glyceryl-ferulate and ferulic-acid

We recently reported that two water-soluble derivatives of ferulic acid (1-feruloyl glycerol, 1-feruloyl diglycerol) previously developed by our group exhibited protective effects against amyloid-β-induced neurodegeneration in vitro and in vivo. In the current study, we aimed to further understand this process by examining the derivatives' ability to suppress abnormal activation of astrocytes, the key event of neurodegeneration. We investigated the effects of ferulic acid (FA) derivatives on nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression in rat primary astrocytes. The results showed that these compounds inhibited NO production and iNOS expression in a concentration-dependent manner and that the mechanism underlying these effects was the suppression of the nuclear factor-κB pathway. This evidence suggests that FA and its derivatives may be effective neuroprotective agents and could be useful in the treatment of neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease.

Topics: Amyloid beta-Peptides; Animals; Astrocytes; Cerebral Cortex; Coumaric Acids; Dose-Response Relationship, Drug; Embryo, Mammalian; Gene Expression Regulation; Lipopolysaccharides; Monoglycerides; Neuroprotective Agents; NF-kappa B; Nitric Oxide; Nitric Oxide Synthase Type II; Primary Cell Culture; Rats; Signal Transduction; Solubility

Feruloylated monoacyl- and diacyl-glycerols (FMAGs and FDAGs) are lipophilic antioxidants and potential UV absorbers. FMAGs and FDAGs were synthesized by a novel chemoenzymatic method: firstly, ferulic acid was esterified with glycerol to synthesize glyceryl ferulate, using p-toluenesulfonic acid as chemical catalyst in 1-butyl-3-methylimidazolium tetrafluoroborate ([Bmim]BF(4)); secondly, glyceryl ferulate was esterified with oleic acid to synthesize FMAGs and FDAGs, using Novozym 435 as biocatalyst in 1-butyl-3-methylimidazolium hexafluorophosphate ([Bmim]PF(6)). The conversion of ferulic acid and yield of glyceryl ferulate in the first reaction were both 98%. The yields of FMAGs and FDAGs in the second reaction reached 34 +/- 2% and 66 +/- 3%, respectively.

Topics: Antioxidants; Benzenesulfonates; Coumaric Acids; Enzymes, Immobilized; Fungal Proteins; Imidazoles; Ionic Liquids; Lipase; Monoglycerides; Oleic Acid; Radiation-Protective Agents

Glyceryl ferulate was synthesized by the condensation of ferulic acid with glycerol using Pectinase PL "Amano" from Aspergillus niger, which contained ferulic acid esterase, to improve the water-solubility of ferulic acid. The optimum reaction medium was glycerol/0.1 M acetate buffer, pH 4.0, (98:2 v/v). The enzyme immobilized onto Chitopearl BCW3003 exhibited the highest activity among the those immobilized onto various kinds of Chitopearl BCW resins. The optimum temperature for the immobilized enzyme was 50 degrees C, and it could be reused at least five times without a significant loss in activity for the synthesis of glyceryl ferulate in batch reaction. Storage of the reaction mixture at 25 degrees C improved the molar fraction of glyceryl ferulate relative to the dissolved ferulic residues.

Topics: Aspergillus niger; Carboxylic Ester Hydrolases; Chromatography, High Pressure Liquid; Coumaric Acids; Enzymes, Immobilized; Glycerol; Monoglycerides; Polygalacturonase; Solubility; Temperature

Commercially available enzyme preparations were screened for enzymes that have a high ability to catalyze direct ester-synthesis of ferulic acid with glycerol. Only a preparation, Pectinase PL "Amano" produced by Aspergillus niger, feruloylated glycerol under the experimental conditions. The enzyme responsible for the esterification was purified and characterized. This enzyme, called FAE-PL, was found to be quite similar to an A. niger ferulic acid esterase (FAE-III) in terms of molecular mass, pH and temperature optima, substrate specificity on synthetic substrates, and the N-terminal amino acid sequence. FAE-PL highly catalyzed direct esterification of ferulic acid and sinapinic acid with glycerol. FAE-PL could feruloylate monomeric sugars including arabinose, fructose, galactose, glucose, and xylose. We determined the suitable conditions for direct esterification of ferulic acid with glycerol to be as follows: 1% ferulic acid in the presence of 85% glycerol and 5% dimethyl sulfoxide at pH 4.0 and 50 degrees C. Under these conditions, 81% of ferulic acid could be converted to 1-glyceryl ferulate, which was identified by (1)H-NMR. The ability of 1-glyceryl ferulate to scavenge 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals was higher than that of the anti-oxidant butyl hydroxytoluene.

Topics: Antioxidants; Aspergillus niger; Biphenyl Compounds; Catalysis; Coumaric Acids; Esterases; Free Radicals; Glycerol; Hydrazines; Hydrogen-Ion Concentration; Hydrolysis; Magnetic Resonance Spectroscopy; Models, Chemical; Monoglycerides; Picrates; Polymers; Protein Structure, Tertiary; Substrate Specificity; Temperature