@article{miranda_sarandy_altoe_bastos_melo_novaes_esposito_goncalves_2024, title={Antioxidant and Anti-Inflammatory Potential of <i>Brassica oleracea</i> Accelerates Third-Degree Burn Healing in Rats}, volume={11}, ISSN={["2079-9284"]}, url={https://doi.org/10.3390/cosmetics11010027}, DOI={10.3390/cosmetics11010027}, abstractNote={Burns account for more than 265,000 deaths per year in the world, mainly associated with infections. Therefore, the shorter the healing time, the better the prognosis. Based on this, the objective of the present study was to investigate the effect of an ointment based on Brassica oleracea var. capitata extract in the third-degree healing process. Twenty-five male Wistar rats (335 ± 16 g, three months of life) were individualized in cages with food and water ad libitum. After anesthesia, two circular third-degree burn wounds (12 mm in diameter) were made on the animals, which were randomly separated into five treatments (n = 5/group), i.e., SAL: saline solution 0.9%; OV: ointment vehicle; SS: silver sulfadiazine 1%; PB1: 10% B. oleracea extract; and PB2: 20% B. oleracea extract. The animals were treated with the ointment daily for eight days. Every four days, the area and the wound contraction index were evaluated. Tissue samples were taken for histopathological analysis (cellularity, blood vessels, and extracellular matrix components) and analysis of oxidative/nitrosative status (antioxidant enzymes, lipid, and protein oxidation markers, as well as nitric oxide (NO) and hydrogen peroxide (H2O2)). The ointment based on B. oleracea var. capitata at 10 and 20% concentrations increased the number of cells, blood vessels, and fibrous components of the extracellular matrix and the activity of antioxidant enzymes, promoting a fast and efficient cutaneous repair in third-degree burn wounds.}, number={1}, journal={COSMETICS}, author={Miranda, Lyvia Lopes and Sarandy, Mariaurea Matias and Altoe, Luciana Schulthais and Bastos, Daniel Silva Sena and Melo, Fabiana Cristina Silveira Alves and Novaes, Romulo Dias and Esposito, Debora Araujo and Goncalves, Reggiani Vilela}, year={2024}, month={Feb} }
 @article{dantas araujo_xavier-santos_silva_lima_schlamb_fernandes-pedrosa_silva junior_araujo junior_rathinasabapathy_moncada_et al._2023, title={Gel formulated with Bryophyllum pinnatum leaf extract promotes skin wound healing in vivo by increasing VEGF expression: A novel potential active ingredient for pharmaceuticals}, volume={13}, ISSN={["1663-9812"]}, DOI={10.3389/fphar.2022.1104705}, abstractNote={Bryophyllumpinnatum(Crassulaceae) is used in traditional medicine for treating skin wounds. In our previous study, a topical gel containingB. pinnatumaqueous leaf extract showed a preclinical anti-inflammatory effect inin vivoacute edema models. In continuation, the present study aims to evaluate the phytochemical content and the stability of a formulation in gel containingB. pinnatumaqueous leaf extract and its healing properties and mechanism of action through an experimental model of induction of skin wounds in rats andin vitroassays. The animals were treated topically for 7 or 14 days with a formulation in gel containing extract at 5% or a placebo or Fibrinase®in cream. In addition, to establish some quality control parameters, the total phenolic content (TPC), total flavonoid content (TFC), and a study focusing on the phytochemical and biological stability of a gel for 30 days at two different conditions (room temperature and 40°C/75% RH) were performed. Gel formulation containing extract showed a TPC and TFC of 2.77 ± 0.06 mg of gallic acid/g and 1.58 ± 0.03 mg of quercetin/g, respectively. Regarding the stability study, the formulation in gel showed no significant change in the following parameters: pH, water activity, chromatographic profile, and the content of the major compound identified in the extract. The gel formulation containing extract stimulated skin wound healing while reducing the wound area, as well as decreasing the inflammatory infiltrate, reducing the levels of IL-1β and TNF-α, and stimulating angiogenesis with increased expression of VEGF, an effect similar to Fibrinase. In conclusion, the gel formulation containing extract exhibited relevant skin wound healing properties and, therefore, has the potential to be applied as a novel active ingredient for developing wound healing pharmaceuticals.}, journal={FRONTIERS IN PHARMACOLOGY}, author={Dantas Araujo, Edilane Rodrigues and Xavier-Santos, Jacinthia Beatriz and Silva, Valeria Costa and Lima, Juliana Bessa and Schlamb, Jade and Fernandes-Pedrosa, Matheus de Freitas and Silva Junior, Arnobio Antonio and Araujo Junior, Raimundo Fernandes and Rathinasabapathy, Thirumurugan and Moncada, Marvin and et al.}, year={2023}, month={Jan} }
 @article{silva_guerra_araujo_schlamb_silva_tavares_dantas-medeiros_abreu_tavares_araujo junior_et al._2023, title={Phenolic-rich extract of Nopalea cochenillifera attenuates gastric lesions induced in experimental models through inhibiting oxidative stress, modulating inflammatory markers and a cytoprotective effect}, volume={2}, ISSN={["2042-650X"]}, DOI={10.1039/d2fo03735a}, abstractNote={
            Nopalea cochenillifera (Cactaceae), popularly known as “palma” or “palma doce”, is from Mexico, but it was widely introduced in Brazil through crops.}, journal={FOOD & FUNCTION}, author={Silva, Elaine Cristine Souza and Guerra, Gerlane Coelho Bernardo and Araujo, Edilane Rodrigues Dantas and Schlamb, Jade and Silva, Valeria Costa and Tavares, Emanuella de Aragao and Dantas-Medeiros, Renato and Abreu, Lucas Silva and Tavares, Josean Fechine and Araujo Junior, Raimundo Fernandes and et al.}, year={2023}, month={Feb} }
 @misc{mattosinhos_sarandy_novaes_esposito_goncalves_2022, title={Anti-Inflammatory, Antioxidant, and Skin Regenerative Potential of Secondary Metabolites from Plants of the Brassicaceae Family: A Systematic Review of In Vitro and In Vivo Preclinical Evidence (Biological Activities Brassicaceae Skin Diseases)}, volume={11}, ISSN={["2076-3921"]}, url={https://doi.org/10.3390/antiox11071346}, DOI={10.3390/antiox11071346}, abstractNote={The Brassicaceae family constitutes some of the most well-studied natural products in the world, due to their anti-inflammatory, anti-oxidative, and pro-regenerative properties as well as their ubiquitous distribution across the world. To evaluate the potential efficacy of the Brassicaceae family in the treatment of inflammatory skin disorders and wounds, based on preclinical evidence from in vivo and in vitro studies. This systematic review was performed according to the PRISMA guidelines, using a structured search on the PubMed-Medline, Scopus, and Web of Science platforms. The studies included were those that used murine models and in vitro studies to investigate the effect of Brassicaceae on skin disorders. Bias analysis and methodological quality assessments were examined through SYRCLE’s RoB tool. Brassicaceae have shown positive impacts on inflammatory regulation of the skin, accelerating the wound healing process, and inhibiting the development of edema. The studies showed that the Brassicaceae family has antioxidant activity and effects on the modulation of cyclooxygenase 2 and the nuclear factor kappa β (NFκβ) pathway. The secondary metabolites present in Brassicas are polyphenols (68.75%; n = 11), terpenes/carotenoids (31.25%; n = 5), and glycosylates (25%; n = 4), which are responsible for their anti-inflammatory, healing, and antioxidant effects. In addition, the current evidence is reliable because the bias analysis showed a low risk of bias. Our review indicates that compounds derived from Brassicaceae present exceptional potential to treat inflammatory skin diseases and accelerate cutaneous wound healing. We hope that our critical analysis can help to expedite clinical research and to reduce methodological bias, thereby improving the quality of evidence in future research. The registration number on the Prospero platform is CRD42021262953.}, number={7}, journal={ANTIOXIDANTS}, author={Mattosinhos, Patricia da Silva and Sarandy, Mariaurea Matias and Novaes, Romulo Dias and Esposito, Debora and Goncalves, Reggiani Vilela}, year={2022}, month={Jul} }
 @article{xiong_bonney_goncalves_esposito_2022, title={Brassinosteroids control the inflammation, oxidative stress and cell migration through the control of mitochondrial function on skin regeneration}, volume={307}, ISSN={["1879-0631"]}, DOI={10.1016/j.lfs.2022.120887}, abstractNote={Brassinosteroids (BRs) are the class of phytohormones with great importance in agriculture and potential diverse effects on human welfare, including skin disease treatment. In this sense, BRs are a promising tool for promoting skin regeneration.Therefore, the objective of the present work was to analyze the effect of BRs in wound repair, mainly the inflammatory and proliferative phases, and their influence on migratory abilities in human dermal fibroblasts (HDFa), and consequently understand the mitochondrial metabolism.We measured nine natural and synthetic BRs for the inflammatory response in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. We further evaluated the migration activity in HDFa modeling promotion of wound closure after BRs exposure. In addition, we evaluated the 84 gene profiles linked to wound healing response using RT2 Profiler PCR Array and examined cellular bioenergetics using an extracellular flux analyzer.Results showed that LPS-induced cells had around 10 % lower reactive oxygen species and nitric oxide accumulation when treated with some BRs compounds. HDFa treated with homobrassinolide-based and homocastasterone-based compounds resulted in the greatest migratory activity and presents the best results for mitochondrial responses.Together, these results provided strong evidence for BRs' ability to promote skin health, particularly through contributions to both reducing excessive oxidative stress and controlling the inflammation process resulting in the best HDFa cell migration through the control of mitochondrial function.}, journal={LIFE SCIENCES}, author={Xiong, Jia and Bonney, Sierra and Goncalves, Reggiani Vilela and Esposito, Debora}, year={2022}, month={Oct} }
 @article{goncalves_freitas_esposito_2022, title={Cellular and Molecular Mechanisms of Oxidative Stress in Wound Healing}, volume={2022}, ISSN={["1942-0994"]}, url={https://doi.org/10.1155/2022/9785094}, DOI={10.1155/2022/9785094}, journal={OXIDATIVE MEDICINE AND CELLULAR LONGEVITY}, author={Goncalves, Reggiani Vilela and Freitas, Mariella Bontempo and Esposito, Debora}, year={2022}, month={Jun} }
 @article{goncalves_sarandy_esposito_gouveia peluzio_2022, title={Mechanisms, Biomarkers, and Therapeutics Involved in Inflammatory Disorders and Tissue Repair 2021}, volume={2022}, ISSN={["1942-0994"]}, url={https://doi.org/10.1155/2022/9806128}, DOI={10.1155/2022/9806128}, journal={OXIDATIVE MEDICINE AND CELLULAR LONGEVITY}, publisher={Hindawi Limited}, author={Goncalves, Reggiani Vilela and Sarandy, Mariaurea Matias and Esposito, Debora and Gouveia Peluzio, Maria do Carmo}, year={2022}, month={Mar} }
 @article{pereira silva_cavalcanti inacio_silva_silva_luz_almeida_moraes_esposito_ferreira_zucolotto_2022, title={The First Optimization Process from Cultivation to Flavonoid-Rich Extract from Moringa oleifera Lam. Leaves in Brazil}, volume={11}, ISSN={["2304-8158"]}, url={https://www.mdpi.com/2304-8158/11/10/1452}, DOI={10.3390/foods11101452}, abstractNote={Flavonoids are significant antioxidant and anti-inflammatory agents and have multiple potential health applications. Moringa oleifera is globally recognized for its nutritional and pharmacological properties, correlated to the high flavonoid content in its leaves. However, the bioactive compounds found in plants may vary according to the cultivation, origin, season, and extraction process used, making it difficult to extract reliable raw material. Hence, this study aimed to standardize the best cultivation and harvest season in Brazil and the best extraction process conditions to obtain a flavonoid-rich extract from M. oleifera as a final product. Firstly, ultrasound-assisted extraction (UAE) was optimized to reach the highest flavonoid content by three-level factorial planning and response surface methodology (RSM). The optimal cultivation condition was mineral soil fertilizer in the drought season, and the optimized extraction was with 80% ethanol and 13.4 min of extraction time. The flavonoid-rich extract was safe and significantly decreased reactive oxygen species (ROS) and nitric oxide (NO) in LPS-treated RAW 264.7 cells. Lastly, the major flavonoids characterized by HPLC-ESI-QTRAP-MS/MS were compounds derived from apigenin, quercetin, and kaempferol glycosides. The results confirmed that it was possible to standardize the flavonoid-rich extract leading to a standardized and reliable raw material extracted from M. oleifera leaves.}, number={10}, journal={FOODS}, author={Pereira Silva, Larissa Marina and Cavalcanti Inacio, Maria Raquel and Silva, Gualter Guenter and Silva, Jucier Magson and Luz, Jefferson Romaryo and Almeida, Maria das Gracas and Moraes, Edgar Perin and Esposito, Debora and Ferreira, Leandro De Santis and Zucolotto, Silvana Maria}, year={2022}, month={May} }
 @article{editorial: cosmeceuticals from medicinal plants_2020, url={http://dx.doi.org/10.3389/fphar.2020.01149}, DOI={10.3389/fphar.2020.01149}, abstractNote={1 Department of Plant and Soil Sciences, Faculty of Natural and Agricultural Sciences, University of Pretoria, Pretoria, South Africa, 2 School of Natural Resources, University of Missouri, Columbia, MO, United States, 3 College of Pharmacy, JSS Academy of Higher Education and Research, Mysuru, India, 4 Department of Health Sciences, Faculty of Science, University of Mauritius, Réduit, Mauritius, 5 Department of Animal Science, North Carolina State University, Raleigh, NC, United States, 6 Department of Pharmacology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa, 7 Department of Biology, Science Faculty, Selcuk University, Konya, Turkey}, journal={Frontiers in Pharmacology}, year={2020}, month={Jul} }
 @article{lily steroidal glycoalkaloid promotes early inflammatory resolution in wounded human fibroblasts_2020, url={http://dx.doi.org/10.1016/j.jep.2020.112766}, DOI={10.1016/j.jep.2020.112766}, abstractNote={The bulbs and flowers of plants from the Lilium genus have historically been used in Asian and Greco-Roman medicine to treat burns and promote skin healing. To evaluate a steroidal glycoalkaloid isolated from Easter lily bulbs for its potential wound healing promoting properties. A lily-derived steroidal glycoalkaloid (LSGA), (22R, 25R)-spirosol-5-en-3β-yl O-α-L-rhamnopyranosyl-(1→2)-β-D-glucopyranosyl-(1→4)-β-D-glucopyranoside, was isolated from Easter lily bulbs, and its structure was confirmed by LC-MS and NMR spectrometry. LSGA effects on wound scratch closure were evaluated in a primary human dermal fibroblast cell culture, and the changes in gene expression profiles were quantitated using an 84 wound-related gene qPCR microarray. LSGA promoted migration of dermal fibroblasts into the wounded area. The treatment was associated with a rapid upregulation of early inflammatory (CD40LG, CXCL11, IFNG, IL10, IL2 and IL4), cell growth (CSF3 and TNF) and remodeling (CTSG, F13A1, FGA, MMP and PLG) genes both in the wounded and unwounded cells treated with LSGA. A selective decrease in gene expression profiles associated with inflammatory (CXCL2 and CCL7) and remodeling (MMP7 and PLAT) phases was observed in wounded cells treated with LSGA, in contrast to the wounded cells (control). This study demonstrates that a glycoalkaloid present in lilies promoted fibroblast migration in vitro and affected inflammatory, remodeling and growth factor gene expression. The decreases in expression of key genes may impact the wound healing process, possibly contributing to an earlier end of the inflammatory response and shortening the early phases of model tissue reconstitution. The results of this preliminary investigation may provide a basis for the historical use of lily bulbs to promote dermal healing after injury.}, journal={Journal of Ethnopharmacology}, year={2020}, month={Aug} }
 @article{xiong_matta_grace_lila_ward_felipe-sotelo_esposito_2020, title={Phenolic content, anti-inflammatory properties, and dermal wound repair properties of industrially processed and non-processed acai from the Brazilian Amazon}, volume={11}, url={http://dx.doi.org/10.1039/c9fo03109j}, DOI={10.1039/c9fo03109j}, abstractNote={Industrial processing affected polyphenol content, anti-inflammatory properties, and dermal wound repair properties of Brazilian Amazon Acai extracts.}, number={6}, journal={Food & Function}, publisher={Royal Society of Chemistry (RSC)}, author={Xiong, Jia and Matta, Fernanda V. and Grace, Mary and Lila, Mary Ann and Ward, Neil I. and Felipe-Sotelo, Monica and Esposito, Debora}, year={2020}, pages={4903–4914} }
 @article{nogueira_campos_alves_sarandy_novaes_esposito_gonçalves_2020, title={What Is the Impact of Depletion of Immunoregulatory Genes on Wound Healing? A Systematic Review of Preclinical Evidence}, volume={2020}, url={https://doi.org/10.1155/2020/8862953}, DOI={10.1155/2020/8862953}, abstractNote={Cytokines and growth factors are known to play an important role in the skin wound closure process; however, in knockout organisms, the levels of these molecules can undergo changes that result in the delay or acceleration of this process. Therefore, we systematically reviewed evidence from preclinical studies about the main immunoregulatory molecules involved in skin repair through the analysis of the main mechanisms involved in the depletion of immunoregulatory genes, and we carried out a critical analysis of the methodological quality of these studies. We searched biomedical databases, and only original studies were analyzed according to the PRISMA guidelines. The included studies were limited to those which used knockout animals and excision or incision wound models without intervention. A total of 27 studies were selected; data for animal models, gene depletion, wound characteristics, and immunoregulatory molecules were evaluated and compared whenever possible. Methodological quality assessments were examined using the ARRIVE and SYRCLE’s bias of risk tool. In our review, the extracellular molecules act more negatively in the wound healing process when silenced and the metabolic pathway most affected involved in these processes was TGF-β/Smad, and emphasis was given to the importance of the participation of macrophages in TGF-β signaling. Besides that, proinflammatory molecules were more evaluated than anti-inflammatory ones, and the main molecules evaluated were, respectively, TGF-β1, followed by VEGF, IL-6, TNF-α, and IL-1β. Overall, most gene depletions delayed wound healing, negatively influenced the concentrations of proinflammatory cytokines, and consequently promoted a decrease of inflammatory cell infiltration, angiogenesis, and collagen deposition, compromising the formation of granulation tissue. The studies presented heterogeneous data and exhibited methodological limitations; therefore, mechanistic and highly controlled studies are required to improve the quality of the evidence.}, journal={Oxidative Medicine and Cellular Longevity}, publisher={Hindawi Limited}, author={Nogueira, Bárbara Cristina Félix and Campos, Artur Kanadani and Alves, Raul Santos and Sarandy, Mariáurea Matias and Novaes, Rômulo Dias and Esposito, Debora and Gonçalves, Reggiani Vilela}, editor={Bekeschus, SanderEditor}, year={2020}, month={Dec}, pages={1–19} }
 @article{esposito_overall_grace_komarnytsky_lila_2019, title={Alaskan Berry Extracts Promote Dermal Wound Repair Through Modulation of Bioenergetics and Integrin Signaling}, volume={10}, ISSN={["1663-9812"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85073015678&partnerID=MN8TOARS}, DOI={10.3389/fphar.2019.01058}, abstractNote={Various wild berry species endemic to Alaska and the circumpolar North that exhibit unique medicinal properties have long been appreciated by indigenous Arctic communities. Traditional use of Alaskan berry preparations in the treatment of skin wounds is recorded but has not been scientifically evaluated. Alaskan wild berries feature diverse phytochemical compositions that contain a variety of bioactive polyphenols exhibiting anti-inflammatory, antioxidant, and antimicrobial properties, making them ideal for wound healing interventions and natural anti-aging cosmeceutical formulations. Given increasing interest in identifying biologically active plant constituents for wound care and cosmeceutical applications, the objective of this study was to screen several wild berry species endemic to Alaska and the circumpolar Artic for wound healing and in the crude, polyphenol-enriched, and further fractionated extracts of: Empetrum nigrum (crowberry), Vaccinium uliginosum (bog blueberry), and V. vitis-idaea (low-bush cranberry or lingonberry). A cell migration assay with human dermal fibroblasts (HDFa) was performed to model promotion of wound closure, revealing that bog blueberry extract most actively promoted migration, whereas divergent effects observed with other berry extracts were related to compositional disparities. Lipopolysaccharide (LPS)-stimulated inflammatory response variables measured in RAW 264.7 macrophages [reactive oxygen species (ROS), NO production, prostaglandin-endoperoxide synthase 2 (COX-2), and inducible nitric oxide synthase (iNOS) expression] were suppressed by most extracts/fractions, but especially bog blueberry and proanthocyanidin (PAC) fractions. Wild berry germplasm contained abundant complex flavonoid structures such as PAC and anthocyanins (ANCs), associated with enhanced repair and inflammatory resolution in these models. Next, underlying mechanisms by which PACs and bioactive metabolites (B2 dimer and epicatechin) could influence wound repair and tissue regeneration were examined. PAC metabolites promoted scratch-wound closure and appeared to exert the highest impacts on early stages of wound healing through stimulating mitochondrial bioenergetics (basal respiration, ATP production, and maximum respiratory capacity) and upregulating expression of important extracellular matrix (ECM) proteins (integrin-ß1 and collagen type I α2 chain). Targeting cellular bioenergetics and integrin-mediated cell–ECM signaling with bioactives from Alaskan wild berries shows considerable therapeutic promise to treat chronic skin wounds and inflammatory skin disorders, as well as more generally to support regenerative healing responses and restore function in a variety of tissue and organ settings after injury or aging.}, number={SEP}, journal={FRONTIERS IN PHARMACOLOGY}, author={Esposito, Debora and Overall, John and Grace, Mary H. and Komarnytsky, Slavko and Lila, Mary Ann}, year={2019}, month={Sep} }
 @article{velde_esposito_grace_pirovani_lila_2019, title={Anti-inflammatory and wound healing properties of polyphenolic extracts from strawberry and blackberry fruits}, volume={121}, ISSN={["1873-7145"]}, url={http://dx.doi.org/10.1016/j.foodres.2018.11.059}, DOI={10.1016/j.foodres.2018.11.059}, abstractNote={The polyphenolic profiles by HPLC-TOF-MS of strawberry ‘San Andreas’ and blackberry ‘Black Satin’ crude extracts (CE) were analyzed. Anthocyanin-enriched fractions (AEFs) and proanthocyanidin-enriched fractions (PEFs) were prepared, and all samples were probed for in vitro anti-inflammatory and wound healing effects in a LPS-stimulated RAW 264.7 macrophage model and in a skin fibroblast migration and proliferation assay, respectively. Blackberry samples exhibited higher ROS reduction than strawberry's (up to 50% ROS suppression). Berries CEs exhibited 20% inhibition in Cox-2 gene expression, while AEFs and PEFs were inactive at the same concentration. Strawberry AEF and PEF were more active against IL-1β and IL-6 gene expressions than the similar fractions from blackberry, where PEF was more active than AEF (75% suppression by strawberry PEF). Moreover, berry PEFs were the active polyphenol fraction against iNOS gene expression (50% and 65% gen suppression by strawberry and blackberry PEF, respectively), mirroring results of NO synthesis suppression. The cell migration potential of berry polyphenolics was associated with anthocyanins. AEFs showed fibroblast migration around 50% of that registered for the positive control. Results obtained in this work highlight the anti-inflammatory properties of berry polyphenolics, especially due to proanthocyanidins. Moreover, promising results were obtained about the effects of berry anthocyanins on wound healing.}, journal={FOOD RESEARCH INTERNATIONAL}, author={Velde, Franco and Esposito, Debora and Grace, Mary H. and Pirovani, Maria E. and Lila, Mary A.}, year={2019}, month={Jul}, pages={453–462} }
 @article{hoskin_xiong_esposito_lila_2019, title={Blueberry polyphenol-protein food ingredients: The impact of spray drying on the in vitro antioxidant activity, anti-inflammatory markers, glucose metabolism and fibroblast migration}, volume={280}, ISSN={0308-8146}, url={http://dx.doi.org/10.1016/j.foodchem.2018.12.046}, DOI={10.1016/j.foodchem.2018.12.046}, abstractNote={Wild blueberry pomace extract complexed with wheat or chickpea flour or soy protein isolate produced spray dried and freeze-dried polyphenol-protein particles. To evaluate the impact of spray drying on the biological activity of these food ingredients in vitro antioxidant and anti-inflammatory activities, regulation of glucose metabolism and ability to stimulate fibroblast migration were tested. Extracts from polyphenol-protein particles significantly decreased reactive oxygen species (ROS) production and down-regulated the gene expression of inflammation markers (COX-2 and IL-1β). Milder suppression of nitric oxide production and inducible nitric oxide synthase (iNOS) gene expression was evident. The extracts significantly inhibited phosphoenolpyruvate carboxykinase (PEPCK) and accelerated fibroblast cell migration up to 3-fold after 24 h. Complexed polyphenols retained their structural integrity and bioactive potency for both lyophilized and spray dried treatments. The data suggests that spray drying is a convenient and cost-effective technique to produce blueberry-polyphenol food ingredients with preserved phytochemicals with biological activities.}, journal={Food Chemistry}, publisher={Elsevier BV}, author={Hoskin, Roberta Targino and Xiong, Jia and Esposito, Debora Araújo and Lila, Mary Ann}, year={2019}, month={May}, pages={187–194} }
 @article{velde_esposito_overall_mendez-galarraga_grace_piroyani_lila_2019, title={Changes in the bioactive properties of strawberries caused by the storage in oxygen- and carbon dioxide-enriched atmospheres}, volume={7}, ISSN={["2048-7177"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85070678260&partnerID=MN8TOARS}, DOI={10.1002/fsn3.1099}, abstractNote={Abstract}, number={8}, journal={FOOD SCIENCE & NUTRITION}, author={Velde, Franco and Esposito, Debora and Overall, John and Mendez-Galarraga, Maria Paula and Grace, Mary and Piroyani, Maria Elida and Lila, Mary Ann}, year={2019}, month={Aug}, pages={2527–2536} }
 @article{walter_lin_jacobi_käser_esposito_odle_2019, title={Dietary arachidonate in milk replacer triggers dual benefits of PGE2 signaling in LPS-challenged piglet alveolar macrophages}, volume={10}, ISSN={2049-1891}, url={http://dx.doi.org/10.1186/s40104-019-0321-1}, DOI={10.1186/s40104-019-0321-1}, abstractNote={Respiratory infections challenge the swine industry, despite common medicinal practices. The dual signaling nature of PGE2 (supporting both inflammation and resolution) makes it a potent regulator of immune cell function. Therefore, the use of dietary long chain n-6 PUFA to enhance PGE2 effects merits investigation. Day-old pigs (n = 60) were allotted to one of three dietary groups for 21 d (n = 20/diet), and received either a control diet (CON, arachidonate = 0.5% of total fatty acids), an arachidonate (ARA)-enriched diet (LC n-6, ARA = 2.2%), or an eicosapentaenoic (EPA)-enriched diet (LC n-3, EPA = 3.0%). Alveolar macrophages and lung parenchymal tissue were collected for fatty acid analysis. Isolated alveolar macrophages were stimulated with LPS in situ for 24 h, and mRNA was isolated to assess markers associated with inflammation and eicosanoid production. Culture media were collected to assess PGE2 secretion. Oxidative burst in macrophages was measured by: 1) oxygen consumption and extracellular acidification (via Seahorse), 2) cytoplasmic oxidation and 3) nitric oxide production following 4, 18, and 24 h of LPS stimulation. Concentration of ARA (% of fatty acids, w/w) in macrophages from pigs fed LC n-6 was 86% higher than CON and 18% lower in pigs fed LC n-3 (P < 0.01). Following LPS stimulation, abundance of COX-2 and TNF-α mRNA (P < 0.0001), and PGE2 secretion (P < 0. 01) were higher in LC n-6 PAM vs. CON. However, ALOX5 abundance was 1.6-fold lower than CON. Macrophages from CON and LC n-6 groups were 4-fold higher in ALOX12/15 abundance (P < 0.0001) compared to LC n-3. Oxygen consumption and extracellular acidification rates increased over 4 h following LPS stimulation (P < 0.05) regardless of treatment. Similarly, increases in cytoplasmic oxidation (P < 0.001) and nitric oxide production (P < 0.002) were observed after 18 h of LPS stimulation but were unaffected by diet. We infer that enriching diets with arachidonic acid may be an effective means to enhance a stronger innate immunologic response to respiratory challenges in neonatal pigs. However, further work is needed to examine long-term safety, clinical efficacy and economic viability.}, number={1}, journal={Journal of Animal Science and Biotechnology}, publisher={Springer Science and Business Media LLC}, author={Walter, Kathleen R. and Lin, Xi and Jacobi, Sheila K. and Käser, Tobias and Esposito, Debora and Odle, Jack}, year={2019}, month={Feb} }
 @article{grace_xiong_esposito_ehlenfeldt_lila_2019, title={Simultaneous LC-MS quantification of anthocyanins and non-anthocyanin phenolics from blueberries with widely divergent profiles and biological activities}, volume={277}, ISSN={0308-8146}, url={http://dx.doi.org/10.1016/j.foodchem.2018.10.101}, DOI={10.1016/j.foodchem.2018.10.101}, abstractNote={A sensitive and straightforward LC-IT-TOF-MS method was validated for the profiling and simultaneous quantification of anthocyanins, flavan-3-ols, flavonols, phenolic acids, and resveratrol in blueberry genotypes with fruit color ranging from deep purple (Vaccinium angustifolium) to various shades of pink (crosses of V. corymbosum, V. darrowii, and V. ashei). Standard calibration curves were linear for all analytes with correlation coefficients >0.99. The relative standard deviation for intra- and inter-day precision was lower than 10%. The method allowed an easy and selective identification and quantification of phenolics in blueberries with divergent profiles. The in vitro antioxidant assay results were strongly correlated with total phenolics and total anthocyanin content. Lowbush blueberry extracts (50 μg/mL) reduced ROS and NO production, and inhibited the transcription of the proinflammatory cytokines IL-6β, COX2, iNOS, and IL-6 in the in vitro assays at much lower concentrations than pink fruited berries (250 μg/mL).}, journal={Food Chemistry}, publisher={Elsevier BV}, author={Grace, Mary H. and Xiong, Jia and Esposito, Debora and Ehlenfeldt, Mark and Lila, Mary Ann}, year={2019}, month={Mar}, pages={336–346} }
 @article{skates_overall_dezego_wilson_esposito_lila_komarnytsky_2018, title={Berries containing anthocyanins with enhanced methylation profiles are more effective at ameliorating high fat diet-induced metabolic damage}, volume={111}, ISSN={["1873-6351"]}, url={https://doi.org/10.1016/j.fct.2017.11.032}, DOI={10.1016/j.fct.2017.11.032}, abstractNote={Driven by the need for alternative whole food options to manage metabolic syndrome, multiple dietary interventions are suggested to achieve a better control of metabolic risk factors and molecular networks that regulate cellular energy metabolism. It is generally accepted that anthocyanin-rich diets are beneficial for maintaining healthy body weight, improving glucose and lipid metabolism, and determining inflammatory status of key metabolic tissues. However, anthocyanins are a structurally diverse group of phenolic compounds and their individual contributions to improving metabolic health are not clear. In this study, we show that consumption of berries containing anthocyanins with enhanced methylation profiles (malvidin and petunidin) is more effective at reducing high fat diet-induced metabolic damage in the C57BL/6 mouse model of polygenic obesity. Blueberries and Concord grapes (57% and 33% anthocyanins as malvidin, petunidin, or peonidin, respectively) improved body composition through individual significant effects on energy expenditure and increased activity. Methylated anthocyanins are also more effective at enhancing mitochondrial respiration and dissipation of the mitochondrial proton gradient (proton leak) in adipose tissue, thus counteracting mitochondrial dysfunction associated with metabolic stress. Together, these results provide direct proof of the higher protective potential of methylated anthocyanins against the metabolic consequences of chronic exposure to calorie-dense foods.}, journal={FOOD AND CHEMICAL TOXICOLOGY}, publisher={Elsevier BV}, author={Skates, Emily and Overall, John and DeZego, Katelyn and Wilson, Mickey and Esposito, Debora and Lila, Mary Ann and Komarnytsky, Slavko}, year={2018}, month={Jan}, pages={445–453} }
 @article{nieman_gillitt_sha_esposito_ramamoorthy_2018, title={Metabolic recovery from heavy exertion following banana compared to sugar beverage or water only ingestion: A randomized, crossover trial}, volume={13}, DOI={10.1371/journal.pone.0194843}, abstractNote={Objectives and methods Using a randomized, crossover, counterbalanced approach, cyclists (N = 20, overnight fasted state) engaged in the four 75-km time trials (2-week washout) while ingesting two types of bananas with similar carbohydrate (CHO) but different phenolic content (Cavendish, CAV; mini-yellow, MIY, 63% higher polyphenols), a 6% sugar beverage (SUG), and water only (WAT). CHO intake was set at 0.2 g/kg every 15 minutes. Blood samples were collected pre-exercise and 0 h-, 0.75 h-,1.5 h-, 3 h-, 4.5 h-, 21 h-, 45 h-post-exercise. Results Each of the CHO trials (CAV, MIY, SUG) compared to water was associated with higher post-exercise plasma glucose and fructose, and lower leukocyte counts, plasma 9+13 HODES, and IL-6, IL-10, and IL-1ra. OPLS-DA analysis showed that metabolic perturbation (N = 1,605 metabolites) for WAT (86.8±4.0 arbitrary units) was significantly greater and sustained than for CAV (70.4±3.9, P = 0.006), MIY (68.3±4.0, P = 0.002), and SUG (68.1±4.2, P = 0.002). VIP ranking (<3.0, N = 25 metabolites) showed that both CAV and MIY were associated with significant fold changes in metabolites including those from amino acid and xenobiotics pathways. OPLS-DA analysis of immediate post-exercise metabolite shifts showed a significant separation of CAV and MIY from both WAT and SUG (R2Y = 0.848, Q2Y = 0.409). COX-2 mRNA expression was lower in both CAV and MIY, but not SUG, versus WAT at 21-h post-exercise in THP-1 monocytes cultured in plasma samples. Analysis of immediate post-exercise samples showed a decrease in LPS-stimulated THP-1 monocyte extracellular acidification rate (ECAR) in CAV and MIY, but not SUG, compared to WAT. Conclusions CHO ingestion from bananas or a sugar beverage had a comparable influence in attenuating metabolic perturbation and inflammation following 75-km cycling. Ex-vivo analysis with THP-1 monocytes supported a decrease in COX-2 mRNA expression and reduced reliance on glycolysis for ATP production following ingestion of bananas but not sugar water when compared to water alone. Trial registration ClinicalTrials.gov, U.S. National Institutes of Health, identifier: NCT02994628}, number={3}, journal={PLoS One}, author={Nieman, D. C. and Gillitt, N. D. and Sha, W. and Esposito, Debora and Ramamoorthy, S.}, year={2018} }
 @article{walter_xi_jacobi_esposito_odle_2017, title={Dietary long-chain PUFAs enrich porcine alveolar macrophages and alter Prostaglandin E-2 Production Following LPS Challenge}, volume={31}, journal={FASEB Journal}, author={Walter, K. R. and Xi, L and Jacobi, S.K. and Esposito, D. and Odle, J.}, year={2017} }
 @article{bussler_dezego_bowen_buige_esposito_lila_komarnytsky_2017, title={Health modifying regions in the oat (Avena sativa) genome responsible for beneficial effects on immune and gastrointestinal health}, volume={31}, journal={FASEB Journal}, author={Bussler, W. W. and Dezego, K. and Bowen, M. and Buige, A. and Esposito, D. and Lila, M. A. and Komarnytsky, S.}, year={2017} }
 @article{overall_bonney_wilson_beermann_grace_esposito_lila_komarnytsky_2017, title={Metabolic Effects of Berries with Structurally Diverse Anthocyanins}, volume={18}, ISSN={["1422-0067"]}, url={http://dx.doi.org/10.3390/ijms18020422}, DOI={10.3390/ijms18020422}, abstractNote={Overconsumption of energy dense foods and sedentary lifestyle are considered as major causes of obesity-associated insulin resistance and abnormal glucose metabolism. Results from both cohort studies and randomized trials suggested that anthocyanins from berries may lower metabolic risks, however these reports are equivocal. The present study was designed to examine effects of six berries with structurally diverse anthocyanin profiles (normalized to 400 µg/g total anthocyanin content) on development of metabolic risk factors in the C57BL/6 mouse model of polygenic obesity. Diets supplemented with blackberry (mono-glycosylated cyanidins), black raspberry (acylated mono-glycosylated cyanidins), blackcurrant (mono- and di-glycosylated cyanidins and delphinidins), maqui berry (di-glycosylated delphinidins), Concord grape (acylated mono-glycosylated delphinidins and petunidins), and blueberry (mono-glycosylated delphinidins, malvidins, and petunidins) showed a prominent discrepancy between biological activities of delphinidin/malvidin-versus cyanidin-type anthocyanins that could be explained by differences in their structure and metabolism in the gut. Consumption of berries also resulted in a strong shift in the gastrointestinal bacterial communities towards obligate anaerobes that correlated with decrease in the gastrointestinal luminal oxygen and oxidative stress. Further work is needed to understand mechanisms that lead to nearly anoxic conditions in the gut lumens, including the relative contributions of host, diet and/or microbial oxidative activity, and their implication to human health.}, number={2}, journal={INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, author={Overall, John and Bonney, Sierra A. and Wilson, Mickey and Beermann, Arnold and Grace, Mary H. and Esposito, Debora and Lila, Mary Ann and Komarnytsky, Slavko}, year={2017}, month={Feb} }
 @article{xiong_grace_esposito_komarnytsky_wang_lila_2017, title={Polyphenols isolated from Acacia mearnsii bark with anti-inflammatory and carbolytic enzyme inhibitory activities}, volume={15}, ISSN={1875-5364}, url={http://dx.doi.org/10.1016/S1875-5364(18)30015-3}, DOI={10.1016/s1875-5364(18)30015-3}, abstractNote={The present study was designed to characterize the polyphenols isolated from Acacia mearnsii bark crude extract (B) and fractions (B1-B7) obtained by high-speed counter-current chromatography (HSCCC) and evaluate their anti-inflammatory and carbolytic enzymes (α-glucosidase and α-amylase) inhibitory activities. Fractions B4, B5, B6, B7 (total phenolics 850.3, 983.0, 843.9, and 572.5 mg·g−1, respectively; proanthocyanidins 75.7, 90.5, 95.0, and 44.8 mg·g−1, respectively) showed significant activities against reactive oxygen species (ROS), nitric oxide (NO) production, and expression of pro-inflammatory genes interleukin-1β (IL-1β) and inducible nitric oxide synthase (iNOS) in a lipopolysaccharide (LPS)-stimulated mouse macrophage cell line RAW 264.7. All the extracts suppressed α-glucosidase and α-amylase activities, two primary enzymes responsible for carbohydrate digestion. A. mearnsii bark samples possessed significantly stronger inhibitory effects against α-glucosidase enzyme (IC50 of 0.4−1.4 μg·mL−1) than the pharmaceutical acarbose (IC50 141.8 μg·mL−1). B6 and B7 (IC50 17.6 and 11.7 μg·mL−1, respectively) exhibited α-amylase inhibitory activity as efficacious as acarbose (IC50 15.4 μg·mL−1). Moreover, B extract, at 25 µg·mL−1, significantly decreased the non-mitochondrial oxidative burst that is often associated with inflammatory response in human monocytic macrophages.}, number={11}, journal={Chinese Journal of Natural Medicines}, publisher={Elsevier BV}, author={Xiong, Jia and Grace, Mary H and Esposito, Debora and Komarnytsky, Slavko and Wang, Fei and Lila, Mary Ann}, year={2017}, month={Nov}, pages={816–824} }
 @article{jackson_rathinasabapathy_esposito_komarnytsky_2017, title={Structural constraints and importance of caffeic acid moiety for anti-hyperglycemic effects of caffeoylquinic acids from chicory}, volume={61}, ISSN={["1613-4133"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85018313098&partnerID=MN8TOARS}, DOI={10.1002/mnfr.201601118}, abstractNote={SCOPE
Chicory (Cichorium intybus L.) is a perennial herb often consumed as a vegetable, whereas the ground and roasted roots are blended as a coffee substitute. Caffeoylquinic or chlorogenic acids (CQA), the abundant intermediates of lignin biosynthesis in chicory, have been reported to improve glucose metabolism in humans, but the functional group in their structure responsible for this effect has not been yet characterized.


METHODS AND RESULTS
Here, we showed that three di-O-caffeoylquinic acids suppressed hepatic glucose production in H4IIE rat hepatoma cells by reducing expression of glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK), two key enzymes that regulate hepatic gluconeogenesis. Direct comparisons between CQAs and their metabolites (3-caffeoylquinic, caffeic, and quinic acids) revealed the caffeic acid moiety alone was responsible for the observed effects. Further analysis suggested the activation of PI3K and MAPK pathways as a method of controlling gene expression was shared between caffeoylquinic and caffeic acids. These compounds promoted increased mitochondrial respiration and cellular metabolism, in part by inducing oxidative phosphorylation and proton leak.


CONCLUSION
We concluded that the caffeic acid moiety was important for suppression of hepatic gluconeogenesis and hyperglycemia, ultimately strengthening the link between dietary interventions based on caffeic acid-containing plant foods and healthy glucose metabolism.}, number={9}, journal={MOLECULAR NUTRITION & FOOD RESEARCH}, author={Jackson, Kimberly M. Palatini and Rathinasabapathy, Thirumurugan and Esposito, Debora and Komarnytsky, Slavko}, year={2017}, month={Sep} }
 @article{rathinasabapathy_palatini jackson_thor_buru_esposito_li_pichika_hamzah_komarnytsky_2017, title={Thiazolopyridines Improve Adipocyte Function by Inhibiting 11 Beta-HSD1 Oxoreductase Activity}, volume={2017}, ISSN={2090-9063 2090-9071}, url={http://dx.doi.org/10.1155/2017/3182129}, DOI={10.1155/2017/3182129}, abstractNote={Background. Glucocorticoid excess has been linked to clinical observations associated with the pathophysiology of metabolic syndrome. The intracellular glucocorticoid levels are primarily modulated by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme that is highly expressed in key metabolic tissues including fat, liver, and the central nervous system. Methods. In this study we synthesized a set of novel tetrahydrothiazolopyridine derivatives, TR-01–4, that specifically target 11β-HSD1 and studied their ability to interfere with the glucocorticoid and lipid metabolism in the 3T3-L1 adipocytes. Results. Based on the docking model and structure-activity relationships, tetrahydrothiazolopyridine derivatives TR-02 and TR-04 showed the highest potency against 11β-HSD1 by dose-dependently inhibiting conversion of cortisone to cortisol (IC50 values of 1.8 μM and 0.095 μM, resp.). Incubation of fat cells with 0.1–10 μM TR-01–4 significantly decreased cortisone-induced lipid accumulation in adipocytes and suppressed 11β-HSD1 mRNA expression. Observed reduction in adipocyte fat stores could be partially explained by decreased expression levels of adipogenic markers (PPAR-γ, aP2) and key enzymes of lipid metabolism, including fatty acid synthase (FAS), hormone sensitive lipase (HSL), and lipoprotein lipase (LPL). Conclusions. The tetrahydrothiazolopyridine moiety served as an active pharmacophore for inhibiting 11β-HSD1 and offered a novel therapeutic strategy to ameliorate metabolic alterations found in obesity and diabetes.}, journal={Journal of Chemistry}, publisher={Hindawi Limited}, author={Rathinasabapathy, Thirumurugan and Palatini Jackson, Kimberly Marie and Thor, Yiwen and Buru, Ayuba Sunday and Esposito, Debora and Li, Xu and Pichika, Mallikarjuna Rao and Hamzah, Ahmad Sazali and Komarnytsky, Slavko}, year={2017}, pages={1–10} }
 @article{correia_grace_esposito_lila_2017, title={Wild blueberry polyphenol-protein food ingredients produced by three drying methods: Comparative physico-chemical properties, phytochemical content, and stability during storage}, volume={235}, ISSN={["1873-7072"]}, url={http://dx.doi.org/10.1016/j.foodchem.2017.05.042}, DOI={10.1016/j.foodchem.2017.05.042}, abstractNote={Particulate colloidal aggregate food ingredients were prepared by complexing wheat flour, chickpea flour, coconut flour and soy protein isolate with aqueous wild blueberry pomace extracts, then spray drying, freeze drying, or vacuum oven drying to prepare dry, flour-like matrices. Physico-chemical attributes, phytochemical content and stability during storage were compared. Eighteen anthocyanins peaks were identified for samples. Spray dried matrices produced with soy protein isolate had the highest concentration of polyphenols (156.2 mg GAE/g) and anthocyanins (13.4 mg/g) and the most potent DPPH scavenging activity (714.1 μmoles TE/g). Spray dried blueberry polyphenols complexed with protein were protected from degradation during 16 weeks at 4 °C and 20 °C. Soy protein isolate more efficiently captured and stabilized wild blueberry pomace phytochemicals than other protein sources. Overall, spray drying the blueberry extracts complexed with protein proved to be an environment-friendly strategy to produce stable functional ingredients with multiple applications for the food industry.}, journal={FOOD CHEMISTRY}, publisher={Elsevier BV}, author={Correia, Roberta and Grace, Mary H. and Esposito, Debora and Lila, Mary Ann}, year={2017}, month={Nov}, pages={76–85} }
 @article{grace_esposito_timmers_xiong_yousef_komarnytsky_lila_2016, title={Chemical composition, antioxidant and anti-inflammatory properties of pistachio hull extracts}, volume={210}, ISSN={0308-8146}, url={http://dx.doi.org/10.1016/j.foodchem.2016.04.088}, DOI={10.1016/j.foodchem.2016.04.088}, abstractNote={Phytochemical and bioactivity analyses of pistachio hulls revealed the presence of anacardic acids (3198 mg/100 g), fatty acids (1500 mg/100 g), and phytosterols (192 mg/100 g) as major components. Carotenoids (4.93 mg/100 g), chlorophylls (10.27 mg/100 g), tocopherols (8.83 mg/100 g), and three triterpene acids (mangiferolic, isomangiferolic and mangiferonic acids) were characterized. A polar (P) extract contained quercetin-3-O-glucoside (6.27 mg/g), together with smaller concentrations of quercetin, myricetin and luteolin flavonoids, accounting for 5.53 mg/g. Gallotannins and other phenolic compounds esterified with a gallic acid moiety characterized the P extract. P extract potently inhibited the release of nitric oxide (NO) and reactive oxygen species (ROS) in lipopolysaccharide-stimulated RAW 264.7 macrophage cells. The mRNA expression levels of the anti-inflammatory cytokine COX-2 were significantly inhibited by fractions P2-P5, while IL-6 was only inhibited by fraction P3. Moreover, the P extract significantly decreased the non-mitochondrial oxidative burst associated with inflammatory response in macrophages.}, journal={Food Chemistry}, publisher={Elsevier BV}, author={Grace, Mary H. and Esposito, Debora and Timmers, Michael A. and Xiong, Jia and Yousef, Gad and Komarnytsky, Slavko and Lila, Mary Ann}, year={2016}, month={Nov}, pages={85–95} }
 @article{schneider_esposito_lila_foegeding_2016, title={Formation of whey protein–polyphenol meso-structures as a natural means of creating functional particles}, volume={7}, ISSN={2042-6496 2042-650X}, url={http://dx.doi.org/10.1039/C5FO01499A}, DOI={10.1039/C5FO01499A}, abstractNote={Whey proteins provide structure and nutritional properties in food, while berry juices are thought to have biological activity that can impart anti-inflammatory health effects.}, number={3}, journal={Food & Function}, publisher={Royal Society of Chemistry (RSC)}, author={Schneider, Margaret and Esposito, Debora and Lila, Mary Ann and Foegeding, E. Allen}, year={2016}, pages={1306–1318} }
 @article{grace_esposito_timmers_xiong_yousef_komarnytsky_lila_2016, title={In vitro lipolytic, antioxidant and anti-inflammatory activities of roasted pistachio kernel and skin constituents}, volume={7}, ISSN={2042-6496 2042-650X}, url={http://dx.doi.org/10.1039/c6fo00867d}, DOI={10.1039/c6fo00867d}, abstractNote={A comprehensive phytochemical analysis was conducted on pistachios to identify the differential contributions of skin and kernel phytochemicals toin vitrobioactivity.}, number={10}, journal={Food & Function}, publisher={Royal Society of Chemistry (RSC)}, author={Grace, Mary H. and Esposito, Debora and Timmers, Michael A. and Xiong, Jia and Yousef, Gad and Komarnytsky, Slavko and Lila, Mary Ann}, year={2016}, pages={4285–4298} }
 @article{xiong_grace_esposito_wang_lila_2016, title={Phytochemical Characterization and Anti-inflammatory Properties of Acacia mearnsii Leaves}, volume={11}, url={http://dx.doi.org/10.1177/1934578x1601100524}, DOI={10.1177/1934578x1601100524}, abstractNote={ This study was performed to investigate potential bioactive secondary metabolites from the leaves of Acacia mearnsii, a forest waste product in China. The polyphenol constituents and bioactivity of crude extract (L) and semi purified fractions (L1-L4) were examined. The L and L1-L4 showed qualitative and quantitative differences in their phenolic content, antioxidant activities and the activities against inflammation-related genes such as the inducible forms of COX-2, iNOS, and the pro-inflammatory IL in lipopolysaccharide (LPS)-stimulated mouse macrophage cell line RAW 264.7. All the fractions depressed reactive oxygen species (ROS) in LPS-stimulated RAW 264.7 macrophage cells, and (except L2) inhibited the release of nitric oxide (NO). Fractions L3 and L4 significantly inhibited the mRNA expression levels of the anti-inflammatory cytokine IL-1β, COX-2, iNOS, and IL-6. In addition, L4 (1.8 g obtained from 5 g crude leaves extract) which contained 646.6 mg/g gallic acid equivalent total phenolic content and consisted of primarily proanthocyanidins (12.6 mg/g as procyanidin B2 equivalent by the DMAC assay) showed the best activity in all the assays. Results indicate that A. mearnsii leaves, a forest waste product, could be a valuable natural source of anti-inflammatory and functional components related to human health. }, number={5}, journal={Natural Product Communications}, author={Xiong, Jia and Grace, Mary H and Esposito, Debora and Wang, F. and Lila, Mary Ann}, year={2016}, month={May}, pages={649–653} }
 @article{xiong_grace_esposito_wang_lila_2016, title={Phytochemical characterization and anti-inflammatory properties of Acacia mearnsii leaves}, volume={11}, number={5}, journal={Natural Product Communications}, author={Xiong, J. and Grace, M. H. and Esposito, D. and Wang, F. and Lila, M. A.}, year={2016}, pages={649–653} }
 @article{velde_grace_esposito_elida pirovani_lila_2016, title={Quantitative comparison of phytochemical profile, antioxidant, and anti-inflammatory properties of blackberry fruits adapted to Argentina}, volume={47}, ISSN={["1096-0481"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84956598220&partnerID=MN8TOARS}, DOI={10.1016/j.jfca.2016.01.008}, abstractNote={The phytochemical profile by HPLC-TOF-MS of three blackberry cultivars (‘Jumbo’, ‘Black Satin’ and ‘Dirksen’), adapted to the central-east of Argentina, was determined. The antioxidant capacity by DPPH and FRAP assays, and the effect of the blackberry extracts on lipopolysaccharide (LPS)-induced nitric oxide (NO) production, reactive oxygen species (ROS) production, and biomarkers of inflammation were also evaluated. ‘Dirksen’ fruits exhibited the highest vitamin C content (24 and 14% higher than values found in ‘Black Satin’ and ‘Jumbo’, respectively). However, ‘Jumbo’ and ‘Black Satin’ fruits presented higher total phenolic contents (more than 15%) than ‘Dirksen’. Cyanidin-3-O-glucoside was the main polyphenolic compound quantified in all samples. ‘Jumbo’ and ‘Black Satin’ cultivars exhibited higher antioxidant capacity, and significantly reduced the release of ROS. The mRNA expression levels of cyclooxygenase-2 (Cox-2) and interleukin-6 (IL-6) were reduced consistently (more than 30%) by extracts of both cultivars, and showed slight suppressions on NO production. However, effective inhibition in the gene expression of interleukin-1β (IL-1β) and nitric oxide synthase (iNOS) was not observed by any extract. These results suggest the potential of blackberries cultivars ‘Black Satin’ and ‘Jumbo’ to contribute to a healthy diet, based on their higher polyphenol content, providing higher antioxidant and anti-inflammatory properties.}, journal={JOURNAL OF FOOD COMPOSITION AND ANALYSIS}, author={Velde, Franco and Grace, Mary H. and Esposito, Debora and Elida Pirovani, Maria and Lila, Mary Ann}, year={2016}, month={Apr}, pages={82–91} }
 @article{ricciardi_bae_esposito_komarnytsky_hu_chen_zhao_2015, title={1,25-Dihydroxyvitamin D-3/vitamin D receptor suppresses brown adipocyte differentiation and mitochondrial respiration}, volume={54}, ISSN={["1436-6215"]}, DOI={10.1007/s00394-014-0778-9}, abstractNote={{"Label"=>"PURPOSE", "NlmCategory"=>"OBJECTIVE"} The vitamin D system plays a role in metabolism regulation. 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) suppressed 3T3-L1 white adipocyte differentiation. Vitamin D receptor (VDR) knockout mice showed increased energy expenditure, whereas mice with adipose-specific VDR over-expression showed decreased energy expenditure. Brown adipose tissue (BAT), now known to be present in adult humans, functions in non-shivering thermogenesis by uncoupling ATP synthesis from respiration and plays an important role in energy expenditure. However, the effects of 1,25(OH)2D3/VDR on brown adipocyte differentiation and mitochondrial respiration have not been reported. {"Label"=>"METHODS", "NlmCategory"=>"METHODS"} mRNA expression of VDR and the metabolizing enzymes 1α-hydroxylase (CYP27B1) and 24-hydroxylase (CYP24A1) were examined in BAT of mice models of obesity and during brown adipocyte differentiation. The effects of 1,25(OH)2D3 and VDR over-expression on brown adipocyte differentiation and functional outcomes were evaluated. {"Label"=>"RESULTS", "NlmCategory"=>"RESULTS"} No significant changes in mRNA of VDR and CYP27B1 were noted in both diet-induced obese (DIO) and ob/ob mice, whereas uncoupling protein 1 mRNA was downregulated in BAT of ob/ob, but not DIO mice when compared to the controls. In contrast, mRNA of VDR, CYP24A1, and CYP27B1 were downregulated during brown adipocyte differentiation in vitro. 1,25(OH)2D3 dose-dependently suppressed brown adipocyte differentiation, accompanied by suppressed isoproterenol-stimulated oxygen consumption rates (OCR), maximal OCR and OCR from proton leak. Consistently, over-expression of VDR also suppressed brown adipocyte differentiation. Further, both 1,25(OH)2D3 and VDR over-expression suppressed PPARγ transactivation in brown preadipocytes. {"Label"=>"CONCLUSION", "NlmCategory"=>"CONCLUSIONS"} Our results demonstrate the suppressive effects of 1,25(OH)2D3/VDR signaling on brown adipocyte differentiation and mitochondrial respiration. The role of 1,25(OH)2D3/VDR system in regulating BAT development and function in obesity warrant further investigation.}, number={6}, journal={EUROPEAN JOURNAL OF NUTRITION}, publisher={Springer Science \mathplus Business Media}, author={Ricciardi, Carolyn J. and Bae, Jiyoung and Esposito, Debora and Komarnytsky, Slavko and Hu, Pan and Chen, Jiangang and Zhao, Ling}, year={2015}, month={Sep}, pages={1001–1012} }
 @article{kellogg_esposito_grace_komarnytsky_lila_2015, title={Alaskan seaweeds lower inflammation in RAW 264.7 macrophages and decrease lipid accumulation in 3T3-L1 adipocytes}, volume={15}, ISSN={["2214-9414"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84929231499&partnerID=MN8TOARS}, DOI={10.1016/j.jff.2015.03.049}, abstractNote={Chronic inflammation is characterized by macrophage accumulation in adipose tissue, which subsequently up-regulates pro-inflammatory cytokines and promotes the dysregulation of lipid metabolism, ultimately leading to insulin resistance. This study was designed to examine the effects of coastal Alaskan seaweeds on the macrophage inflammatory response and lipid metabolism of adipocytes. Two bioactive subfractions from the brown alga Fucus distichus, a monoglycosyldiacylglycerol subfraction and a phlorotannin subfraction, decreased mRNA expression of acute and chronic inflammatory biomarkers. Expression of Toll-like receptors TLR4 and TLR9 were also reduced, suggesting a potential mechanism of anti-inflammatory activity via TLR attenuation. F. distichus fractions decreased lipid accumulation up to 55% and increased free glycerol concentrations by 28–45%. This result was supported by increases in adiponectin and UCP-1 and decreases in leptin mRNA expression. Overall, the Alaskan seaweed F. distichus inhibited proinflammatory responses and improved lipid metabolism, suggesting the potential for seaweed phytochemicals to attenuate inflammatory diseases.}, journal={JOURNAL OF FUNCTIONAL FOODS}, publisher={Elsevier BV}, author={Kellogg, Joshua and Esposito, Debora and Grace, Mary H. and Komarnytsky, Slavko and Lila, Mary Ann}, year={2015}, month={May}, pages={396–407} }
 @article{esposito_damsud_wilson_grace_strauch_li_lila_komarnytsky_2015, title={Black Currant Anthocyanins Attenuate Weight Gain and Improve Glucose Metabolism in Diet-Induced Obese Mice with Intact, but Not Disrupted, Gut Microbiome}, volume={63}, ISSN={["1520-5118"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84937064835&partnerID=MN8TOARS}, DOI={10.1021/acs.jafc.5b00963}, abstractNote={Black currant (Ribes nigrum L.) is a rich source of anthocyanins; however, the relationship between their apparently limited bioavailability and significant protection against metabolic pathologies is poorly understood. This study examined the gastrointestinal distribution of black currant anthocyanins and their phenolic acid metabolites in lean and diet-induced obese mice with healthy and antibiotic-disrupted microbiomes. Daily consumption of low- or high-fat diet supplemented with 1% black currant powdered extract (32% anthocyanins) for 8 weeks reduced body weight gain and improved glucose metabolism only in mice with the intact gut microbiome. Administration of antibiotic cocktail resulted in a 16-25-fold increase (P < 0.001) in anthocyanin content of feces, and cyanidin-based anthocyanins showed the largest increase in fecal content upon disruption of gut microbiome (92.3 ± 16.3 vs 4719 ± 158 μg/g feces), indicating their high susceptibility to microbial degradation in the gut. A 3-fold enrichment (P < 0.05) in gallic over protocatechuic acid was observed in the jejunum of both intact and antibiotic-treated animals, suggesting that this effect was likely independent of their gut microbiome status. Taken together, the data clearly demonstrate that gut microbiome and the type of the anthocyanin aglycone moiety can alter the protective effect of anthocyanins against obesity and associated insulin resistance.}, number={27}, journal={JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY}, publisher={American Chemical Society (ACS)}, author={Esposito, Debora and Damsud, Thanakorn and Wilson, Mickey and Grace, Mary H. and Strauch, Renee and Li, Xu and Lila, Mary Ann and Komarnytsky, Slavko}, year={2015}, month={Jul}, pages={6172–6180} }
 @article{timmers_guerrero-medina_esposito_grace_paredes-lopez_garcia-saucedo_ann lila_2015, title={Characterization of Phenolic Compounds and Antioxidant and Antiinflammatory Activities from Mamuyo (Styrax ramirezii Greenm.) Fruit}, volume={63}, ISSN={["1520-5118"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84949504941&partnerID=MN8TOARS}, DOI={10.1021/acs.jafc.5b04781}, abstractNote={Extracts of Styrax ramirezii Greenm., a fruit traditionally valued for health and wellness in Mexico, were analyzed phytochemically and evaluated for antioxidant and anti-inflammatory activity. Six norneolignans were identified by HPLC-TOF-MS, and the two major compounds were isolated for further evaluation. The effects of the isolated norneolignans, egonol and homoegonol, on lipopolysaccharide (LPS)-induced nitric oxide (NO) production, reactive oxygen species (ROS) production, and biomarkers of inflammation were evaluated. Of the tested compounds, egonol potently inhibited the production of NO and also significantly reduced the release of ROS. Consistent with these observations, the mRNA expression levels of inducible nitric oxide synthase (iNOS) (0.668 ± 0.108), cyclooxygenase-2 (COX-2) (0.553 ± 0.007), interleukin-1β (IL-1β) (0.093 ± 0.005), and interleukin-6 (IL-6) (0.298 ± 0.076) were reduced by egonol. The activity for both egonol and homoegonol increased in a concentration-dependent manner. These results suggest the potential of S. ramirezii Greenm. fruit to contribute to a healthy diet, rich in antioxidant and anti-inflammatory compounds.}, number={48}, journal={JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY}, author={Timmers, Michael A. and Guerrero-Medina, Jorge L. and Esposito, Debora and Grace, Mary H. and Paredes-Lopez, Octavio and Garcia-Saucedo, Pedro A. and Ann Lila, Mary}, year={2015}, month={Dec}, pages={10459–10465} }
 @article{graf_cheng_esposito_shertel_poulev_plundrich_itenberg_dayan_lila_raskin_2015, title={Compounds leached from quinoa seeds inhibit matrix metalloproteinase activity and intracellular reactive oxygen species}, volume={37}, ISSN={["1468-2494"]}, DOI={10.1111/ics.12185}, abstractNote={Synopsis}, number={2}, journal={INTERNATIONAL JOURNAL OF COSMETIC SCIENCE}, author={Graf, B. L. and Cheng, D. M. and Esposito, D. and Shertel, T. and Poulev, A. and Plundrich, N. and Itenberg, D. and Dayan, N. and Lila, M. A. and Raskin, I.}, year={2015}, month={Apr}, pages={212–221} }
 @article{tang_munafo_palatini_esposito_huang_komarnytsky_ho_gianfagna_2015, title={Hepatoprotective Activity of Easter Lily (Lilium longiflorum Thunb.) Bulb Extracts}, volume={63}, ISSN={["1520-5118"]}, DOI={10.1021/acs.jafc.5b04078}, abstractNote={The hepatoprotective activities of two different extracts, a hydroethanolic crude bulb extract (CB) and a steroidal glycoside-rich 1-butanol extract (BuOH), prepared from the bulbs of Easter lily (Lilium longiflorum Thunb.), were evaluated in a 24 week study in the female KK.Cg-A(y)/J Type 2 diabetic mouse model. Animals were divided into six groups (n = 16): control mice received Easter lily bulb extract-free drinking water together with a low- or high-fat diet (diabetic control); drinking water for the remaining groups was supplemented with CB extract (1%), BuOH extract (0.1 or 0.2%), and reference drug Metformin (0.001%), together with a high-fat diet. Both CB and BuOH extract treatment groups exhibited significantly improved liver function based on comparisons of triglycerides [diabetic 219 ± 34 mg/dL, CB 131 ± 27 mg/dL, BuOH(0.2%) 114 ± 35 mg/dL], CB total cholesterol (TC) (diabetic 196 ± 12 mg/dL, CB 159 ± 5 mg/dL), average liver mass [diabetic 2.96 ± 0.13 g, CB 2.58 ± 0.08 g, BuOH(0.1%) 2.48 ± 0.13 g], alanine transferase [diabetic 74 ± 5 units/L, CB 25 ± 1 units/L, BuOH(0.1%) 45 ± 1 units/L], and histological examinations. Glucose metabolism was improved only in CB, which was confirmed by oral glucose tolerance tests (OGTT) in diet-induced obese C57BL/6J mice exposed to CB extract. These data suggest that steroidal glycosides 1-5 might play a role in the hepatoprotective activity of the BuOH extracts, while the results of the TC measurements and OGTT study indicate that other constituents present in the CB extract are responsible for its hypocholesterolemic and hypoglycemic activity.}, number={44}, journal={JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY}, publisher={American Chemical Society (ACS)}, author={Tang, Wenping and Munafo, John P., Jr. and Palatini, Kimberly and Esposito, Debora and Huang, Mou-Tuan and Komarnytsky, Slavko and Ho, Chi-Tang and Gianfagna, Thomas J.}, year={2015}, month={Nov}, pages={9722–9728} }
 @article{graf_poulev_kuhn_esposito_lila_raskin_2015, title={Method to harness bioactive secondary metabolites from intact Quinoa seeds with implications for chronic disease prevention}, volume={81}, ISSN={0032-0943 1439-0221}, url={http://dx.doi.org/10.1055/S-0035-1556449}, DOI={10.1055/S-0035-1556449}, abstractNote={Quinoa (Chenopodium quinoa Willd.) is an Andean seed crop rich in bioactive phytochemicals, including phytoecdysteroids (PE) and flavonoid glycosides (FG). Innovations designed to harness the pharmacological value of quinoa through simple, food-grade technologies may facilitate the development of functional foods and nutraceuticals to combat global human health challenges. We optimized a method to leach and concentrate quinoa bioactives from intact (un-macerated) quinoa seeds into aqueous ethanol, yielding a complex phytochemical mixture termed quinoa leachate (QL). QL, comprised of 1.0% PE and 2.6% FG, contained essentially all PE and FG available in the initial seeds compared with traditional extraction of macerated seed powder (567.6 µg PE and 540.9 µg FG/g seed). QL significantly lowered fasting blood glucose in obese, hyperglycemic C57Bl/6J mice and significantly attenuated lipopolysaccharide (LPS)-induced reactive oxygen species (ROS) production in human dermal fibroblasts. Quinoa seed leaching provides an efficient means to produce a food-grade mixture that may be applicable for the treatment and prevention of chronic, complex diseases, while rendering intact post-leached seeds available for additional uses in food.}, number={11}, journal={Planta Medica}, publisher={Georg Thieme Verlag KG}, author={Graf, BL and Poulev, A and Kuhn, P and Esposito, D and Lila, MA and Raskin, I}, year={2015}, month={Jun} }
 @article{bae_ricciardi_esposito_komarnytsky_hu_curry_brown_gao_biggerstaff_chen_et al._2014, title={Activation of pattern recognition receptors in brown adipocytes induces inflammation and suppresses uncoupling protein 1 expression and mitochondrial respiration}, volume={306}, ISSN={["1522-1563"]}, DOI={10.1152/ajpcell.00249.2013}, abstractNote={ Pattern recognition receptors (PRR), Toll-like receptors (TLR), and nucleotide-oligomerization domain-containing proteins (NOD) play critical roles in mediating inflammation and modulating functions in white adipocytes in obesity. However, the role of PRR activation in brown adipocytes, which are recently found to be present in adult humans, has not been studied. Here we report that mRNA of TLR4, TLR2, NOD1, and NOD2 is upregulated, paralleled with upregulated mRNA of inflammatory cytokines and chemokines in the brown adipose tissue (BAT) of the obese mice. During brown adipocyte differentiation, mRNA and protein expression of NOD1 and TLR4, but not TLR2 and NOD2, is also increased. Activation of TLR4, TLR2, or NOD1 in brown adipocytes induces activation of NF-κB and MAPK signaling pathways, leading to inflammatory cytokine/chemokine mRNA expression and/or protein secretion. Moreover, activation of TLR4, TLR2, or NOD1 attenuates both basal and isoproterenol-induced uncoupling protein 1 (UCP-1) expression without affecting mitochondrial biogenesis and lipid accumulation in brown adipocytes. Cellular bioenergetics measurements confirm that attenuation of UCP-1 expression by PRR activation is accompanied by suppression of both basal and isoproterenol-stimulated oxygen consumption rates and isoproterenol-induced uncoupled respiration from proton leak; however, maximal respiration and ATP-coupled respiration are not changed. Further, the attenuation of UCP-1 by PRR activation appears to be mediated through downregulation of the UCP-1 promoter activities. Taken together, our results demonstrate the role of selected PRR activation in inducing inflammation and downregulation of UCP-1 expression and mitochondrial respiration in brown adipocytes. Our results uncover novel targets in BAT for obesity treatment and prevention. }, number={10}, journal={AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY}, author={Bae, Jiyoung and Ricciardi, Carolyn J. and Esposito, Debora and Komarnytsky, Slavko and Hu, Pan and Curry, Benjamin J. and Brown, Patricia L. and Gao, Zhanguo and Biggerstaff, John P. and Chen, Jiangang and et al.}, year={2014}, month={May}, pages={C918–C930} }
 @article{grace_yousef_esposito_raskin_lila_2014, title={Bioactive Capacity, Sensory Properties, and Nutritional Analysis of a Shelf Stable Protein-rich Functional Ingredient with Concentrated Fruit and Vegetable Phytoactives}, volume={69}, ISSN={["1573-9104"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84916603152&partnerID=MN8TOARS}, DOI={10.1007/s11130-014-0444-7}, abstractNote={Well-known health-protective phytochemicals from muscadine grape and kale were stably complexed with food grade protein (soy or hemp protein isolates) to create biofortified food ingredients for use in a variety of convenient, portable food formulations. The bioactive (anti-inflammatory) potential, sensory attributes and proximates of the prepared formulations were evaluated in this study. Anti-inflammatory properties of the protein-phytoactive ingredient particles were contributed by the polyphenolic content (muscadine-protein) or the combination of polyphenol, carotenoid, and glucosinolate content (kale-protein aggregates). Phytoactive compounds from the fortified matrices suppressed at least two biomarkers of inflammation; most notable with the expression of chronic pro-inflammatory genes IL-6 and Mcp1. Sensory analysis suggested both sweet and savory functional food applications for the biofortified ingredients. Proximate analyses determined that fortification of the soy protein isolate (SPI) with muscadine or kale bioactives resulted in elevated dietary fibers, total carbohydrates, and free sugars, but did not increase calories/100 g dry matrix compared to unfortified SPI. Overall protein content in the aggregate matrices was about 37% less (muscadine-SPI, kale-SPI and kale- HP50) or 17.6% less (muscadine-HP50) on a weight basis, likely due to solubility of some proteins during preparation and partial displacement of some protein mass by the fruit and vegetable phytoactive constituents.}, number={4}, journal={PLANT FOODS FOR HUMAN NUTRITION}, author={Grace, Mary H. and Yousef, Gad G. and Esposito, Debora and Raskin, Ilya and Lila, Mary Ann}, year={2014}, month={Dec}, pages={372–378} }
 @article{grace_esposito_dunlap_lila_2014, title={Comparative Analysis of Phenolic Content and Profile, Antioxidant Capacity, and Anti-inflammatory Bioactivity in Wild Alaskan and Commercial Vaccinium Berries}, volume={62}, ISSN={["1520-5118"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84900331828&partnerID=MN8TOARS}, DOI={10.1021/jf403810y}, abstractNote={Wild Alaskan Vaccinium berries, V. vitis-idaea (lowbush cranberry) and V. uliginosum (bog blueberry), were investigated in parallel with their commercial berry counterparts, V. macrocarpon (cranberry) and V. angustifolium (lowbush blueberry). Lowbush cranberry accumulated about twice the total phenolics (624.4 mg/100 g FW) and proanthocyanidins (278.8 mg/100 g) content as commercial cranberries, but A-type proanthocyanidins were more prevalent in the latter. Bog blueberry anthocyanin and total phenolic contents of 220 and 504.5 mg/100 g, respectively, significantly exceeded those of the lowbush blueberry. Chlorogenic acid, however, was quite high in lowbush blueberry (83.1 mg/100 g), but undetected in bog blueberry, and the proanthocyanidins of lowbush blueberry had significantly higher levels of polymerization. Antioxidant capacity (DPPH, APTS, and FRAP) correlated with phenolic content for each berry. A polyphenol-rich fraction from lowbush cranberry exhibited dose-dependent inhibition of LPS-elicited induction of IL-1β in RAW 264.7 cells, indicative of strong anti-inflammatory activity. These results corroborate the historic use of wild Alaskan berries as medicinally important foods in Alaska Native communities.}, number={18}, journal={JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY}, author={Grace, Mary H. and Esposito, Debora and Dunlap, Kriya L. and Lila, Mary Ann}, year={2014}, month={May}, pages={4007–4017} }
 @article{le_esposito_grace_ha_pham_bortolazzo_bevens_kim_okuda_komarnytsky_et al._2014, title={Cytotoxic Effects of Ellagitannins Isolated from Walnuts in Human Cancer Cells}, volume={66}, ISSN={["1532-7914"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84911418409&partnerID=MN8TOARS}, DOI={10.1080/01635581.2014.956246}, abstractNote={Walnuts contain many bioactive components that may slow cancer growth. A previous report showed that a diet supplemented with walnuts decreased the tumor size formed by MDA-MB-231 human cancer cells injected into nude mice. However, the mechanism of action was never determined. We characterized the effects of a methanol extract prepared from walnuts on human MDA-MB-231, MCF7, and HeLa cells. The extract was cytotoxic to all cancer cells. We identified compounds from the methanol extract that induced this cytotoxicity. The predominant compounds were Tellimagrandin I and Tellimagrandin II, members of the ellagitannin family. We also show a walnut extract decreases the intracellular pH, depolarizes the mitochondrial membrane with release of cytochrome c and phosphatidylserine flipping. The antimitogenic effects of walnut extract were associated with a twofold reduction of mitochondria respiration. These results suggest impairment of mitochondrial function and apoptosis as relevant mechanism of anticancer effects of the walnut extract.}, number={8}, journal={NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL}, publisher={Informa UK Limited}, author={Le, Vy and Esposito, Debora and Grace, Mary H. and Ha, Danny and Pham, Anh and Bortolazzo, Anthony and Bevens, Zackery and Kim, John and Okuda, Roy and Komarnytsky, Slavko and et al.}, year={2014}, month={Nov}, pages={1304–1314} }
 @article{esposito_chen_grace_komarnytsky_lila_2014, title={Inhibitory Effects of Wild Blueberry Anthocyanins and Other Flavonoids on Biomarkers of Acute and Chronic Inflammation in Vitro}, volume={62}, ISSN={["1520-5118"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84905574450&partnerID=MN8TOARS}, DOI={10.1021/jf4051599}, abstractNote={Wild lowbush blueberries (Vaccinium angustifolium Ait) are a rich source of anthocyanins and other flavonoids with anti-inflammatory activities; however, their individual effects on cellular signaling remain to be elucidated. This study determined the capacity of blueberry bioactives to protect murine RAW 264.7 macrophages from lipopolysaccharide-induced inflammation. Fractionation of the crude extract (CE) into polyphenol-rich (PPR), anthocyanin-rich (ANC), and proanthocyanidin-rich (PAC) fractions and an ethyl acetate fraction (EA) revealed that PPR, ANC, and PAC components most effectively suppressed mRNA biomarkers of acute inflammation (Cox-2, iNOS, and IL-1β). Among major polyphenols found in the wild blueberries, malvidin-3-glucoside was significantly more effective than epicatechin or chlorogenic acid in reducing the expression of pro-inflammatory genes in vitro.}, number={29}, journal={JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY}, publisher={American Chemical Society (ACS)}, author={Esposito, Debora and Chen, Amelia and Grace, Mary H. and Komarnytsky, Slavko and Lila, Mary Ann}, year={2014}, month={Jul}, pages={7022–7028} }
 @article{komarnytsky_esposito_rathinasabapathy_poulev_raskin_2013, title={Effects of Pregnane Glycosides on Food Intake Depend on Stimulation of the Melanocortin Pathway and BDNF in an Animal Model}, volume={61}, ISSN={0021-8561 1520-5118}, url={http://dx.doi.org/10.1021/jf3033649}, DOI={10.1021/jf3033649}, abstractNote={Pregnane glycosides appear to modulate food intake by possibly affecting the hypothalamic feeding circuits; however, the mechanisms of the appetite-regulating effect of pregnane glycosides remain obscure. Here, we show that pregnane glycoside-enriched extracts from swamp milkweed Asclepias incarnata at 25-100 mg/kg daily attenuated food intake (up to 47.1 ± 8.5% less than controls) and body weight gain in rats (10% for males and 9% for females, respectively) by activating melanocortin signaling and inhibiting gastric emptying. The major milkweed pregnane glycoside, ikemagenin, exerted its appetite-regulating effect by decreasing levels of agouti-related protein (0.6-fold) but not NPY satiety peptides. Ikemagenin treatment also increased secretion of brain-derived neurotropic factor (BDNF) downstream of melanocortin receptors in the hypothalamus (1.4-fold) and in the C6 rat glioma cell culture in vitro (up to 6-fold). These results support the multimodal effects of pregnane glycosides on feeding regulation, which depends on the activity of the melanocortin signaling pathway and BDNF.}, number={8}, journal={Journal of Agricultural and Food Chemistry}, publisher={American Chemical Society (ACS)}, author={Komarnytsky, Slavko and Esposito, Debora and Rathinasabapathy, Thirumurugan and Poulev, Alexander and Raskin, Ilya}, year={2013}, month={Feb}, pages={1841–1849} }
 @article{komarnytsky_esposito_poulev_raskin_2013, title={Pregnane glycosides interfere with steroidogenic enzymes to down-regulate corticosteroid production in human adrenocortical H295R cells}, volume={228}, ISSN={["0021-9541"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84873858511&partnerID=MN8TOARS}, DOI={10.1002/jcp.24262}, abstractNote={Abstract}, number={5}, journal={JOURNAL OF CELLULAR PHYSIOLOGY}, author={Komarnytsky, Slavko and Esposito, Debora and Poulev, Alexander and Raskin, Ilya}, year={2013}, month={May}, pages={1120–1126} }
 @article{esposito_munafo_lucibello_baldeon_komarnytsky_gianfagna_2013, title={Steroidal glycosides from the bulbs of Easter lily (Lilium longiflorum Thunb.) promote dermal fibroblast migration in vitro}, volume={148}, ISSN={["0378-8741"]}, DOI={10.1016/j.jep.2013.04.032}, abstractNote={Preparations derived from bulbs of various Lilium species have been used to promote the healing of skin abrasions, sores and burns and to aid in healing wounds in Traditional Chinese and Greco-Roman Medicine. To evaluate fractionated Easter lily bulb extracts and their steroidal glycosides (1–5) for the promotion of dermal fibroblast migration in vitro, a model for the early events in wound healing. An activity-guided screening approach was used by coupling sequential solvent extraction, gel permeation chromatography (GPC), and semi-preparative reverse-phase high performance liquid chromatography (RP-HPLC) with an in vitro dermal fibroblast migration assay. Cytotoxicity was evaluated with methyl thiazole tetrazolium (MTT). To gain insight into the mode of action of the steroidal glycosides, nitric oxide (NO) production, and expression of genes for transforming growth factor beta-1 (TGF-β) and its receptors were evaluated. Fractionated bulb extracts and the two isolated steroidal glycoalkaloids (1) and (2) induced NO production and TGF-β receptor I mRNA expression in fibroblast cell culture. In a cytotoxicity assay, steroidal glycosides (1) and (3) had IC50 values of 8.2 and 8.7 µM, but the natural acetylation of the C-6″′ hydroxy of the terminal glucose unit in (2) resulted in a 3-fold decrease in cell cytotoxicity when compared with (1). Results from the dermal fibroblast migration assay revealed that the steroidal glycoalkaloids (1) and (2), and the furostanol saponin (3) promoted fibroblast migration from the range of 23.7±5.7 to 37.7±5.1%, as compared with the control. Collectively, our data demonstrate that the steroidal glycosides present in Easter lily bulbs induce, at least in part, the observed dermal fibroblast migration activity of the bulb extracts. This is the first evidence that steroidal glycosides from Lilium longiflorum may potentially play a role in the wound healing process and may provide a scientific basis for the historical use of lily bulbs for this purpose.}, number={2}, journal={JOURNAL OF ETHNOPHARMACOLOGY}, publisher={Elsevier BV}, author={Esposito, Debora and Munafo, John P., Jr. and Lucibello, Teresa and Baldeon, Manuel and Komarnytsky, Slavko and Gianfagna, Thomas J.}, year={2013}, month={Jul}, pages={433–440} }
 @article{esposito_raskin_komarnytsky_2012, title={Modulation of muscle mass and myogenic stem cells with natural products}, volume={78}, ISSN={0032-0943 1439-0221}, url={http://dx.doi.org/10.1055/s-0032-1320461}, DOI={10.1055/s-0032-1320461}, abstractNote={Muscle satellite cells are widely accepted as the resident stem cells of skeletal muscle, supplying myoblasts for growth, homeostasis and repair. Activation of these cells in response to muscle mechanical change or injury involves activation of the muscle-specific transcription networks. Previously we reported that brassinosteroids, a group of natural plant hormones that regulate growth and development, triggered an anabolic response when fed orally to rats. Here we show that this effect was associated with increased expression of the myogenic transcription factors and quiescent myogenic satellite cell Pax3/7 markers. In L6 rat myoblast lineage cells, brassinosteroid treatment accelerated differentiation, expression of structural proteins, and fusion into multinucleated myotubes. Collectively, these data indicate that activation, increased proliferation, and subsequent fusion of myogenic cells may be an important mechanism by which brassinosteroids enhance muscle hypertrophy. Thus, in appropriate doses, brassinosteroids may have therapeutic applications for the treatment of diseases associated with muscle loss.}, number={11}, journal={Planta Medica}, publisher={Georg Thieme Verlag KG}, author={Esposito, D and Raskin, I and Komarnytsky, S}, year={2012}, month={Jul} }
 @inproceedings{esposito_raskin_komarnytsky_2012, title={Modulation of muscle mass and myogenic stem cells with natural products}, volume={78}, number={11}, booktitle={Planta Medica}, author={Esposito, D. and Raskin, I. and Komarnytsky, S.}, year={2012}, pages={1096–1096} }
 @article{esposito_rathinasabapathy_poulev_komarnytsky_raskin_2011, title={Akt-Dependent Anabolic Activity of Natural and Synthetic Brassinosteroids in Rat Skeletal Muscle Cells}, volume={54}, ISSN={0022-2623 1520-4804}, url={http://dx.doi.org/10.1021/jm200028h}, DOI={10.1021/jm200028h}, abstractNote={Brassinosteroids are plant-derived polyhydroxylated derivatives of 5α-cholestane, structurally similar to cholesterol-derived animal steroid hormones and insect ecdysteroids. In this study, we synthesized a set of brassinosteroid analogues of a natural brassinosteroid (22S,23S)-homobrassinolide (HB, 1), including (22S,23S)-homocastasterone (2), (22S,23S)-3α-fluoro-homobrasinolide (3), (22S,23S)-3α-fluoro-homocastasterone (4), (22S,23S)-7-aza-homobrassinolide (5), and (22S,23S)-6-aza-homobrassinolide (6) and studied their anabolic efficacy in the L6 rat skeletal muscle cells in comparison to other synthetic and naturally occurring brassinosteroids (22R,23R)-homobrassinolide (7), (22S,23S)-epibrassinolide (8), and (22R,23R)-epibrassinolide (9). Presence of the 6-keto group in the B ring and stereochemistry of 22α,23α-vicinal hydroxyl groups in the side chain were critical for the anabolic activity, possibly due to higher cytotoxicity of the 22β,23β-hydroxylated brassinosteroids. All anabolic brassinosteroids tested in this study selectively activated PI3K/Akt signaling pathway as evident by increased Akt phosphorylation in vitro. Plant brassinosteroids and their synthetic derivatives may offer a novel therapeutic strategy for promoting growth, repair, and maintenance of skeletal muscles.}, number={12}, journal={Journal of Medicinal Chemistry}, publisher={American Chemical Society (ACS)}, author={Esposito, Debora and Rathinasabapathy, Thirumurugan and Poulev, Alexander and Komarnytsky, Slavko and Raskin, Ilya}, year={2011}, month={Jun}, pages={4057–4066} }