Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Pharmacokinetic Alteration of Paclitaxel by Ferulic Acid Derivative.

ABSTRACT: P-glycoprotein (P-gp) is known to be involved in multidrug resistance (MDR) and modulation of pharmacokinetic (PK) profiles of substrate drugs. Here, we studied the effects of synthesized ferulic acid (FA) derivatives on P-gp function in vitro and examined PK alteration of paclitaxel (PTX), a well-known P-gp substrate drug by the derivative. Compound 5c, the FA derivative chosen as a significant P-gp inhibitor among eight FA candidates by in vitro results, increased PTX AUCinf as much as twofold versus the control by reducing PTX elimination in rats. These results suggest that FA derivative can increase PTX bioavailability by inhibiting P-gp existing in eliminating organs.

SUBMITTER: Lee J

PROVIDER: S-EPMC6920777 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Pharmacokinetic Alteration of Paclitaxel by Ferulic Acid Derivative.

Lee Jaeok J Chae Song Wha SW Ma LianJi L Lim So Yeon SY Alnajjar Sarah S Park Choo Hea-Young HY Lee Hwa Jeong HJ Rhie Sandy Jeong SJ

Pharmaceutics 20191109 11

P-glycoprotein (P-gp) is known to be involved in multidrug resistance (MDR) and modulation of pharmacokinetic (PK) profiles of substrate drugs. Here, we studied the effects of synthesized ferulic acid (FA) derivatives on P-gp function in vitro and examined PK alteration of paclitaxel (PTX), a well-known P-gp substrate drug by the derivative. Compound <b>5c</b>, the FA derivative chosen as a significant P-gp inhibitor among eight FA candidates by in vitro results, increased PTX AUC<sub>inf</sub> ...[more]

PMID: 31717555

Similar Datasets

A dicarboxylic fatty acid derivative of paclitaxel for albumin-assisted drug delivery.

Project description:Paclitaxel (PTX) is a potent chemotherapy for many cancers but it suffers from very poor solubility. Consequently, the TAXOL formulation uses copious amounts of the surfactant Cremophor EL to solubilize the drug for injection, resulting in severe hypersensitivity and neutropenia. In contrast to Cremophor EL, presented is a way to solubilize PTX by conjugation of a dicarboxylic fatty acid for specific binding to the ubiquitous protein, serum albumin. The conjugation chemistry was simplified to a single step using the activated anhydride form of 3-pentadecylglutaric (PDG) acid, which is reactive to a variety of nucleophiles. The PDG derivative is less cytotoxic than the parent compound and was found to slowly hydrolyze to PTX (≈ 5% over 72 h) in serum, tumor cytosol, and tumor tissue homogenate. When injected intravenously to tumor-bearing mice, [(3) H]-PTX in the TAXOL formulation was cleared rapidly with a half-life of 7 h. In the case of the PDG derivative of PTX, the drug is quickly distributed and approximately 20% of the injected dose remained in the vasculature experiencing a 23 h half-life. These improvements from modifying PTX with the PDG fatty acid present the opportunity for PDG to become a generic modification for the improvement of many therapeutics.

| S-EPMC3617480 | biostudies-literature

Integrated mass spectrometry imaging reveals spatial-metabolic alteration in diabetic cardiomyopathy and the intervention effects of ferulic acid.

Project description:Diabetic cardiomyopathy (DCM) is a metabolic disease and a leading cause of heart failure among people with diabetes. Mass spectrometry imaging (MSI) is a versatile technique capable of combining the molecular specificity of mass spectrometry (MS) with the spatial information of imaging. In this study, we used MSI to visualize metabolites in the rat heart with high spatial resolution and sensitivity. We optimized the air flow-assisted desorption electrospray ionization (AFADESI)-MSI platform to detect a wide range of metabolites, and then used matrix-assisted laser desorption ionization (MALDI)-MSI for increasing metabolic coverage and improving localization resolution. AFADESI-MSI detected 214 and 149 metabolites in positive and negative analyses of rat heart sections, respectively, while MALDI-MSI detected 61 metabolites in negative analysis. Our study revealed the heterogenous metabolic profile of the heart in a DCM model, with over 105 region-specific changes in the levels of a wide range of metabolite classes, including carbohydrates, amino acids, nucleotides, and their derivatives, fatty acids, glycerol phospholipids, carnitines, and metal ions. The repeated oral administration of ferulic acid during 20 weeks significantly improved most of the metabolic disorders in the DCM model. Our findings provide novel insights into the molecular mechanisms underlying DCM and the potential of ferulic acid as a therapeutic agent for treating this condition.

| S-EPMC10785252 | biostudies-literature

Ferulic Acid Challenge of Lactobacillus brevis

Project description:The presence of anti-microbial phenolic compounds, such as the model compound ferulic acid, in biomass hydrolysates poses significant challenges to the widespread use of biomass in conjunction with whole cell biocatalysis or fermentation. Currently, these inhibitory compounds must be removed through additional downstream processing to create feedstock suitable for most industrially important microbial strains. This study explores the high ferulic acid tolerance in Lactobacillus brevis (L. brevis), a lactic acid bacteria often found in fermentation processes, by global transcriptional response analysis. The transcriptional profile of L. brevis under ferulic acid stress reveals that the presence of ferulic acid primarily triggers the expression of membrane proteins to counteract ferulic acid induced changes in membrane fluidity and ion leakage, in the midst of a generalized stress response. Several promising routes for understanding phenolic acid tolerance have been identified based upon these findings. These insights may be used to guide further engineering of model industrial organisms to better tolerate phenolic compounds in processed biomass.

2011-12-31 | GSE22826 | GEO

Alteration of metabolic profiles in Lemna paucicostata culture and enhanced production of GABA and ferulic acid by ethephon treatment.

Project description:Lemna species have been used in the food, feed, and pharmaceutical industries, as they are inexpensive sources of proteins, starches, and fatty acids. In this study, we treated L. paucicostata with different concentrations (0.05, 0.1, 0.2, 0.5, or 1 mM) of ethephon. The total dry weight decreased in all ethephon-treated groups compared to the control group. We also investigated the alteration of metabolic profiles induced by ethephon treatment by using gas chromatography-mass spectrometry. This analysis identified 48 metabolites, and the relative levels of most of alcohols, amino acids, fatty acids, and phenols increased by the ethephon treatment, whereas levels of organic acids and sugars decreased. Among these, the highest production of γ-aminobutyric acid (GABA, 5.041 ± 1.373 mg/L) and ferulic acid (0.640 ± 0.071 mg/L) was observed in the 0.5 mM and the 0.2 mM ethephon treatment groups, respectively. These results could be useful for large-scale culture of L. paucicostata with enhanced GABA and ferulic acid content for utilization in the food, feed, cosmetic, and pharmaceutical industries.

| S-EPMC7162458 | biostudies-literature

Effects of Piperazine Derivative on Paclitaxel Pharmacokinetics.

Project description:Paclitaxel (PTX) is an anticancer agent that is used to treat many cancers but it has a very low oral bioavailability due, at least in part, to the drug efflux transporter, P-glycoprotein (P-gp). Therefore, this study was performed to enhance oral bioavailability of PTX. In this study, we investigated the effects of several piperazine derivatives on P-gp function in vitro. Compound 4 was selected as the most potent P-gp inhibitor from the in vitro results for examining the pharmacokinetic (PK) changes of PTX in rats. Compound 4 increased the AUCinf of PTX without alterations in the Cmax value. The elimination half-life was extended and the oral clearance decreased. Additionally, the Tmax was delayed or widened in the treatment groups. Therefore, the bioavailability (BA) of PTX was improved 2.1-fold following the co-administration of 5 mg/kg of the derivative. A piperazine derivative, compound 4, which was confirmed as a substantial P-gp inhibitor in vitro increased the BA of PTX up to 2-fold by a lingering absorption, in part due to inhibition of intestinal P-gp and a low oral clearance of PTX. These results suggest that co-administering compound 4 may change the PK profile of PTX by inhibiting P-gp activity in the body.

| S-EPMC6359037 | biostudies-literature

A biorefinery approach for the production of ferulic acid from agroresidues through ferulic acid esterase of lactic acid bacteria.

Project description:Ferulic acid is a known precursor for vanillin production but the significance of agro waste as substrates for its extraction, in combination with microbes is a less explored option. Various lactic acid bacteria were screened for the production of ferulic acid esterase (FAE) and Enterococcus lactis SR1 was found to produce maximum FAE (7.54 ± 0.15 IU/ml) in the synthetic medium under submerged fermentation. To make the process cost effective, various lignocellulosic agroresidues were evaluated for the production of FAE from the bacterium. It was found that wheat bran serves as the best substrate for FAE production (4.18 ± 0.12 IU/ml) from E. lactis SR1. Further, optimization of fermentation conditions for FAE production from E. lactis SR1 using wheat bran as carbon source led to an increase in the enzyme production (7.09 ± 0.21 IU/ml) by 1.5 fold. The FAE produced was used alone or in combination with commercial holocellulase for biological release of FA from the tested agroresidues. The highest release of FA (mg/g) by enzymatic extraction occurred in sugarbeet pulp (2.56), followed by maize bran (1.45), wheat bran (1.39) and rice bran (0.87), when both the enzymes (FAE and holocellulase) were used together. Alkaline extraction and purification of ferulic acid (FA) from these agro residues also showed that sugarbeet pulp contains the highest amount of FA (5.5 mg/g) followed by maize bran (3.0 mg/g), wheat bran (2.8 mg/g) and rice bran (1.9 mg/g), similar to the trend obtained in biological/enzymatic extraction of FA from these residues. Furthermore, the substrates were found to release higher reducing sugars when both commercial holocellulase and FAE were used in combination than by the use of holocellulase alone. Thus, FAEs not only release FA but also enabled hemicellulase and cellulase to release more sugars from plant material.

| S-EPMC7395923 | biostudies-literature

Interactions of ferulic acid and ferulic acid methyl ester with endogenous proteins: Determination using the multi-methods.

Project description:Ferulic acid (FA) and ferulic acid methyl ester (FAM) are important phenolic compounds in Baijiu. In this study, the interaction of FA and FAM with human serum albumin (HSA) and lysozyme (LZM) was investigated using multispectral methods and molecular dynamics simulation. FA and FAM could interact with HSA and LZM, changing the conformation and hydrophilicity of the protein. The quenching mechanisms of FA-HSA, FA-LZM, FAM-HSA, and FAM-LZM were all static-quenching. In the FA-HSA, FAM-HSA, and FA-LZM systems, the interaction forces were mainly hydrophobic interactions and hydrogen bonding. In the FAM-LZM system, the interaction forces were mainly hydrophobic interactions, hydrogen bonding, and van der Waals force. Common metal ions such as K+, Ca2+, Cu2+, Mg2+, and Mn2+ could affect the binding ability of FA and FAM to HSA and LZM. Moreover, FA and FAM could increase the stability of HSA and LZM, and the protein bound to FA/FAM was more stable than the free protein. FA and FAM had varying degrees of impact on the physiological activities of HSA and LZM. This study provides relevant information on the interactions and metabolic mechanisms of FA and its derivatives with endogenous proteins.

| S-EPMC10835327 | biostudies-literature

Ferulic Acid Challenge of Lactobacillus brevis

2011-12-31 | E-GEOD-22826 | biostudies-arrayexpress

Expression data from ferulic acid treated C. elegans

Project description:Gene expression in N2 worms treated with 500 μM or 0 μM ferulic acid, at days 5. Effects of ferulic acid in C. elegans gene expression is studied, as our results indicate a lifespan extension effect produced by this molecule. RNA-seq were used to detail the global programme of gene expression underlying the lifespan extension and identified distinct classes of up/down-regulated genes in animals treated with ferulic acid.

2021-05-05 | GSE171836 | GEO

Improvement of the Solubility and Evaluation of the Physical Properties of an Inclusion Complex Formed by a New Ferulic Acid Derivative and ?-Cyclodextrin.

Project description:Ferulic acid derivative 012 (FAD012) is a ferulic acid (FA) derivative. The current study prepared a solid dispersion of FAD012 and ?-cyclodextrin (?CD) and ground it using a three-dimensional ball mill (3DGM) to prepare an inclusion complex. This study also assessed the physicochemical properties such as solubility of that complex. A Job's plot indicated that FAD012 and ?CD formed an inclusion complex at a molar ratio of 1:1. Phase solubility diagrams revealed that FAD012 produced a BS diagram. According to PXRD, FAD012 produced a diffraction peak at 2? = 7.0° and ?CD produced a diffraction peak at 2? = 9.1°. Those two peaks were not produced by the 3DGM, but new peaks (2? = 7.3 and 16.5°) were evident. DSC patterns revealed an endothermic peak due to the melting of FAD012 at 190 °C, but no endothermic peaks were evident with the 3DGM. NIR spectra of the 3DGM indicated that the methyl group of FAD012 produced a higher peak and that the OH groups of ?CD produced a higher peak. 1H-1H ROESY NMR spectra (D2O) revealed cross peaks for protons of the methyl group of FAD012 and a proton (H-3) in the cavity of ?CD, so FAD012 presumably interacts with the wide opening of the ?CD torus. A solubility test (25 °C) indicated that solubility improved about 5-fold for the 3DGM in comparison to the solubility of FAD012 alone (about 140 ?g/mL). Based on these findings, an FAD012/?CD complex was formed by cogrinding, and its solubility improved. These observations are expected to expand the usefulness of cogrinding of FAD012 with ?CD using a 3D ball mill.

| S-EPMC7271043 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data