluorescence, cell morphology and flow cytometric assays confirm the apoptotic activity. Crude vesicle venom was partially purified by size exclusion chromatography. PAGE analysis shows that this venom contains low weight polypeptides but no measurable protein. The apoptotic activity is heat labile, and the observed peptides concurrent with this activity have a molecular weight of approximately 2000 Da. This manuscript is the first report of biologically active molecules and peptides associated with columnar vesicles of anemones, and the first to confirm that the tentacles of B. cangicum do not contain cytotoxic venom, and express spirocytes exclusively.
Subject(s)
Apoptosis/drug effects , Cnidarian Venoms/pharmacology , Peptides/metabolism , Sea Anemones/metabolism , Animals , Cell Line , Chromatography, Gel , Electrophoresis, Polyacrylamide Gel , Microscopy, Electron, Scanning , ZebrafishABSTRACT
Visando melhor aproveitamento do soro de queijo estudou-se a influência da proporção de soro e da concentração de hidrocoloide nos teores de lactose, ácido lático e tempo de fermentação de bebidas lácteas. Utilizou-se planejamento composto central rotacional com 3 pontos centrais, totalizando 11 experimentos. Empregaram-se as proporções soro/leite de 51, 55, 65, 75 e 79%, e as concentrações de hidrocoloide de 0,03; 0,04; 0,07; 0,10 e 0,11%. Os resultados foram tratados por análise de variância ao nível de significância de 5%. A proporção de soro influenciou significativamente (p<0,05) as variáveis resposta tempo de fermentação, lactose, sólidos totais e acidez titulável, porém não houve influência significativa (p<0,05) para a concentração de hidrocoloide. Menores tempos de fermentação foram atingidos quando se utilizou até 65% de soro. Os maiores teores de lactose foram obtidos nos experimentos com maior proporção de soro, enquanto que as bebidas com menor proporção de soro apresentaram maior teor de sólidos totais e acidez titulável.
