Bioactivity of phenolic acids: Metabolites versus parent compounds: A review

Phenolic acids are present in our diet in different foods. In particular, mushrooms are a good source of these molecules. Due to their bioactive properties, phenolic acids are extensively studied and there is evidence of their role in disease prevention. Nevertheless, in vivo, these compounds are metabolized and circulate in the organism as glucuronated, sulfated and methylated metabolites, displaying higher or lower bioactivity. To clarify the importance of the metabolism of phenolic acids, the knowledge about the bioactivity of the metabolites is extremely important. In this review, chemical features, biosynthesis and bioavailability of phenolic acids are discussed as well as the chemical and enzymatic synthesis of their metabolites. Finally, the metabolites bioactive properties are compared with that of the corresponding parental compounds.

The powerful in vitro bioactivity of Euterpe oleracea Mart. seeds and related phenolic compounds

The Euterpe oleracea Mart. (açaí) is a plant from the Amazon region, classified as "super fruit" because of its various functional properties. However, limited investigation has been performed on açaí by-products, such as seeds. Therefore, the aim of this work was to characterized the phenolic compounds of the aqueous extract of açaí seeds and further evaluate its bioactivity (antioxidant and cytotoxic activities. Only proanthocyanidins were detected, being a B-type (epi)catechin tetramer the most abundant; however, procyanidin trimmers were the most predominant form. Açaí seeds extract revealed a high antioxidant (EC50 ranging from 3.6 to 19.4 μg/mL) and cytotoxic activity, being more effective in the cervical carcinoma cell line (HeLa; GI50 = 18 μg/mL); it did not show toxicity for non-tumor cells. Açaí seeds are considered a waste and could have an added economic benefit, through the extraction of natural antioxidants, particularly proanthocyanidins, that could find applications in food and pharmaceutical industries.

Chemical composition, antioxidant activity and bioaccessibility studies in phenolic extracts of two Hericium wild edible species

Mushrooms are rich sources of bioactive compounds such as phenolic acids. When ingested, these molecules have to be released from the matrix to be transformed/absorbed by the organism, so that they can exert their bioactivity. Several in vitro methodologies have been developed in order to evaluate the bioavailability of bioactive compounds. Herein, two Hericium species were analyzed for their chemical composition and antioxidant activity. Furthermore, an in vitro digestion of the mushrooms and mushroom phenolic extracts was performed, and the digested samples were also submitted to antioxidant activity evaluation in order to evaluate the bioaccessibility of the phenolic acids identified in the samples. Hericium species showed similar chemical profiles (except for tocopherols), varying only in the concentration of the compounds. The phenolic extracts revealed higher antioxidant activity than the in vitro digested samples, meaning that this process decrease the antioxidant properties of the extract/mushroom. Nevertheless, phenolic acids were found in the digested samples, meaning that those molecules are bioaccessible.

The contribution of phenolic acids to the anti-inflammatory activity of mushrooms: Screening in phenolic extracts, individual parent molecules and synthesized glucuronated and methylated derivatives

In the present study, the ethanolic extracts of fourteen edible mushrooms were investigated for their anti-inflammatory potential in LPS (lipopolysaccharide) activated RAW 264.7 macrophages. Furthermore the extracts were chemically characterized in terms of phenolic acids and related compounds. The identified molecules (p-hydroxybenzoic, p-coumaric and cinnamic acids) and their glucuronated and methylated derivatives obtained by chemical synthesis were also evaluated for the same bioactivity, in order to establish structure-activity relationships and to comprehend the effects of in vivo metabolism reactions in the activity of the compounds. The extracts of Pleurotus ostreatus, Macrolepiota procera, Boletus impolitus and Agaricus bisporus revealed the strongest anti-inflammatory potential (EC50 values 96 ± 1 to 190 ± 6 µg/mL, and also the highest concentration of cinnamic acid (656 to 156 µg/g), which was also the individual compound with the highest anti-inflammatory activity. The derivatives of p-coumaric acid revealed the strongest properties, specially the derivative methylated in the carboxylic group (CoA-M1) that exhibited similar activity to the one showed by dexamethaxone used as anti-inflammatory standard; by contrast, the derivatives of p-hydroxybenzoic revealed the lowest inhibition of NO production. All in all, whereas the conjugation reactions change the chemical structure of phenolic acids and may increase or decrease their activity, the glucuronated and methylated derivatives of the studied compounds are still displaying anti-inflammatory activity.

Microbial production of potent phenolic-antioxidants through solid state fermentation

The agroindustrial residues including plant tissues rich in polyphenols were explored for microbial production of potent phenolics under solid state fermentation processes. The fungal strains capable of hydrolyzing tannin-rich materials were isolated from Mexican semidesert zones. These microorganisms have been employed to release potent phenolic antioxidants during the solid state fermentation of different materials (pomegranate peels, pecan nut shells, creosote bush and tar bush). This chapter includes the critical parameters for antioxidants production from selective microbes. Technical aspects of the microbial fermentation of antioxidants have also been discussed.

Fotoestabilidad de compuestos fenólicos. Evaluación de su potencial capacidad como aditivos antioxidantes. Photostability of phenolic compounds. Assessment of their potential antioxidant activity as additives.

La autooxidación es la forma de deterioro de los productos grasos más importante después de las alteraciones producidas por microorganismos, lo que representa un tema de gran interés económico para las industrias alimenticia y cosmética, ya que da lugar a la aparición de sabores y olores desagradables lo que hace que estos productos sean inaceptables para el consumidor o que reduzcan su vida útil. Dicho proceso se inicia a partir de la reacción de ácidos grasos con oxígeno y puede ser desencadenado por la exposición del producto graso a la luz medioambiental. En estos casos ocurre un proceso de fotooxidación sensibilizada, con la participación de especies reactivas de oxígeno (ROS). Por esta razón, la preservación de producto graso al efecto de las ROS es un punto de capital importancia. Las industrias intentan evitar la oxidación de los productos grasos mediante diferentes técnicas, como el envasado al vacío o en recipientes opacos, pero también utilizando antioxidantes agregados ex-profeso. En particular, los fenoles son secuestradores no enzimáticos de ROS y radicales libres. Actúan como antioxidantes secundarios o interruptores de la cadena oxidativa de lípidos, desactivando las especies reactivas en sus etapas iniciales y evitando que el proceso oxidativo continúe. Por tal motivo, para el presente Proyecto hemos escogido, como potenciales antioxidantes, dos fenoles estructuralmente relacionados con el hidroxitirosol-un antioxidante natural del aceite de oliva-. A través de reacciones fotosensibilizadas, mediante un estudio cinético, mecanístico, de relaciones estructura-reactividad y de dilucidación de fotoproductos se intentará obtener la información que satisface los objetivos específicos de este Proyecto, a saber: a) la resistencia de dHT frente a la oxidación fotopromovida, y en particular a los procesos fotosensibilizados; b) la propensión de dHT para generar especies oxidantes ya sea por irradiación directa o por interacciones específicas con estados excitados de otras moléculas; c) la influencia del medio sobre la capacidad antioxidante de dHT; d) el establecimiento de relaciones estructura-reactividad en lo referida a la actividad antioxidante de dHT. Se trabajará con distintos tipos de sensibilizadores como generadores de diferentes ROS. Para establecer y dilucidar los aspectos cinéticos y mecanísticos mencionados es necesario obtenerinformación acerca de las constantes cinéticas de los diferentes procesos involucrados. La estrategia de trabajo consistirá en abordar condiciones experimentales tales que inhiban determinadas reacciones competitivas y permitan el desarrollo de otras. Se espera que el conocimiento que se genere a partir de los resultados del presente Proyecto, constituya un importante aporte para el diseño y desarrollo de nuevos antioxidantes liposolubles que posean exacerbadas sus propiedades como fotoprotectores frente a eventuales oxidaciones a las que pueda estar expuesto un producto graso.

Simultaneous Evaluation of Intact Glucosinolates and Phenolic Compounds by UPLC-DAD-MS/MS in Brassica oleracea L. var. botrytis

A method for the simultaneous determination of intact glucosinolates and main phenolic compounds (flavonoids and sinapic acid derivatives) in Brassica oleracea L. var. botrytis was proposed. A simplified sample extraction procedure and a UPLC separation were carried out to reduce the total time of analysis. Brassica oleracea samples were added with internal standards (glucotropaeolin and rutin), and extracted with boiling methanol. Crude extracts were evaporated under nitrogen, redissolved in mobile phase and analyzed by UPLC with double detection (ESI--MRM for glucosinolates and flavonoids, and DAD for main sinapic acid derivatives). The proposed method allowed a satisfactory quantification of main native sinapic acid derivatives, flavonoids and glucosinolates with a reduced time of analysis.

Green propolis phenolic compounds act as vaccine adjuvants, improving humoral and cellular responses in mice inoculated with inactivated vaccines

Adjuvants play an important role in vaccine formulations by increasing their immunogenicity. In this study, the phenolic compound-rich J fraction (JFR) of a Brazilian green propolis methanolic extract stimulated cellular and humoral immune responses when co-administered with an inactivated vaccine against swine herpesvirus type 1 (SuHV-1). When compared to control vaccines that used aluminium hydroxide as an adjuvant, the use of 10 mg/dose of JFR significantly increased (p < 0.05) neutralizing antibody titres against SuHV-1, as well as the percentage of protected animals following SuHV-1 challenge (p < 0.01). Furthermore, addition of phenolic compounds potentiated the performance of the control vaccine, leading to increased cellular and humoral immune responses and enhanced protection of animals after SuHV-1 challenge (p < 0.05). Prenylated compounds such as Artepillin C that are found in large quantities in JFR are likely to be the substances that are responsible for the adjuvant activity.

Identification by a monoclonal antibody of a glycolipid highly expressed by cells from the human myeloid lineage.

A monoclonal antibody (MAb) HL-C5, which bound selectively to cells of the myeloid lineage tested, was derived from a fusion between P3/NS2/1-AG8 myeloma cells and splenocytes from a mouse immunized with cells of the promyelocytic leukemia line HL-60. Among a panel of 29 human cell lines derived from either hematopoietic or solid tumors, MAb HL-C5 was found to react exclusively with cells from the five differentiated acute myeloid leukemia lines, HL-60, ML1, ML2, ML3, KG-1B and not with the less differentiated myeloid lines. Fluorescence-activated cell sorter analysis of normal bone marrow samples confirmed that the reactivity of MAb HL-C5 was limited to myeloid cells, from the promyelocytic stage of differentiation to the mature granulocytes. Indirect immunoperoxidase staining of cytocentrifuge preparations of normal bone marrow and peripheral blood leukocytes confirmed these results and showed that MAb HL-C5 stained neutrophils but not eosinophils or basophils. The antigen recognized by HL-C5 was recovered in the upper phase of chloroform-methanol-water lipid extracts prepared from HL-60 cells. By competitive binding experiments, it was found that MAb HL-C5 recognizes the same antigenic determinant as MAb WGHS 29-1, which has been reported to react with glycolipids containing the sugar sequence lacto-N-fucopentaose 111. Autoradiographs of thin layer chromatograms of HL-60 glycolipid extracts which were revealed by incubation with MAb HL-C5 or WGHS 29-1 followed by the addition of 125I-labelled rabbit anti-mouse immunoglobulin antibody confirmed that the two MAbs reacted with the same or structurally very similar glycolipids.

Transcriptional profiling of Gram-positive Arthrobacter in the phyllosphere: induction of pollutant degradation genes by natural plant phenolic compounds.

Arthrobacter chlorophenolicus A6 is a Gram-positive, 4-chlorophenol-degrading soil bacterium that was recently shown to be an effective colonizer of plant leaf surfaces. The genetic basis for this phyllosphere competency is unknown. In this paper, we describe the genome-wide expression profile of A.chlorophenolicus on leaves of common bean (Phaseolus vulgaris) compared with growth on agar surfaces. In phyllosphere-grown cells, we found elevated expression of several genes known to contribute to epiphytic fitness, for example those involved in nutrient acquisition, attachment, stress response and horizontal gene transfer. A surprising result was the leaf-induced expression of a subset of the so-called cph genes for the degradation of 4-chlorophenol. This subset encodes the conversion of the phenolic compound hydroquinone to 3-oxoadipate, and was shown to be induced not only by 4-chlorophenol but also hydroquinone, its glycosylated derivative arbutin, and phenol. Small amounts of hydroquinone, but not arbutin or phenol, were detected in leaf surface washes of P.vulgaris by gas chromatography-mass spectrometry. Our findings illustrate the utility of genomics approaches for exploration and improved understanding of a microbial habitat. Also, they highlight the potential for phyllosphere-based priming of bacteria to stimulate pollutant degradation, which holds promise for the application of phylloremediation.

An improved synthesis of dansylated α-galactosylceramide and its use as a fluorescent probe for the monitoring of glycolipid uptake by cells.

A highly efficient synthesis of the biologically important fluorescent probe dansyl α-GalCer is presented. Key in our strategy is the incorporation of the fluorescent dansyl group at an early stage in the synthesis to facilitate in the monitoring and purification of intermediates via TLC and flash column chromatography, respectively, and the use of a high yielding α-selective glycosylation reaction between the phytosphingosine lipid and a galactosyl iodide donor. The ability of dansyl α-GalCer to activate iNKT cells and to serve as a fluorescent marker for the uptake of glycolipid by dendritic cells is also presented.

Mycorrhizal colonization and phenolic compounds accumulation on roots of Eucalyptus dunnii maiden inoculated with ectomycorrhizal fungi

Compatibility between Eucalyptus dunnii and the ectomycorrhizal fungi Hysterangium gardneri and Pisolithus sp. - from Eucalyptus spp. -, Rhizopogon nigrescens and Suillus cothurnatus - from Pinus spp.-, was studied in vitro. Pisolithus sp., H. gardneri and S. cothurnatus colonized the roots. Pisolithus sp. mycorrhizas presented mantle and Hartig net, while H. gardneri and S. cothurnatus mycorrhizas presented only mantle. S. cothurnatus increased phenolics level on roots. Pisolithus sp. and R. nigrescens decreased the level of these substances. The isolates from Eucalyptus seem to be more compatible towards E. dunnii than those from Pinus. The mechanisms involved could be related, at least in the cases of Pisolithus and Suillus, to the concentration of phenolics in roots.