bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting inflammation and synaptic plasticity with bioactive polyphenol metabolites promotes resilience against stress disorder and depression
Authors: Pasinetti Giulio Maria 
Published: November 2023

It is estimated that current pharmacological treatments for depression produce temporary remission in less than 50% of patients. Given the multifaceted nature of mood‐related disorders, there is a long‐standing need for innovative strategies to treat depression. Stress‐mediated synaptic maladaptations of nucleus accumbens (NAc) medium spiny neurons and induction of interleukin 6 (IL‐6) in the periphery contribute to depression‐like behaviors both in humans and in experimental models. We report for the first time that dietary supplementation with a polyphenol‐rich preparation significantly promotes resilience to stress‐induced depression phenotypes in a repeated social defeat stress (RSDS) model of depression. We identified two phytochemicals, malvidin‐3′‐O‐glucoside (Mal‐gluc) and dihydrocaffeic acid (DHCA), as the bioactive compounds from the polyphenol‐rich preparation. We demonstrated that oral supplementation with combined Mal‐gluc/DHCA can prophylactically and therapeutically promote resilience against RSDS‐mediated depression‐like phenotypes through structural and functional normalization of stress‐induced synaptic maladaptation in the NAc, and attenuation of stress‐mediated induction of IL‐6 in the periphery. Moreover, Mal‐gluc/DHCA is also therapeutically effective in treating depression‐like phenotypes in a model of increased systemic inflammation where mice were transplanted with hematopoietic progenitor cells from stress‐susceptible mice. Our studies provide novel experimental evidence that Mal‐gluc/DHCA can modulate stress‐induced depression‐like phenotypes by simultaneously targeting multiple underlying pathogenic mechanisms that are not addressed by currently available antidepressants. Given their excellent safety, drug‐like properties and their lack of interaction with monoamine receptors/transporters, our study can immediately translate into human clinical studies for the treatment of stress disorders and depression either alone or in combination with currently available antidepressants.Support or Funding InformationFunding was provided by the P50 AT008661‐01 from the National Center for Complementary and Integrative Health (NCCIH) and the Office of Dietary Supplements (ODS), NIH R01 MH090264, NIH R01 MH104559 and NSF81200862.
Comparative Effect of an Anthocyanin‐Rich Extract from Purple Corn and Pure Anthocyanins on 3T3‐L1 Adipocytes under Different Physiological Conditions
Authors: Luna‐Vital Diego Armando , Weiss Matthew , De Mejia Elvira Gonzalez 
Published: November 2023

The prevention of obesity and its related inflammatory effects using natural compounds has gained attention. The aim was to compare the effect of an anthocyanin‐rich extract from purple corn pericarp (PCW) and pure anthocyanins on 3T3‐L1 adipocytes on basal and inflammatory conditions. PCW had mainly cyanidin‐3‐O‐glucoside (C3G) and in a lesser proportion pelargonidin‐3‐O‐glucoside (Pg3G), and peonidin‐3‐O‐glucoside (P3G). Preadipocytes (3T3‐L1) were treated during differentiation with or without PCW (0.125 to 1.0 mg/mL) for ten days. Lipid concentration and expression of peroxisome proliferator‐activated receptor gamma (PPAR‐γ) were determined throughout differentiation. Differentiated adipocytes were treated either individually or in combination with 1 ng/mL tumor necrosis factor alpha (TNF‐α), with 0.4 mg/mL of PCW, 50 μM of either pure C3G, Pg3G, or P3G for 24 h, and the concentration of triglycerides and free glycerol was quantified. A dose‐response inhibition of preadipocyte differentiation due to PCW (IC50 = 0.4 mg/mL) was observed and these results correlated with PPAR‐γ reduction in expression (IC50 = 0.28 mg/mL) (p < 0.05) compared to untreated adipocytes. PCW reduced triglyceride concentration by 45% (p < 0.05) in basal conditions, whereas pure anthocyanins did not exert effects at the concentrations used. Only pure C3G reduced TNF‐α‐dependent triglyceride concentration by 43%. PCW increased 2‐fold glycerol concentration in culture media of adipocytes in basal conditions (p < 0.05), while pure anthocyanins increased 2.8‐fold, compared to untreated adipocytes. In contrast, PCW reduced TNF‐α‐dependent free glycerol concentration by 52%. The contrast of the effects on lipolysis could be due to expression/activity rate of lipogenic and lipolytic enzymes. According to the molecular docking analysis, C3G can bind (−8.9 kcal/mol) to the Ser‐Asp‐His conserved motif of lipoprotein lipase and also to the thioesterase (−9.3 kcal/mol), and β‐ketoacyl reductase (−8.7 kcal/mol) domains of fatty acid synthase. PCW reduced TNF‐α‐dependent inflammatory status increasing adiponectin (39%), leukemia inhibition factor (80%), vascular‐endothelial growth factor (46%), and decreasing leptin (−88%), endocan (−80%), among others. The results suggest that PCW has potential to prevent adipocyte differentiation, lipid accumulation and to act as antagonist of PPAR‐γ on adipocytes in basal conditions. Moreover, PCW reduced the inflammatory status of differentiated adipocytes suggesting that it may be used to combat hyperglycemia associated with the metabolic syndrome or type 2 diabetes.Support or Funding InformationOffice of Research, University of Illinois
Role of Estrogen Receptor Alpha in Protective Effects of Soy in Adipose Tissue Following Ovariectomy
Authors: McCabe Leighton Thomas , Zidon Terese M. , Welly Rebecca J. , Porter Jay W. , Winn Nathan C. , Stricklin Olivia E. , Gastecki Michelle L. , Lubahn Dennis B. , Padilla Jaume , Vieira‐Potter Victoria Jeanne 
Published: November 2023

Loss of ovarian hormone production (e.g., menopause) increases adiposity, adipose tissue (AT) inflammation, and insulin resistance (IR), increasing risk for developing type II diabetes in women. Dietary soy protein extract high in phytoestrogens (~600ppm) (i.e., “SOY”) improves these metabolic parameters in ovariectomized (OVX) rodents, but the mechanisms are not known. We recently demonstrated that the adiposity‐reducing and insulin‐sensitizing effects of SOY were present in estrogen receptor (ER)β‐null, but not ERα‐null mice, leading us to hypothesize that the beneficial effects of SOY were through ERα. To test the hypothesis that SOY has protective effects in AT following OVX that are mediated through ERα, we removed ovaries from ERα‐null (i.e., ERαKO) mice, and their littermate wild‐type (WT) controls, and randomized them to receive either SOY or a control diet devoid of SOY (i.e., “CON”) creating the four groups: ERαWT/CON, ERαWT/SOY, ERαKO/CON, ERαKO/SOY (n=7–12/group; age at start, ~1 yr) which were compared for the outcomes described below using 2‐way ANOVA (i.e., main and interaction effects of genotype (G) and diet (D); p<0.05 considered significant, SPSS v.24). Prior to OVX, ERαKOs weighed more with a greater body fat % (EchoMRI), had greater AT inflammation (i.e., □CD11c and TNFα mRNA), and greater HOMA‐IR values (G, p<0.05 for all). Following OVX, there were no longer differences between KO and WT mice in body fat % or perigonadal white AT weights, and KO mice actually had smaller adipocytes than WT mice (G, p=0.044). Moreover, neither HOMA‐IR nor Adipo‐IR (a surrogate measure of AT IR) were different between genotypes following OVX. However, despite not having greater adiposity or adipocyte hypertrophy, AT from OVX/KO had lower GLUT4 protein and greater inflammatory mRNA (i.e., CD11c) compared to OVX/WT (G, p<0.03), suggesting AT metabolic dysfunction. Counter to our hypothesis, SOY was ineffective at reducing those variables in either genotype, and had no effect on AT insulin signaling proteins (e.g., GLUT4, p‐AKT) in the basal state. This may suggest that other tissues (e.g., skeletal muscle and/or liver) are responsible for the systemic metabolic protection conferred by SOY, or that its positive effects in AT are nullified in the presence of ERβ. Ongoing studies are testing these hypotheses.Support or Funding InformationMU‐CBIS pilot grant (NCCAM/ODS/NCI #P50AT006273)
Cornus officinalis Polyphenols Reduce Senescence of Vascular Cells by Modulating the Antioxidant Response
Authors: Salazar Gloria , Morgan Hannah , Feresin Rafaela G , Klarich Dawn Kylee S 
Published: November 2023

Physiological changes observed during aging, like accumulation of senescent cells, are strongly associated with the development of cardiovascular disease (CVD). Senescent cells secrete reactive oxygen species (ROS), inflammatory molecules and extracellular matrix components causing inflammation and oxidative stress that accelerate tissue dysfunction during aging. The purpose of this study was to investigate whether the cornus officinalis (CO) berry, used in Traditional Chinese Medicine can protect vascular cells from cellular senescence and the molecular mechanism involved. We used vascular smooth muscle cells (VSMCs) treated with angiotensin II (Ang II), a strong stimulator of oxidative stress and senescence, as a model. VSMCs were treated with and without Ang II and CO polyphenol extract for measurements of ROS levels (cytosol and mitochondria), senescence, and expression of antioxidant enzymes as well as NADPH oxidases (Nox). We found that 50–100 microg/ml CO polyphenol extract strongly downregulated the increase in ROS levels and senescence induced by Ang II. This effect was associated with the upregulation of the antioxidant enzymes SOD1, SOD2 and catalase and the downregulation of Nox1. Further, CO polyphenol extract reduced mitochondrial ROS, suggesting that polyphenol compounds in this berry may target the two major sources of ROS, Nox and mitochondria, to reduce senescence of VSMCs. In conclusion, our data suggest that CO polyphenols may slowdown the progression of vascular aging and the incidence of CVD.Support or Funding InformationAmerican Heart Association (14GRNT20180028) and the Florida State University Council on Research and Creativity (COFRS)
The Effect of Daily Soy Isoflavone Supplementation for One Year on Endogenous Steroid Metabolism in Healthy Postmenopausal Women
Authors: Wang Li , Gaikwad Nilesh W. , Steinberg Francene M. 
Published: November 2023

Isoflavones are soy phytoestrogens that have been shown to exert hormonal effects and suggested to be anticarcinogenic. Few studies have investigated long‐term soy isoflavone supplementation on endogenous estrogen metabolism in postmenopausal women. A random subset of samples was selected from the original randomized, double‐blinded, placebo‐controlled 2‐year trial of daily supplementation with 80 or 120 mg hypocotyl isoflavones in healthy postmenopausal women (OPUS trial). Thirty‐eight women (age 41–61y, 95% Caucasian, 0 mg/d placebo group: n=12; 80 mg/d group: n=13, 120 mg/d group: n=12). Each isoflavone tablet had an average content of 34.10 mg aglycone equivalent of total isoflavones (daizein: 22.01 mg, glycitein, 13.54 mg; genistein: 5.00 mg). Serum and urine samples from baseline and after 1year, were analyzed for serum isoflavone metabolites by high performance liquid chromatography (HPLC) – mass spectrometry (MS) and urine steroid metabolites by an ultra performance liquid chromatography (UPLC)‐tandem mass spectrometry (MS/MS) method. Serum concentrations of daidzein, dihydrodaidzein, and O‐desmethylangolensin (O‐DMA) were significantly increased from baseline after 1 year supplementation of both 80 mg and 120 mg isoflavones (p<0.04 for all). The increase of O‐DMA also had a significant dose‐response effect in the 120 mg/d group compared to 80 mg/d group (p<0.05), which validated the study compliance. 28% participants in the supplementation groups were equol producers. Urine concentrations of estrone (E1) and estradiol (E2) were significantly increased (p=0.05 and p=0.02) by 120mg isoflavone supplementation compared to baseline. The change of E2 in the 120mg group was significantly correlated with the change of serum dihydrodaidzein (r=0.69, p=0.01). The concentrations of other endogenous steroids, including estrogen metabolites and the ratio of 2‐OH E1/16α‐OH E1 were not changed in both 80 mg/d and 120 mg/d groups. In conclusion, 1‐year daily supplementation of 120 mg isoflavones increased urine E1 and E2 concentrations, but did not affect the appearance of potential carcinogenic or anticarcinogenic estrogen metabolites. Our findings suggest daily soy hypocotyl isoflavone supplementation for one year has minimal effect on endogenous steroid metabolism in healthy postmenopausal women.Support or Funding InformationFunding from UC Davis Department of Nutrition unrestricted research funds (Steinberg)
Hypoglycaemic and Hypolipidemic Effect of Standardized Small Millet (Paspalum scrobiculatum, Panicum miliare, Setaria italica) Incorporated Cookies fed rats
Authors: Packiyam Karuppasamy , Durairaj Malathi , Nachimuthu Varadharaju 
Published: November 2023

Minor millets are small grained cereals and are the staple food of millions inhabitating the arid and semiarid tropics of ancient world. But there was an lack of consumption of millets in modern diet. Minor millets are so important because of its uniquely high content of nutrients and fibre. Our aim is to increase the consumption of millet and make it beneficial. The aim of this study was to develope millet composite cookies feeding with wistar rats and study the hypoglycemic and hypolipidemic effect for the period of 28 days feeding trial. Rats were grouped into G1‐Normal, G2‐Diabetic control, G3‐Refined wheat cookies, G4‐Kodo millet cookies, G5‐Little millet cookies, G6‐Foxtail millet cookies, G7‐Refined wheat cookies with fructose, G8‐Kodo millet cookies with fructose, G9‐Little millet cookies with fructose and G10‐Foxtail millet cookies with fructose. The results observed that initial blood glucose level of control group (G3–G6) ranged between 90.1 ± 4.1 (G6) to 91.9 ± 3.7(G3), whereas the diabetic group ranged from 154.2 ± 3.5 (G10) to 172.1 ± 4.3 (G7) mg/dl. Among the perse control group (G3–G6) decreased the blood glucose level in rats fed composite cookies as compared to rats fed refined wheat cookies. The haemoglobin (Hb) content of normal (G1) and diabetic control (G2) group was 12.2± 1.2g and 6.1± 0.6g/dl respectively. Similarly, Hb content of perse control group ranged from 11.5± 1.0(G4) to 12± 1.2 (G5) and diabetic treatment control group was 9.3± 0.8(G10) to 10± 0.9(G9) g/dL. The total cholesterol of G1 was 85.8 ± 2.4mg/dL while that of G2 was 236.9 ± 6.3mg/dL. The total cholesterol level of control groups G3, G4, G5 and G6 was 82.8 ± 2.6, 75.7 ± 2.5, 79.7 ± 2.5 and 77.4 ± 2.7 respectively and that of diabetic treatment groups G7, G8, G9 and G10 were 92.4 ± 2.9, 81.7 ± 2.4, 83.2 ± 2.2 and 82.7 ± 2.5mg/dL in blood respectively. This study clearly indicated that rats given composite cookies and kodo millet cookies showed hypoglycemic and hypolipidemic effect. It also improved plasma insulin level, HDL cholesterol and Hb content as compared to control group and rats given refined wheat cookies. This minor millet cookies also takes place at a slow pace and hence, glucose is released slowly into the blood.Support or Funding Information
Polyphenol Antioxidants Bind Irreversibly to Protein Under Oxidative Conditions
Authors: Sun Xiaowei , Engstrom Marica T. , Salminen Juha‐Pekka , Hagerman Ann E. 
Published: November 2023

Consumption of food and forage plants containing polyphenols with high antioxidant potential may have positive health benefits. In addition, many high molecular weight polyphenols (tannins) characteristically interact strongly with protein, forming complexes that affect perceived taste, nutritional status and health of the consumer. Under oxidative stress, tannins form reactive intermediates that may go on to form very stable complexes with proteins. Polyphenols that are tightly bound to protein may represent a pool of nutrient phytochemicals with fates and effects very different from those of polyphenols that are not protein‐bound throughout digestion. In the present study, the interaction between bovine serum albumin (BSA), and each of seven hydrolyzable tannins or epigallocatechin gallate (EGCg) was examined. The objective was to define the role of tannin oxidation in the formation of highly stabilized tannin‐protein complexes, to determine how the reaction depended on the pH conditions, and to characterize the end products of the reaction. We measured tannin oxidation as oxidative browning or as degradation monitored by HPLC. Gel electrophoresis and MALDI‐TOF‐MS were used to assess the formation of tannin‐protein complexes. Proteomic tools were used to identify modified amino acid residues. The results showed that tannin oxidizability was directly correlated with the tendency of the tannins to form highly stabilized complexes with BSA at increased pH (7.6). However, at slightly lower pH (6.7), other tannin features, such as the size and flexibility of the tannin, appeared to dictate the formation of highly stabilized tannin‐protein complexes. Among all the tannins examined in the study, the green tea polyphenol EGCg formed the most stable complexes with BSA. More than one EGCg molecule could be bound per BSA depending on the ratio of the reactants. The complex was very stable and EGCg could not be released by guanidine HCl, SDS, DTT, low pH, or heating. Mass spectral analysis of hydrolysis products of the complex are being used to verify covalent binding of EGCg to BSA, and to further characterize its binding site.Support or Funding InformationThis work was partially supported by NIDDK R15K069285 (to A.E.H.) and by the Academy of Finland (Grant no. 258992 to J.‐P.S.).
Effects of Ginkgo biloba Intake on Markers of Liver Function in a Large Representative Sample of the U.S. Population
Authors: Agarwal Sanjiv , Lieberman Harris R , Fulgoni Victor L 
Published: November 2023

Ginkgo biloba is a dietary supplement used extensively for various purported therapeutic benefits. However, a series of studies reported ginkgo increased risk of liver cancer in laboratory animals. Therefore, the association between ginkgo consumption and liver function was examined using a very large comprehensive epidemiologic database of the U.S. population, the National Health and Nutrition Examination Survey (NHANES; 2001–2012; N = 29,684). Ginkgo intake of adults was assessed as were multiple clinical markers of impaired liver function: alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyltransferase (GGT), lactate dehydrogenase (LDH) and bilirubin. Approximately 2.51% of NHANES 2001–2012 adult participants were ginkgo consumers (N = 616) and their mean intake of ginkgo was 65.1±4.4 mg/day. When levels of markers of liver function (activities of ALP, ALT, AST, GGT and LDH, and bilirubin level) in ginkgo consumers were compared to non‐consumers, the differences were not statistically significant (P > 0.01). In addition, no significant differences (P > 0.01) in liver enzymes and bilirubin levels between consumers and non‐consumers were observed when the data were stratified by sex. Activities of liver enzymes and bilirubin levels for high ginkgo (above median intake) consumers and low ginkgo (below median intake) consumers did not differ from non‐consumers in male and female adults, as well as when the sexes were combined (P > 0.01). No significant trends (P > 0.01) were noted for ALP, ALT, AST, GGT or LDH activities or bilirubin levels across non‐consumers, low ginkgo consumers and high ginkgo consumers. These data indicate moderate ginkgo intake typical of US consumers does not alter liver function. Biomarkers from NHANES may be useful to examine adverse effects of supplements for which insufficient human adverse event and toxicity data are available.Views expressed here are those of the authors and do not reflect official policy of the US Army, Department of Defense, or US Government.Support or Funding InformationSupport: DoD/MRMC
Snacking Trends in US Adults Over a 35 Year Period from 1977–2012
Authors: Dunford Elizabeth , Popkin Barry 
Published: November 2023

PurposePrevious studies have indicated that snacking is contributing to increased calories in the American diet, and that the energy density of snacks has increased in recent decades. We examined trends in the energy density and food sources of snacks for US adults over 35 years from 1977–2012, and whether these trends differ across sociodemographic groups.MethodsWe used data from eight nationally representative cross‐sectional surveys of food intake in US adults aged ≥19 years between 1977 and 2012 (n=74,291).ResultsFor all US adults there was a significant increase in per capita energy intake from snacks from 1977 to 2012 (P<0.01). In all sociodemographic groups there was a decrease in kcal/day from snacking observed from 2003–06 to 2009–12 except for Hispanics which showed a slight increase. Non‐Hispanic blacks had the highest snacking energy intake from sugar‐sweetened beverages (SSBs) in each year, with a peak intake in 2003–06 of 76 kcal per capita per day. Intake of desserts and sweets increased in all groups between 1977 and 2012, with non‐Hispanic blacks having the highest intake in 2009–12. No significant differences were found between income or education groups.ConclusionSnacking trends appear to be changing in recent years, and in most cases show total energy intake from snacking decreasing, mainly from reductions in beverage consumption. However, our finding that non‐Hispanic blacks are consuming a higher proportion of SSBs than other groups, and showing the largest increase in energy intake deriving from snacks overall over the past 35 years is concerning.Support or Funding InformationFunding for this study comes from the Robert Wood Johnson Foundation (Grants 67506, 68793,70017, 71837), NIH (R01DK098072; DK56350) and the CPC (P2C HD050924). E Dunford is supported by a National Health and Medical Research Council of Australia Early Career Fellowship.