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Bioacessibility studies related to antioxidant phenolic extracts from two edible species of the genus Hericium

Publication . Heleno, Sandrina A.; Barros, Lillian; Martins, Anabela; Queiroz, Maria João R.P.; Morales, Patricia; Fernández-Ruiz, Virginia; Ferreira, Isabel C.F.R.

Mushrooms are rich sources of nutrients, but also of bioactive molecules such as phenolic compounds. Phenolic acids are among the major low molecular weight bioactive components usually found in mushroom species, contributing to their antioxidant properties [1]. Following the ingestion, these molecules have to be released from the food matrix and further transformed by the organism, to became accessible and exert their bioactive properties [2]. Several in vitro methodologies have been developed in arder to evaluate the bioacessibility of bioactive compounds, proving to be easy, cheap and reproducible, being possible to evaluate the digestivo stability of the food constituents [3]. Herein, two wild edible mushroom species originated from Northeast Portugal (Herícium erinaceus (Buli.) Persoon and Hericium coralloides (Scop.) Pers.), were analysed for their nutritional value, detailed chemical composition and antioxidant properties. Furthermore, in arder to evaluate the bioaccessibiljty of the compounds responsible for the mushrooms antioxidant properties, a digestion of the dry powder and phenolic extracts was performed under in vitro conditions. The Hericium species showed similar chemical profiles (except for tocopherols), varying only in the concentration of these compounds. The phenolic extracts presented the highest antioxidant activity that is in agreement with the highest concentration in phenolic acids found in those samples before in vitro digestion. This means that after in vitro gastrointestinal digestion, the bioactive compounds can suffer structural changes (losing the OH groups responsible for the antioxidant activity) that decreased the antioxidant properties. Nevertheless, they are bioaccessible and still display antioxidant activity.

2015Conference object

Open access

Wild Roman chamomile extracts and phenolic compounds: enzymatic assays and molecular modelling studies with VEGFR-2 tyrosine kinase

Publication . Guimarães, Rafaela; Calhelha, Ricardo C.; Froufe, Hugo J.C.; Abreu, Rui M.V.; Carvalho, Ana Maria; Queiroz, Maria João R.P.; Ferreira, Isabel C.F.R.

Angiogenesis is a process by which new blood vessels are formed from the pre-existing vasculature, and it is a key process that leads to tumour development. Some studies have recognized phenolic compounds as chemopreventive agents; flavonoids, in particular, seem to suppress the growth of tumor cells modifying the cell cycle. Herein, the antiangiogenic activity of Roman chamomile (Chamaemelum nobile L.) extracts (methanolic extract and infusion) and the main phenolic compounds present (apigenin, apigenin-7-O-glucoside, caffeic acid, chlorogenic acid, luteolin, and luteolin-7-O-glucoside) was evaluated through enzymatic assays using the tyrosine kinase intracellular domain of the Vascular Endothelium Growth Factor Receptor-2 (VEGFR-2), which is a transmembrane receptor expressed fundamentally in endothelial cells involved in angiogenesis, and molecular modelling studies. The methanolic extract showed a lower IC50 value (concentration that provided 50% of VEGFR-2 inhibition) than the infusion, 269 and 301 μg mL(-1), respectively. Regarding phenolic compounds, luteolin and apigenin showed the highest capacity to inhibit the phosphorylation of VEGFR-2, leading us to believe that these compounds are involved in the activity revealed by the methanolic extract.

2016Journal article

Open access

Synthesis, antiangiogenesis evaluation and molecular docking studies of 1-aryl-3-[(thieno[3,2-b]pyridin-7-ylthio)phenyl]ureas: Discovery of a new substitution pattern for type II VEGFR-2 Tyr kinase inhibitors

Publication . Machado, Vera A.; Peixoto, Daniela; Costa, Raquel; Froufe, Hugo J.C.; Calhelha, Ricardo C.; Abreu, Rui M.V.; Ferreira, Isabel C.F.R.; Soares, Raquel; Queiroz, Maria João R.P.

The synthesis and biological evaluation of novel 1-aryl-3-[2-, 3- or 4-(thieno[3,2-b]pyridin-7-ylthio)phenyl] ureas 3, 4 and 5 as VEGFR-2 tyrosine kinase inhibitors, are reported. The 1-aryl-3-[3-(thieno[3,2-b]- pyridin-7-ylthio)phenyl]ureas 4a–4h, with the arylurea in the meta position to the thioether, showed the lowest IC50 values in enzymatic assays (10–206 nM), the most potent compounds 4d–4h (IC50 10– 28 nM) bearing hydrophobic groups (Me, F, CF3 and Cl) in the terminal phenyl ring. A convincing rationalization was achieved for the highest potent compounds 4 as type II VEGFR-2 inhibitors, based on the simultaneous presence of: (1) the thioether linker and (2) the arylurea moiety in the meta position. For compounds 4, significant inhibition of Human Umbilical Vein Endothelial Cells (HUVECs) proliferation (BrdU assay), migration (wound-healing assay) and tube formation were observed at low concentrations. These compounds have also shown to increase apoptosis using the TUNEL assay. Immunostaining for total and phosphorylated (active) VEGFR-2 was performed by Western blotting. The phosphorylation of the receptor was significantly inhibited at 1.0 and 2.5 lM for the most promising compounds. Altogether, these findings point to an antiangiogenic effect in HUVECs.

2015Journal article

Open access

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

Publication . Taofiq, Oludemi; Calhelha, Ricardo C.; Heleno, Sandrina A.; Barros, Lillian; Martins, Anabela; Santos-Buelga, Celestino; Queiroz, Maria João R.P.; Ferreira, Isabel C.F.R.

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.

2015Journal article

Restricted access