P-hydroxybenzoic Acid Methyl Ester Research Articles

Amino Carbonylation of Epidermal Basement Membrane Inhibits Epidermal Cell Function and Is Suppressed by Methylparaben

This study investigated the effect of amino carbonylation (Maillard reaction) on the function of the epidermal basement membrane (BM) by analyzing epidermal cell proliferation and keratinization and stratum corneum barrier function using a three-dimensional human epidermal BM model treated with glyceraldehyde. Intracellular ATP levels were lower in cells cultured on amino-carbonylated epidermal BM as compared to those in normal epidermal BM (control). Moreover, trans-epidermal water loss was increased by culturing on amino-carbonylated BM relative to the control; this was accompanied by downregulation of filaggrin, transglutaminase-1, and serine palmitoyltransferase 2 mRNA levels. p-Hydroxybenzoic acid methyl ester (methylparaben) abrogated the decrease in ATP production and filaggrin expression in human keratinocytes induced by amino-carbonylated collagen. Thus, amino carbonylation of the epidermal BM inhibits moisture retention, keratinization, and ceramide synthesis and disrupts the barrier function of the stratum corneum. These findings suggest that methylparaben can be an effective additive to cosmetics for improving epidermal function that is compromised by amino carbonylation.

Effect of alcohol on skin permeation and metabolism of an ester-type prodrug in Yucatan micropig skin

We studied the effect that three alcohols, ethanol (EA), propanol (PA), and isopropanol (IPA), have on the skin permeation of p-hydroxy benzoic acid methyl ester (HBM), a model ester-type prodrug. HBM was applied to Yucatan micropig skin in a saturated phosphate buffered solution with or without 10% alcohol, and HBM and related materials in receptor fluid and skin were determined with HPLC. In the absence of alcohol, p-hydroxy benzoic acid (HBA), a metabolite of HBM, permeated the skin the most. The three alcohols enhanced the penetration of HBM at almost the same extent. The addition of 10% EA or PA to the HBM solution led to trans-esterification into the ethyl ester or propyl ester of HBA, and these esters permeated skin as well as HBA and HBM did. In contrast, the addition of 10% IPA promoted very little trans-esterification. Both hydrolysis and trans-esterification in the skin S9 fraction were inhibited by BNPP, an inhibitor of carboxylesterase (CES). Western blot and native PAGE showed the abundant expression of CES in micropig skin. Both hydrolysis and trans-esterification was simultaneously catalyzed by CES during skin permeation. Our data indicate that the alcohol used in dermal drug preparations should be selected not only for its ability to enhance the solubility and permeation of the drug, but also for the effect on metabolism of the drug in the skin.

Determination of Phytochemical Compounds, and Tyrosinase Inhibitory and Antimicrobial Activities of Bioactive Compounds from <i>Streblus ilicifolius</i> (S Vidal) Corner

Purpose: To determine the phytochemical content, and tyrosinase inhibitory and antimicrobial activities of the wood from Streblus ilicifolius ( S. Vidal ) Corner Methods: The dried wood of S. ilicifolius (8.70 kg) was extracted by maceration to give petroleum ether, ethyl acetate, ethanol and water extracts, respectively. Dopachrome method was used to determine antityrosinase activity. Agar disc diffusion and modified broth microdilution methods were used to determine antimicrobial activity. Chromatographic techniques were used for phytochemical investigation. The structures elucidation of isolated compounds were identified by physical properties and spectroscopic data including UV, IR, NMR and MS data and confirmed by comparison with previously reports. Results: The ethanol extract exhibited tyrosinase inhibition and antimicrobial activity against the Grampositive bacteria, Staphylococcus epidermidis and S. aureus . Phytochemical investigation showed five compounds, namely, (E)-2,4-dihydroxy-3 (3,7-dimethyl-2,6-octadienyl) benzaldehyde (1), phydroxybenzoic acid methyl ester (2), umbelliferone (3), moracin M (4), trans-resveratrol (5). Compound 4 exhibited tyrosinase inhibition with half maximal inhibitory concentration (IC50) of 67.69 μg/ml, while compound 1 displayed strong activity against S. epidermidis , S. aureus and methicillin-resistant S. aureus (MRSA) with minimum inhibitory concentration (MIC) of 8, 4 and 8 μg/ml, respectively and minimum bactericidal concentration (MBC) of 32, 16 and 64 μg/ml, respectively. Conclusion: This is the first report of the biological activities and phytochemical composition of S. ilicifolius and the results indicate the high potentials of the plant for commercial applications such as in facial whitening and anti-acne cream. Keywords: Streblus ilicifolius , Moraceae, Tyrosinase inhibition, Antimicrobial, Anti-acne, Methicillinresistant Staphylococcus aureus

Antioxidative iridoid glycosides and phenolic compounds from Veronica peregrina

Eight iridoid glycosides and four phenolic compounds were isolated from the EtOAc soluble fraction of Veronica peregrina MeOH extract as the radical scavengers for antioxidant activity. The compounds were identified as protocatechuic acid (1), luteolin (2), veronicoside (3), minecoside (4), specioside (5), amphicoside (6), catalposide (7), 6-O-cis-p-coumaroyl catalpol (8), p-hydroxy benzoic acid methyl ester (9), verproside (10), verminoside (11), and chrysoeriol 7-glucuronide (12) by spectroscopic analysis. All compounds except for 1 and 2 were isolated for the first time from this plant. The antioxidant activity was evaluated by the ORAC(Oxygen Radical Absorbance Capacity) assay, which measures scavenging activity against peroxy radicals induced by 2,2'-azobis (2-methoxypropion-amidine) dihydrochloride, and the ORAC value is expressed as relative trolox equivalent. Compounds 2, 4, 5, 6, 8, and 12 exhibited potent antioxidant activity, and compounds 1, 11 had similar activity with trolox, whereas the other compounds showed weaker activity than trolox.

Inhibition of Salmonella enterica Cells in Deli-Type Salad by Enterocin AS-48 in Combination with Other Antimicrobials.

The cyclic antibacterial peptide enterocin AS-48 acted synergistically with p-hydroxybenzoic acid methyl ester (PHBME) and with 2-nitropropanol against Salmonella enterica serovar Enteritidis CECT 4300 in Russian salad. In challenge tests on a cocktail of Salmonella strains (S.enterica ssp. enterica serotype Typhi CECT 409, S.enterica ssp. enterica serovar Choleraesuis CECT 915, S.enterica ssp. enterica serovar Enteritidis CECT 4300, S.enterica ssp. arizonae serovar Arizonae CECT 4395, and S.enterica ssp. salamae CECT 4000) in salad at 10°C, the combinations of PHBME and AS-48 (80μg/g) or 2-nitropropanol and AS-48 (40μg/g) reduced the concentrations of viable Salmonella from 4.27 to 4.75 log CFU/g down to the limit of detection for 7days. Salmonella populations did not increase in control samples (without any antimicrobials or in the presence of AS-48 alone) probably due to the low pH of this type of salad and low temperature of incubation, but retained over 85% viability after 1week. This work opens new possibilities to expand the spectrum of inhibition of enterocin AS-48 against Salmonellaenterica.

P-Hydroxybenzoic Acid Synthesis in Mycobacterium tuberculosis

Glycosylated p-hydroxybenzoic acid methyl esters and structurally related phenolphthiocerol glycolipids are important virulence factors of Mycobacterium tuberculosis. Although both types of molecules are thought to be derived from p-hydroxybenzoic acid, the origin of this putative biosynthetic precursor in mycobacteria remained to be established. We describe the characterization of a transposon mutant of M. tuberculosis deficient in the production of all forms of p-hydroxybenzoic acid derivatives. The transposon was found to be inserted in Rv2949c, a gene located in the vicinity of the polyketide synthase gene pks15/1, involved in the elongation of p-hydroxybenzoate to phenolphthiocerol in phenolic glycolipid-producing strains. A recombinant form of the Rv2949c enzyme was produced in the fast-growing non-pathogenic Mycobacterium smegmatis and purified to near homogeneity. The recombinant enzyme catalyzed the removal of the pyruvyl moiety of chorismate to form p-hydroxybenzoate with an apparent K(m) value for chorismate of 19.7 microm and a k(cat) value of 0.102 s(-1). Strong inhibition of the reaction by p-hydroxybenzoate but not by pyruvate was observed. These results establish Rv2949c as a chorismate pyruvate-lyase responsible for the direct conversion of chorismate to p-hydroxybenzoate and identify Rv2949c as the sole enzymatic source of p-hydroxybenzoic acid in M. tuberculosis.

Spinal Cord Injury in a Child Caused by an Accidental Dural Puncture with a Single-Shot Thoracic Epidural Needle

Spinal Cord Injury in a Child Caused by an Accidental Dural Puncture with a Single-Shot Thoracic Epidural Needle

P-Hydroxybenzoic acid alkyl esters in Andrographis paniculata herbs, commercial extracts, and formulated products.

Analysis of two commercial extracts of Andrographis paniculata using high-performance liquid chromatography (HPLC) with photodiode array absorbance detection showed the presence of several unexpected compounds, which were isolated and identified as methyl, ethyl, and propyl esters of p-hydroxybenzoic acid by using high-resolution mass spectrometry and nuclear magnetic resonance. Quantitative analysis using HPLC revealed the presence of 0.22% p-hydroxybenzoic acid methyl ester (methlyparaben) in one commercial extract, and both 0.11% p-hydroxybenzoic acid ethyl ester (ethylparaben) and 0.20% p-hydroxybenzoic acid propyl ester (propylparaben) in a second commercial extract of A. paniculata. Analyses of additional commercial products of A. paniculata in tablet form purchased from Chicago pharmacies also showed the presence of methyl- and ethylparabens. To determine whether these compounds were natural chemical constituents of the plant, pharmacopoeial reference A. paniculata plant powder as well as samples of authenticated A. paniculata plant materials collected from Indonesia, Hong Kong, and mainland China were obtained and analyzed by HPLC-tandem mass spectrometry (LC-MS-MS). LC-MS-MS analyses confirmed the presence of trace concentrations (<0.0008% w/w) of p-hydroxybenzoic acid methyl ester but no p-hydroxybenzoic acid ethyl or propyl esters in these plant samples. The limits of detection of the LC-MS-MS assay for these compounds were 5 pg on-column and 5 ppb in the plant material. The levels of these p-hydroxybenzoic acid esters measured in the commercial products of A. paniculata suggest that they were introduced inadvertently during processing or as artificial additives.

Interfacial Effect of Molecules on Nucleation Kinetics

Interfacial effects of molecules on nucleation kinetics of paracetamol were systematically examined for the first time. The effects can be classified into (a) the interfacial nucleation barrier lowering effects, described by a so-called interfacial correlation parameter, f(m,R‘); and (b) the kink integration effect, described by kink kinetic coefficient βkink. The second effect includes that the effect of desolvation of additives or impurities from the adsorption sites of embryo surface, and the induced pre-ordering of liquid at the substrate-fluid interface. Additives m-acetamidophenol and p-acetoxyacetanilide inhibit paracetamol nucleation by adsorbing on the surface of paracetamol, which suppresses the interface epitaxial effect (the nucleation barrier lowering effect) (f(m,R‘) → 1) and enhancing the desolvation energy barrier (βkink → 0), whereas p-hydroxybenzoic acid methyl ester only inhibits paracetamol nucleation by enhancing slightly the desolvation energy barrier. Polysaccharide, which forms str...

Simultaneous determination of antioxidants, preservatives and sweeteners permitted as additives in food by mixed micellar electrokinetic chromatography

A micellar electrokinetic chromatography method was developed to simultaneously analyse commonly used food additives. The additive mixture, comprising propyl gallate, octyl gallate, dodecyl gallate, butylated hydroxyanisole, butylated hydroxytoluene, tertiary butylhydroquinone, p-hydroxybenzoic acid methyl ester, p-hydroxybenzoic acid ethyl ester, benzoic acid, sorbic acid, saccharin, aspartame and acesulfame-K, was not resolved using single surfactant micellar systems consisting of sodium dodecyl sulfate (SDS), sodium cholate (SC) or sodium deoxycholate (SDC). The separation of these additives using mixed micellar systems, involving SDS/SC, SDS/SDC and SC/SDC, was investigated. Organic solvents were added to the mixed micellar phases to optimise the separation. The mixture was successfully separated using a 20 m M borate buffer with 35 m M SC, 15 m M SDS and 10% methanol added at pH 9.3. Additives in cola beverages and low-joule jam were investigated and quantified using this method.

EFFECT OF BENZOIC ACID AND SOME OF ITS DERIVATIVES ON THE RATE OF DL-DOPA OXIDATION BY MUSHROOM TYROSINASE

Vanillic acid and salicylic acid inhibited the rate of dihydroxyphenylalanine (DL-DOPA) oxidation to dopachrome (λ max = 475 nm) by tyrosinase at all concentrations tested. Benzoic acid and p-hydroxybenzoic acid (PHBA), at relatively low concentrations, slightly stimulated the rate of DL-DOPA oxidation, whereas at higher concentrations each inhibited the reaction. p-Hydroxybenzoic acid methyl ester (PHBAME), at relatively low concentrations, had a pronounced synergistic effect on the reaction, whereas at relatively high concentrations it inhibited the rate of DL-DOPA oxidation. The synergistic effect of 1. 6-6. 6 mM PHBAME on the rate ofDL-DOPA oxidation to dopachrome was found to be only an apparent effect due to the ability of PHBAME to be hydroxylated very slowly by tyrosinase to a yellow pigmented product(s) with DL-DOPA serving as a reductant (AH 2 ) for the hydroxylation reaction, thus hastening the conversion of PHBAME to pigmented product(s). Vanillic acid, salicylic acid, benzoic acid and PHBA could not be hydroxylated by tyrosinase.

Chemisorbates of p-hydroxybenzoic acid methyl ester on silica as a new type of pro-drug IV. Drug release from chemisorbates dispersed in lipophilic vehicles

The hydrolysis of the chemisorbate of p-hydroxybenzoic acid methyl ester (PHBAME) on porous silica (KG 100) incorporated in lipophilic vehicles such as liquid paraffin, synthetic oil Miglyol® 818 and white petrolatum was examined in dissolution media at pH 2 and 7.4, respectively. Chemisorbed PHBAME on KG 100 is released more rapidly in alkaline than in acidic dissolution fluids. Dispersions of the PHBAME-KG 100 chemisorbate in lipophilic vehicles modify the hydrolysis significantly. Drug release from chemisorbate dispersed in lipophilic vehicles may be controlled by the polarity of the vehicles. However, the viscosity of the vehicle, and not the polarity, exerts the strongest influence on the drug release.

Chemiadsorbates of p-hydroxybenzoic acid methyl ester on silica as a new type of pro-drug. III. Modeling and simulation of drug release from chemiadsorbates to acid aqueous solution

The in vitro release of physi- and chemiadsorbates of p-hydroxybenzoic acid methyl ester (PHBAME) on a colloidal (Aerosil 0 × 50; BET surface 50 m 2 g −1) and a porous silica support (KG 100; mean pore size 10 nm, BET surface 300 m 2 g −1) in an acidic dissolution fluid was investigated and the release kinetics described by mathematical modeling with an analog-hybrid computer. The release from physiadsorbates on both the colloidal and the porous silica proved to be a fast process, best described by two release constants. The release from the chemiadsorbates, however, is based on different mechanisms: from the plain surface of colloidal silica (fractal dimension 2.0) the drug release can be best described by two hydrolysis reaction rates while four different reaction rates were evaluated for the release of PHBAME from the porous support. From the reaction rates and the activation energies it is concluded that the hydrolysis of the surface link between the PHBAME and the silica surface, the Si-O-c bond is strongly influenced by the surface character of the supports, described by their different fractal dimensions (porous support fractal dimension 2.56).

Characterization of p-hydroxybenzoic acid methylester physi- and chemiadsorbates on silica by IR and UV-spectroscopy

Physiadsorbates and chemiadsorbates of p-hydroxybenzoic acid methylester (pHBAME) on colloidal and porous silicas were studied by IR and UV spectroscopy. In the IR spectra of self-supporting discs of the adsorbates, typical features were detected which allow differentiation between the physi- and the chemiadsorbed state: a strong absorption band at 1417 cm−1 characterizes the chemiabsorbate. Dehydration by annealing and rehydration of the adsorbates proceeded also in a different way, indicated by absorption bands both in the carbonyl group and in the ring vibration frequency range. In the UV spectra the absorption maximum of the chemiadsorbate occured at 250 nm and that of the physiadsorbate at 255.5 nm (from cyclohexane suspensions of the adsorbates).

Improved Sample Collection Technique for Capillary Blood on Filter Paper for Determination of Glycated Haemoglobin

A simple and practical method of sampling capillary blood was tested. This method was used for determination of glycated haemoglobin by ion exchange chromatography. Capillary blood was collected onto filter paper and placed in a small polypropylene tube containing phosphate-buffered sodium chloride with EDTA and p-hydroxybenzoic acid methyl ester. There was good correlation between filter paper sampling and conventional sampling in tubes with EDTA as anticoagulant. With this new sampling technique the glycated haemoglobin value was stable for 7 days at room temperature and for at least 10 days at +4 degrees C. Sampling can be performed by the patient at home and the sample then mailed to the laboratory, thus enabling analysis to be performed prior to the patient's visit to the physician.

1513. The diphenylamine story concluded: Thomas, J. O., Ribelin, W. E., Wilson, R. H., Keppler, D. C. & DeEds, F. (1967). Chronic toxicity of diphenylamine to albino rats. Toxic. appl. Pharmac.10, 362

A micellar electrokinetic chromatography method was developed to simultaneously analyse commonly used food additives. The additive mixture, comprising propyl gallate, octyl gallate, dodecyl gallate, butylated hydroxyanisole, butylated hydroxytoluene, tertiary butylhydroquinone, p-hydroxybenzoic acid methyl ester, p-hydroxybenzoic acid ethyl ester, benzoic acid, sorbic acid, saccharin, aspartame and acesulfame-K, was not resolved using single surfactant micellar systems consisting of sodium dodecyl sulfate (SDS), sodium cholate (SC) or sodium deoxycholate (SDC). The separation of these additives using mixed micellar systems, involving SDS/SC, SDS/SDC and SC/SDC, was investigated. Organic solvents were added to the mixed micellar phases to optimise the separation. The mixture was successfully separated using a 20 mM borate buffer with 35 mM SC, 15 mM SDS and 10% methanol added at pH 9.3. Additives in cola beverages and low-joule jam were investigated and quantified using this method.