@article{milhem_hamilton_skates_wilson_johanningsmeier_komarnytsky_2024, title={Biomarkers of Metabolic Adaptation to High Dietary Fats in a Mouse Model of Obesity Resistance}, volume={14}, ISSN={["2218-1989"]}, url={https://doi.org/10.3390/metabo14010069}, DOI={10.3390/metabo14010069}, abstractNote={Obesity-resistant (non-responder, NR) phenotypes that exhibit reduced susceptibility to developing obesity despite being exposed to high dietary fat are crucial in exploring the metabolic responses that protect against obesity. Although several efforts have been made to study them in mice and humans, the individual protective mechanisms are poorly understood. In this exploratory study, we used a polygenic C57BL/6J mouse model of diet-induced obesity to show that NR mice developed healthier fat/lean body mass ratios (0.43 ± 0.05) versus the obesity-prone (super-responder, SR) phenotypes (0.69 ± 0.07, p < 0.0001) by upregulating gene expression networks that promote the accumulation of type 2a, fast-twitch, oxidative muscle tissues. This was achieved in part by a metabolic adaptation in the form of blood glucose sparing, thus aggravating glucose tolerance. Resistance to obesity in NR mice was associated with 4.9-fold upregulated mitoferrin 1 (Slc25a37), an essential mitochondrial iron importer. SR mice also showed fecal volatile metabolite signatures of enhanced short-chain fatty acid metabolism, including increases in detrimental methyl formate and ethyl propionate, and these effects were reversed in NR mice. Continued research into obesity-resistant phenotypes can offer valuable insights into the underlying mechanisms of obesity and metabolic health, potentially leading to more personalized and effective approaches for managing weight and related health issues.}, number={1}, journal={METABOLITES}, author={Milhem, Fadia and Hamilton, Leah M. and Skates, Emily and Wilson, Mickey and Johanningsmeier, Suzanne D. and Komarnytsky, Slavko}, year={2024}, month={Jan} }
 @article{tanveer_shehzad_komarnytsky_butt_shahid_aadil_2024, title={Comparative evaluation of the antioxidant and anti-inflammatory potential of fennel essential oil obtained by conventional and supercritical fluid extraction}, volume={2}, ISSN={["2190-6823"]}, DOI={10.1007/s13399-024-05405-8}, journal={BIOMASS CONVERSION AND BIOREFINERY}, author={Tanveer, Mahwish and Shehzad, Aamir and Komarnytsky, Slavko and Butt, Masood Sadiq and Shahid, Muhammad and Aadil, Rana Muhammad}, year={2024}, month={Feb} }
 @article{surzenko_bastidas_reid_curaba_zhang_bostan_wilson_dominique_roberson_ignacio_et al._2024, title={Functional recovery following traumatic brain injury in rats is enhanced by oral supplementation with bovine thymus extract}, volume={38}, ISSN={["1530-6860"]}, DOI={10.1096/fj.202301859R}, abstractNote={Abstract}, number={3}, journal={FASEB JOURNAL}, author={Surzenko, Natalia and Bastidas, Johana and Reid, Robert W. and Curaba, Julien and Zhang, Wei and Bostan, Hamed and Wilson, Mickey and Dominique, Ashley and Roberson, Julia and Ignacio, Glicerio and et al.}, year={2024}, month={Feb} }
 @article{milhem_skates_wilson_komarnytsky_2024, title={Obesity-Resistant Mice on a High-Fat Diet Display a Distinct Phenotype Linked to Enhanced Lipid Metabolism}, volume={16}, ISSN={["2072-6643"]}, url={https://doi.org/10.3390/nu16010171}, DOI={10.3390/nu16010171}, abstractNote={Individually, metabolic variations can significantly influence predisposition to obesity in the form of the obesity-prone (super-responders) and obesity-resistant (non-responders) phenotypes in response to modern calorie-dense diets. In this study, C57BL/6J mice (n = 76) were randomly assigned to either a low-fat diet (LFD) or a high-fat diet (HFD) for 6 weeks, followed by selection of the normally obese (HFD), non-responders (NR), super-responders (SR), or super-responders switched back to the low-fat diet (SR-LFD) for an additional 8 weeks. SR mice showed the highest gains in body weight, lean and fat body mass, and total and free water, in part due to increased feed efficiency, despite having a respiratory exchange ratio (RER) similar to that of NR mice. A switch to the LFD was sufficient to revert most of the observed physiological changes in the SR-LFD mice; however, voluntary physical activity and exercise capacity did not return to the basal level. NR mice showed the highest food intake, lowest feed efficiency, increased oxygen consumption during the light (rest) cycle, increased physical activity during the dark (active) cycle, and increased heat production during both cycles. These variations were observed in the absence of changes in food intake and fecal parameters; however, NR fecal lipid content was lower, and the NR fecal microbiome profile was characterized by reduced abundance of Actinobacteria. Taken together, our findings suggest that NR mice showed an increased ability to metabolize excessive dietary fats in skeletal muscle at the expense of reduced exercise capacity that persisted for the duration of the study. These findings underscore the need for further comprehensive investigations into the mechanisms of obesity resistance, as they hold potential implications for weight-loss strategies in human subjects.}, number={1}, journal={NUTRIENTS}, author={Milhem, Fadia and Skates, Emily and Wilson, Mickey and Komarnytsky, Slavko}, year={2024}, month={Jan} }
 @article{grodsky_wilson_rathinasabapathy_komarnytsky_2024, title={Triptolide Administration Alters Immune Responses to Mitigate Insulin Resistance in Obese States}, volume={14}, ISSN={["2218-273X"]}, url={https://doi.org/10.3390/biom14040395}, DOI={10.3390/biom14040395}, abstractNote={Individuals who are overweight or obese are at increased risk of developing prediabetes and type 2 diabetes, yet the direct molecular mechanisms that connect diabetes to obesity are not clear. Chronic, sustained inflammation is considered a strong risk factor in these interactions, directed in part by the short-lived gene expression programs encoding for cytokines and pro-inflammatory mediators. In this study, we show that triptolide administration in the C57BL/6 diet-induced obese mice at up to 10 μg/kg/day for 10 weeks attenuated the development of insulin resistance and diabetes, but not obesity, in these animals. Significant reductions in adipose tissue inflammation and improved insulin sensitivity were observed in the absence of changes in food intake, body weight, body composition, or energy expenditure. Analysis of the core cluster of biomarkers that drives pro-inflammatory responses in the metabolic tissues suggested TNF-α as a critical point that affected the co-development of inflammation and insulin resistance, but also pointed to the putatively protective roles of increased COX-2 and IL-17A signaling in the mediation of these pathophysiological states. Our results show that reduction of diet-induced inflammation confers partial protection against insulin resistance, but not obesity, and suggest the possibility of achieving overweight phenotypes that are accompanied by minimal insulin resistance if inflammation is controlled.}, number={4}, journal={BIOMOLECULES}, author={Grodsky, Lyudmila and Wilson, Mickey and Rathinasabapathy, Thirumurugan and Komarnytsky, Slavko}, year={2024}, month={Apr} }
 @article{carlisle_polley_panda_barron_hamrock_dominique_metzger_le brun-blashka_komarnytsky_2023, title={Alleviation of Pain, PAIN Interference, and Oxidative Stress by a Novel Combination of Hemp Oil, Calamari Oil, and Broccoli: A Randomized, Double-Blind, Placebo-Controlled Trial}, volume={15}, ISSN={["2072-6643"]}, url={https://doi.org/10.3390/nu15122654}, DOI={10.3390/nu15122654}, abstractNote={Chronic pain is a critical health issue in the US that is routinely managed pharmacologically with diminishing results. The widespread misuse and abuse of prescription opioid pain medications have caused both healthcare providers and patients to seek alternative therapeutic options. Several dietary ingredients have been traditionally used for pain relief and are known to have potential analgesic properties. This double-blind, placebo-controlled randomized clinical trial aimed to test whether a novel combination of full spectrum hemp oil (phytocannabinoids), calamari oil (omega-3 fatty acids), and broccoli (glucosinolates) could reduce chronic pain and attenuate damage from oxidative stress in adults seeking chiropractic care. Participants (average age = 54.8 ± 13.6 years old) were randomly assigned to consume a whole-food, multi-ingredient supplement (n = 12, intervention and standard chiropractic care) or placebo (n = 13, mineral oil and standard chiropractic care) daily for 12 weeks. The subjects’ self-reported perceived pain, pain interference, and reactive oxygen species (ROS) status in the peripheral blood mononuclear cells (PBMC) were quantified at baseline, mid-checkpoint, and postintervention. The intervention was positively associated with a 52% decrease in pain intensity and several parameters of pain interference, including quality of sleep. Decreases in the markers of oxidative stress were also observed in the participants from the intervention group (29.4% decrease in PMBC ROS). Our findings indicated that supplementation with a novel combination of hemp oil, calamari oil, and broccoli has the potential to manage chronic pain when combined with standard chiropractic care, as suggested by its effects on pain intensity and oxidative stress.}, number={12}, journal={NUTRIENTS}, author={Carlisle, Carolina and Polley, Kristine and Panda, Chinmayee and Barron, Keri and Hamrock, Meghan and Dominique, Ashley and Metzger, Brandon and Le Brun-Blashka, Sara and Komarnytsky, Slavko}, year={2023}, month={Jun} }
 @article{komarnytsky_wagner_gutierrez_shaw_2023, title={Berries in Microbiome-Mediated Gastrointestinal, Metabolic, and Immune Health}, volume={2}, ISSN={["2161-3311"]}, url={https://doi.org/10.1007/s13668-023-00449-0}, DOI={10.1007/s13668-023-00449-0}, abstractNote={{"Label"=>"PURPOSE OF REVIEW"} Current research has shown that berry-derived polymeric substrates that resist human digestion (dietary fibers and polyphenols) are extensively metabolized in the gastrointestinal tract dominated by microbiota. This review assesses current epidemiological, experimental, and clinical evidence of how berry (strawberry, blueberry, raspberry, blackberry, cranberry, black currant, and grapes) phytochemicals interact with the microbiome and shape health or metabolic risk factor outcomes. {"Label"=>"RECENT FINDINGS"} There is a growing evidence that the compositional differences among complex carbohydrate fractions and classes of polyphenols define reversible shifts in microbial populations and human metabolome to promote gastrointestinal health. Interventions to prevent gastrointestinal inflammation and improve metabolic outcomes may be achieved with selection of berries that provide distinct polysaccharide substrates for selective multiplication of beneficial microbiota or oligomeric decoys for binding and elimination of the pathogens, as well as phenolic substrates that hold potential to modulate gastrointestinal mucins, reduce luminal oxygen, and release small phenolic metabolites signatures capable of ameliorating inflammatory and metabolic perturbations. These mechanisms may explain many of the differences in microbiota and host gastrointestinal responses associated with increased consumption of berries, and highlight potential opportunities to intentionally shift gut microbiome profiles or to modulate risk factors associated with better nutrition and health outcomes.}, journal={CURRENT NUTRITION REPORTS}, author={Komarnytsky, Slavko and Wagner, Charles and Gutierrez, Janelle and Shaw, Odette M.}, year={2023}, month={Feb} }
 @misc{balfany_gutierrez_moncada_komarnytsky_2023, title={Current Status and Nutritional Value of Green Leaf Protein}, volume={15}, ISSN={["2072-6643"]}, url={https://doi.org/10.3390/nu15061327}, DOI={10.3390/nu15061327}, abstractNote={Green leaf biomass is one of the largest underutilized sources of nutrients worldwide. Whether it is purposely cultivated (forage crops, duckweed) or upcycled as a waste stream from the mass-produced agricultural crops (discarded leaves, offcuts, tops, peels, or pulp), the green biomass can be established as a viable alternative source of plant proteins in food and feed processing formulations. Rubisco is a major component of all green leaves, comprising up to 50% of soluble leaf protein, and offers many advantageous functional features in terms of essential amino acid profile, reduced allergenicity, enhanced gelation, foaming, emulsification, and textural properties. Nutrient profiles of green leaf biomass differ considerably from those of plant seeds in protein quality, vitamin and mineral concentration, and omega 6/3 fatty acid profiles. Emerging technological improvements in processing fractions, protein quality, and organoleptic profiles will enhance the nutritional quality of green leaf proteins as well as address scaling and sustainability challenges associated with the growing global demand for high quality nutrition.}, number={6}, journal={NUTRIENTS}, author={Balfany, Connor and Gutierrez, Janelle and Moncada, Marvin and Komarnytsky, Slavko}, year={2023}, month={Mar} }
 @misc{alghamdi_gutierrez_komarnytsky_2023, title={Essential Minerals and Metabolic Adaptation of Immune Cells}, volume={15}, ISSN={["2072-6643"]}, url={https://doi.org/10.3390/nu15010123}, DOI={10.3390/nu15010123}, abstractNote={Modern lifestyles deviated considerably from the ancestral routines towards major shifts in diets and increased sedentarism. The trace elements status of the human body is no longer adequately supported by micronutrient-inferior farmed meats and crop commodities produced by the existing agricultural food systems. This is particular evident in the increased obesogenic adipogenesis and low-grade inflammation that fails to resolve with time. The metabolically restrictive environment of the inflamed tissues drives activation and proliferation of transient and resident populations of immune cells in favor of pro-inflammatory phenotypes, as well as a part of the enhanced autoimmune response. As different stages of the immune activation and resolution depend on the availability of specific minerals to maintain the structural integrity of skin and mucus membranes, activation and migration of immune cells, activation of the complement system, and the release of pro-inflammatory cytokines and chemokines, this review discusses recent advances in our understanding of the contribution of select minerals in optimizing the responses of innate and adaptive immune outcomes. An abbreviated view on the absorption, transport, and delivery of minerals to the body tissues as related to metabolic adaptation is considered.}, number={1}, journal={NUTRIENTS}, author={Alghamdi, Malak and Gutierrez, Janelle and Komarnytsky, Slavko}, year={2023}, month={Jan} }
 @article{panda_komarnytsky_fleming_marsh_barron_le brun-blashka_metzger_2023, title={Guided Metabolic Detoxification Program Supports Phase II Detoxification Enzymes and Antioxidant Balance in Healthy Participants}, volume={15}, ISSN={["2072-6643"]}, url={https://doi.org/10.3390/nu15092209}, DOI={10.3390/nu15092209}, abstractNote={Adequate antioxidant supply is essential for maintaining metabolic homeostasis and reducing oxidative stress during detoxification. The emerging evidence suggests that certain classes of phytonutrients can help support the detoxification process by stimulating the liver to produce detoxification enzymes or acting as antioxidants that neutralize the harmful effects of free radicals. This study was designed to examine the effects of a guided 28-day metabolic detoxification program in healthy adults. The participants were randomly assigned to consume a whole food, multi-ingredient supplement (n = 14, education and intervention) or control (n = 18, education and healthy meal) daily for the duration of the trial. The whole food supplement contained 37 g/serving of a proprietary, multicomponent nutritional blend in the form of a rehydratable shake. Program readiness was ensured at baseline using a validated self-perceived wellness score and a blood metabolic panel, indicating stable emotional and physical well-being in both groups. No significant changes or adverse effects were found on physical or emotional health, cellular glutathione (GSH) and the GSH:GSSG ratio, porphyrin, and hepatic detoxification biomarkers in urine. The intervention was positively associated with a 23% increase in superoxide dismutase (p = 0.06) and a 13% increase in glutathione S-transferase (p = 0.003) activities in the blood. This resulted in a 40% increase in the total cellular antioxidant capacity (p = 0.001) and a 13% decrease in reactive oxygen species (p = 0.002) in isolated PBMCs from participants in the detoxification group. Our findings indicate that consuming a whole food nutritional intervention as a part of the guided detoxification program supported phase II detoxification, in part, by promoting enhanced free radical scavenging and maintaining redox homeostasis under the body’s natural glutathione recycling capacity.}, number={9}, journal={NUTRIENTS}, author={Panda, Chinmayee and Komarnytsky, Slavko and Fleming, Michelle Norton and Marsh, Carissa and Barron, Keri and Le Brun-Blashka, Sara and Metzger, Brandon}, year={2023}, month={May} }
 @misc{milhem_komarnytsky_2023, title={Progression to Obesity: Variations in Patterns of Metabolic Fluxes, Fat Accumulation, and Gastrointestinal Responses}, volume={13}, ISSN={["2218-1989"]}, url={https://doi.org/10.3390/metabo13091016}, DOI={10.3390/metabo13091016}, abstractNote={Obesity is a multifactorial disorder that is remarkably heterogeneous. It presents itself in a variety of phenotypes that can be metabolically unhealthy or healthy, associate with no or multiple metabolic risk factors, gain extreme body weight (super-responders), as well as resist obesity despite the obesogenic environment (non-responders). Progression to obesity is ultimately linked to the overall net energy balance and activity of different metabolic fluxes. This is particularly evident from variations in fatty acids oxidation, metabolic fluxes through the pyruvate-phosphoenolpyruvate-oxaloacetate node, and extracellular accumulation of Krebs cycle metabolites, such as citrate. Patterns of fat accumulation with a focus on visceral and ectopic adipose tissue, microbiome composition, and the immune status of the gastrointestinal tract have emerged as the most promising targets that allow personalization of obesity and warrant further investigations into the critical issue of a wider and long-term weight control. Advances in understanding the biochemistry mechanisms underlying the heterogenous obesity phenotypes are critical to the development of targeted strategies to maintain healthy weight.}, number={9}, journal={METABOLITES}, author={Milhem, Fadia and Komarnytsky, Slavko}, year={2023}, month={Sep} }
 @article{garcia_you_aleman_king_komarnytsky_hoskin_moncada_2023, title={Total Utilization-Upcycling of Mushroom Protein By-Product: Characterization and Assessment as an Alternative Batter Ingredient for Fried Shrimp}, volume={12}, ISSN={["2304-8158"]}, url={https://doi.org/10.3390/foods12040763}, DOI={10.3390/foods12040763}, abstractNote={Mushroom by-products are economical and eco-friendly raw materials with bioactive and functional characteristics that allow for potential uses as food ingredients. However, mushroom upcycling has yet to be fully exploited, despite the many opportunities that mushrooms may offer. The mushroom protein by-product (MPBP) resulting from mushroom protein production was characterized (chemical composition, physicochemical attributes, and functional properties) and incorporated into plant-based batter formulations to prepare four experimental groups with different ratios (w/w, %) of wheat flour (W) to MPBP (100 W, 75 W/25 MPBP, 25 W/75 MPBP, and 100 MPBP). Subsequently, the batter was used for frying batter-coated shrimp, which was evaluated for cooking loss, coating pick-up, oil absorption, and color parameters (L*, a*, and b*). MPBP showed high content of dietary fiber, mainly insoluble fiber (49%), and it is potentially suited for the formulation of high-fiber food products. The MPBP physicochemical attributes pH (11.69), water activity (0.34), L* (58.56), a* (5.61), b* (18.03), and particle size distribution (250–500 µm (22.12%), 125–250 µm (41.18%), 63–125 µm (37.53%), and < 63 µm (0.82%) were noted. Concerning the MPBP functional characteristics, solubility (12.7%), emulsifying activity index (7.6 m2/gr), emulsion stability index (52.4 min), water holding capacity (4.9%), and oil holding capacity (4.8%) were reported. Adding MPBP into batter formulations for batter-coated shrimp resulted in higher values of cooking loss, oil absorption, coating pick-up, and a* color, while lowering L* and b* values. The best experimental results were reported for group 75 W/25 MPBP, which indicates that MPBP can potentially be accepted as a novel batter ingredient for partial substitution of wheat flour.}, number={4}, journal={FOODS}, author={Garcia, Diego and You, Seung Woon and Aleman, Ricardo S. and King, Joan M. and Komarnytsky, Slavko and Hoskin, Roberta Targino and Moncada, Marvin}, year={2023}, month={Feb} }
 @misc{vong_rathinasabapathy_moncada_komarnytsky_2022, title={All Polyphenols Are Not Created Equal: Exploring the Diversity of Phenolic Metabolites}, volume={70}, ISSN={["1520-5118"]}, url={https://doi.org/10.1021/acs.jafc.1c07179}, DOI={10.1021/acs.jafc.1c07179}, abstractNote={Dietary intake of plant polyphenols is significant, and many of them enter a human body as a highly diverse pool of ring-fission phenolic metabolites arising from digestion and microbial catabolism of the parental structures. Difficulty in designing the uniform intervention studies and limited tools calibrated to detect and quantify the inherent complexity of phenolic metabolites hindered efforts to establish and validate protective health effects of these molecules. Here, we highlight the recent findings that describe novel complex downstream metabolite profiles with a particular focus on dihydrophenolic (phenylpropanoic) acids of microbial origin, ingested and phase II-transformed methylated phenolic metabolites (methylated sinks), and small phenolic metabolites derived from the breakdown of different classes of flavonoids, stilbenoids, and tannins. There is a critical need for precise identification of the individual phenolic metabolite signatures originating from different polyphenol groups to enable future translation of these findings into break-through nutritional interventions and dietary guidelines.}, number={7}, journal={JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY}, author={Vong, Chi In and Rathinasabapathy, Thirumurugan and Moncada, Marvin and Komarnytsky, Slavko}, year={2022}, month={Feb}, pages={2077–2091} }
 @article{rathinasabapathy_lomax_srikanth_esposito_kay_komarnytsky_2022, title={Effect of Wild Blueberry Metabolites on Biomarkers of Gastrointestinal and Immune Health In Vitro}, volume={2}, url={https://doi.org/10.3390/immuno2020019}, DOI={10.3390/immuno2020019}, abstractNote={Wild blueberries (Vaccinium angustifolium Aiton.) are a rich source of dietary fiber and (poly)phenols with gastrointestinal and immune health-promoting properties, however, their mechanisms of action on the intestinal epithelial cells and transient tissue macrophages remain to be elucidated. In this study, we evaluated the individual effects of anthocyanins, short-chain fatty acids (metabolites derived from fiber), and a series of hydroxycinnamic and hydroxybenzoic acid metabolites common to anthocyanins and other polyphenols on epithelial gut homeostasis in human colon epithelial CCD-18 cells and murine RAW 264.7 macrophages. Gastrointestinal cell migration was enhanced in response to anthocyanin glucosides with the maximum effect observed for malvidin-3-glucoside, and a structural subset of hydroxybenzoic acids, especially 2-hydroxybenzoic acid. Enhanced staining for ZO-1 protein in the junctional complexes was observed in CCD-18 cells treated with malvidin and butyrate, as well as several phenolic metabolites, including hydroxybenzoic and hydroxycinnamic acids. Nitric oxide production and pro-inflammatory gene expression profiles in the LPS-stimulated macrophages were mostly affected by treatments with 3-caffeoylquinic (chlorogenic) and 3,4-dihydroxycinnamic (caffeic) acids, as well as 2-hydroxybenzoic acid. This study lays the foundation for future investigations evaluating the effects of dietary interventions on managing gastrointestinal and inflammatory pathophysiological outcomes.}, number={2}, journal={Immuno}, publisher={MDPI AG}, author={Rathinasabapathy, Thirumurugan and Lomax, Jade and Srikanth, Kavin and Esposito, Debora and Kay, Colin D. and Komarnytsky, Slavko}, year={2022}, month={Mar}, pages={293–306} }
 @misc{komarnytsky_retchin_vong_lila_2022, title={Gains and Losses of Agricultural Food Production: Implications for the Twenty-First Century}, volume={13}, ISSN={["1941-1421"]}, DOI={10.1146/annurev-food-082421-114831}, abstractNote={ The world food supply depends on a diminishing list of plant crops and animal livestock to not only feed the ever-growing human population but also improve its nutritional state and lower the disease burden. Over the past century or so, technological advances in agricultural and food processing have helped reduce hunger and poverty but have not adequately addressed sustainability targets. This has led to an erosion of agricultural biodiversity and balanced diets and contributed to climate change and rising rates of chronic metabolic diseases. Modern food supply chains have progressively lost dietary fiber, complex carbohydrates, micronutrients, and several classes of phytochemicals with high bioactivity and nutritional relevance. This review introduces the concept of agricultural food systems losses and focuses on improved sources of agricultural diversity, proteins with enhanced resilience, and novel monitoring, processing, and distribution technologies that are poised to improve food security, reduce food loss and waste, and improve health profiles in the near future. }, journal={ANNUAL REVIEW OF FOOD SCIENCE AND TECHNOLOGY}, author={Komarnytsky, Slavko and Retchin, Sophia and Vong, Chi In and Lila, Mary Ann}, year={2022}, pages={239–261} }
 @article{you_hoskin_komarnytsky_moncada_2022, title={Mushrooms as Functional and Nutritious Food Ingredients for Multiple Applications}, volume={6}, ISSN={["2692-1944"]}, url={https://doi.org/10.1021/acsfoodscitech.2c00107}, DOI={10.1021/acsfoodscitech.2c00107}, abstractNote={The interest in mushrooms as functional ingredients has increased in the past decade. Mushrooms have low fat content and high fiber and protein contents and are natural sources of valuable food molecules such as ergosterol, polyphenols, terpene and terpenoids, and mannitol and trehalose. Mushrooms have been used as ingredients in meat- and starch-based food formulations with varying degrees of success, but their technological and functional performances in food formulations are yet to be investigated and fully explored for applications directed to the emerging alternative, meat-free, clean-label marketplace. Therefore, in this review, the current scientific data regarding the attributes of mushrooms that elicit their unique functional and nutritional properties, their relevance to the food industry, and potential opportunities for developing innovative, good-tasting, protein-rich foods from mushrooms are presented and discussed.}, journal={ACS FOOD SCIENCE & TECHNOLOGY}, author={You, Seung Woon and Hoskin, Roberta Targino and Komarnytsky, Slavko and Moncada, Marvin}, year={2022}, month={Jun} }
 @misc{rathinasabapathy_sakthivel_komarnytsky_2022, title={Plant-Based Support of Respiratory Health during Viral Outbreaks}, volume={70}, ISSN={["1520-5118"]}, url={https://doi.org/10.1021/acs.jafc.1c06227}, DOI={10.1021/acs.jafc.1c06227}, abstractNote={Respiratory viruses are linked to major epidemic events that have plagued humans through recorded history and possibly much earlier, ranging from common colds, influenza, and coronavirus infections to measles. However, difficulty in developing effective pharmaceutical solutions to treat infected individuals has hindered efforts to manage and minimize respiratory viral outbreaks and the associated mortality. Here we highlight a series of botanical interventions with different and often overlapping putative mechanisms of action to support the respiratory system, for which the bioactive pharmacophore was suggested and the initial structure-activity relationships have been explored (Bupleurum spp., Glycyrrhiza spp., Andrographis spp.), have been proposed with uncertainty (Echinacea spp., Zingiber spp., Verbascum spp., Marrubium spp.), or remained to be elucidated (Sambucus spp., Urtica spp.). Investigating these metabolites and their botanical sources holds potential to uncover new mediators of the respiratory health outcomes as well as molecular targets for future break-through therapeutic interventions targeting respiratory viral outbreaks.}, number={7}, journal={JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY}, author={Rathinasabapathy, Thirumurugan and Sakthivel, Lakshmana Prabu and Komarnytsky, Slavko}, year={2022}, month={Feb}, pages={2064–2076} }
 @misc{komarnytsky_rathinasabapathy_wagner_metzger_carlisle_panda_le brun-blashka_troup_varadharaj_2021, title={Endocannabinoid System and Its Regulation by Polyunsaturated Fatty Acids and Full Spectrum Hemp Oils}, volume={22}, ISSN={["1422-0067"]}, url={https://doi.org/10.3390/ijms22115479}, DOI={10.3390/ijms22115479}, abstractNote={The endocannabinoid system (ECS) consists of endogenous cannabinoids, their receptors, and metabolic enzymes that play a critical homeostatic role in modulating polyunsaturated omega fatty acid (PUFA) signaling to maintain a balanced inflammatory and redox state. Whole food-based diets and dietary interventions linked to PUFAs of animal (fish, calamari, krill) or plant (hemp, flax, walnut, algae) origin, as well as full-spectrum hemp oils, are increasingly used to support the ECS tone, promote healthy metabolism, improve risk factors associated with cardiovascular disorders, encourage brain health and emotional well-being, and ameliorate inflammation. While hemp cannabinoids of THC and CBD groups show distinct but complementary actions through a variety of cannabinoid (CB1 and CB2), adenosine (A2A), and vanilloid (TRPV1) receptors, they also modulate PUFA metabolism within a wide variety of specialized lipid mediators that promote or resolve inflammation and oxidative stress. Clinical evidence reviewed in this study links PUFAs and cannabinoids to changes in ECS tone, immune function, metabolic and oxidative stress adaptation, and overall maintenance of a well-balanced systemic function of the body. Understanding how the body coordinates signals from the exogenous and endogenous ECS modulators is critical for discerning the underlying molecular mechanisms of the ECS tone in healthy and disease states. Nutritional and lifestyle interventions represent promising approaches to address chronic metabolic and inflammatory disorders that may overlap in the population at risk. Further investigation and validation of dietary interventions that modulate the ECS are required in order to devise clinically successful second-generation management strategies.}, number={11}, journal={INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, author={Komarnytsky, Slavko and Rathinasabapathy, Thirumurugan and Wagner, Charles and Metzger, Brandon and Carlisle, Carolina and Panda, Chinmayee and Le Brun-Blashka, Sara and Troup, John P. and Varadharaj, Saradhadevi}, year={2021}, month={Jun} }
 @article{esposito_overbaugh_xiong_rathinasabapathy_komarnytsky_silva_esposito_2021, title={Immune Responses Are Differentially Regulated by Root, Stem, Leaf, and Flower Extracts of Female and Male CBD Hemp (Cannabis sativa L.) Plants}, url={https://doi.org/10.3390/immuno1040025}, DOI={10.3390/immuno1040025}, abstractNote={Industrial hemp (Cannabis sativa L.) has many applications, including the production of textiles, agricultural extracts, nutritional products, and botanicals enriched with cannabinoids and full-spectrum terpenes naturally present in the plant. In this study, the dynamics of distribution and accumulation of 10 main cannabinoids in hemp were quantified. Hemp bioactive compounds were evaluated for anti-inflammatory activity in lipopolysaccharide-induced RAW 264.7 macrophage cells. While all tissues of hemp showed moderate anti-inflammatory properties, female flowers demonstrated the highest activity. CBD showed the strongest anti-inflammatory activity with suppression of nitric oxide production at 2 μg/mL and the reduced expressions of the pro-inflammatory genes COX-2, IL-6, and TNF-α at as low as 2 ng/mL. The topical hemp inflorescences (1–50 μg/mL) and CBD alone (20–200 ng/mL) also improved mitochondrial respiration. These data contribute to the future development of agricultural and plant management techniques to produce hemp with specific metabolite profiles to selectively support immune health.}, journal={Immuno}, author={Esposito, Laura G. A. and Overbaugh, Ezekial and Xiong, Jia and Rathinasabapathy, Thirumurugan and Komarnytsky, Slavko and Silva, Derly José Henriques and Esposito, Debora A.}, year={2021}, month={Oct} }
 @article{chiang_ray_lomax_goertzen_komarnytsky_ho_munafo_2021, title={Modulation of Brain-Derived Neurotrophic Factor (BDNF) Signaling Pathway by Culinary Sage (Salvia officinalis L.)}, volume={22}, ISSN={["1422-0067"]}, url={https://doi.org/10.3390/ijms22147382}, DOI={10.3390/ijms22147382}, abstractNote={Culinary sage (Salvia officinalis L.) is a common spice plant in the mint family (Lamiaceae) well known for its distinctive culinary and traditional medicinal uses. Sage tea has been used traditionally as a brain-enhancing tonic and extracts from sage have been reported to have both cognitive and memory enhancing effects. Brain-derived neurotrophic factor (BDNF) is an endogenous signaling molecule involved in cognition and memory function. In this study, activity-guided fractionation employing preparative reverse-phase high performance liquid chromatography (RP-HPLC) of culinary sage extracts led to the discovery of benzyl 6-O-β-D-apiofuranosyl-β-D-glucoside (B6AG) as a natural product that upregulates transcription of neurotrophic factors in C6 glioma cells. Purified B6AG showed a moderate dose response, with upregulation of BDNF and with EC50 at 6.46 μM. To better understand the natural variation in culinary sage, B6AG was quantitated in the leaves of several commercial varieties by liquid chromatography-mass spectrometry (LC-MS). The level of B6AG in dried culinary sage was found to range from 334 ± 14 to 698 ± 65 μg/g. This study provided a foundation for future investigations, including quantitative inquiries on the distribution of B6AG within the different plant organs, explorations in optimizing post-harvest practices, and aid in the development of sage varieties with elevated levels of B6AG.}, number={14}, journal={INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, publisher={MDPI AG}, author={Chiang, Nancy and Ray, Shahla and Lomax, Jade and Goertzen, Sydney and Komarnytsky, Slavko and Ho, Chi-Tang and Munafo, John P., Jr.}, year={2021}, month={Jul} }
 @article{wilson_konda_heidt_rathinasabapathy_desai_komarnytsky_2021, title={Rheum rhaponticum Root Extract Improves Vasomotor Menopausal Symptoms and Estrogen-Regulated Targets in Ovariectomized Rat Model}, volume={22}, ISSN={["1422-0067"]}, url={https://doi.org/10.3390/ijms22031032}, DOI={10.3390/ijms22031032}, abstractNote={Ovarian insufficiency and ovariectomy are characterized by deregulated heat loss mechanisms. Unlike hormone therapy, ERr 731 (a standardized botanical extract of Siberian rhubarb Rheum rhaponticum L. high in rhaponticin) acts like a selective estrogen receptor modulator for ERβ receptors and may offer a higher degree of safety while maintaining the desired efficacy profile. In this study, we examined the relationship between oral administration of ERr 731 and the underlying components of skin vasomotion responses in an ovariectomized (OVX) rat model. ERr 731 dose-dependently reduced tail skin temperature (Tskin) values by an average of 1 °C. The rapid onset of this effect was observed in 1 and 3 mg/kg/day ERr 731 groups as early as day 2 of administration, and remained in place for the duration of the treatment (2 weeks). Substituting ERr 731 after E2 withdrawal helped maintain body temperature similarly to E2 alone, suggesting the usefulness of ERr 731 for replacing existing hormonal therapy in humans. ERr 731 also acted as a highly selective agonist for ERβ in the hypothalamus of OVX rats, as well as in ERα/β cell-based reporter assays. These data validate the OVX/Tskin rat model as a suitable screening platform to evaluate botanical and pharmaceutical treatments of menopause, while providing further evidence for the efficacy of ERr 731 towards alleviating vasomotor menopausal symptoms and improving wellbeing during the menopausal transition.}, number={3}, journal={INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, publisher={MDPI AG}, author={Wilson, Mickey and Konda, Veera and Heidt, Kathryn and Rathinasabapathy, Thirumurugan and Desai, Anuradha and Komarnytsky, Slavko}, year={2021}, month={Feb} }
 @misc{wagner_de gezelle_komarnytsky_2020, title={Celtic Provenance in Traditional Herbal Medicine of Medieval Wales and Classical Antiquity}, volume={11}, ISSN={["1663-9812"]}, DOI={10.3389/fphar.2020.00105}, abstractNote={The Celtic linguistic community dominated large spans of Central and Western Europe between 800 BC and 500 AD, but knowledge of their traditional medicine is very limited. Multiple progressive plant gains in Neolithic settlements along the Danube and up the Rhine valleys suggested that taxon diversity of gathered plants peaked at the Balkans and was subsequently reduced as crop and gathered plants packages were adopted and dispersed throughout Neolithic Europe. This process coincided with the Bronze Age migration of the R1b proto-Celtic tribes, and their herbal traditions were occasionally recorded in the classic Greco-Roman texts on herbal medicines. The provenance of Celtic (Gallic) healing methods and magical formulas as recorded by Pliny, Scribonius Largus, and Marcellus Empiricus can still be found in the first part of the medieval Welsh (Cymry) herbal manuscript Meddygon Myddfai (recipes 1–188). Although the majority of Myddfai I recipes were based on the Mediterranean herbal tradition of Dioscorides and Macer Floridus, they preserved the unique herbal preparation signatures distinct from continental and Anglo-Saxon counterparts in increased use of whey and ashes as vehicles for formulation of herbal remedies. Six plants could be hypothetically attributed to the Celtic (Welsh) herbal tradition including foxglove (Digitalis purpurea L.), corn bellflower (Legousia speculum-veneris L.), self-heal (Prunella vulgaris L.), sharp dock (Rumex conglomeratus Murray), water pimpernel (Samolus valerandi L.), and river startip (Scapania undulata L.) This review provides initial evidence for traces of Celtic framework in the Welsh herbal tradition and warrants further investigations of bioactivity and clinical applications of the described plant leads.}, journal={FRONTIERS IN PHARMACOLOGY}, author={Wagner, Charles and De Gezelle, Jillian and Komarnytsky, Slavko}, year={2020}, month={Feb} }
 @article{xiong_chan_rathinasabapathy_grace_komarnytsky_lila_2020, title={Enhanced stability of berry pomace polyphenols delivered in protein-polyphenol aggregate particles to an in vitro gastrointestinal digestion model}, volume={331}, url={https://doi.org/10.1016/j.foodchem.2020.127279}, DOI={10.1016/j.foodchem.2020.127279}, abstractNote={Stability of protein-polyphenol aggregate particles, created by complexing polyphenols from blueberry and muscadine grape pomaces with a rice-pea protein isolate blend, was evaluated in an in vitro gastrointestinal model. Recovery index (RI; % total phenolics present post-digestion) was 69% and 62% from blueberry and muscadine grape protein-polyphenol particles, compared to 23% and 31% for the respective pomace extracts. Anthocyanins RI was 52% and 42% from particles (6% and 13% from pomace extracts), and proanthocyanidins RI was 77% and 73% from particles (25% and 14% from pomace extracts), from blueberry and grape, respectively. Protein-polyphenol particle digests retained 1.5 to 2-fold higher antioxidant capacity and suppressed the expression of pro-inflammatory cytokines, iNOS, IL6, and IL1β, compared to unmodified extract digests, which only suppressed IL6. Protein-polyphenol particles as a delivery vehicle in foods may confer better stability during gastrointestinal transit, allow protected polyphenols to reach the gut microbiota, and preserve polyphenol bioactivity.}, journal={Food Chemistry}, publisher={Elsevier BV}, author={Xiong, Jia and Chan, Yu Hsuan and Rathinasabapathy, Thirumurugan and Grace, Mary H. and Komarnytsky, Slavko and Lila, Mary Ann}, year={2020}, month={Nov}, pages={127279} }
 @article{de canha_komarnytsky_langhansova_lall_2020, title={Exploring the Anti-Acne Potential of Impepho [Helichrysum odoratissimum (L.) Sweet] to Combat Cutibacterium acnes Virulence}, volume={10}, ISSN={["1663-9812"]}, DOI={10.3389/fphar.2019.01559}, abstractNote={The Gram-positive bacterium Cutibacterium acnes (previously Propionibacterium acnes), plays an important role in the pathogenesis and progression of the dermatological skin disorder acne vulgaris. The methanolic extract of Helichrysum odoratissimum (L.) Sweet (HO-MeOH) was investigated for its ability to target bacterial growth and pathogenic virulence factors associated with acne progression. The gas chromatography–mass spectrometry (GC-MS) analysis of HO-MeOH identified α-humulene (3.94%), α-curcumene (3.74%), and caryophyllene (8.12%) as major constituents, which correlated with previous reports of other Helichrysum species. The HO-MeOH extract exhibited potent antimicrobial activity against C. acnes (ATCC 6919) with a minimum inhibitory concentration (MIC) of 7.81 µg/ml. It enhanced the antimicrobial activity of benzoyl peroxide (BPO). The extract showed high specificity against C. acnes cell aggregation at sub-inhibitory concentrations, preventing biofilm formation. Mature C. acnes biofilms were disrupted at a sub-inhibitory concentration of 3.91 µg/ml. At 100 µg/ml, HO-MeOH reduced interleukin-1α (IL-1α) cytokine levels in C. acnes-induced human keratinocytes (HaCaT) by 11.08%, highlighting its potential as a comedolytic agent for the treatment of comedonal acne. The extract exhibited a 50% inhibitory concentration (IC50) of 157.50 µg/ml against lipase enzyme activity, an enzyme responsible for sebum degradation, ultimately causing inflammation. The extract’s anti-inflammatory activity was tested against various targets associated with inflammatory activation by the bacterium. The extract inhibited pro-inflammatory cytokine levels of IL-8 by 48.31% when compared to C. acnes-induced HaCaT cells at 7.81 µg/ml. It exhibited cyclooxygenase-II (COX-II) enzyme inhibition with an IC50 of 22.87 µg/ml. Intracellular nitric oxide (NO) was inhibited by 40.39% at 7.81 µg/ml when compared with NO production in lipopolysaccharide (LPS)-induced RAW264.7 cells. The intracellular NO inhibition was potentially due to the 2.14 fold reduction of inducible nitric oxide synthase (iNOS) gene expression. The HO-MeOH extract exhibited an IC50 of 145.45 µg/ml against virulent hyaluronidase enzyme activity, which is responsible for hyaluronan degradation and scar formation. This study provides scientific validation for the traditional use of H. odoratissimum as an ointment for pimples, not only due to its ability to control C. acnes proliferation but also due to its inhibitory activity on various targets associated with bacterial virulence leading to acne progression.}, journal={FRONTIERS IN PHARMACOLOGY}, author={De Canha, Marco Nuno and Komarnytsky, Slavko and Langhansova, Lenka and Lall, Namrita}, year={2020}, month={Jan} }
 @article{tanveer_wagner_haq_ribeiro_rathinasabapathy_butt_shehzad_komarnytsky_2020, title={Spicing up gastrointestinal health with dietary essential oils}, volume={19}, url={https://doi.org/10.1007/s11101-020-09664-x}, DOI={10.1007/s11101-020-09664-x}, number={2}, journal={Phytochemistry Reviews}, publisher={Springer Science and Business Media LLC}, author={Tanveer, Mahwish and Wagner, Charles and Haq, Muhammad Ikram and Ribeiro, Nilton C. and Rathinasabapathy, Thriumurugan and Butt, Masood Sadiq and Shehzad, Aamir and Komarnytsky, Slavko}, year={2020}, month={Apr}, pages={243–263} }
 @misc{moore_wagner_komarnytsky_2020, title={The Enigma of Bioactivity and Toxicity of Botanical Oils for Skin Care}, volume={11}, ISSN={["1663-9812"]}, DOI={10.3389/fphar.2020.00785}, abstractNote={Botanical oils have a long history of traditional use and are routinely applied to skin care. The focus of this review is to contrast the functionality of skin oils versus the differential biological and toxicological effects of major plant oils, and to correlate them to their compositional changes. In total, over 70 vegetable oils were clustered according to their lipid composition to promote awareness of health practitioners and botanical product manufacturers for the safety and efficacy of oil-based interventions based on their fatty acid profiles. Since multiple skin disorders result in depletion or disturbance of skin lipids, a tailored mixture of multiple botanical oils to simultaneously maintain natural skin-barrier function, promote repair and regeneration of wounded tissues, and achieve corrective modulation of immune disorders may be required. As bioactive constituents of botanical oils enter the human body by oral or topical application and often accumulate in measurable blood concentrations, there is also a critical need for monitoring their hazardous effects to reduce the possible over-added toxicity and promote maximal normal tissue sparing. The review also provides a useful tool to improve efficacy and functionality of fatty acid profiles in cosmetic applications.}, journal={FRONTIERS IN PHARMACOLOGY}, author={Moore, Erin M. and Wagner, Charles and Komarnytsky, Slavko}, year={2020}, month={May} }
 @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{murray_palatini_komarnytsky_gianfagna_munafo_2019, title={Phenylpropanoid Glycerol Glucosides Attenuate Glucose Production in Hepatocytes}, volume={4}, ISSN={["2470-1343"]}, DOI={10.1021/acsomega.9b00751}, abstractNote={An activity-guided fractionation approach revealed several phenylpropanoid glycerol glucosides isolated from the bulbs of Lilium longiflorum Thunb. (Easter lily) with gluconeogenesis inhibitory activities. The strongest activity was observed for (2S)-1-O-p-coumaroyl-2-O-β-d-glucopyranosylglycerol (3), (2S)-1-O-caffeoyl-2-O-β-d-glucopyranosylglycerol (1), and (2R)-1-O-β-d-glucopyranosyl-2-O-p-coumaroylglycerol (2) with inhibitions of 51.2, 39.2, and 36.8%, respectively. The p-coumaroyl-based (3) and its acetylated derivative (5) exhibited differential inhibition activity (51.2% as compared to 3.6%), suggesting that natural acetylation decreases the hypoglycemic activity of these compounds. Direct structure–activity analysis of phenylpropanoid glycerol glucosides indicated that the hydroxylation pattern of the hydroxy cinnamic acid moiety and acetylation were responsible for the differences in activity. This is the first report of phenylpropanoid glycerol glucosides as a phytochemical class of hepatic glucose production inhibitors.}, number={6}, journal={ACS OMEGA}, author={Murray, Anne F. and Palatini, Kimberly and Komarnytsky, Slavko and Gianfagna, Thomas J. and Munafo, John P., Jr.}, year={2019}, month={Jun}, pages={10670–10676} }
 @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{kozlowska_wagner_moore_matkowski_komarnytsky_2018, title={Botanical Provenance of Traditional Medicines From Carpathian Mountains at the Ukrainian-Polish Border}, volume={9}, ISSN={["1663-9812"]}, DOI={10.3389/fphar.2018.00295}, abstractNote={Plants were an essential part of foraging for food and health, and for centuries remained the only medicines available to people from the remote mountain regions. Their correct botanical provenance is an essential basis for understanding the ethnic cultures, as well as for chemical identification of the novel bioactive molecules with therapeutic effects. This work describes the use of herbal medicines in the Beskid mountain ranges located south of Krakow and Lviv, two influential medieval centers of apothecary tradition in the region. Local botanical remedies shared by Boyko, Lemko, and Gorale ethnic groups were a part of the medieval European system of medicine, used according to their Dioscoridean and Galenic qualities. Within the context of ethnic plant medicine and botanical classification, this review identified strong preferences for local use of St John's-wort (Hypericum perforatum L.), wormwood (Artemisia absinthium L.), garlic (Allium sativum L.), gentian (Gentiana lutea L.), lovage (Levisticum officinale W.D.J. Koch), and lesser periwinkle (Vinca minor L.). While Ukrainian ethnic groups favored the use of guilder-rose (Viburnum opulus L.) and yarrow (Achillea millefolium L.), Polish inhabitants especially valued angelica (Angelica archangelica L.) and carline thistle (Carlina acaulis L.). The region also holds a strong potential for collection, cultivation, and manufacture of medicinal plants and plant-based natural specialty ingredients for the food, health and cosmetic industries, in part due to high degree of biodiversity and ecological preservation. Many of these products, including whole food nutritional supplements, will soon complement conventional medicines in prevention and treatment of diseases, while adding value to agriculture and local economies.}, journal={FRONTIERS IN PHARMACOLOGY}, author={Kozlowska, Weronika and Wagner, Charles and Moore, Erin M. and Matkowski, Adam and Komarnytsky, Slavko}, year={2018}, month={Apr} }
 @article{overall_lila_komarnytsky_2017, title={Anthocyanins in metabolic health and disease}, journal={Nutrigenomics and proteomics in health and disease: towards a systems-level understanding of gene-diet interactions, 2nd edition}, author={Overall, J. and Lila, M. A. and Komarnytsky, S.}, year={2017}, pages={92–124} }
 @article{wagner_de gezelle_robertson_robertson_wilson_komarnytsky_2017, title={Antibacterial activity of medicinal plants from The Physicians of Myddvai, a 14th century Welsh medical manuscript}, volume={203}, ISSN={["1872-7573"]}, DOI={10.1016/j.jep.2017.03.039}, abstractNote={Antimicrobial drug resistance is a growing threat to global public health. Historical records and herbal texts relating to traditional Celtic medicine indicate an extensive pharmacopeia of plants for treating infections likely caused by microbes. However, a major barrier for successful integration of these remedies into mainstream practice is the current lack of accurate interpretation and scientific validation. We investigated the flora of the Isle of Arran, Scotland, via in situ targeted screening of 83 out of 138 plants identified in Meddygion Myddvai (a 14th century Welsh manuscript) to treat conditions related to microbial infections, and an additional 18 plants from modern ethnobotanical knowledge on the island (Scottish School of Herbal Medicine). In a follow-up proof-of-concept study, bioassay-guided fractionation was performed to identify bioactive constituents from two high scoring hits that inhibited Staphylococcus aureus (Gram-positive) and Escherichia coli (Gram-negative) bacterial growth. 67 historical plants (80.7%) and 14 modern plants (77.8%) were found to have detectable levels of antimicrobial activity when tested using Mobile Discovery kits, with human saliva as a source of bacteria for screening. Sabinene, a natural bicyclic monoterpene from juniper “berries” (Juniperus communis L.) and alliin, a natural sulfoxide from garlic cloves (Allium sativum L.), were isolated and confirmed as primary antibacterial leads. Using historical medical sources such as those associated with traditional Celtic medicine to guide rigorous, evidence-based scientific investigation, provides additional leads for new and alternative bioactive molecules for combating bacterial diseases.}, journal={JOURNAL OF ETHNOPHARMACOLOGY}, publisher={Elsevier BV}, author={Wagner, Charles Stephen and De Gezelle, Jillian and Robertson, Maureen and Robertson, Keith and Wilson, Mickey and Komarnytsky, Slavko}, year={2017}, month={May}, pages={171–181} }
 @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://www.scopus.com/inward/record.url?eid=2-s2.0-85013078281&partnerID=MN8TOARS}, 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{graf_kamat_cheong_komarnytsky_driscoll_di_2017, title={Phytoecdysteroid-enriched quinoa seed leachate enhances healthspan and mitochondrial metabolism in Caenorhabditis elegans}, volume={37}, ISSN={["1756-4646"]}, DOI={10.1016/j.jff.2017.07.016}, abstractNote={Quinoa (Chenopodium quinoa Willd.) phytochemicals have exhibited metabolic benefit in mammals, though their effects on aging and mechanisms of action remain unknown. Caenorhabditis elegans offers a practical in vivo model to study bioactivity since major metabolic pathways are conserved across phyla. We explored the effects of phytoecdysteroid-enriched quinoa seed preparation, termed quinoa leachate (QL), on behavioral and biochemical endpoints of wild-type C. elegans health. QL treatment (1.0 mg/mL or less) increased median lifespan from 9 to 11 d, improved locomotory performance from 103.5 to 114.9 head thrashes/min, and enhanced basal respiration rate by 37%. QL also reduced advanced glycation end-product (AGE) pigments by 24%, reactive oxygen species (ROS) by 20%, and body fat by 14%. 20-Hydroxyecdysone (20HE), the primary phytoecdysteroid in QL, conferred statistically similar benefit compared to QL at equivalent doses. Data suggest that quinoa supplementation slows C. elegans aging and improves metabolic health, and 20HE is the primary bioactive constituent responsible for favorable effects.}, journal={JOURNAL OF FUNCTIONAL FOODS}, author={Graf, Brittany L. and Kamat, Shaunak and Cheong, Kuan Yu and Komarnytsky, Slavko and Driscoll, Monica and Di, Rong}, year={2017}, month={Oct}, pages={1–7} }
 @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{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{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{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{bussler_hildebrand_mixon_wagoner_komarnytsky_harris_2015, title={Flavonoid Supplementation and Cardiovascular Disease}, DOI={10.1201/b18490-14}, journal={Dietary Supplements in Health Promotion}, publisher={Informa UK Limited}, author={Bussler, Weston and Hildebrand, Joseph and Mixon, Catherine and Wagoner, Ty and Komarnytsky, Slavko and Harris, Gabriel}, year={2015}, month={May}, pages={281–318} }
 @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{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{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{esposito_rathinasabapathy_schmidt_shakarjian_komarnytsky_raskin_2013, title={Acceleration of cutaneous wound healing by brassinosteroids}, volume={21}, ISSN={["1524-475X"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84883490805&partnerID=MN8TOARS}, DOI={10.1111/wrr.12075}, abstractNote={Abstract}, number={5}, journal={WOUND REPAIR AND REGENERATION}, publisher={Wiley-Blackwell}, author={Esposito, Debora and Rathinasabapathy, Thirumurugan and Schmidt, Barbara and Shakarjian, Michael P. and Komarnytsky, Slavko and Raskin, Ilya}, year={2013}, month={Sep}, pages={688–696} }
 @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_kizelsztein_komarnytsky_raskin_2012, title={Hypoglycemic effects of brassinosteroid in diet-induced obese mice}, volume={303}, ISSN={["0193-1849"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84865726866&partnerID=MN8TOARS}, DOI={10.1152/ajpendo.00024.2012}, abstractNote={ The prevalence of obesity is increasing globally, and obesity is a major risk factor for metabolic diseases such as type 2 diabetes. Previously, we reported that oral administration of homobrassinolide (HB) to healthy rats triggered a selective anabolic response that was associated with lower blood glucose. Therefore, the aim of this study was to evaluate the effects of HB administration on glucose metabolism, insulin sensitivity, body composition, and gluconeogenic gene expression profiles in liver of C57BL/6J high-fat diet-induced obese mice. Acute oral administration of 50–300 mg/kg HB to obese mice resulted in a dose-dependent decrease in fasting blood glucose within 3 h of treatment. Daily chronic administration of HB (50 mg/kg for 8 wk) ameliorated hyperglycemia and improved oral glucose tolerance associated with obesity without significantly affecting body weight or body composition. These changes were accompanied by lower expression of two key gluconeogenic enzymes, phospho enolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G-6-Pase), and increased phosphorylation of AMP-activated protein kinase in the liver and muscle tissue. In vitro, HB treatment (1–15 μM) inhibited cyclic AMP-stimulated but not dexamethasone-stimulated upregulation of PEPCK and G-6-Pase mRNA levels in H4IIE rat hepatoma cells. Among a series of brassinosteroid analogs related to HB, only homocastasterone decreased glucose production in cell culture significantly. These results indicate the antidiabetic effects of brassinosteroids and begin to elucidate their putative cellular targets both in vitro and in vivo. }, number={5}, journal={AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM}, author={Esposito, Debora and Kizelsztein, Pablo and Komarnytsky, Slavko and Raskin, Ilya}, year={2012}, month={Sep}, pages={E652–E658} }
 @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{komarnytsky_borisjuk_2012, title={Plant-Derived Antibodies for Academic, Industrial, and Therapeutic Applications}, DOI={10.1002/9781118229019.ch17}, abstractNote={Molecular pharming can be defined as an expression of a commercially valuable protein with specific therapeutic or diagnostic activity outside its natural source of origin. The process of molecular pharming requires prior knowledge of the sequence of the target protein, its structure requirements, and the ability to express the target protein in the heterologous host system [1]. Several key discoveries led to the development of molecular pharming. In 1869, Johann Miescher identified DNA, a weakly acidic substance in the human cell nucleus. The relationship between DNA and protein biosynthesis was hypothesized for the first time by Archibald Garrod in 1909. Subsequently, James Watson, Francis Crick, and Sidney Brenner discovered the molecular structure of DNA (1953) and established the notion that different codons are used to specify individual amino acids (1961). The next step toward molecular pharming was Hamilton Smith’s discovery of restriction enzymes that digest DNA at well-defined locations (1970). By combining restriction digestion and ligation of the DNA fragments, Stanley Cohen and Herbert Boyer created the first recombinant DNA in 1972. Six years later, somatostatin became the first human protein to be manufactured using prokaryote recombinant technology [2].}, journal={Antibody-Mediated Drug Delivery Systems}, publisher={Wiley-Blackwell}, author={Komarnytsky, Slavko and Borisjuk, Nikolai}, year={2012}, month={Apr}, pages={365–381} }
 @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} }
 @article{esposito_komarnytsky_shapses_raskin_2011, title={Anabolic effect of plant brassinosteroid}, volume={25}, ISSN={["1530-6860"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-80053916822&partnerID=MN8TOARS}, DOI={10.1096/fj.11-181271}, abstractNote={Brassinosteroids are plant‐derived polyhydroxylated derivatives of 5a‐cholestane, structurally similar to cholesterol‐derived animal steroid hormones and insect ecdysteroids, with no known function in mammals. 28‐Homobrassinolide (HB), a steroidal lactone with potent plant growth‐promoting property, stimulated protein synthesis and inhibited protein degradation in L6 rat skeletal muscle cells (EC50 4 μM) mediated in part by PI3K/Akt signaling pathway. Oral administration of HB (20 or 60 mg/kg/d for 24 d) to healthy rats fed normal diet (protein content 23.9%) increased food intake, body weight gain, lean body mass, and gastrocnemius muscle mass as compared with vehicle‐treated controls. The effect of HB administration increased slightly in animals fed a high‐protein diet (protein content 39.4%). Both oral (up to 60 mg/kg) and subcutaneous (up to 4 mg/kg) administration of HB showed low androgenic activity when tested in the Hershberger assay. Moreover, HB showed no direct binding to the androgen receptor in vitro. HB treatment was also associated with an improved physical fitness of untrained healthy rats, as evident from a 6.7% increase in lower extremity strength, measured by grip test. In the gastrocnemius muscle of castrated animals, HB treatment significantly increased the number of type IIa and IIb fibers and the cross‐sectional area of type I and type IIa fibers. These findings suggest that oral application of HB triggers selective anabolic response with minimal or no androgenic side‐effects and begin to elucidate the putative cellular targets for plant brassinosteroids in mammals.—Esposito, D., Komarnytsky, S., Shapses, S., Raskin, I. Anabolic effect of plant brassinosteroid. FASEB J. 25, 3708–3719 (2011). www.fasebj.org}, number={10}, journal={FASEB JOURNAL}, author={Esposito, Debora and Komarnytsky, Slavko and Shapses, Sue and Raskin, Ilya}, year={2011}, month={Oct}, pages={3708–3719} }
 @article{komarnytsky_cook_raskin_2011, title={Potato protease inhibitors inhibit food intake and increase circulating cholecystokinin levels by a trypsin-dependent mechanism}, volume={35}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-79951682968&partnerID=MN8TOARS}, DOI={10.1038/ijo.2010.192}, abstractNote={To investigate the mechanisms underlying the satiety-promoting effects of a novel protease inhibitor concentrate derived from potato (PPIC).The acute and prolonged effects of oral PPIC administration (100 mg kg(-1) per day) on food intake, body weight and gastric emptying were evaluated in healthy rats. Parameters of body weight, food intake, plasma glucose, insulin and cholecystokinin (CCK) were measured. Duodenal proteolytic activity and CCK expression were determined in tissue extracts. Intestinal STC-1 cell culture model was used to investigate the direct effect of PPIC on CCK transcript level and secretion.Acute oral administration of PPIC reduced immediate food intake during the first 2 h following the treatment, delayed gastric emptying and decreased proteolytic activity in the duodenum. Repeated oral ingestion of PPIC reduced weight gain in male rats and significantly elevated the plasma CCK levels. Although duodenal mucosal CCK mRNA levels increased in response to PPIC administration, the concentrate failed to elevate CCK expression or release in STC-1 cells. The 14-day ascending dose range study (33-266 mg kg(-1) PPIC per day) showed no adverse side effects associated with PPIC administration.These findings provided evidence that PPIC is effective in reducing food intake and body weight gain in healthy rats when administered orally by increasing circulating CCK levels through a trypsin-dependent mechanism.}, number={2}, journal={International Journal of Obesity}, author={Komarnytsky, S. and Cook, A. and Raskin, I.}, year={2011}, pages={236–243} }
 @article{kizelsztein_govorko_komarnytsky_evans_wang_cefalu_raskin_2009, title={20-Hydroxyecdysone decreases weight and hyperglycemia in a diet-induced obesity mice model}, volume={296}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-64749102394&partnerID=MN8TOARS}, DOI={10.1152/ajpendo.90772.2008}, abstractNote={The steroid hormone 20-hydroxyecdysone (20HE) is an essential signaling molecule that modulates molting response in insects and may function as a putative anabolic factor in vertebrate animals, although no mammalian 20HE receptor has been identified. Here we show that in H4IIE cell culture, 20HE treatment decreased expression of phospho enolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase), reduced glucose production, and induced Akt2 phosphorylation sensitive to the phosphoinositide-3 kinase pathway-specific inhibitor LY-294002. Daily oral administration of 20HE (10 mg/kg for 13 wk) ameliorated obesity and insulin resistance in C57BL/6J mice fed a high-fat diet and produced a significant decrease of body weight gain and body fat mass compared with nontreated animals as demonstrated by dual-energy X-ray absorptiometry analysis. In addition, plasma insulin levels and glucose tolerance were significantly lowered by 20HE treatment. These changes were accompanied by the reduced hepatic expression of PEPCK and G6Pase and increased adiponectin production by visceral fat tissue. These studies demonstrate the anti-obesity and anti-diabetic effects of 20HE and begin to elucidate its putative cellular targets both in vitro and in vivo.}, number={3}, journal={American Journal of Physiology - Endocrinology and Metabolism}, author={Kizelsztein, P. and Govorko, D. and Komarnytsky, S. and Evans, A. and Wang, Z. and Cefalu, W.T. and Raskin, I.}, year={2009} }
 @article{kizelsztein_komarnytsky_raskin_2009, title={Oral administration of triptolide ameliorates the clinical signs of experimental autoimmune encephalomyelitis (EAE) by induction of HSP70 and stabilization of NF-κB/IκBα transcriptional complex}, volume={217}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-70449635134&partnerID=MN8TOARS}, DOI={10.1016/j.jneuroim.2009.08.017}, abstractNote={Available treatments for multiple sclerosis (MS) require frequent injections and have significant side effects. In this study, we examined the immunomodulatory properties of orally administered triptolide, a major diterpenoid triepoxide isolated from a twining vine Tripterygium wilfordii. SJL/J mice were primed with PLP139–151 peptide and orally treated with triptolide (100 μg/kg per day) from the day of EAE induction (preventive regime) and after the onset of clinical signs (therapeutic regime). Triptolide delayed disease onset, reduced clinical symptoms, decreased the relapse rate, and suppressed inflammation and demyelination in CNS tissue of EAE mice when compared to vehicle-treated animals. Molecular analysis revealed a marked increase of heat shock protein 70 (Hsp70) mRNA and protein in the CNS tissue of triptolide-treated animals. Cytokine and chemokine expression analysis from EAE tissues and in vitro macrophages detected a decrease of key pro-inflammatory mRNAs. Triptolide inhibited IκBα phosphorylation and NF-κB nuclear translocation by stabilization of NF-κB/IκBα complex, possibly due to a direct physical interaction between NF-κB and Hsp70 proteins. Lymph node cell proliferation assay in EAE confirmed the immunosuppressive efficacy of triptolide. Our data indicate that daily oral administration of triptolide exhibits not only a preventive but also a therapeutic effect on EAE. These effects might be explained by the increase in Hsp70 levels driven by triptolide and stabilization of the NF-κB/IκBα complex leading to an attenuated inflammatory response.}, number={1-2}, journal={Journal of Neuroimmunology}, author={Kizelsztein, P. and Komarnytsky, S. and Raskin, I.}, year={2009}, pages={28–37} }
 @article{govorko_logendra_wang_esposito_komarnytsky_ribnicky_poulev_wang_cefalu_raskin_2007, title={Polyphenolic compounds from Artemisia dracunculus L. inhibit PEPCK gene expression and gluconeogenesis in an H4IIE hepatoma cell line}, volume={293}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-37149014571&partnerID=MN8TOARS}, DOI={10.1152/ajpendo.00420.2007}, abstractNote={An ethanolic extract of Russian tarragon, Artemisia dracunculus L., with antihyperglycemic activity in animal models was reported to decrease phospho enolpyruvate carboxykinase (PEPCK) mRNA expression in STZ-induced diabetic rats. A quantitative polymerase chain reaction (qPCR) assay was developed for the bioactivity-guided purification of the compounds within the extract that decrease PEPCK expression. The assay was based on the inhibition of dexamethasone-stimulated PEPCK upregulation in an H4IIE hepatoma cell line. Two polyphenolic compounds that inhibited PEPCK mRNA levels were isolated and identified as 6-demethoxycapillarisin and 2′,4′-dihydroxy-4-methoxydihydrochalcone with IC50values of 43 and 61 μM, respectively. The phosphoinositide-3 kinase (PI3K) inhibitor LY-294002 showed that 6-demethoxycapillarisin exerts its effect through the activation of the PI3K pathway, similarly to insulin. The effect of 2′,4′-dihydroxy-4-methoxydihydrochalcone is not regulated by PI3K and dependent on activation of AMPK pathway. These results indicate that the isolated compounds may be responsible for much of the glucose-lowering activity of the Artemisia dracunculus extract.}, number={6}, journal={American Journal of Physiology - Endocrinology and Metabolism}, author={Govorko, D. and Logendra, S. and Wang, Y. and Esposito, D. and Komarnytsky, S. and Ribnicky, D. and Poulev, A. and Wang, Z. and Cefalu, W.T. and Raskin, I.}, year={2007} }
 @article{okunji_komarnytsky_fear_poulev_ribnicky_awachie_ito_raskin_2007, title={Preparative isolation and identification of tyrosinase inhibitors from the seeds of Garcinia kola by high-speed counter-current chromatography}, volume={1151}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-34247554803&partnerID=MN8TOARS}, DOI={10.1016/j.chroma.2007.02.085}, abstractNote={In continuation of our search for bioactive natural products that can be used for the treatment of dermatological disorders associated with melanin hyperpigmentation, 50 extracts/fractions from 21 families of medicinal plants from West and Central Africa were evaluated for inhibitory activity against tyrosinase (E:C:1.14.18.1), the rate-limiting enzyme in melanin synthesis. Four extracts including the methanol extract of Garcinia kola seeds at 100 μg/ml displayed >60% inhibition of tyrosinase activity. Preparative high-speed counter-current chromatography with solvent system composed of n-hexane–ethyl acetate–methanol–water (3:5:3:5) successfully separated the most active extract from G. kola seed. By stepwise increase of the flow-rate of the mobile phase, five major biflavanones including GB-I-glucoside (1) GB-1a (2), GB-1 (3), GB-2 (4), kolaflavonone (5) were successfully isolated in 6 h. Compound (4) was the most potent (IC50 582 μM) and compared favorably with a reference tyrosinase inhibitor (kojic acid, IC50 130 μM).}, number={1-2}, journal={Journal of Chromatography A}, author={Okunji, C. and Komarnytsky, S. and Fear, G. and Poulev, A. and Ribnicky, D.M. and Awachie, P.I. and Ito, Y. and Raskin, I.}, year={2007}, pages={45–50} }
 @article{fear_komarnytsky_raskin_2007, title={Protease inhibitors and their peptidomimetic derivatives as potential drugs}, volume={113}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-33846415469&partnerID=MN8TOARS}, DOI={10.1016/j.pharmthera.2006.09.001}, abstractNote={Precise spatial and temporal regulation of proteolytic activity is essential to human physiology. Modulation of protease activity with synthetic peptidomimetic inhibitors has proven to be clinically useful for treating human immunodeficiency virus (HIV) and hypertension and shows potential for medicinal application in cancer, obesity, cardiovascular, inflammatory, neurodegenerative diseases, and various infectious and parasitic diseases. Exploration of natural inhibitors and synthesis of peptidomimetic molecules has provided many promising compounds performing successfully in animal studies. Several protease inhibitors are undergoing further evaluation in human clinical trials. New research strategies are now focusing on the need for improved comprehension of protease-regulated cascades, along with precise selection of targets and improved inhibitor specificity. It remains to be seen which second generation agents will evolve into approved drugs or complementary therapies.}, number={2}, journal={Pharmacology and Therapeutics}, author={Fear, G. and Komarnytsky, S. and Raskin, I.}, year={2007}, pages={354–368} }
 @article{komarnytsky_borisjuk_yakoby_garvey_raskin_2006, title={Cosecretion of protease inhibitor stabilizes antibodies produced by plant roots}, volume={141}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-33747144853&partnerID=MN8TOARS}, DOI={10.1104/pp.105.074419}, abstractNote={Abstract}, number={4}, journal={Plant Physiology}, author={Komarnytsky, S. and Borisjuk, N. and Yakoby, N. and Garvey, A. and Raskin, I.}, year={2006}, pages={1185–1193} }
 @article{komarnytsky_gaume_garvey_borisjuk_raskin_2004, title={A quick and efficient system for antibiotic-free expression of heterologous genes in tobacco roots}, volume={22}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-2442419120&partnerID=MN8TOARS}, DOI={10.1007/s00299-004-0761-7}, abstractNote={Requirement for antibiotic-resistance selection markers and difficulty in identifying transgenes with the highest expression levels remain the major obstacles for rapid production of recombinant proteins in plants. An alternative approach to producing transgenic plants free of antibiotic-resistance markers is the phenotypic-based selection with root-proliferation genes (rol genes) of Agrobacterium rhizogenes. By using Agrobacterium tumefaciens harboring the pRYG transformation vector with a cluster of rol genes linked to a heterologous gene of interest, we have developed a rapid transformation tool using hairy root formation as a selection marker. The expression of beta-glucuronidase in newly induced transgenic tobacco roots could be detected as early as 12 days after inoculation. Higher levels of transgene expression in the roots correlated positively with the rates of root elongation on hormone-free medium and thus could be used for positive selection. When tobacco plants were transformed with pRYG harboring the expression cassette for secreted alkaline phosphatase (SEAP), the release of SEAP from roots of the fully regenerated transgenic plants could be quantified at rates as high as 28 microg/g root dry weight per day.}, number={10}, journal={Plant Cell Reports}, author={Komarnytsky, S. and Gaume, A. and Garvey, A. and Borisjuk, N. and Raskin, I.}, year={2004}, pages={765–773} }
 @article{komarnytsky_borisjuk_2003, title={Functional Analysis of Promoter Elements in Plants}, DOI={10.1007/978-1-4615-0073-5_6}, journal={Genetic Engineering}, publisher={Springer Science \mathplus Business Media}, author={Komarnytsky, Slavko and Borisjuk, Nikolai}, year={2003}, pages={113–141} }
 @article{komarnytsky_borisjuk_2003, title={Functional analysis of promoter elements in plants.}, volume={25}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-3543141756&partnerID=MN8TOARS}, journal={Genetic engineering}, author={Komarnytsky, S. and Borisjuk, N.}, year={2003}, pages={113–141} }
 @article{gaume_komarnytsky_borisjuk_raskin_2003, title={Rhizosecretion of recombinant proteins from plant hairy roots}, volume={21}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0041473693&partnerID=MN8TOARS}, DOI={10.1007/s00299-003-0660-3}, abstractNote={Rhizosecretion of a target protein in the hydroponic medium provides an alternative manufacturing platform that simplifies the downstream purification procedure and increases protein yield. In order to increase the production rates of rhizosecreted proteins, we have exploited the ability of Agrobacterium rhizogenes to induce the formation of large amounts of root tissue on transgenic tobacco plants engineered to secrete a model recombinant protein, human secreted alkaline phosphatase (SEAP). The secretion of SEAP from hairy roots induced on the stems of transgenic tobacco plants was 5-7 times higher than that from adventitious transgenic roots.}, number={12}, journal={Plant Cell Reports}, author={Gaume, A. and Komarnytsky, S. and Borisjuk, N. and Raskin, I.}, year={2003}, pages={1188–1193} }
 @article{raskin_ribnicky_komarnytsky_ilic_poulev_borisjuk_brinker_moreno_ripoll_yakoby_et al._2002, title={Plants and human health in the twenty-first century}, volume={20}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-6444244303&partnerID=MN8TOARS}, DOI={10.1016/S0167-7799(02)02080-2}, abstractNote={The concept of growing crops for health rather than for food or fiber is slowly changing plant biotechnology and medicine. Rediscovery of the connection between plants and health is responsible for launching a new generation of botanical therapeutics that include plant-derived pharmaceuticals, multicomponent botanical drugs, dietary supplements, functional foods and plant-produced recombinant proteins. Many of these products will soon complement conventional pharmaceuticals in the treatment, prevention and diagnosis of diseases, while at the same time adding value to agriculture. Such complementation can be accelerated by developing better tools for the efficient exploration of diverse and mutually interacting arrays of phytochemicals and for the manipulation of the plant's ability to synthesize natural products and complex proteins. This review discusses the history, future, scientific background and regulatory issues related to botanical therapeutics.}, number={12}, journal={Trends in Biotechnology}, publisher={Elsevier BV}, author={Raskin, Ilya and Ribnicky, David M. and Komarnytsky, Slavko and Ilic, Nebojsa and Poulev, Alexander and Borisjuk, Nikolai and Brinker, Anita and Moreno, Diego A. and Ripoll, Christophe and Yakoby, Nir and et al.}, year={2002}, pages={522–531} }
 @article{komarnytsky_komarnytsky_2001, title={Phylogenetic tree of the australian species of Nicotiana based on the random amplified polymorphic DNA}, volume={17}, DOI={10.7124/bc.0005b8}, number={4}, journal={Biopolymers and Cell}, publisher={Institute of Molecular Biology and Genetics (NAS Ukraine)}, author={Komarnytsky, S. I. and Komarnytsky, I. K.}, year={2001}, month={Jul}, pages={278–282} }
 @article{komarnytsky_borisjuk_borisjuk_alam_raskin_2000, title={Production of recombinant proteins in tobacco guttation fluid}, volume={124}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0033729827&partnerID=MN8TOARS}, number={3}, journal={Plant Physiology}, author={Komarnytsky, S. and Borisjuk, N.V. and Borisjuk, L.G. and Alam, M.Z. and Raskin, I.}, year={2000}, pages={927–933} }
 @article{borisjuk_borisjuk_komarnytsky_timeva_hemleben_gleba_raskin_2000, title={Tobacco ribosomal DNA spacer element stimulates amplification and expression of heterologous genes}, volume={18}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0033674453&partnerID=MN8TOARS}, DOI={10.1038/82430}, abstractNote={Here we show that the cis-acting genetic element aps (amplification-promoting sequence), isolated from the nontranscribed spacer region of tobacco ribosomal DNA (rDNA), increases the level of expression of recombinant proteins. Transgenic tobacco plants, transformed with expression cassettes containing the herbicide-resistant acetolactate synthase (hr-ALS) gene or the green fluorescent protein (GFP) gene fused to the aps sequence, had greater levels of corresponding messenger RNAs (mRNAs) and proteins compared to transformants lacking aps. Analysis of transgenic plants showed that aps increased the copy number and transcription of the adjacent heterologous genes and, in the case of hr-ALS, enhanced the herbicide resistance phenotype. Both the increased transgene copy number and enhanced expression were stably inherited. These data provide the first evidence that the aps sequence can be used for gene amplification in transgenic plants and possibly other multicellular organisms.}, number={12}, journal={Nature Biotechnology}, author={Borisjuk, N. and Borisjuk, L. and Komarnytsky, S. and Timeva, S. and Hemleben, V. and Gleba, Y. and Raskin, I.}, year={2000}, pages={1303–1306} }