Suchergebnisse

Phenolic compounds, which are secondary plant metabolites, are considered an integral part of the human diet. Physiological properties of dietary polyphenols have come to the attention in recent years. Especially, proanthocyanidins (ranging from dimers to decamers) have demonstrated potential interactions with biological systems, such as antiviral, antibacterial, molluscicidal, enzyme-inhibiting, antioxidant, and radical-scavenging properties. Agroindustry produces a considerable amount of phenolic-rich sources, and the ability of polyphenolic structures to interacts with other molecules in living organisms confers their beneficial properties. Cocoa wastes and grape seeds and skin byproducts are a source of several phenolic compounds, particularly mono-, oligo-, and polymeric proanthocyanidins. The aim of this work is to compare the phenolic composition of Theobroma cacao and Vitis vinifera grape seed extracts by high pressure liquid chromatography coupled to a quadrupole time-of-flight mass spectrometer and equipped with an electrospray ionization interface (HPLC-ESI-QTOF-MS) and its phenolic quantitation in order to evaluate the proanthocyanidin profile. The antioxidant capacity was measured by different methods, including electron transfer and hydrogen atom transfer-based mechanisms, and total phenolic and flavan-3-ol contents were carried out by Folin–Ciocalteu and Vanillin assays. In addition, to assess the anti-inflammatory capacity, the expression of MCP-1 in human umbilical vein endothelial cells was measured. ; This work was supported by the project AGL2011-29857-C03-02 and BFU2014-52433-C3-2-R (Spanish Ministry of Science and Innovation), as well as P10-FQM-6563 and P11-CTS-7625 (Andalusian Regional Government Council of Innovation and Science). The author Isabel Borrás Linares acknowledges financial support from the Spanish Ministry of Economy and Competitiveness (MINECO) and the European Social Fund (FSE) for the contract PTQ-13-06429. Authors are also grateful to the Universitat Rovira I Virgili for the Martí I Franquès Grant 2016PMF-POST-02 awarded to Salvador Fernández-Arroyo.

In an extensive search for bioactive compounds from plant sources, the composition of different extracts of rosemary leaves collected from different geographical zones of Serbia was studied. The qualitative and quantitative characterization of 20 rosemary (Rosmarinus officinalis) samples, obtained by microwave-assisted extraction (MAE), was determined by high performance liquid chromatography coupled to electrospray quadrupole-time of flight mass spectrometry (HPLC–ESI-QTOF-MS). The high mass accuracy and true isotopic pattern in both MS and MS/MS spectra provided by the QTOF-MS analyzer enabled the characterization of a wide range of phenolic compounds in the extracts, including flavonoids, phenolic diterpenes and abietan-type triterpenoids, among others. According to the data compiled, rosemary samples from Sokobanja presented the highest levels in flavonoids and other compounds such as carnosol, rosmaridiphenol, rosmadial, rosmarinic acid, and carnosic acid. On the other hand, higher contents in triterpenes were found in the extracts of rosemary from Gložan (Vojvodina). ; This work was financially supported by the Ministry of Education, Science and Technological Development of the Republic of Serbia through a national project (Project Number TR 31014) and through scientific and technological cooperation between the Republic of Serbia and Spain (Project Number RE451-03-02635/2011-14/4). The authors are also grateful to the Spanish Ministry of Science and Innovation for the project AGL2011-29857-C03-02 and the grant FPI BES-2009-028128, Andalusian Regional Government Council of Innovation and Science for the Excellence Projects P09-CTS-4564, P10-FQM-6563 and P11-CTS-7625

Lippia citriodora has been demonstrated to have a wide variety of phytochemicals which provide benefits to human health acting as antioxidants or anti-obesogenics. In this study, these phytochemicals were recovered using a microwave-assisted technology and applying optimal conditions and microencapsulated using spray drying. In this study, two di erent carbohydrates, maltodextrin (MD) and inulin (IN), were compared as carriers in the encapsulation procedure. The spray drying process was optimized by using a response surface methodology (RSM) based on a central composite design 22, where air inlet temperature and the sample:encapsulating agent ratio (S:EA) were selected as independent variables. Both designs were analyzed equally to evaluate di erences between each carrying agent on polar compounds' encapsulation (process yield (Y%), encapsulation e ciency (EE%) and recovery of compounds (R%)) during the spray drying. The EE% and R% of each polar compound was monitored by High Performance Liquid Chromatography coupled to Time-of-Flight mass spectrometer by electrospray interface (HPLC-ESI-TOF-MS). The results showed that the use of IN as a carrier increased the powder recovered and the recovery of polar compounds after the spray dry process, whereas MD achieved a higher encapsulation efficiency. ; Spanish Government RTI2018-096724-B-C22

The work was supported by the project P18-TP-3589 (Regional Ministry of Economy, Knowledge, Enterprise and Universities of Andalusia). The author A.R.-G. would like to thank the project P18-TP-3589, University of Granada and AGR274 group for the contract (265).The author A.G.-V. would like to thank the Spanish National Youth Guarantee Implementation Plan for her contract. The author M.d.C.V.-A. would like to thank the Spanish Ministry of Science,Innovation, and Universities for the grant FPU19/01146. The author M.d.l.L.C.-G. would like to thank the Regional Ministry of Economy, Knowledge, Enterprise and Universities of Andalusia for the contract for Young Researchers (PAIDI) at the University of Granada. ; The increasing production of tropical fruits followed by their processing results in tons of waste, such as skins or seeds. However, these by-products have been reported to be rich in bioactive compounds (BACs) with excellent properties of interest in the cosmeceutical industry: antioxidant, anti-aging, anti-inflammatory, antimicrobial and photoprotective properties. This review summarizes the tropical fruits most produced worldwide, their bioactive composition and the most important and studied therapeutic properties that their by-products can contribute to skin health, as well as the different approaches for obtaining these compounds using techniques by conventional (Soxhlet, liquid-liquid extraction or maceration) and non-conventional extractions (supercritical fluid extraction (SFE), ultrasound-assisted extraction (UAE), microwave-assisted extraction (MAE), pressurized liquid extraction (PLE) and two-phase aqueous system), followed by their identification by HPLC-MS or GC-MS analysis. Moreover, this work encompasses several studies that may prove the effects of seeds and skins from tropical fruits against oxidative stress, hyperpigmentation, acne, aging or UV radiation. Therefore, the investigation of functional components present in tropical fruit by-products under a circular bioeconomy model could be of great interest for the cosmeceutical industry and a very promising option for obtaining new cosmeceutical formulations. ; Regional Ministry of Economy, Knowledge, Enterprise and Universities of Andalusia P18-TP-3589 ; Spanish National Youth Guarantee Implementation Plan P18-TP-3589 ; University of Granada AGR274 group 265 ; Spanish National Youth Guarantee Implementation Plan ; Spanish Government FPU19/01146 AGR274

Previous findings on the capacity of Hibiscus sabdariffa (HS) polyphenols to ameliorate metabolic disturbances justify the necessity of studies oriented to find the potential metabolites responsible for such an effect. The present study examined the intestinal epithelial membrane permeability of polyphenols present in a phenolic-enriched Hibiscus sabdariffa extract (PEHS), free and encapsulated, using the Caco-2 cell line. Additionally, selected polyphenols (quercetin, quercetin-3-glucoside, quercetin-3-glucuronide, and N-feruloyltyramine) were also studied in the same absorption model. The powerful analytical platform used ultra-high-performance liquid chromatography coupled with ultra-high-resolution quadrupole time-of-flight mass spectrometry (UHPLC-ESI-UHR-Qq-TOF-MS), and enabled the characterization of seven new compounds in PEHS. In the permeation study, only a few compounds were able to cross the cell monolayer and the permeability was lower when the extract was in an encapsulated form. Pure compounds showed a moderate absorption in all cases. Nevertheless, these preliminary results may need further research to understand the complete absorption mechanism of Hibiscus polyphenols. ; This work was supported by projects AGL2011-29857-C03-02 and AGL2011-29857-C03-03 (Spanish Ministry of Science and Innovation), in addition to P10-FQM-6563 and P11-CTS-7625 (Andalusian Regional Government Council of Innovation and Science), PROMETEO/2012/007 and ACOMP/2013/093 (Generalitat Valenciana), and CIBER (CB12/03/30038, Fisiopatología de la Obesidad y la Nutrición, CIBERobn, Instituto de Salud Carlos III). The authors are grateful to the Spanish Ministry of Science and Innovation for the grant FPI (BES-2009-028128), and the Spanish Ministry of Economy and Competitiveness (MINECO) in association with the European Social Fund (FSE) for the contract PTQ-13-06429. MH is a recipient of a VALi + D fellowship from GV (ACIF/2010/162). The authors are especially grateful to Bruker Daltonik GmbH (Bremen, Germany) for their help and support during this research.

Marine compounds are a potential source of new anticancer drugs. In this study, the antiproliferative effects of 20 invertebrate marine extracts on three colon cancer cell models (HGUE-C-1, HT-29, and SW-480) were evaluated. Extracts from two nudibranchs (Phyllidia varicosa, NA and Dolabella auricularia, NB), a holothurian (Pseudocol ochirus violaceus, PS), and a soft coral (Carotalcyon sp., CR) were selected due to their potent cytotoxic capacities. The four marine extracts exhibited strong antiproliferative effects and induced cell cycle arrest at the G2/Mtransition, which evolved into early apoptosis in the case of the CR, NA, and NB extracts and necrotic cell death in the case of the PS extract. All the extracts induced, to some extent, intracellular ROS accumulation, mitochondrial depolarization, caspase activation, and DNA damage. The compositions of the four extracts were fully characterized via HPLC-ESI-TOF-MS analysis, which identified up to 98 compounds. We propose that, among the most abundant compounds identified in each extract, diterpenes, steroids, and sesqui- and seterterpenes (CR); cembranolides (PS); diterpenes, polyketides, and indole terpenes (NA); and porphyrin, drimenyl cyclohexanone, and polar steroids (NB) might be candidates for the observed activity. We postulate that reactive oxygen species (ROS) accumulation is responsible for the subsequent DNA damage, mitochondrial depolarization, and cell cycle arrest, ultimately inducing cell death by either apoptosis or necrosis. ; This research was funded by projects AGL2015-67995-C3-1-R, AGL2015-67995-C3-2-R AGL2015-67995-C3-3-R, RTI2018-096724-B-C21, and 2018-096724-B-C22 from the Spanish Ministry of Science, Innovation and Universities; Project P11-CTS-7625 from Andalusian Regional Government Council of Innovation and Science; projects PROMETEO/2012/007, PROMETEO/2016/006, and VALi+D fellowship (ACIF/2015/158) from Generalitat Valenciana to VR-Tand CIBER (CB12/03/30038, Fisiopatología de la Obesidad y la Nutrición, CIBERobn).

Marine compounds are a potential source of new anticancer drugs. In this study, the antiproliferative e_ects of 20 invertebrate marine extracts on three colon cancer cell models (HGUE-C-1, HT-29, and SW-480) were evaluated. Extracts from two nudibranchs (Phyllidia varicosa, NA and Dolabella auricularia, NB), a holothurian (Pseudocol ochirus violaceus, PS), and a soft coral (Carotalcyon sp., CR) were selected due to their potent cytotoxic capacities. The four marine extracts exhibited strong antiproliferative e_ects and induced cell cycle arrest at the G2/Mtransition, which evolved into early apoptosis in the case of the CR, NA, and NB extracts and necrotic cell death in the case of the PS extract. All the extracts induced, to some extent, intracellular ROS accumulation, mitochondrial depolarization, caspase activation, and DNA damage. The compositions of the four extracts were fully characterized via HPLC-ESI-TOF-MS analysis, which identified up to 98 compounds. We propose that, among the most abundant compounds identified in each extract, diterpenes, steroids, and sesqui- and seterterpenes (CR); cembranolides (PS); diterpenes, polyketides, and indole terpenes (NA); and porphyrin, drimenyl cyclohexanone, and polar steroids (NB) might be candidates for the observed activity. We postulate that reactive oxygen species (ROS) accumulation is responsible for the subsequent DNA damage, mitochondrial depolarization, and cell cycle arrest, ultimately inducing cell death by either apoptosis or necrosis ; This research was funded by projects AGL2015-67995-C3-1-R, AGL2015-67995-C3-2-R AGL2015-67995-C3-3-R, RTI2018-096724-B-C21, ; and 2018-096724-B-C22 from the Spanish Ministry of Science, Innovation and Universities; ; Project P11-CTS-7625 from Andalusian Regional Government Council of Innovation and Science ; projects PROMETEO/2012/007, PROMETEO/2016/006, and VALi+D fellowship (ACIF/2015/158) from Generalitat Valenciana to VR-Tand CIBER (CB12/03/30038

Posidonia oceanica waste biomass has been valorised to produce extracts by means of different methodologies and their bioactive properties have been evaluated. Water-based extracts were produced using ultrasound-assisted and hot water methods and classified according to their ethanol-affinity (E1: ethanol soluble; E2: non-soluble). Moreover, a conventional protocol with organic solvents was applied, yielding E3 extracts. Compositional and structural characterization confirmed that while E1 and E3 extracts were mainly composed of minerals and lipids, respectively, E2 extracts were a mixture of minerals, proteins and carbohydrates. All the extracts showed remarkably high antioxidant capacity, which was not only related to phenolic compounds but also to the presence of proteins and polysaccharides. All E2 and E3 extracts inhibited the growth of several foodborne fungi, while only E3 extracts decreased substantially the infectivity of feline calicivirus and murine norovirus. These results show the potential of P. oceanica waste biomass for the production of bioactive extracts. ; This work was financially supported by the project GV/2018//149, the "Agencia Estatal de Investigación" and cofunded by the European Union's Horizon 2020 research and innovation programme (ERA-Net SUSFOOD2). Marta Martinez-Sanz is recipient of a Juan de la Cierva (IJCI-2015-23389) contract from the Spanish Ministry of Economy, Industry and Competitiveness.

Background: Imbalances in the functional binding of fibroblast growth factors (FGFs) to their receptors (FGFRs) have consequences for cell proliferation and differentiation that in chondrocytes may lead to degraded cartilage. The toxic, proinflammatory, and oxidative response of cytokines and FGFs can be mitigated by dietary polyphenols. Objective: We explored the possible effects of polyphenols in the management of osteoarticular diseases using a model based on the transduction of a mutated human FGFR3 (G380R) in murine chondrocytes. This mutation is present in most cases of skeletal dysplasia and is responsible for the overexpression of FGFR3 that, in the presence of its ligand, FGF9, results in toxic effects leading to altered cellular growth. Design: Different combinations of dietary polyphenols derived from plant extracts were assayed in FGFR3 (G380R) mutated murine chondrocytes, exploring cell survival, chloride efflux, extracellular matrix (ECM) generation, and grade of activation of mitogen-activated protein kinases. Results: Bioactive compounds from Hibiscus sabdariffa reversed the toxic effects of FGF9 and restored normal growth, suggesting a probable translation to clinical requests in humans. Indeed, these compounds activated the intracellular chloride efflux, increased ECM generation, and stimulated cell proliferation. The inhibition of mitogen-activated protein kinase phosphorylation was interpreted as the main mechanism governing these beneficial effects. Conclusions: These findings support the rationale behind the encouragement of the development of drugs that repress the overexpression of FGFRs and suggest the dietary incorporation of supplementary nutrients in the management of degraded cartilage. ; The authors are grateful for the constant support provided by the Hospital Universitari de Sant Joan and the Universitat Rovira i Virgili. Salvador Fernández-Arroyo is the recipient of a Sara Borrell grant (CD12/00672) from the Instituto de Salud Carlos III, Madrid, Spain. The authors also thank the Andalusian Regional Government Council of Innovation and Science for the Excellence Project P11-CTS-7625 and Generalitat Valenciana for the project PROMETEO/2012/007. This work was also supported by projects of the Fundación Areces and the Fundación MAGAR.

We are grateful to Custodio Borrego for giving us free use of the photograph he took of EVOO and olive trees in Granada (Spain), which have been included in Figure 7. This work has been awarded with the IV Premio Internacional Castillo de Canena de Investigación Oleícola 'LUIS VAÑÓ'(IV Edition of Castillo de Canena LUIS VAÑÓ Award for Research on Olive Cultivation and Olive Oil; UC Davis Olive Center, Castillo de Canena, and Universidad de Jaén). ; The authors would like to thank Dr Kenneth McCreath for editorial support. We are greatly indebted to Prof Robert A. Weinberg (Whitehead Institute for Biomedical Research, Cambridge, MA) for providing the HMLERshCntrol/HMLERshEcad cells used in this work. ; Targeting tumor-initiating, drug-resistant populations of cancer stem cells (CSC) with phytochemicals is a novel paradigm for cancer prevention and treatment. We herein employed a phenotypic drug discovery approach coupled to mechanism-of-action profiling and target deconvolution to identify phenolic components of extra virgin olive oil (EVOO) capable of suppressing the functional traits of CSC in breast cancer (BC). In vitro screening revealed that the secoiridoid decarboxymethyl oleuropein aglycone (DOA) could selectively target subpopulations of epithelial-like, aldehyde dehydrogenase (ALDH)-positive and mesenchymal-like, CD44+CD24−/low CSC. DOA could potently block the formation of multicellular tumorspheres generated from single-founder stem-like cells in a panel of genetically diverse BC models. Pretreatment of BC populations with noncytotoxic doses of DOA dramatically reduced subsequent tumor-forming capacity in vivo. Mice orthotopically injected with CSC-enriched BC-cell populations pretreated with DOA remained tumor-free for several months. Phenotype microarray-based screening pointed to a synergistic interaction of DOA with the mTOR inhibitor rapamycin and the DNA methyltransferase (DNMT) inhibitor 5-azacytidine. In silico computational studies indicated that DOA binds and inhibits the ATP-binding kinase domain site of mTOR and the S-adenosyl-l-methionine (SAM) cofactorbinding pocket of DNMTs. FRET-based Z-LYTE™ and AlphaScreen-based in vitro assays confirmed the ability of DOA to function as an ATP-competitive mTOR inhibitor and to block the SAM-dependent methylation activity of DNMTs. Our systematic in vitro, in vivo and in silico approaches establish the phenol-conjugated oleoside DOA as a dual mTOR/DNMT inhibitor naturally occurring in EVOO that functionally suppresses CSC-like states responsible for maintaining tumorinitiating cell properties within BC populations. ; This work was supported by grants from the Ministerio de Ciencia e Innovación (Grant SAF2016-80639-P to J.A.M.), Plan Nacional de I+D+I, Spain, the Agència de Gestió d'Ajuts Universitaris i de Recerca (AGAUR; Grant 2014 SGR229 to J.A.M.), Departament d'Economia i Coneixement, Catalonia, Spain, the Andalusian Regional Government Council of Innovation and Science (Grant P11-CTS-7625 to A.S.-C.), the Ministerio de Economía, Industria y Competitividad, Spain (Grants AGL2015- 67995-C2-3-R and AGL2015-67995-C3-1-R to A.S.-C. and V.M.) and Conselleria d'Educació, Investigació, Cultura I Esport, Generalitat Valenciana, Spain (Grant PROMETEO/2016/006 to V.M). E.C. is supported by the Sara Borrell post doctoral contract (CD15/00033) from the Ministerio de Sanidad y Consumo, Fondo de Investigación Sanitaria (FIS), Spain.