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1.
Mar Drugs ; 21(2)2023 Jan 27.
Article in English | MEDLINE | ID: mdl-36827132

ABSTRACT

Brain-derived neurotrophic factor (BDNF) regulates dendritic branching and dendritic spine morphology, as well as synaptic plasticity and long-term potentiation. Consequently, BDNF deficiency has been associated with some neurological disorders such as Alzheimer's, Parkinson's or Huntington's diseases. In contrast, elevated BDNF levels correlate with recovery after traumatic central nervous system (CNS) injuries. The utility of BDNF as a therapeutic agent is limited by its short half-life in a pathological microenvironment and its low efficacy caused by unwanted consumption of non-neuronal cells or inappropriate dosing. Here, we tested the activity of chitosan microsphere-encapsulated BDNF to prevent clearance and prolong the efficacy of this neurotrophin. Neuritic growth activity of BDNF release from chitosan microspheres was observed in the PC12 rat pheochromocytoma cell line, which is dependent on neurotrophins to differentiate via the neurotrophin receptor (NTR). We obtained a rapid and sustained increase in neuritic out-growth of cells treated with BDNF-loaded chitosan microspheres over control cells (p < 0.001). The average of neuritic out-growth velocity was three times higher in the BDNF-loaded chitosan microspheres than in the free BDNF. We conclude that the slow release of BDNF from chitosan microspheres enhances signaling through NTR and promotes axonal growth in neurons, which could constitute an important therapeutic agent in neurodegenerative diseases and CNS lesions.


Subject(s)
Brain-Derived Neurotrophic Factor , Chitosan , Rats , Animals , Brain-Derived Neurotrophic Factor/metabolism , Chitosan/metabolism , Microspheres , Neurons/metabolism , Neuronal Plasticity
2.
Food Chem Toxicol ; 120: 462-471, 2018 Oct.
Article in English | MEDLINE | ID: mdl-30055313

ABSTRACT

Phosphatidyl-hydroxytyrosol, a carrier of hydroxytyrosol under the form of phospholipid with high antioxidant capacity, is being actively studied as a potential ingredient of functional foods and supplements. To support the safety, phosphatidyl-hydroxytyrosol has been examined in an acute and in a 28-day repeated dose oral toxicity studies in rats. Phosphatidyl-hydroxytyrosol administered in a single oral gavage dose of 2000 mg/kg of body weight (bw) resulted in no adverse events or mortality. In addition, phosphatidyl-hydroxytyrosol administered as a daily dose of 2000 mg/kg bw for 28 days by gavage resulted in no adverse events or mortality. No evidence or treatment related toxicity was detected during both studies. Data analysis of body weight gain, food consumption, clinical observations, blood biochemical, haematology, organ weight ratios and histopathological findings did not show significant differences between control and treated groups. It is concluded that phosphatidyl-hydroxytirosol orally administered to rats was safe and that no treatment-related toxicity was detected even at the high doses investigated in both acute (2000 mg/kg bw) and repeated dose (28-day) oral (2000 mg/kg bw) toxicity studies.


Subject(s)
Functional Food , Phenylethyl Alcohol/analogs & derivatives , Phospholipids/administration & dosage , Toxicity Tests , Administration, Oral , Animals , Chromatography, High Pressure Liquid , Drug Administration Schedule , Female , Male , No-Observed-Adverse-Effect Level , Phenylethyl Alcohol/administration & dosage , Phenylethyl Alcohol/adverse effects , Phospholipids/adverse effects , Rats, Wistar
3.
J Agric Food Chem ; 62(40): 9751-9, 2014 Oct 08.
Article in English | MEDLINE | ID: mdl-25255083

ABSTRACT

Intestinal digestion of phosphatidyl derivatives of HT (PHT) and its bioaccessibility under in vitro conditions was performed. First, an in vitro intestinal digestion model for phospholipids was developed. The impact of digestion in the antioxidant ability of PHT was also assayed. PHT was progressively hydrolyzed to lyso-PHT. However, digestion was slower than the phospholipid control. Nevertheless, most hydrolysis products were found at the micellar phase fraction, meaning a high bioaccessibility. Either PHT or digested PHT showed lower antioxidant activity than HT. However, PHT improved its antioxidant ability after digestion, likely related to lyso-PHT. As a summary, the synthetic phosphatidyl derivative of HT as PHT is recognized by phospholipases during simulation of intestinal digestion, although less efficiently than analogous phospholipids. Nevertheless, taking into account the bioaccessibility and the antioxidant activity of digested PHT, the potential of carriers of HT under the form of phospholipids might be of interest.


Subject(s)
Antioxidants/pharmacokinetics , In Vitro Techniques/methods , Intestinal Mucosa/metabolism , Phenylethyl Alcohol/analogs & derivatives , Phenylethyl Alcohol/pharmacokinetics , Phosphatidic Acids/pharmacokinetics , Biological Availability , Hydrolysis , Intestines/drug effects , Phenylethyl Alcohol/chemistry , Phospholipids/chemistry , Phospholipids/metabolism
4.
Methods Mol Biol ; 861: 495-523, 2012.
Article in English | MEDLINE | ID: mdl-22426737

ABSTRACT

Mammal, plant, and mainly microbial phospholipases are continuously being studied, experimented, and some of them are even commercially available at industrial scale for food industry. This is because the use of phospholipases in the production of specific foods leads to attractive advantages, such as yield improvement, energy saving, higher efficiency, improved properties, or better quality of the final product. Furthermore, biocatalysis approaches in the food industry are of current interest as non-pollutant and cleaner technologies. The present chapter reviews the most representative examples of the use of phospholipases in food industry, namely edible oils, dairy, and baking products, emulsifying agents, as well as the current trend to the development of novel molecular species of phospholipids with added-value characteristics.


Subject(s)
Bacterial Proteins/chemistry , Food Technology/methods , Fungal Proteins/chemistry , Green Chemistry Technology/methods , Phospholipases/chemistry , Dairy Products , Dietary Fats, Unsaturated/chemical synthesis , Egg Yolk/chemistry , Emulsifying Agents/chemical synthesis , Phospholipases/isolation & purification , Phospholipids/chemical synthesis
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