bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of dietary strawberries on inflammatory biomarkers in participants with abdominal obesity and dyslipidemia
Authors: BASU ARPITA , FOSTER MEGAN , BETTS NANCY , NGUYEN ANGEL , FU DONGXU , LYONS TIMOTHY
Published: November 2023

Dietary flavonoid intake, especially berry flavonoids, has been associated with anti‐inflammatory effects in experimental models, though supporting clinical studies are a few in number. We examined the hypothesis that freeze‐dried strawberries (FDS) improve inflammatory biomarkers in adults with abdominal adiposity and elevated serum lipids. In a randomized dose‐response controlled trial, 60 volunteers [5 men and 55 women; age: 49 ± 10 years; BMI: 36 ± 5 kg/m2 (mean±SD)] were assigned to one of the following arms: low dose FDS (LD‐FDS) (25g/d), low dose control (LD‐C), high dose FDS (HD‐FDS) (50g/d), and high dose control (HD‐C) beverages for 12 weeks. Control beverages were matched for calories and total fiber. Serum levels of interleukins (IL) (−1β, −6 and −18), nitrite and adiponectin were examined at screening (0 week) and after 12 weeks intervention. At 12 weeks, serum nitrite was significantly lower (P<0.05), and IL‐6 levels tended to be lower in HD‐FDS vs. LD‐FDS, as well as vs. HD‐C (P<0.1). No differences were noted in serum IL‐1β, IL‐18 and adiponectin following FDS intervention. Thus, dietary strawberries may selectively lower inflammatory biomarkers that influence risk factors of chronic diseases in obese adults.

Support or Funding Information

Funding: California Strawberry Commission & OSU Dean's Research Incentive
The Effects of Dietary Cocoa Powder on Inflammatory Markers and Catalase Activity in Participants with Type 2 Diabetes Following a Fast Food Style Meal Challenge
Authors: Foster Megan , Betts Nancy , Fu Dongxu , Lyons Timothy , Basu Arpita
Published: November 2023

Dietary polyphenols, such as those in cocoa, have been shown to counteract chronic inflammation in animal models as well as in clinical studies. However, limited data exist on the role of dietary cocoa on postprandial inflammation and oxidative stress. Using a randomized placebo‐controlled crossover trial, we investigated the postprandial effects of a cocoa beverage (960 mg total polyphenols) vs. placebo in participants with type 2 diabetes (n=18; age (mean±SE): 56±3y; BMI: 35.3±2.0 kg/m2; 14 women; 4 men) following a high‐fat meal challenge. Blood draws were conducted at fasting, 30 minutes, 1, 2, 4, and 6 hours of the postprandial phase. We measured selected markers of inflammation and catalase enzyme activity at these time points using the quantitative sandwich enzyme immunoassay technique, as well as non‐enzymatic colorimetric assays. Interleukin‐18 (IL‐18) was shown to be significantly lower at 1, 4, and 6 hours, while catalase activity was lower at 1 hour postprandially after cocoa vs. placebo supplementation (all p<0.05). No significant effects were noted in interleukin‐6 (IL‐6), adiponectin, and nitrite concentrations between the two treatments. Thus, cocoa polyphenols may exert modest effects in reducing postprandial inflammation and in modulating catalase activity in type 2 diabetes.

Support or Funding Information

The Hershey Company & OSU Dean's Research Incentive Award
Fermented Korean red ginseng ameliorates 1‐chloro‐2,4‐dinitrobenzene‐induced atopic dermatitis via MAPKs/NF‐κB pathway in mice
Authors: Sohn Eunhwa , Kang Se Chan , Jang Seon‐A , Kwon Jung Eun , Pyo Suhkneung , Koo Hyun Jung
Published: November 2023

Fermented red ginseng (FRG) are known to show different pharmacological effects by changed composition of saponins through fermentation, but the effect of FRG on allergic responses is not known yet. The present study investigated the effect of FRG on atopic dermatitis or skin allergic inflammation by examining the frequency of scratching and detecting representative allergic markers in 1‐chloro‐2,4‐dinitrobenzene(DNCB)‐stimulated mice. The anti‐atopic activities were examined in a DNCB‐induced atopic dermatitis (AD)‐like mouse model, and mice were treated with subcutaneous of FRG. Following application of FRG, scratching behavior and serum IgE level were measured. We also identified NF‐κB activity as a possible transcription factor and MAPKs as intracellular signal pathways triggered by FRG in DNCB‐treated primary splenocytes in mice. FRG administration significantly suppressed the atopic dermatitis lesion, scratching behaviors and serum IgE levels. In FRG‐treated mice splenocytes, the mRNA expression levels of IL‐4 and IL‐10 were significantly decreased, as well as IL‐4 production compared to the AD‐like mice. The FRG also suppressed the DNCB‐induced phosphorylation of MAPKs and nuclear translocation of NF‐κB. These results demonstrated that FRG may be useful in prevention and treatment of atopic dermatitis.

Support or Funding Information

This work was carried out with the support of “Cooperative Research Program for Agriculture Science & Technology Development (Project No. PJ01128102)” Rural Development Administration, Republic of Korea.
In vitro and in vivo antioxidant potential of pistachios (Pistacia vera L.)
Authors: Mandalari Giuseppina , Paterniti Irene , Esposito Emanuela , Carughi Arianna , Cuzzocrea Salvatore
Published: November 2023

Acute inflammation occurs as a defensive response to invasion, often microbial in nature. It is generally a localised protective response involving a complex series of events, including dilatation of arterioles, venules and capillaries, exudation of fluids such as plasma proteins, and leukocyte migration into the inflammatory area. Certain polyphenols have been found to possess antioxidant and anti‐inflammatory properties.

The aim of the present study was to investigate the efficacy of a polyphenol‐rich extract from natural raw pistachios (NP) and roasted salted pistachios (RP) on cell cultures in vivo. The monocyte/macrophage cell line J774 was used to assess the extent of protection exerted by NP and RP against lipopolysaccharide (LPS)‐induced inflammation. Antioxidant activity was assessed by NO production and iNOS expression. NP and RP were also tested for their protective role against carrageenan‐induced paw edema in rats, a model of acute inflammation.

Results from the in vitro study demonstrated that pre‐treatment with NP at the concentration of 0.01, 0.1 and 0.5 mg/ml and RP at the concentration of 0.01 and 0.1 mg/ml exerted a significant protection against LPS induced inflammation. Western blot analysis showed NP reduced the degradation of IkB‐a, although not significantly, whereas both NP and RP decreased the TNF‐a and IL‐1b production in a dose‐dependent way. Pre‐treatment with NP and RP significantly reduced the iNOS expression, COX‐2 levels and NO production.

A significant reduction of paw edema volume was observed in the rats treated with NP compared to the vehicle group. Treatment with RP did not reduce paw edema significantly.

This data demonstrated polyphenols present in pistachios possess antioxidant and anti‐inflammatory properties. This contributes towards a better understanding to the beneficial health effects associated with consumption of pistachios.

Support or Funding Information

This work was supported by American Pistachio Growers (USA).
Simultaneous determination of 30 phenolic compounds in Epimedium herb using HPLC‐DAD‐ESI‐MS/MS
Authors: Jang Miran , Kim Gun‐Hee
Published: November 2023

Herba Epimedii (family Berberidaceae), is one of the commonly used Asia traditional medicines. Phenolic compounds; Flavonoids are considered as its active components. In this study, HPLC method was developed for simultaneous determination of 30 phenolic compounds in five different species of Epimedium. The analysis was performed by using a Symmetry‐C18 analytical column (250mm×4.6mm I.D., 5 μm) at gradient elution of water (with formic acid) and acetonitrile (with formic acid) with diode‐array detection (270 nm). This method was successfully applied for the analysis of 30 phenolic compounds in different species of Epimedium which had great variation on the contents of investigated phenolic compounds. Hierarchical clustering analysis based on the characteristics of 30 investigated compound peaks in HPLC profiles showed that 5 samples were divided into three main clusters, which were in accordance with their phenolic contents.

Support or Funding Information

This research was supported by a grant (14162MFD971) from Ministry of Food and Drug Safety, in 2015
Changes of Lignan Content and Antioxidant activity of Fermented Sesame(sesame indicum L.) by Cultivars
Authors: Jung Tae‐Dong , Shin Gi‐Hae , Kim Jae‐Min , Oh Ji‐Won , Choi Sun‐Il , Lee Jin‐Ha , Lee Sang Jong , Heo In Young , Park Seon Ju , Kim Sung‐Up , Jung Chan‐Sik , Lee Ok‐Hwan
Published: November 2023

This study investigated the lignan content, total phenol content, β‐glucan content, antioxidant activities (DPPH radical scavenging and oxygen radical absorbance capacity(ORAC)) of fermented sesame by cultivars. Our results showed that the total lignan content of fermented sesame ranged from 2.35~6.58 mg/g, and non‐fermented ranged from 2.17 to 6.58 mg/g, respectively. The highest total phenol content of fermented sesame were 51.90 mg GAE/g, and non‐fermented sesame was 25.94 mg GAE/g. β‐Glucan content was 0.07 to 0.19 in non‐fermented and fermented sesame, respectively. DPPH radical scavenging and ORAC value were from 37.95 to 82.57% and from 172.34 to 1,067.80 μM TE/g in non‐fermented and fermented sesame, respectively. Fermented sesame had higher in lignan content, total phenol content and antioxidant activities than those of non‐fermented sesame. As the result, the fermented sesame by bioconversion had the increase of lignan content and high antioxidant activity.
Comparison of pretreatment methods for the simultaneous determination of synthetic antioxidants in edible oil
Authors: CHOI SUNIL , Kim Jae‐Min , Shin Gi‐Hae , Jung Tae‐Dong , Oh Ji‐Won , Choi Seung‐Hyun , Cho Bong‐Yeon , Lee Jin‐Ha , Lee Ok‐Hwan
Published: November 2023

Synthetic antioxidants such as propyl gallate (PG), octyl gallate (OG), dodecyl gallate (DG), 2,4,5‐trihydroxybutyrophenone (THBP), tert‐butylhydroquinone (TBHQ), butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) have been used to prevent oxidative degradation in edible oils and fats. These antioxiants in USA, EU and other countries can be added singly or together up to the final concentration of 200 mg/kg. Although the PG, TBHQ, BHA and BHT are an antioxidant authorized as a food additive in Korea, the OG, DG and THBP are unauthorized. In our previous study, we developed a simultaneous method to identify synthetic antioxidants using high‐performance liquid chromatography with UV detector (HPLC‐UV). However, pretreatment with high recoveries are not established yet. Therefore pretreatment method is needed to detect synthetic antioxidant in edible oil. The present study was conducted to compare the different pretreatment methods including Korean Food Standards Codex, AOAC, AOCS and article. The results showed that Korean Food Standards Codex official method is more suitable for the simultaneous determination of synthetic antioxidants compared to other methods. Recoveries of synthetic antioxidants were in the range from 89.6 to 98.8% with RSDs between 2.8 to 4.2%. The Korean Food Standards Codex official method has been successfully applied to edible oil.
Narirutin fraction from citrus peels attenuates LPS‐stimulated inflammatory response through inhibition of NF‐κB and MAPKs activation
Authors: Park Ho‐Young , Ha Sang Keun , Choi Inwook
Published: November 2023

In this study, we examined the regulatory activity of narirutin fraction from citrus peels on the production of inflammatory mediators managing acute or chronic inflammatory diseases in macrophages. Narirutin fraction inhibited the release, by lipopolysaccharide (LPS)‐stimulated macrophages, of nitric oxide (NO) and prostaglandin E2 (PGE2) through suppressing the expression of inducible NO synthase (iNOS) and cyclooxygenase‐2 (COX‐2), respectively. The release, by LPS stimulated macrophages, of interleukin (IL)‐1β and tumor necrosis factor (TNF)‐α was also reduced by narirutin fraction in a dose‐dependent manner. Furthermore, narirutin fraction inhibited the LPS‐mediated activation of nuclear factor (NF)‐κB and mitogen‐activated protein kinases (MAPKs), which are signaling molecules involved in production of pro‐inflammatory factors. As a result of these properties, narirutin fraction has the potential to be used as a functional dietary supplement and effective anti‐inflammatory agent.
Fresh pear (Pyrus communis) consumption may improve blood pressure in middle‐aged men and women with metabolic syndrome
Authors: Johnson Sarah A. , Navaei Negin , Pourafshar Shirin , Akhavan Neda S. , Elam Marcus L. , Foley Elizabeth , Clark Elizabeth A. , Payton Mark E. , Arjmandi Bahram H.
Published: November 2023

Metabolic syndrome (MetS) is a cluster of major cardiovascular risk factors including abdominal obesity, elevated blood pressure, atherogenic dyslipidemia and insulin resistance, and a pro‐inflammatory and pro‐thrombotic state, and is highly associated with the development of chronic diseases such as cardiovascular disease and type II diabetes. The primary treatment goals for individuals with MetS is to improve modifiable underlying risk factors such as body weight, physical activity, and diet through lifestyle changes. Pears (Pyrus communis) are a commonly consumed fruit and are an excellent source of soluble and insoluble dietary fiber, a good source of vitamin C and contains potassium and vitamin K, and bioactive compounds including flavonoids (e.g. anthocyanins and flavanols) and phenolic acids (e.g. gallic acid and chlorogenic acid). Although there is a paucity of clinical research that has investigated the impact of pear consumption on human health, previous research with pears supports their potential as a functional food for promoting overall health, especially with respect to the characteristics of MetS. One of the objectives of this randomized, placebo‐controlled crossover clinical trial was to evaluate the antihypertensive effects of fresh pear consumption in middle‐aged men and women with MetS. Fifty men and women aged 45 to 65 years with three of the five features of MetS were randomly assigned to receive either 2 medium‐sized fresh pears (~178 g) or 50 g pear‐flavored drink mix (placebo) per day for 12 weeks. Resting seated brachial systolic and diastolic blood pressures, heart rate, and pulse pressure were evaluated at baseline, 6 weeks, and 12 weeks. Preliminary analyses of 36 participants show that after 12 weeks of fresh pear consumption, systolic blood pressure (− 5 mmHg, P < 0.05) and pulse pressure (−5 mmHg, P < 0.01) were significantly lower than baseline levels whereas there were no changes in the control group. No changes were noted in diastolic blood pressure or heart rate for either group at any time point. The results of this study indicate that regular fresh pear consumption may improve blood pressure and vascular function in older men and women with MetS. Future research is needed to confirm the antihypertensive effects of fresh pears as well as to assess their impact on vascular function.

Support or Funding Information

Supported by the Pear Bureau Northwest and the Fresh Pear Committee of Federal Marketing Order 927.
Effects of almonds on cardiovascular risk factors in overweight and obese Koreans
Authors: Jung Hana , Chen C‐Y. Oliver , Blumberg Jeffrey B. , Kwak Ho‐Kyung
Published: November 2023

Clinical studies conducted in Americans, Britons, Canadians, and Chinese suggest that almond consumption decreases the risk of cardiovascular disease (CVD) through beneficial actions on blood glucose and lipids, inflammation, and/or oxidative stress. As background diet and ethnicity can modulate these benefits, we examined whether daily consumption of almonds would improve vitamin E status, lipid profile, and biomarkers of oxidative stress and inflammation in free‐living overweight/obese Korean adults in a randomized, crossover clinical trial. The protocol included a 2‐wk run‐in period, two 4‐wk intervention phases, and a 2‐wk washout period between the crossover. Of 90 eligible participants who were randomly assigned to consume either 56 g almonds or isocaloric cookies daily for 4‐wk, 85 (10 M/75 F; 52.4 ± 0.6 y; 25.4 ± 0.22 kg/m2) completed the trial. Mean % daily energy intake was 32 vs. 26% from fat and 55 vs. 61% from carbohydrates during the almond and cookie phases, respectively. Energy from protein was similar between the 2 groups. The addition of almonds to habitual diet of the participants increased the intake of poly‐(13.1 vs. 7.8 mg/d) and mono‐unsaturated (26.6 vs. 12.8 mg/d) fat, dietary fiber (25.5 vs. 20.9 g/d), and α‐tocopherol (29.7 vs. 14.0 mg/d) compared to the cookie control (P ≤ 0.001). Neither treatment affected body weight. Almonds tended to decrease serum triglycerides, vascular cell adhesion molecule‐1, and intercellular adhesion molecule‐1. In conclusion, the addition of 56 g/d almonds to Korean diet improves nutrition status and tends to improve selected CVD risk factors.

Support or Funding Information

Supported by Almond Board of California and USDA
Characterization of Kombucha Tea as an Inhibitor of α‐Amylase
Authors: Mann Francis M. , Dickman Mallory , Schneider Rebecca , Armando Samantha , Seehusen Katherine , Strauss Michael
Published: November 2023

Kombucha tea (KT) is a fermented beverage gaining mainstream popularity due to purported and demonstrated health benefits. KT has previously demonstrated a hypoglycemic effect in an induced diabetes rat model which indicates bioactive compounds within KT may act as effective anti‐diabetic agents. One method by which KT may induce hypoglycemia in a biological model is via inhibition of α‐amylase. Indeed, KT inhibits α‐amylase with an IC50 of 0.16±0.06% (v/v) in vitro. Two potential mechanisms to explain this phenomenon were explored, including acid‐based inhibition and inhibition by phenolic molecules present in the pre‐fermentation substrate. Initial results indicate that KT‐dependent inhibition of α‐amylase is not completely dependent on pH, as neutralized KT retains partial inhibitory properties (IC50=1.2±0.23% (v/v)), however complete inhibition is not observed (Activity minimum = 49.8±5.1%). However, pre‐fermentation black tea substrate fails to demonstrate any inhibition of α‐amylase activity which indicates that KT fermentation may either biotransform inactive substrate molecules or synthesize new inhibitory molecules de novo. Further experimentation with Kombucha fermented in the absence of tea (MT) resulted in retention of partial acid‐dependent inhibition (IC50=6.3±5.4%(v/v)) but loss of pH‐independent inhibition. Corresponding analysis of the phenolic profile of MT and KT support the hypothesis that tea phenolics undergo fermentative biotransformation resulting in increased α‐amylase inhibition and provides evidence that KT fermentation may result in synthesis of a novel hypoglycemic agent.
Anti‐hyperglycemic effects and Antioxidant Activities of 6 selected Natural Food Coloring Agents
Authors: JANG SOOIN , LEE JUNGYUN , KANG YURI , CHOI HWANGYONG , KWON YOUNGIN
Published: November 2023

Inhibition of α‐amylase and α‐glucosidase involved in the digestion and absorption of carbohydrates can significantly decrease the postprandial increase of blood glucose level after a mixed carbohydrate diet. Therefore, it is important strategy for management of calorie control to screen these enzyme inhibitors from natural food products. In the current study, we evaluated the inhibitory activities of 6 selected natural food coloring agents used in recent food industry widely, such as Monascus color (MC), Red beet color (RBC), Grape skins color (GSC), Gardenia Blue color (GBC), Squid ink color (SIC), and Red cabbage color (RCC) against rat intestinal α‐glucosidases (sucrase, maltase, and glucoamylase) and porcine pancreatic α‐amylase. We also evaluated total phenolics, and oxygen radical absorbance capacity (ORAC) of different 6 selected natural food coloring agents. Among 6 natural food coloring agents RCC had the lowest IC50 of Surcrase (0.105), GBC had the lowest IC50 of Maltase (0.484 mg/mL) and total phenolic showed the highest inhibitory activity is the GSC (96.532 mg/g‐dried weight) with high ORAC value (4.620 TE). These results indicate that natural color agent which has high antioxidant and anti‐hyperglycemic activities has the potential to contribute as a useful food design strategy for controlling postprandial hyperglycemia and calorie management.
Fermented Soybean Products Chungkookjang And Nattδ Inhibits Intracellular Lipid Accumulation in Adipocyte And Prevents Weight Gain in High‐Fat Diet Induced Obese Mice
Authors: Byun Moon‐Sun , Yu Ok‐Kyeong , Baek Hyun‐Hwa , Cha Youn‐Soo
Published: November 2023

In this study, we investigated the anti‐obesity effects and the mechanism of action of two fermented soybean products Chungkookjang (CKJ) and Nattδ (NT) extract in 3T3‐L1 cell line and high‐fat diet (HFD) induced obese mice. In vitro, CKJ and NT were examined for their anti‐adipogenic effects using Oil‐Red O staining method. For in‐vivo study the C57BL/6 mice were fed a normal diet (ND), high fat diet (HD), high fat diet plus 20% CKJ (CKJ20), high fat diet plus 20% NT (NT20) for 12 weeks and were sacrificed. Both of the extracts without exerting any cell cytotoxicity inhibited the intracellular lipid accumulation in 3T3‐L1 cells, visualized using Oil Red O stains. Bodyweight, bodyweight gain, serum lipid profiles, and serum insulin, leptin level were reduced in the CKJ and NT groups compared to the HD group. CKJ and NT treatment resulted in a significant amelioration in the mRNA levels of adipogenesis‐related genes, such as PPARγ and SREBP‐1c along with anti‐lipogenic genes such as PPARα, CPT1α in 3T3‐L1 cell line and white adipose tissue (WAT) of HFD‐induced obese mice. These results suggested that the supplementation of CKJ and NT have an anti‐obesity effect on high fat diet induced obesity in the mouse model.

Support or Funding Information

This research was supported by the Globalization of Korean Foods R&D program, funded by the Korean Institute of Planning & Evaluation for Technology in Food, Agriculture Forestry & Fisheries (iPET), Republic of Korea
Relative Proportions of Individual Blueberry Anthocyanins Vacillate Within and Between Growing Seasons
Authors: Timmers Michael Anthony , Grace Mary , Yousef Gad , Lila Mary Ann
Published: November 2023

Blueberries accumulate up to 18 different types of anthocyanins unlike most other berries, such as blackberries and blackcurrant that tpically contain only 5–8, with different genotypes varying in their anthocyanin profile. Individual anthocyanin moietes vary in health‐relevant biological activity due to differences in their chemical structures, absorption, and metabolism in the gut. Variation in total anthocyanin content between growing seasons has been previously documented, but our study is the first in which inter‐ and intra‐seasonal fluctuations of individual blueberry anthocyanins across genotypes has been examined. The anthocyanin profiles of six blueberry genotypes were assessed weekly over two growing seasons by analyzing anthocyanin extracts of ripe berries by HPLC. While individual genotypes differed in total and relative anthocyanin content, all experienced similar trends across each season. Total anthocyanin content ranged between 10–28 mg per gram fresh weight and, despite some fluctuation, increased as the season progressed for all genotypes, even though only berries at peak ripeness were harvested at any time point. Relative levels of malvidin and delphinidin glycosides displayed fluctuations between 3–20% of total anthocyanin content over the course of either picking season for each genotype, and interestingly, were inversely proportional throughout the season. This shift was most pronounced in the Legacy variety, where delphinidin levels increased by 15% and malvidin decreased by 16% over the course of the growing season in 2014. The opposite trend was observed in 2015, with delphinidin decreasing 10% and malvidin increasing 10% across the season. Delphinidin and malvidin are in the same biosynthetic pathway, separated only by 2 methylation steps. While these two were observed to be inversely propotional, the single‐methylated intermediate, petunidin, remains relatively constant across the season for all varieties with a maximum of 2% change for the Legacy variety. These results suggest that an increase in expression in the methylation biosynthetic step involving O‐dihydroxyphenol O‐methyltransferase from delphinidin favors an increase in the two‐step methylation to malvidin over the single methylation to petunidin. Given the many health benefits of blueberries and specifically anthocyanins, the flux in specific anthocyanin concentrations over multiple seasons is of interest in order to determine not only peak concentrations of anthocyanins present, but also the most favorable anthocyanin profile for specific interventions in human health and metabolism.
Protective effect of Pteropyrum scoparium and Oxalis corniculata against streptozotocin‐ induced diabetes in rats
Authors: Al‐Qalhati Iman Rashid Sultan , Waly Mostafa , Al‐Attabi Zahir , Al‐Subhi Lyutha Khalfan
Published: November 2023

Background

Type 2 diabetes represents a major health concern among Omani adults population, and it is perceived as a lifestyle‐related disease. There is a lack of research that identifies the potential anti‐diabetic effects of edible wild Omani plants. Therefore understanding the value and usability of edible wild Omani plants in the food chain of Omani adults might be considered as an effective intervention for the primary prevention of type 2 diabetes.

Objective

This study aimed to assess the in‐vivo potential anti‐diabetic and antioxidants effects of Pteropyrum scoparium and Oxalis corniculata plants or their mixture.

Methods

Forty five adult Sprague Dawley rats, weighting 250–300 grams, were allocated as into 5 groups (9 rats/group): non‐diabetic control that received chow diet; diabetic group that received chow diet; and diabetic groups that received chow diet plus oral feeding of Pteropyrum scoparium, Oxalis corniculata extracts or their mixture. Diabetes was induced by a single intraperitoneal injection dose of streptozotocin (STZ) drug, 60 gm/kg body weight. At the end of the experimental trial, after 8 weeks, all rats were fasted overnight and sacrificed; serum was collected for measurement of glucose, meanwhile pancreatic tissues was dissected and homogenized for the biochemical assessment of antioxidant enzyme (superoxide dismutase) and oxidative stress markers (glutathione and total antioxidant capacity).

Results

Diabetic rats treated with plants extracts had shown a significant protective effect against STZ‐induced hyperglycemia and oxidative stress as compared with the control group. Microscopic examination of pancreatic diabetic treated groups showed no histopathological changes indicating that the treatment with plants extracts or their mixture have no effect on the pancreatic tissues.

Conclusion

This study demonstrated that Pteropyrum scoparium and Oxalis corniculata combated the STZ‐mediated hyperglycemia and oxidative stress. Histopathological examination revealed that there was no observed effect on the cellular pancreatic moiety, indicating safety of the used plants extracts.

Support or Funding Information

This research was supported by internal grant funding, IG/AGR/FOOD/14/2, from Sultan Qaboos University
Comparison of Estimated and Measured Isoflavone Content of Foods Commonly Consumed by Adventists in the United States and Canada
Authors: Heskey Celine , Sirirat Rawiwan , Franke Adrian , Jaceldo‐Siegl Karen
Published: November 2023

Agricultural, growth, and genetic factors; storage, and processing techniques can have an effect on isoflavone content in foods, and may contribute to differences between food composition databases and content measured by chemical analyses. Errors in estimating nutrient composition of dietary exposure variables can contribute to mixed research findings in evaluating the association between diet and disease. The objective of this study was to compare estimated and measured soy isoflavone content of soy food products.

Thirty‐eight most frequently consumed soy food items were identified based on 40,000 responses to the Adventist Health Study‐2 food frequency questionnaire (FFQ). The FFQ included 51 soy‐containing food items and open‐ended questions about the use of meat analogues and soy milk. Soy protein and isoflavone content (in aglycone equivalents) estimates were based on the soy ingredients contained in recipes. The isoflavone content of these 38 food items was measured by liquid chromatography methods on two samples of each food. Corrected (to remove the measured isoflavone between and within variance) Spearman correlations were calculated between estimated and measured isoflavone content.

The estimated total isoflavones from meat analogs and soymilk ranged from 0.19 to 225 μg/g. Estimates for daidzein, genistein, and glycitein were 0.08 to 82, 0.07 to 116 and 0.04 to 27 μg/g respectively. Mean laboratory measures of aglycone content ranged from 0.00 to 24 μg/g for daidzein, 0.00 to 31 μg/g for genistein, and 0.00 to 5 μg/g for glycitein. Mean measured glucosides ranged from 0.00 to 292, 0.14 to 345, and 0.00 to 28 μg/g for daidzin, genistin, and glycitin respectively. Mean measures of total isoflavone (aglycones plus glucosides) content was 0.45 to 699 μg/g.

Estimated isoflavone content was moderately correlated with measured aglycones (r=0.56 for total; r=0.53 for daidzein, r=0.66 for genistein), except for a weak correlation with glycitein (r=0.32). Estimated isoflavone content was moderately correlated with measured glucosides (r=0.63) and total measured isoflavones (r=0.64). The correlation between estimated soy protein and total measured isoflavones was 0.61.

Observed moderate correlations, indicate that our estimated isoflavone content may be a good measure of actual content.

Support or Funding Information

McClean Funds for Nutrition Research
The Total Phenolics Content of Fruit & Vegetable Extracts Does Not Correlate with Activation of the Anti‐Oxidant Response in Human Cells
Authors: Orena Stephen Joseph , Owen Jennifer , Jin Fuxia , Fabian Morgan , Gillitt Nicholas , Zeisel Steven
Published: November 2023

Anti‐oxidants in foods are traditionally thought to act by trapping free radicals thereby preventing cellular damage to organelles, membranes and DNA. However the structures and properties of many of these molecules suggest they are poor free radical scavengers and may even function as weak pro‐oxidants (electrophiles) that can activate the NRF2/anti‐oxidant response element (ARE) pathway in cells. Traditional approaches for identifying anti‐oxidant molecules in foods, such as total phenolics (TP) content or oxygen radical absorption capacity (ORAC) do not measure the capacity to activate AREs.

Fruits and vegetables were homogenized, extracted with acidified ethanol, lyophilized, and resuspended in growth medium. The TP content and ORAC activity were measured for each extract. Extracts were screened for activation of the anti‐oxidant response element (ARE)‐Firefly luciferase reporter in transiently transfected human IMR‐32 neuroblastoma cells treated for 5 hours. Firefly luciferase was normalized to constitutively expressed Renilla luciferase with tertiary‐butylhydroquinone (tBHQ) as a positive control. Relationships between TP and ORAC with ARE activity were determined. Extracts identified as active in the ARE reporter screen were then tested for activation of anti‐oxidant genes in human peripheral blood mononuclear cells (PBMCs). After a 5 hour exposure, total RNA was purified and RT‐PCR performed to assess expression of the anti‐oxidant genes NAD(P)H:quinone oxidoreductase 1 (NQO1), glutamate cysteine ligase modifier subunit (GCLM), thioredoxin reductase 1 (TXNRD1), and glutathione reductase (GSR). Relationships between TP and gene expression activity were determined.

107 of 134 extracts tested significantly activated the ARE luciferase reporter from 1.2 to 58 fold above that of the solvent control (P<0.05) in human IMR‐32 cells. ARE activity, TP content, and ORAC ranked higher in peels versus associated flesh. Despite this relation, ARE activity did not correlate with TP content (Spearman rho=0.05, P=0.6) and only modestly but negatively correlated with ORAC (Spearman rho=−0.2, P<0.01). Many extracts activated the ARE more than predicted by the TP content or ORAC. Active extracts from the ARE screen significantly increased expression of anti‐oxidant genes in PBMCs. As with the ARE reporter, TP content of the extracts did not correlate with extract‐induced expression of NQO1 (Spearman rho=−0.3, P=0.3), GCLM (Spearman rho=−0.2, P=0.5), TXNRD1 (Spearman rho=−0.1, P=0.8) and GSR (Spearman rho=−0.3, P=0.3).

These data suggest that measuring the endogenous anti‐oxidant gene expression response is likely a better predictor of the anti‐oxidant benefits of fruits and vegetables than TP content or ORAC.

Support or Funding Information

Dole Food Company
Clinical Evidence of a Protective Role for CXCL5 in Coronary Artery Disease Progression in the Elderly
Authors: Schisler Jonathan C. , Schuck Robert , Dai Xuming , Lenhart Kaitlin , Lee Craig R. , Stouffer George A. , Patterson Cam
Published: November 2023

Advanced age is associated with higher risk for cardiovascular disease and poor prognosis in patients with established cardiovascular disease. Moreover, the pathophysiology underlying CAD in older individuals may be distinct from that in younger individuals. Therefore, we utilized candidate biomarker and systems biology approaches to improve our understanding of the pathogenesis and progression of CAD in older adults. We enrolled individuals who were at least 65 years of age and undergoing diagnostic cardiac catheterization. Coronary artery disease (CAD) severity was quantified in each subject via coronary angiography by calculating a CAD score. Circulating biomarkers of inflammation and mRNA expression levels in peripheral blood mononuclear cells were quantified. We identified 553 genes (FDR<7%) that correlated with CAD severity and consisted of clusters of inflammatory genes, p38 MAPK signaling genes, and leukocyte activation, consistent with a heightened inflammatory state. The enriched expression of genes related to leukocyte activation suggested that inflammation mediated by the mobilization of leukocytes impacts the CAD gene expression signature and perhaps the extent of disease. We used the functional gene expression analysis to identify candidate circulating molecules that could propagate the CAD‐associated inflammatory response through recruitment of leukocytes to the area of injury. One class of molecules known to recruit leukocytes is the ELR+‐CXCL chemokine family. One chemokine of interest was the leukocyte‐derived CXCL5 (initially described as ENA‐78) in particular due to its ability to activate p38 and its proposed role as a key mediator in the formation of a inflammatory microenvironment in cancer and tuberculosis. Therefore, we hypothesized that the CXCL5 levels would be higher in patients with obstructive CAD and with increased CAD severity. We performed the analyses on CXCL5 plasma levels and surprisingly we observed a negative association of CXCL5 levels with CAD at an odds ratio (OR) of 0.46 (95% confidence interval: 0.27 − 0.75). Controlling for known covariates including gender and statin use, the OR was not significantly affected, 0.54 (0.30 − 0.91), consistent with a protective role for CXCL5 in coronary atherosclerosis. Our data are consistent with a recent study in a mouse model of atherosclerosis that demonstrated that CXCL5 is protective in atherosclerosis by limiting foam cell accumulation at the site of injury (doi:10.1172/JCI66580). It is unclear if CXCL5 limits foam cell formation in humans, however our clinical findings are consistent with the emerging link between chemokines and foam cell formation and represents a new therapeutic target for CAD.

Support or Funding Information

5R01HL065619‐13 National Heart, Lung, and Blood Institute
Dietary nitrate suppresses platelet reactivity in Apolipoprotein E Knockout Mice
Authors: Filomena Federica , Khambata Rayomand , Ahluwalia Amrita
Published: November 2023

INTRODUCTION

Reduced endothelium‐derived NO bioavailability is a characteristic of the endothelial dysfunction that occurs in the early stages of atherogenesis and is thought to account in part for the enhanced platelet activity that characterises this disease state. Dietary supplementation with inorganic nitrate (NO3−) has been proven to suppress ex vivo platelet activation in healthy volunteers [1, 2] and to reduce platelet activation in hypercholesterolemic patients [3]. This effect relies on the enterosalivary circulation, where the oral microbiome converts NO3− to NO2−, resulting in increased circulating NO2− levels. This NO2− is then converted by mammalian vascular nitrite reductases to NO, which, amongst the other beneficial effects on the vasculature, appears to reduce platelet activation. However, whether dietary NO3− might be an effective antithrombotic agent for therapeutics in atherosclerosis is unknown.

AIM

To investigate whether dietary supplementation with inorganic NO3− reduces platelet activity and thus thrombotic potential in vivo in the apolipoprotein E (ApoE) knock out (KO) mouse model of atherosclerosis.

METHODS

Males or female, 4/6 week old, ApoE KO or wildtype (WT, C57BL6) littermate mice were supplemented with 15mM KNO3 or 15mM KCl in the drinking water for 10 days. Thrombotic potential was assessed in vivo using intravital microscopy following i.v. injection of the platelet marker DyLight488‐labelled CD42 antibody. A 10% FeCl3 solution was applied for 1 min on a mesenteric artery and thrombus formation recorded for 45 min. Tail bleeding time after excision of 0.25cm from the tail tip was also assessed with standard methods. Blood was collected and platelet counts determined using counting beads. Data are shown as mean±s.e.m.

RESULTS

KNO3 feeding raised plasma levels of NO3− and NO2− compared to KCl as assessed using the method of ozone chemiluminescence ([NO2−]μM ApoE KO: KCl=0.6±0.07 KNO3=0.8±0.06, WT: KCl=0.8±0.1 KNO3=1.0±0.1. [NO3−]μM ApoE KO: KCl=17.3±3.2 KNO3=68.1±17.8, WT: KCl=34±4.6 KNO3=100.4±24.1. n=6). Treatment with KNO3 suppressed FeCl3‐induced arterial thrombosis in both WT (n=3) and ApoE KO (n=7) animals (Figure 1). A trend towards a prolonged bleeding time was observed in all mice receiving KNO3, although this did not reach statistical significance (ApoE KO: KCl=3.9±1.2min KNO3=6.6±1.1min, WT: KCl=4.1±1min KNO3=4.9±1min). Platelet count was not different between treatment and control groups (ApoE KO: KCl=2.8×105±0.7×105 KNO3=3×105±0.7×105; ApoE WT: KCl=2.8×105±0.4×105 KNO3=2.8×105±0.7×105).

CONCLUSIONS

We have shown that supplementation with dietary NO3− in the setting of atherosclerosis modestly reduces in vivo platelet reactivity and thus thrombotic potential. Dietary nitrate could represent a cheap and effective strategy to dampen platelet activity in patients at high risk of thrombosis.

Support or Funding Information

FF is supported by a MRC PhD Studentship.
STIM1 deficiency in VSMC promotes vascular calcification in atherosclerosis
Authors: Yang Youfeng , Sun Yong , Chen Yabing
Published: November 2023

Objective

Vascular calcification is a characteristic feature of atherosclerosis. We and others have demonstrated that osteogenic differentiation of vascular smooth muscle cells (VSMC) contribute predominantly to the pathogenesis of vascular calcification in atherosclerosis. The key cellular event that leads to calcification is the secretion of matrix vesicles (MVs), membrane‐bound nanoparticles that carry calcium and matrix proteins to initiate calcification. However, the molecular regulation of MV release and the causal effect of MV release on VSMC calcification are poorly understood. The objective of this study is to investigate the function of a key calcium flux regulator, stromal interaction molecule 1 (STIM1), in regulating MV release and VSMC calcification; and to elucidate the underlying molecular mechanisms.

Methods

SMC‐specific STIM1‐deficient mice (STIM1Δ/Δ SMC) were generated by breeding smooth muscle specific SM22α‐Cre mice with STIM1 floxed mice (STIM1f/f). Primary VSMC isolated from STIM1Δ/Δ SMC and the control STIM1f/f mice were used for in vitro characterization. VSMC was cultured in osteogenic media for 3 weeks; calcification was assessed by Alizarin red staining. Total calcium content was quantified by Arsenazo III method. MVs were collected by sequential centrifugation and characterized by electron microscopy. For in vivo characterization of vascular calcification, the mice were bred into the atherogenic ApoE−/− background.

Results

STIM1 deletion in the STIM1Δ/Δ SMC VSMC promoted VSMC calcification, although STIM1 deficiency has been linked to decreased calcium signals in smooth muscle cells. Increased release of MVs was demonstrated with the STIM1Δ/Δ SMC VSMC compared with the control STIM1f/f VSMC. Using the atherogenic ApoE−/− model, we demonstrated that SMC‐specific STIM1 deficiency increased atherosclerotic vascular calcification in vivo. Consistently, increased MVs were determined in the serum of the STIM1Δ/Δ SMC mice. Mechanistically, we found that STIM1 deficiency did not affect VSMC proliferation and survival, but decreased the expression of SMC‐specific α‐actin. The size of MVs released from STIM1f/f and STIM1Δ/Δ SMC VSMC appeared similar. However, MVs from the STIM1Δ/Δ SMC VSMC contained a greater amount of calcium compared with those from the STIM1f/f VSMC. Furthermore, immunofluorescent staining identified a rearrangement of actin‐filament structure in the STIM1Δ/Δ VSMC, a critical cellular event that controls the release of MVs.

Conclusions

These studies have determined a new causative effect of VSMC‐expressed STIM1 on atherosclerotic vascular calcification; and identified a novel link connecting STIM1 and actin‐cytoskeleton rearrangement in regulating MV release and vascular calcification.

Support or Funding Information

This work was partially supported by grants from the National Institutes of Health HL092215, DK100847 and Veterans Administration BX001591 (project 2) to YC. YY was supported by American Heart Association Grant 14POST20450117.
111In‐DANBIRT as An in Vivo SPECT/CT Imaging Tool for The Expression of LFA‐1 in The Inflammatory Process of Atheroma Development
Authors: Mota Roberto Ivan , Daniels Tamara , Nysus Monique , Lucas Selita , Norenberg Jeffrey , Campen Matthew
Published: November 2023

Objective

Assess inflammatory leukocyte presence and accumulation in vascular atherosclerotic plaque using 111In‐DANBIRT as a non‐invasive diagnostic imaging tool.

Methods

6 week ApoE KO mice were fed either normal or high fat chow (n=8 per group) for 8 weeks to induce vascular atherosclerotic lesions. SPECT/CT imaging was performed 3 hours post injection of ~700uCi of 111In‐DANBIRT at baseline, 4 weeks and 8 weeks. Whole body Autoradiography was performed 24 hours post injection after the 8 week time point. Image processing and analysis was performed by region of interest (ROI) determination in relationship to voxel and volume, uptake quantification was normalized to muscle uptake. Blood partition assays were conducted to ascertain specific binding components.

Results

Autoradiography and SPECT/CT analysis characterized 111In‐DANBIRT distribution in cardiovascular tissues (heart, aortic arch, descending aorta, carotids). A longitudinal increase in uptake was evidenced when comparing high fat diet to normal diet mice along our different time points. Increased uptake was evidenced in the thymus, which would be consistent with increased immune response to vascular injury. Whole blood isolation correlated these findings showing increased specific uptake by neutrophils in our ozone‐exposed group.

Conclusions

This pilot study showed that ApoE KO mice on Western diet exhibit increased cardiovascular and immune tissue uptake of 111In‐DANBIRT compared to mice on a normal diet. We still need to assess vascular lesion development in our disease model using biochemical markers and histology. Findings support future investigation of a more advanced vascular disease model that will validate 111In‐DANBIRT as a diagnostic tool for assessment of inflammation in cardiovascular injury models.

Support or Funding Information

Data was generated in the Keck‐UNM Small‐Animal Imaging Resource Shared Resource Center supported by the University of New Mexico Health Sciences Center, the UNM Cancer Center, and UNM College of Pharmacy. Grant numbers: NIH P30CA118100‐06 & ES0014639.
Sialylation and PECAM‐1‐Dependent Ligand Binding
Authors: Parambath Andrew , Abraham Valsamma , Hyun Sang Won , Liu Anguo , Goldblum Simeon E , DeLisser Horace
Published: November 2023

PECAM‐1, a sialylated cell surface molecule expressed on endothelial cells (ECs), has been implicated in both EC motility and angiogenesis. Neuraminidase 1 (NEU1) sialidase inhibits wound‐induced EC migration and disrupts in vitro tube formation though PECAM‐1‐desialylation. The mechanisms by which desialylation of PECAM‐1 disrupts its activity are undefined. The effects of PECAM‐1 on cell function are mediated by the binding of PECAM‐1 to other PECAM‐1 molecules (homophilic) or to non‐PECAM‐1 molecules (heterophilic), such as heparin/heparan sulfate glycosaminoglycan (GAG)‐containing proteoglycans. We hypothesized that desialylation of PECAM‐1 disrupts PECAM‐1‐dependent ligand binding. For these studies, we employed REN cells (an EC surrogate) expressing mouse PECAM‐1 in mixed aggregation studies in which PECAM‐1‐expressing REN cells are mixed with control REN cells. In this assay, homophilic interactions result in aggregates that are enriched for PECAM‐1‐expressing cells, while heterophilic binding generates aggregates composed of both PECAM‐1 and non‐PECAM‐1 cell types. Analysis of 5‐cell aggregates in mixed aggregation studies for the PECAM‐1‐expressing REN cells resulted in comparable proportions of homophilic (46%) versus heterophilic (34%) aggregates. However, the formation of both homophilic and heterophilic aggregates was suppressed by adenoviral‐mediated overexpression of NEU1 in the PECAM‐1‐expressing REN cells compared to those that were transduced with adenovirus‐expressing GFP alone or when a catalytically‐inactive mutant of NEU1 was overexpressed. These data suggest that NEU1‐mediated inhibition of in vitro EC activity involves the disruption of PECAM‐1‐dependent ligand interactions.

Support or Funding Information

Veterans Administration Merit Award