In vitro anthelmintic activity and colocalization analysis of hydroxycinnamic acids obtained from Chamaecrista nictitans against two Haemonchus contortus isolates.

This study assessed the in vitro anthelmintic activity of ethyl acetate extract (Cn-EtOAc) and its bioactive fractions (CnR3 and CnR5) obtained from Chamaecrista nictitans aerial parts against two Haemonchus contortus (Hc) isolates, one resistant (strain HcIVM-R) and another susceptible (strain HcIVM-S) to ivermectin. Ferulic acid and p-coumaric acid were identified in the bioactive fractions; therefore, their commercial standards were also assessed. A colocalization analysis between the ferulic acid commercial standard and eggs of the HcIVM-R strain was performed using confocal laser scanning microscopy and the ImageJ program. The ovicidal effects of the Cn-EtOAc extract, bioactive fractions and commercial compounds were tested through the egg hatching inhibition (EHI) assay on H. contortus isolates HcIVM-R and HcIVM-S. The Cn-EtOAc caused 88 % and 92 % EHI at 5000 µg/mL on HcIVM-R and HcIVM-S, respectively. Fractions CnR3 and CnR5 displayed the highest ovicidal activity against HcIVM-S, with effective concentrations (EC90) of 2134 and 601 µg/mL, respectively. Meanwhile, the commercial standards ferulic acid and p-coumaric acid also resulted in higher effectiveness on the same strain, with EC90 of 57.5 and 51.1 µg/mL. A colocalization analysis of ferulic acid and eggs of HcIVM-R revealed that this compound is localized to the cuticle surface of the embryo inside the egg parasite. The results demonstrated that both ferulic and p-coumaric acids interrupt the egg-hatching processes of the two Hc isolates. Both phenolic acids isolated from C. nictitans and commercial standards exhibited the best anthelmintic effect on HcIVM-S. These findings indicate that the phenolic acids were less effective in egg hatch inhibiting on the HcIVM-R strain compared to the HcIVM-S strain.

Antifungal Activity, Mode of Action, and Cytotoxicity of 4-Chlorobenzyl p-Coumarate: A Promising New Molecule.

Fungal infections represent a serious health problem worldwide. The study evaluated the antifungal activity of 4-chlorobenzyl p-coumarate, an unprecedented semi-synthetic molecule. Docking molecular and assay experiments were conducted to determine the Minimum Inhibitory Concentration (MIC) and Minimum Fungicidal Concentration (MFC), mode of action, effect on growth, fungal death kinetics, drug association, effects on biofilm, micromorphology, and against human keratinocytes. The investigation included 16 strains of Candida spp, including C. albicans, C. krusei, C. glabrata, C. tropicalis, C. dubliniensis, C. lusitaniae, C. utilis, C. rugosa, C. guilhermondi, and C. parapsilosis. Docking analysis predicted affinity between the molecule and all tested targets. MIC and MFC values ranged from 3.9 µg/mL (13.54 µM) to 62.5 µg/mL (217.01 µM), indicating a probable effect on the plasma membrane. The molecule inhibited growth from the first hour of testing. Association with nystatin proved to be indifferent. All concentrations of the molecule reduced fungal biofilm. The compound altered fungal micromorphology. The tested compound exhibited an IC50 of 7.90±0.40 µg/mL (27.45±1.42 µM) for keratinocytes. 4-chlorobenzyl p-coumarate showed strong fungicidal effects, likely through its action on the plasma membrane and alteration of fungal micromorphology, and mildly cytotoxic to human keratinocytes.

In vitro Evaluation of the Antileishmanial and Antischistosomal Activities of p-Coumaric Acid Prenylated Derivatives.

We have evaluated eight p-coumaric acid prenylated derivatives in vitro for their antileishmanial activity against Leishmania amazonensis promastigotes and their antischistosomal activity against Schistosoma mansoni adult worms. Compound 7 ((E)-3,4-diprenyl-4-isoprenyloxycinnamic alcohol) was the most active against L. amazonensis (IC50=45.92 µM) and S. mansoni (IC50=64.25 µM). Data indicated that the number of prenyl groups, the presence of hydroxyl at C9, and a single bond between C7 and C8 are important structural features for the antileishmanial activity of p-coumaric acid prenylated derivatives.

Cytotoxic and Antifungal Amides Derived from Ferulic Acid: Molecular Docking and Mechanism of Action.

Amides derived from ferulic acid have a wide spectrum of pharmacological activities, including antitumor and antifungal activity. In the present study, a series of ten amides were obtained by coupling reactions using the reagents (benzotriazol-1-yloxy) tripyrrolidinophosphonium hexafluorophosphate (PyBOP) and N,N'-dicyclohexylcarbodiimide (DCC). All the compounds were identified on the basis of their IR, 1H- and 13C-NMR, HRMS data, and with yields ranging from 43.17% to 91.37%. The compounds were subjected to cytotoxic tests by the alamar blue technique and antifungal screening by the broth microdilution method to determine the minimum inhibitory concentration (MIC). The amides 10 and 11 displayed the best result in both biological evaluations, and compound 10 was the most potent and selective in HL-60 cancer cells, with no cytotoxicity on healthy cells. This amide had antifungal activity in all strains and had the lowest MIC against Candida albicans and Candida tropicalis. The possible mechanism of antifungal action occurs via the fungal cell wall. Molecular modeling suggested that compounds 10 and 11 interact with the enzymes GWT1 and GSC1, which are essential for the development of C. albicans. The findings of the present study demonstrated that compounds 10 and 11 may be used as a platform in drug development in the future.

Polyphenolic QTOF-ESI MS Characterization and the Antioxidant and Cytotoxic Activities of Prunus domestica Commercial Cultivars from Costa Rica.

There is an increased interest in plum research because of their metabolites' potential bioactivities. In this study, the phenolic profiles of Prunus domestica commercial cultivars (Methley, Pisardii and Satsuma) in Costa Rica were determined by Ultra Performance Liquid Chromatography coupled with High Resolution Mass Spectrometry using a quadrupole-time-of-flight analyzer (UPLC-ESI-QTOF MS) on enriched phenolic extracts obtained through Pressurized Liquid Extraction (PLE) under acidic and neutral extraction conditions. In total, 41 different phenolic compounds were identified in the skin and flesh extracts, comprising 11 flavan-3-ols, 14 flavonoids and 16 hydroxycinnamic acids and derivatives. Neutral extractions for the skins and flesh from all of the cultivars yielded a larger number of compounds, and were particularly rich in the number of procyanidin trimers and tetramers when compared to the acid extractions. The total phenolic content (TPC) and antioxidant potential using the DPPH and ORAC methods exhibited better results for neutral extracts with Satsuma skins and Methley flesh, which showed the best values (685.0 and 801.6 mg GAE/g extract; IC50 = 4.85 and 4.39 µg/mL; and 12.55 and 12.22 mmol TE/g extract, respectively). A Two-Way ANOVA for cytotoxicity towards AGS gastric adenocarcinoma and SW620 colon adenocarcinoma indicated a significant difference (p < 0.05) for PLE conditions, with better results for neutral extractions, with Satsuma skin delivering the best results (IC50 = 60.7 and 46.7 µg/mL respectively) along with Methley flesh (IC50 = 76.3 and 60.9 µg/mL, respectively). In addition, a significant positive correlation was found between TPC and ORAC (r = 0.929, p < 0.05), as well as a significant negative correlation (p < 0.05) between TPC and cytotoxicity towards AGS and SW620 cell lines (r = -0.776, and -0.751, respectively). A particularly high, significant, negative correlation (p < 0.05) was found between the number of procyanidins and cytotoxicity against the AGS (r = -0.868) and SW620 (r = -0.855) cell lines. Finally, the PCA clearly corroborated that neutral extracts are a more homogenous group exhibiting higher antioxidant and cytotoxic results regardless of the part or cultivar; therefore, our findings suggest that PLE extracts under neutral conditions would be of interest for further studies on their potential health benefits.

Hydroxycinnamic acid-spermidine amides from Tetragonisca angustula honey as anti-Neospora caninum: In vitro and in silico studies.

Tetragonisca angustula honey was fractioned in a SiO2 column to furnish three fractions (A-C) in which four hydroxycinnamic acid-Spermidine amides (HCAAs), known as N', N″, N‴-tris-p-coumaroyl spermidine, N', N″-dicaffeoyl, N‴-coumaroyl spermidine, N', N″, N‴-tris-caffeoyl spermidine and N', N″-dicaffeoyl and N‴-feruloyl spermidine were identified in the fractions B and C by electrospray ionization tandem mass spectrometry. A primary culture model previously infected with Neospora caninum (72 h) was used to evaluate the honey fractions (A-C) for two-time intervals: 24 and 72 h. Parasitic reduction ranged from 38% on fraction C (12.5 µg/ml), after 24 h, to 54% and 41% with fractions B and C (25 µg/ml) after 72 h of treatment, respectively. Additionally, HCAAs did not show any cell toxicity for 24 and 72 h. For infected cultures (72 h), the active fractions B (12.5 µg/ml) and C (25 µg/ml) decreased their NO content. In silico studies suggest that HCAAs may affect the parasite's redox pathway and improve the oxidative effect of NO released from infected cells. Here, we presented for the first time, that HCAAs from T. angustula honey have the potential to inhibit the growth of N. caninum protozoa.

Biosensing Membrane Base on Ferulic Acid and Glucose Oxidase for an Amperometric Glucose Biosensor.

A biosensing membrane base on ferulic acid and glucose oxidase is synthesized onto a carbon paste electrode by electropolymerization via cyclic voltammetry in aqueous media at neutral pH at a single step. The developed biosensors exhibit a linear response from 0.082 to 34 mM glucose concentration, with a coefficient of determination R2 equal to 0.997. The biosensors display a sensitivity of 1.1 µAmM-1 cm-2, a detection limit of 0.025 mM, and 0.082 mM as glucose quantification limit. The studies reveal stable, repeatable, and reproducible biosensors response. The results indicate that the novel poly-ferulic acid membrane synthesized by electropolymerization is a promising method for glucose oxidase immobilization towards the development of glucose biosensors. The developed glucose biosensors exhibit a broader linear glucose response than other polymer-based glucose biosensors.

Cytotoxic Fractions from Hechtia glomerata Extracts and p-Coumaric Acid as MAPK Inhibitors.

Preliminary bioassay-guided fractionation was performed to identify cytotoxic compounds from Hechtia glomerata, a plant that is used in Mexican ethnomedicine. Organic and aqueous extracts were prepared from H. glomerata's leaves and evaluated against two cancer cell lines. The CHCl3/MeOH (1:1) active extract was fractionated, and the resulting fractions were assayed against prostate adenocarcinoma PC3 and breast adenocarcinoma MCF7 cell lines. Active fraction 4 was further analyzed by high-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry analysis to identify its active constituents. Among the compounds that were responsible for the cytotoxic effects of this fraction were flavonoids, phenolic acids, and aromatic compounds, of which p-coumaric acid (p-CA) and its derivatives were abundant. To understand the mechanisms that underlie p-CA cytotoxicity, a microarray assay was performed on PC3 cells that were treated or not with this compound. The results showed that mitogen-activated protein kinases (MAPKs) that regulate many cancer-related pathways were targeted by p-CA, which could be related to the reported effects of reactive oxygen species (ROS). A molecular docking study of p-CA showed that this phenolic acid targeted these protein active sites (MAPK8 and Serine/Threonine protein kinase 3) at the same binding site as their inhibitors. Thus, we hypothesize that p-CA produces ROS, directly affects the MAPK signaling pathway, and consequently causes apoptosis, among other effects. Additionally, p-CA could be used as a platform for the design of new MAPK inhibitors and re-sensitizing agents for resistant cancers.

Ferulic Acid and Cardiovascular Health: Therapeutic and Preventive Potential.

Bioactive compounds found in food and medicinal plants contribute to maintaining health and treating illnesses. For example, hydroxycinnamic acids, such as ferulic acid, are widely present in nature and have several pharmacological properties, including antioxidant, anti-inflammatory, and beneficial effects in parameters of diabetes and hyperlipidemia. The results of studies in animal models and in vitro experiments of ferulic acid suggest its high therapeutic and preventive potential against several pathological disorders, such as cardiovascular diseases. Therefore, in this review, the bioactivities of ferulic acid on the cardiovascular system are described, including the discussion of the mechanisms of action in the various components of the system. In this review, we discuss the pharmacological properties of this versatile natural product in aspects of cardiovascular health, including cardioprotective and antihypertensive actions, and on the metabolism of lipids, diabetes, and thrombosis.

Coumaric acid derivatives as tyrosinase inhibitors: Efficacy studies through in silico, in vitro and ex vivo approaches.

p-Coumaric acid is a known inhibitor of tyrosinase, an enzyme involved in the initial steps of the melanin synthesis in human and other species. However, its low lipophilicity impairs its penetration through skin and efficacy as antimelanogenic agent indeed. Accordingly, this paper reports the assessment of several coumaric acid derivatives as tyrosinase inhibitors and antimelanogenic agents in in vitro, in silico and ex vivo assays. The compounds were designed with modifications in the aromatic and acid moieties of p-coumaric acid, being the coumarate esters the most promising derivatives. The compounds showed higher tyrosinase inhibitory activity (pIC50 3.7-4.2) than the parent acid, being compounds 1d, 1e and 1f the most potent inhibitors. Docking analysis showed that these esters are competitive inhibitors per se, and act independently of a redox mechanism as suggested by DPPH assays. Moreover, the esters showed efficacy in reducing the melanin deposition in human skin fragments at 0.1% concentration, especially compound 1e. In summary, there is an important equilibria between tyrosinase affinity and lipophilicity that must be considered to get effective antimelanogenic agents with adequate permeability in the skin.

Analysis of the phenolic composition and yield of 'BRS Vitoria' seedless table grape under different bunch densities using HPLC-DAD-ESI-MS/MS.

Grapes are considered to be a major source of phenolic compounds as compared with other fruits. To improve the quality of table grapes, some techniques like thinning can be used. In addition, grape cultivars with distinct characteristics are directly linked to its phenolic profile. This study aimed to identify and quantify the phenolic compound profile and yield of the hybrid 'BRS Vitoria' seedless table grape under different bunch densities, using a combination of solid-phase extraction (SPE) methodologies and analytical high-performance liquid chromatography-diode array detector with tandem mass spectrometry (HPLC-DAD-ESI-MS/MS). A trial was carried out in 2016, in a commercial vineyard at Marialva, state of Parana (South Brazil). Three weeks after anthesis, the following bunch densities were evaluated: 4.0, 4.5, 5.0, 5.5, and 6 bunches per m2 (corresponding to an estimation of 16, 18, 20, 22, and 24 tons ha-1). The randomized block design was used as a statistical model with each treatment was replicated four times, with one vine per plot. Different characteristics were evaluated at harvest, e.g., soluble solids content (SS), total acidity (TA), maturation index (MI = SS/TA), bunch and berry masses, yield, as well hydroxycinnamic acid derivative (HCAD), anthocyanin, flavonol, and flavan-3-ol contents by HPLC-DAD-ESI-MS/MS analysis. The evaluated bunch densities did not interfere with the physicochemical characteristics of the berries, such as SS and MI. Under the density of 6.0 bunches per m2, the highest yield of 25 tons ha-1 was reached. Under all bunch densities, the phenolic profile presented the same compounds, but at different concentrations. Under a density of 5.0 bunches per m2, the compounds belonging to the anthocyanin and flavonol families were present in high concentrations. In contrast, at the densities of 4.0 and 4.5 bunches per m2, there was a reduction in the flavan-3-ol content. With respect to stilbenes, only the trans-piceid and its cis- isomer were detected. However, their concentrations had no significant influence on the evaluated bunch densities.

Δ-FeOOH as Support for Immobilization Peroxidase: Optimization via a Chemometric Approach.

Owing to their high surface area, stability, and functional groups on the surface, iron oxide hydroxide nanoparticles have attracted attention as enzymatic support. In this work, a chemometric approach was performed, aiming at the optimization of the horseradish peroxidase (HRP) immobilization process on Δ-FeOOH nanoparticles (NPs). The enzyme/NPs ratio (X1), pH (X2), temperature (X3), and time (X4) were the independent variables analyzed, and immobilized enzyme activity was the response variable (Y). The effects of the factors were studied using a factorial design at two levels (-1 and 1). The biocatalyst obtained was evaluated for the ferulic acid (FA) removal, a pollutant model. The materials were characterized by X-ray powder diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). The SEM images indicated changes in material morphology. The independent variables X1 (-0.57), X2 (0.71), and X4 (0.42) presented the significance effects estimate. The variable combinations resulted in two significance effects estimates, X1*X2 (-0.57) and X2*X4 (0.39). The immobilized HRP by optimized conditions (X1 = 1/63 (enzyme/NPs ratio, X2 = pH 8, X4 = 60 °C, and 30 min) showed high efficiency for FA oxidation (82%).

A novel strategy for glioblastoma treatment combining alpha-cyano-4-hydroxycinnamic acid with cetuximab using nanotechnology-based delivery systems.

Combination therapy that uses multiple drugs against different molecular targets should be considered as interesting alternatives for treating complex diseases such as glioblastoma (GBM). Drugs like alpha-cyano-4-hydroxycinnamic acid (CHC) and the monoclonal antibody cetuximab (CTX) are already explored for their capacity to act against different hallmarks of cancer. Previous reports suggest that the simultaneous use of these drugs, as a novel combining approach, might result in additive or synergistic effects. Therefore, advances in nanotechnology-based delivery systems will inevitably bring nano-mediated therapeutic gains to the proposed combination since they enable the association of different drugs into a single carrier. The current study provides indications that the new dual therapeutic strategy proposed, in association with nanotechnology, provides significative improvements when compared to the use of isolated drugs. Nanotechnological tools were employed by developing polymeric nanoparticles based on poly(lactic-co-glycolic acid) and chitosan for CHC encapsulation. Furthermore, these structures were conjugated with CTX by supramolecular forces. In summary, the encapsulation of the CHC drug into the nanoparticles increased its individual therapeutic capacity. In addition, conjugation with CTX seemed to enhance therapeutic efficacy, especially for U251 GBM cells. In conclusion, developed nanostructured delivery systems exhibited a set of favorable attributes and potential to be applied as a promising new alternative for GBM treatment. Graphical abstract .

Rhodnius spp. are differentiated based on the peptide/protein profile by matrix-assisted laser desorption/ionization mass spectrometry and chemometric tools.

Triatominae are hematophagous insects involved in the transmission of Chagas disease. Among the 19 genera of the subfamily, those with the highest epidemiological importance regarding the dissemination of Trypanosoma cruzi are Panstrongylus, Rhodnius, and Triatoma. Of these three genera, Rhodnius presents the greatest difficulties for specific identification. Thus, there is a need to overcome the difficulties in identifying phenotypes of similar species of this genus. In the present study, the MALDI-TOF MS methodology was used to identify 12 Rhodnius species, among the 21 admitted. The MALDI-TOF MS methodology allowed specific characterization through the identification of peptides and proteins, starting from four different methods of extraction: (A) acetonitrile/formic acid (ACN/AF), (B) acetonitrile/trifluoroacetic acid (ACN/TFA), (C) isopropyl/formic acid (IPA/AF), and (D) methanol/formic acid (MeOH/AF), and four types of MALDI-TOF matrices: α-cyano-4-hydroxycinnamic acid (CHCA), sinapic acid (SA), 6-aza-2-thiothymine (ATT), and 2,6-dihydroxyacetophenone (DHAP). The experiments were performed by combining the four solvents and four matrices to select the best MALDI extraction/matrix. The application of the MALDI-TOF MS technique, through the digital mass spectrometry approach combined with chemometric tools, such as partial least squares-discriminant analysis (PLS-DA), was able to discriminate 12 species of Rhodnius genus, which are difficult to identify using morphological characteristics. Thus, in view of the results obtained, the methodology described in the present article can be applied with speed and efficiency for the discrimination of Triatominae species. Graphical Abstract.

Effect of sinapic acid ester derivatives on the oxidative stability of omega-3 fatty acids rich oil-in-water emulsions.

Oil-in-water (O/W) emulsions are important delivery systems of omega-3 fatty acids (n-3 FA). We investigated the effect of sinapic acid esters concentration and chain length, the electrical charge of the emulsifier and emulsion pH on the oxidative stability of n-3 FA rich O/W emulsions. Echium oil was applied as n-3 FA source. A 24 factorial design was used to simultaneously evaluate these factors. Peroxide value, malondialdehyde, 2,4-heptadienal and 2,4-decadienal were measured in the emulsions. pH and the electrical charge of the emulsifier modulated the antioxidant effectiveness of sinapic acid esters, while concentration was not relevant. The combination of positively charged emulsifier with neutral pH provided the best oxidative stability for echium oil emulsions. Our results also suggested that the increase of length chain of sinapic acid, from C4 to C12, reduced the secondary products of oxidation, when echium oil emulsions were prepared using negatively charged emulsifier under acidic conditions.

Effect of light, oxygen and temperature on the stability of artepillin C and p-coumaric acid from Brazilian green propolis.

Brazilian Green Propolis (BGP) is an important bee product, which displays important biological activities, making it valuable in the international market. The major prenylated phenolic compound in BPG is (E)-artepillin C, along with its precursor (E)-p-coumaric acid, both contributing to the biological effects of BGP. Taking that into account, it was evaluated the effect of light, temperature and air oxygen in their content to establish the best storage and transport conditions for crude BGP and the pure compounds. For that, (E)-artepillin C and (E)-p-coumaric acid were initially submitted to degradation for five days under sunlight and high temperature (50 °C), furnishing three major (E)-Artepillin C isomers and one from (E)-p-coumaric acid. Then, it was developed and validated a Reverse Phase High Performance Liquid Chromatography (RP-HPLC) method for quantifying these compounds in crude BGP and in its extracts. In the stability studies, it was used a Full Factorial and Central Composite Design to establish the desirable storage conditions. (E)-Artepillin C, both pure and in BGP should be kept protected from light and storage below -2.5 °C. (E)-p-Coumaric acid can be stored at room temperature. Therefore, the best storage and transport conditions to keep the content of both compounds in BGP are protection from light at low temperatures.

Trypanocidal Mechanism of Action and in silico Studies of p-Coumaric Acid Derivatives.

Trypanosoma species are responsible for chronic and systemic infections in millions of people around the world, compromising life quality, and family and government budgets. This group of diseases is classified as neglected and causes thousands of deaths each year. In the present study, the trypanocidal effect of a set of 12 ester derivatives of the p-coumaric acid was tested. Of the test derivatives, pentyl p-coumarate (7) (5.16 ± 1.28 µM; 61.63 ± 28.59 µM) presented the best respective trypanocidal activities against both epimastigote and trypomastigote forms. Flow cytometry analysis revealed an increase in the percentage of 7-AAD labeled cells, an increase in reactive oxygen species, and a loss of mitochondrial membrane potential; indicating cell death by necrosis. This mechanism was confirmed by scanning electron microscopy, noting the loss of cellular integrity. Molecular docking data indicated that of the chemical compounds tested, compound 7 potentially acts through two mechanisms of action, whether by links with aldo-keto reductases (AKR) or by comprising cruzain (CZ) which is one of the key Trypanosoma cruzi development enzymes. The results indicate that for both enzymes, van der Waals interactions between ligand and receptors favor binding and hydrophobic interactions with the phenolic and aliphatic parts of the ligand. The study demonstrates that p-coumarate derivatives are promising molecules for developing new prototypes with antiprotozoal activity.

Analysis of Phenolic Composition of Byproducts (Seeds and Peels) of Avocado (Persea americana Mill.) Cultivated in Colombia.

The byproducts (seeds and peels) of an avocado cultivated in the south of Colombia were extracted with aqueous acetone and their antioxidant properties were measured with ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) and DPPH (2,2-diphenyl-1-picrylhydrazyl) assays, and total polyphenol content was determined by Folin-Ciocalteu method. A bioguided fractionation was performed, first by SPE (solid phase extraction) on Amberlite XAD-7, and then by size exclusion chromatography on Sephadex LH-20. The polyphenolic-rich extracts and their fractions were analyzed by ultra-performance liquid chromatography-electrospray ionization-mass spectrometry (UPLC-ESI-MS/MS), finding the presence of organic acids, hydroxycinnamic acids, catechins, free and glycosylated flavonoids, and dimeric and trimeric procyanidins. Catechin, epicatechin, six quercetin derivatives, four dimeric procyanidins (three type B and one type A), and three trimeric procyanidins (two type B and one type A) were detected in the most active fractions of avocado peel and seeds. The most antioxidant fractions contain the higher molecular weight phenolic compounds (condensed tannins).

Zein-casein-lysine multicomposite nanoparticles are effective in modulate the intestinal permeability of ferulic acid.

The objective of this study was to develop zein-casein-lysine nanoparticles to modulate the intestinal permeability of ferulic acid (FA), a bioactive compound with proven antioxidant properties. The nanoparticles were obtained by a liquid-liquid dispersion method and were characterized in terms of mean size, polydispersity index, zeta potential, association efficiency (AE), in vitro drug release, x-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FT-IR). The in vitro intestinal permeability of nanoparticles was evaluated through Caco-2 and Caco-2/HT29-MTX monoculture and co-culture models, respectively. Nanoparticles presented a mean size of 199 nm and zeta potential of -26 mV. The AE of FA was 23% evaluated by high-performance liquid chromatography (HPLC). XRD showed amorphization of FA after association and FT-IR showed no changes in chemical structures of the compounds after nanoencapsulation. The cytotoxicity assays demonstrated that multicomposite nanoparticles presented a safe profile against Caco-2 and HT29-MTX cells. In the in vitro permeability assay, free FA exhibited higher permeability compared to FA-loaded nanoparticles, possibly due to prolonged FA release from nanoparticles. These new developed zein-casein-lysine nanoparticles may be used for FA sustained delivery by the oral route.

Isolation and Characterization of a New Ferulic-Acid-Biotransforming Bacillus megaterium from Maize Alkaline Wastewater (Nejayote).

Nejayote is an alkaline wastewater generated during the nixtamalization process. Nejayote contains high-value compounds such as ferulic acid (FA), which is widely employed as a substrate for the biotechnological production of flavors and aromas. In the present study, the isolation, identification, and characterization of a native strain of Bacillus megaterium were performed, and its capacity to produce 4-vinylguaiacol (4VG) from ferulic acid was evaluated by employing growing cell and resting cell systems. Growing cells of native B. megaterium biotransformed 6 mM crude FA in nejayote into 2.1 mM 4VG, reaching a productivity of 0.21 mM h-1 4VG, while nejayote enriched with FA at 10, 15, and 25 mM resulted in the formation of 2.4, 3.8, and 6.2 mM 4VG and productivities of 0.24, 0.38, and 0.51 mM h-1 4VG, respectively. In the resting cell system, from 6 and 25 mM pure FA, 3.5 mM 4VG was produced (0.18 mM h-1 4VG), while at 10 and 15 mM FA, 4.6 and 5.1 mM 4VG (average of 0.24 mM h-1 4VG) were obtained, respectively. The native B. megaterium strain, isolated from nejayote, showed great biotechnological potential to produce 4VG from crude FA contained in this wastewater, in which other Bacillus species, such as B. licheniformis and B. cereus, were unable to grow and biotransform FA into 4VG.