Article

Anti-inflammatory activity of aronia berry extracts in murine splenocytes

May 2014
Journal of Functional Foods 8(1):68–75

DOI:10.1016/j.jff.2014.03.004

Authors:

University of Connecticut

Aronia berries are a rich source of dietary polyphenols, with diverse polyphenol profiles among its genotypes. The objective of this work was to characterize the anti-inflammatory effects of underutilized aronia berries and their polyphenols using primary C57/BL6 mouse splenocytes. At 125 μg gallic acid equivalents/mL, the commercial ‘Viking’ aronia berry and underutilized aronia extracts inhibited LPS-stimulated IL-6 to a similar extent. ‘Viking’ extracts inhibited IL-6 predominately in CD4− lymphocytes. The primary polyphenol constituents of extracts were subsequently evaluated for inhibition of LPS-stimulated IL-6. Cyanidin-3-arabinoside, but not the primary aronia anthocyanin cyanidin-3-galactoside, inhibited IL-6 at 10 μg/mL. Quercetin, but not its 3-galactoside or glucoside, inhibited LPS-stimulated IL-6. Quercetin also inhibited LPS-stimulated IL-10, whereas ‘Viking’ extract increased splenocyte IL-10 in the absence of LPS. Thus, the capacity of aronia extracts to modulate LPS-stimulated splenocyte IL-6 and IL-10 in vitro was not attributed to its principal polyphenols.

Chokeberry (Aronia melanocarpa) fruit extract modulates immune response in vivo and in vitro

Article

Mar 2020

Chokeberry (Aronia melanocarpa) is known for its anti-oxidant, anti-inflammatory and anti-diabetic properties. Since the effects of chokeberry extract on the immune response have been only sporadically assessed, our aim was to investigate chokeberry fruit water extract on the immune response in vivo and in vitro. When administered orally to healthy mice, the extract exerted immunomodulatory effects in the gut evidenced by the altered proportion of macrophages, dendritic cells and T cells. Importantly, oral consumption of the chokeberry extract resulted in blood glucose level increase in C57BL/6 mice with chemically-induced diabetes. These in vivo results were corroborated by observed up-regulation of nitric oxide and interelukin-1β production in macrophages and dendritic cells, up-regulated phagocytic activity of macrophages, increased T and B lymphocytes proportions and differentiation of interferon-γ-producing T cells in vitro. The obtained results imply that our chokeberry extract stimulates pro-inflammatory properties in immune cells of innate and adaptive immunity.

Aronia berry ( Aronia mitschurinii ‘Viking’) inhibits colitis in mice and inhibits T cell tumour necrosis factor-α secretion

Article

May 2018

Aronia berries are rich in polyphenols with anti-inflammatory activity. We hypothesized that aronia berry consumption modulates intestinal immune function and T cells. The aims of the present work were to assess the immunomodulatory potential of ‘Viking’ aronia berry (black chokeberry, Aronia mitschurinii) in vivo and to determine the extent aronia berry polyphenols or known microbial polyphenol catabolites inhibit T cell tumour necrosis factor (TNF)-α in vitro. Aronia berry consumption increased colonic IL-10 secretion in healthy mice, but did not inhibit ex vivo cytokine secretion of lipopolysaccharide-stimulated spleen and colon tissue. Aronia berry consumption inhibited wasting associated with T cell adoptive transfer and dextran sulphate sodium induced colitis. Aronia extracts, neutral phenols fraction, and the polyphenol catabolites 3,4-dihydroxyphenylacetic acid and 3,4-dihydroxyphenylpropionic acid inhibited TNF-α production in Jurkat T cells. Therefore, T cells and microbial catabolism partly mediate the anti-inflammatory effects of aronia consumption in the colon.

Metabolic impact of polyphenol-rich aronia fruit juice mediated by inflammation status of gut microbiome donors in humanized mouse model

Article

Full-text available

Sep 2023

Background The Aronia melanocarpa fruit is emerging as a health food owing to its high polyphenolic content and associated antioxidant activity. Antioxidant-rich foods, such as Aronia fruit, may counter inflammatory stimuli and positively modulate the gut microbiome. However, a comprehensive study characterizing the impact of Aronia fruit supplementation has not been completed. Therefore, we completed analyses measuring the metabolic, microbial, and inflammatory effects of a diet supplemented with Aronia fruit juice. Method Humanized mice were generated by colonizing gnotobiotic mice with microbiomes from human donors presenting disparate inflammation levels. Blood and fecal samples were collected throughout the course of an 8-week dietary intervention with either Aronia juice or a carbohydrate-matched beverage alone (2 weeks) or in combination with a high-fat diet to induce inflammation (6 weeks). Samples were analyzed using 16S rRNA gene sequencing (stool) and liquid chromatography-mass spectrometry (serum). Results We demonstrated transfer of microbiome composition and diversity and metabolic characteristics from humans with low and high inflammation levels to second-generation humanized mice. Aronia supplementation provided robust protection against high-fat diet induced metabolic and microbiome changes that were dependent in part on microbiome donor. Aronia induced increases in bacteria of the Eggerthellaceae genus (7-fold) which aligns with its known ability to metabolize (poly)phenols and in phosphatidylcholine metabolites which are consistent with improved gut barrier function. The gut microbiome from a low inflammation phenotype donor provided protection against high-fat diet induced loss of microbiome β-diversity and global metabolomic shifts compared to that from the high inflammation donor. Conclusion These metabolic changes elucidate pathway-specific drivers of reduced inflammation stemming from both Aronia and the gut microbiota.

Bioactivity of Aronia Products, and The Promising Use of Aronia in Dairy Industry

Article

Dec 2022

Irem Uzunsoy

Evaluation of Antioxidant and Anti-Inflammatory Activity of Anthocyanin-Rich Water-Soluble Aronia Dry Extracts

Article

Full-text available

Sep 2020
MOLECULES

Aronia fruits contain many valuable components that are beneficial to human health. However, fruits are characterized by significant variations in chemical composition dependent on the growing conditions and harvesting period. Therefore, there is a need to formulate the extracts with a precisely defined content of health-promoting substances. Aronia dry extracts (ADE) were prepared from frozen pomace applying water extraction, followed by purification and spray-drying. Subsequently, the content of anthocyanins, phenolic acids, and polyphenols was determined. The high-quality chokeberry pomace enabled obtaining extracts with anthocyanin content much higher than the typical market standards. Moreover, it was found that the antioxidant capacity of aronia extracts exceeded those found in other fruit preparations. Antioxidant and free-radical scavenging properties were evaluated using a 2,2-diphenyl-1-picrylhydrazyl using Electron Paramagnetic Resonance (EPR) spectroscopy (DPPH-EPR) test and Oxygen Radical Absorbance Capacity (ORAC) assay. The inhibition of lipid peroxidation and the level of inflammatory markers have been also investigated using lipopolysaccharide (LPS)-stimulated RAW 264 cells. It was revealed that ADE standardized to 25% of anthocyanins depresses the level of markers of inflammation and lipid peroxidation (Interleukin 1 beta (IL-1β), tumor necrosis factor alpha (TNF-α), and malondialdehyde (MDA)) in in vitro conditions. Additionally, it was confirmed that ADE at all analyzed concentrations did not show any cytotoxic effect as demonstrated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay.

Comparative Biplot Analysis of Micropropagation of Viking Aronia Cultivar in Different Plant Tissue Culture Media

Article

Full-text available

Jun 2024

In this study, the effect of different concentrations of some plant growth regulators on the in vitro micropropagation of the Viking aronia variety was investigated. In this context, 15 different culture media were used by adding plant growth regulators (BAP, IBA, GA3, TDZ) in various concentrations and combinations to the MS medium (Murashige and Skoog, 1962). Sterilised shoot tips were transferred to the relevant plant tissue culture media in three replications according to the randomized parcels trial pattern, with three explants in each replication. At the end of the four-week development period, average vitrification rate (VIR), average shoot length (SHL) and average number of nodes (NON) parameters were evaluated. Biplot analysis was employed to elucidate the data obtained. According to the biplot analysis, B1I002G1T1: (1.0 mg L-1 BAP+0.02 mg L-1 IBA+1.0 mg L-1 GA3+1.0 mg L-1 TDZ), B1I002G1T05: (1.0 mg L-1 BAP+0.02 mg L-1 IBA+1 mg L-1 GA3+0.5 mg L-1 TDZ) and B1I002G05T1: (1.0 mg L-1 BAP + 0.02 mg L-1 IBA+0.5 mg L-1 GA3+1.0 mg L-1 TDZ) had a more positive effect on the number of nodes and shoot length. This study showed that the Viking aronia variety can be easily grown from cuttings by adjusting the plant growth regulator concentrations and combinations. Different media and plant growth regulators are needed for each aronia variety, so more studies are needed to improve success rates.

Anti-Atherosclerotic Properties of Aronia melanocarpa Extracts Influenced by Their Chemical Composition Associated with the Ripening Stage of the Berries

Article

Full-text available

Apr 2024
INT J MOL SCI

The high content of bioactive compounds in Aronia melanocarpa fruit offers health benefits. In this study, the anti-atherosclerotic effect of Aronia extracts was assessed. The impact on the level of adhesion molecules and the inflammatory response of human umbilical vein endothelial cells (HUVECs) was shown in relation to the chemical composition and the stage of ripening of the fruits. Samples were collected between May (green, unripe) and October (red, overripe) on two farms in Poland, which differed in climate. The content of chlorogenic acids, anthocyanins, and carbohydrates in the extracts was determined using HPLC-DAD/RI. The surface expression of ICAM-1 and VCAM-1 in HUVECs was determined by flow cytometry. The mRNA levels of VCAM-1, ICAM-1, IL-6, and MCP-1 were assessed using the quantitative real-time PCR method. The farms’ geographical location was associated with the quantity of active compounds in berries and their anti-atherosclerotic properties. Confirmed activity for green fruits was linked to their high chlorogenic acid content.

Polyphenol components in black chokeberry ( Aronia melanocarpa ) as clinically proven diseases control factors - An overview

Article

Full-text available

Jun 2023

Evaluation of the antioxidant, anti-inflammatory, and anti-tumoral properties of bioactive compounds extracted from murta berries (Ugni molinae T.) dried by different methods

Article

Full-text available

May 2023

This study evaluated the effects of different drying methods (freeze drying, vacuum drying, infrared drying, convective drying, and sun drying) on the biological properties of berries from the Chilean murta (Ugni molinae Turcz) shrub. Physical-chemical properties (proximal composition, dietary fiber, sugars) were determined. Total phenolic content through the method of Folin-Ciocalteau, the profile of phenol compounds was determined by HPLC, and antioxidant potential by DPPH and ORAC assays were also evaluated. The topic anti-inflammatory effect was evaluated by mice´s ear edema, and in vitro anti-tumoral activity was tested by MTT assay. The chemical properties of dried berries differed significantly based on the drying method: freeze-dried murta berries showed increased total phenolic content extracted over fresh and dried samples. In addition, this lyophilized extract stood out in its antioxidant potential, in both assays evaluated (DPPH and ORAC), compared to the other drying methods. Notwithstanding, vacuum- and infrared-dried murta also showed a higher ORAC value. Antioxidant potential was significantly associated with phenolic compounds catechin and pyrogallol, which were the most abundant phenolic compounds present in all samples. The anti-inflammatory activity was most effective under freeze-drying and vacuumdrying conditions. Moreover, vacuum drying and infrared drying best preserved the anti-tumoral effect on cancer cells.

Health Benefits of Antioxidant Bioactive Compounds in the Fruits and Leaves of Lonicera caerulea L. and Aronia melanocarpa (Michx.) Elliot

Article

Full-text available

Apr 2023

Lonicera caerulaea L. and Aronia melanocarpa (Michx.) Elliot fruits are frequently used for their health benefits as they are rich in bioactive compounds. They are recognized as a source of natural and valuable phytonutrients, which makes them a superfood. L. caerulea presents antioxidant activity three to five times higher than other berries which are more commonly consumed, such as blackberries or strawberries. In addition, their ascorbic acid level is the highest among fruits. The species A. melanocarpa is considered one of the richest known sources of antioxidants, surpassing currants, cranberries, blueberries, elderberries, and gooseberries, and contains one of the highest amounts of sorbitol. The non-edible leaves of genus Aronia became more extensively analyzed as a byproduct or waste material due to their high polyphenol, flavonoid, and phenolic acid content, along with a small amount of anthocyanins, which are used as ingredients in nutraceuticals, herbal teas, bio-cosmetics, cosmeceuticals, food and by the pharmaceutical industry. These plants are a rich source of vitamins, tocopherols, folic acid, and carotenoids. However, they remain outside of mainstream fruit consumption, being well known only to a small audience. This review aims to shed light on L. caerulaea and A. melanocarpa and their bioactive compounds as healthy superfoods with antioxidant, anti-inflammatory, antitumor, antimicrobial, and anti-diabetic effects, and hepato-, cardio-, and neuro-protective potential. In this view, we hope to promote their cultivation and processing, increase their commercial availability, and also highlight the ability of these species to be used as potential nutraceutical sources, helpful for human health.

Dried Fruits, Nuts, and Cancer Risk and Survival: A Review of the Evidence and Future Research Directions

Article

Full-text available

Mar 2023

Dried fruits and nuts contain high amounts of nutrients and phytochemicals-all of which may have anticarcinogenic, anti-inflammatory, and antioxidant properties. This narrative review summarizes the evidence for dried fruits and nuts and cancer incidence, mortality, and survival and their potential anticancer properties. The evidence for dried fruits in cancer outcomes is limited, but existing studies have suggested an inverse relationship between total dried fruit consumption and cancer risk. A higher consumption of nuts has been associated with a reduced risk of several site-specific cancers in prospective cohort studies, including cancers of the colon, lung, and pancreas, with relative risks per 5 g/day increment equal to 0.75 (95% CI 0.60, 0.94), 0.97 (95% CI 0.95, 0.98), and 0.94 (95% CI 0.89, 0.99), respectively. A daily intake of total nuts of 28 g/day has also been associated with a 21% reduction in the rate of cancer mortality. There is also some evidence that frequent nut consumption is associated with improved survival outcomes among patients with colorectal, breast, and prostate cancer; however, further studies are needed. Future research directions include the investigation of additional cancer types, including rare types of cancer. For cancer prognosis, additional studies with pre-and postdiagnosis dietary assessment are warranted.

Structural identification and in vitro antioxidant activities of anthocyanins in black chokeberry (Aronia melanocarpa Elliot)

Article

Full-text available

Dec 2021

Anthocyanins is a natural edible pigment with many health benefits. The aim of this work was the identification of anthocyanins present in Aronia melanocarpa using mass spectrometric features. The anthocyanins of the A. melanocarpa were analyzed by UV-Vis, HPLC-DAD and LC-EIS/MS methods. The four important anthocyanins were identified as follows: cyanidin-3-galactoside (68.68%), cyanidin-3-arabinoside (25.62%), cyanidin-3-glucoside (5.28%) and cyanidin-3-xyloside (0.42%). Among the four anthocyanin monomers, three anthocyanins with the highest content of A. melanocarpa were selected, and the antioxidant activity was studied with the total anthocyanins. The antioxidant capacity was cyanidin-3-galactoside > total anthocyanin > cyanidin-3-arabinoside > cyanidin-3-glucoside. The activity of the four anthocyanin samples was greater than ascorbic acid. The methodology described in this study will provide an effective tool for anthocyanins identification. Our results suggested that anthocyanins from A. melanocarpa exhibited effective antioxidant activity. These findings may be crucial in future research concerning chokeberry based functional food products.

Immunomodulatory activity and protective effects of chokeberry fruit extract on Listeria monocytogenes infection in mice

Article

Jul 2020

Chokeberry (Aronia melanocarpa) fruit extracts (CE) are rich in polyphenols and usually exhibit immunomodulatory, anti-viral and anti-bacterial effects. We have previously shown that the CE used in this study activated macrophages and stimulated effector T cell differentiation in vitro. When applied orally to healthy mice, CE increased the proportion of CD11c⁺ dendritic cells in the gut-associated lymphoid tissue. CE-pretreated BALB/c mice readily eradicated orally ingested Listeria monocytogenes as evidenced by a slighter decrease in body weight and number of bacteria recovered from the spleen and reduced spleen size compared to the control infected mice. CE pretreatment in infected mice resulted in higher proportions of CD11b+ macrophages and CD8⁺ cytotoxic T cells both in the gut and the spleen. Phagocytosis, reactive oxygen species production and the proportions of activated CD86⁺ macrophages (CD11b⁺) and dendritic cells (CD11c⁺) was also enhanced in CE-pretreated infected mice. Further, the expression of inducible nitric oxide synthase and IL-6 was increased in CE-pretreated infected mice and the similar results were obtained in peritoneal macrophages in vitro. This effect of CE was associated with increased phosphorylation of IκB and Notch1 production. Finally, CE pretreatment elevated the proportion of perforin-producing cells in the spleen compared to control infected mice. This study demonstrates that prophylactic treatment with CE leads to more rapid eradication of bacterial infection with Listeria monocytogenes predominantly through increased activity of myeloid cells in the gut and in the spleen.

The polyphenol-rich extract from chokeberry (Aronia melanocarpa L.) modulates gut microbiota and improves lipid metabolism in diet-induced obese rats

Article

Full-text available

Jul 2020
NUTR METAB

Abstract The gut microbiota plays a critical role in obesity and lipid metabolism disorder. Chokeberry (Aronia melanocarpa L.) are rich in polyphenols with various physiological and pharmacological activities. We determined serum physiological parameters and fecal microbial components by using related kits, liquid chromatography-mass spectrometry (LC-MS) and 16S rRNA gene sequencing every 10 days. Real-time PCR analysis was used to measure gene expression of bile acids (BAs) and lipid metabolism in liver and adipose tissues. We analyzed the effects of different Chokeberry polyphenol (CBPs) treatment time on obesity and lipid metabolism in high fat diet (HFD)-fed rats. The results indicated that CBPs treatment prevents obesity, liver steatosis and improves dyslipidemia in HFD-fed rats. CBPs modulated the composition of the gut microbiota with the extended treatment time, reducing the Firmicutes/Bacteroidetes ratio (F/B ratio) and increasing the relative abundance of Bacteroides, Prevotella, Akkermansia and other bacterial species associated with anti-obesity properties. We found that CBPs treatment gradually decreased the total BAs pool and particularly reduced the relative content of cholic acid (CA), deoxycholic acid (DCA) and enhanced the relative content of chenodeoxycholic acid (CDCA). These changes were positively correlated Bacteroides, Prevotella and negatively correlated with Clostridium, Eubacterium, Ruminococcaceae. In liver and white adipose tissues, the gene expression of lipogenesis, lipolysis and BAs metabolism were regulated after CBPs treatment in HFD-fed rats, which was most likely mediated through FXR and TGR-5 signaling pathway to improve lipid metabolism. In addition, the mRNA expression of PPARγ, UCP1 and PGC-1α were upregulated markedly in interscapular brown adipose tissue (iBAT) after CBPs treatment. We confirmed that CBPs could reduce the body weight of HFD-fed rats by accelerating energy homeostasis and thermogenesis in iBAT. Finally, the fecal microbiota transplantation (FMT) experiment results demonstrated that FMT from CBPs-treated rats failed to reduce the weight of HFD-fed rats. However, FMT from CBPs-treated rats improved dyslipidemia and reshaped gut microbiota in HFD-fed rats. In conclusion, CBPs treatment improved obesity and complications by regulating gut microbiota in HFD-fed rats. The gut microbiota plays an important role in BAs metabolism after CBPs treatment, and BAs have therefore emerged as major effectors in microbe-host signaling events that influence host lipid metabolism, energy metabolism and thermogenesis.

The Polyphenol-Rich Extract from Chokeberry (Aronia melanocarpa L.) Modulates Gut Microbiota and Improves Lipid Metabolism in Diet-Induced Obese Rats

Preprint

Full-text available

Feb 2020

The gut microbiota plays a critical role in obesity and lipid metabolism disorder. Chokeberry ( Aronia melanocarpa L . ) are rich in polyphenols with various physiological and pharmacological activities. We determined serum physiological parameters and fecal microbial components by using related kits, liquid chromatography-mass spectrometry (LC-MS) and 16S rRNA gene sequencing every 10 days. Real-time PCR analysis was used to measure gene expression of bile acids (BAs) and lipid metabolism in liver and adipose tissues. We analyzed the effects of different Chokeberry polyphenol (CBPs) treatment time on obesity and lipid metabolism in high fat diet (HFD)-fed rats. The results indicated that CBPs treatment prevents obesity, liver steatosis and improves dyslipidemia in HFD-fed rats. CBPs modulated the composition of the gut microbiota with the extended treatment time, reducing the Firmicutes / Bacteroidetes ratio (F/B ratio) and increasing the relative abundance of Bacteroides , Prevotella , Akkermansia and other bacterial species associated with anti-obesity properties. We found that CBPs treatment gradually decreased the total BAs pool and particularly reduced the relative content of cholic acid (CA), deoxycholic acid (DCA) and enhanced the relative content of chenodeoxycholic acid (CDCA). These changes were positively correlated Bacteroides , Prevotella and negatively correlated with Clostridium , Eubacterium , Ruminococcaceae . In liver and white adipose tissues, the gene expression of lipogenesis, lipolysis and BAs metabolism were regulated after CBPs treatment in HFD-fed rats, which was most likely mediated through FXR and TGR-5 signaling pathway to improve lipid metabolism. In addition, the mRNA expression of PPARγ, UCP1 and PGC-1α were upregulated markedly in interscapular brown adipose tissue (iBAT) after CBPs treatment. We confirmed that CBPs could reduce the body weight of HFD-fed rats by accelerating energy homeostasis and thermogenesis in iBAT. Finally, the fecal microbiota transplantation (FMT) experiment results demonstrated that FMT from CBPs-treated rats failed to reduce the weight of HFD-fed rats. However, FMT from CBPs-treated rats improved dyslipidemia and reshaped gut microbiota in HFD-fed rats. In conclusion, CBPs treatment improved obesity and complications by regulating gut microbiota in HFD-fed rats. The gut microbiota plays an important role in BAs metabolism after CBPs treatment, and BAs have therefore emerged as major effectors in microbe-host signaling events that influence host lipid metabolism, energy metabolism and thermogenesis.

Aronia berry inhibits disruption of Caco-2 intestinal barrier function

Article

May 2020

The objective of this work was to determine how aronia berry polyphenols and its microbial catabolites improve intestinal barrier function. Caco-2 cells were cultured on transwell plates and allowed differentiate to form a model intestinal barrier, having baseline transepithelial electrical resistance (TEER) ≥ 300 Ω cm². Barrier function of differentiated Caco-2 cells was compromised by the addition of an inflammatory cocktail (IC: TNF-α, IL-1β, and IFN-γ to the basolateral media and lipopolysaccharide to the apical media). Polyphenol-rich aronia berry powder or individual polyphenols representative of parent compounds or catabolites were applied to the basolateral media concurrently with IC. TEER was determined subsequently by chopstick electrode or continuous analysis. Permeability was determined by application of 4 kDa FITC-dextran or Lucifer yellow. Expression of tight junction proteins was assessed by qRT-PCR analysis. Application of the IC to differentiated Caco-2 cells routinely reduced TEER by ∼40% within 24 h. Individual polyphenols representative of parent compounds or phenolic microbial catabolites at 100 μM did not inhibit IC reduction of TEER in Caco-2 cells. Whole aronia berry powder inhibited loss of TEER by ∼50% at 24 h after application of the IC. Furthermore 5 mg/mL of aronia berry powder prevented an IC-induced barrier permeability of FITC-dextran and Lucifer yellow. After 12 h of IC treatment, Caco-2 cells had increased claudin 1 (CLDN1) relative to the untreated control. Application of aronia berry powder inhibited CLDN1 and also increased expression of zonula ocludens-1 (ZO-1) after 12 h. In summary, aronia berry, but not its microbiota-derived catabolites improved intestinal barrier function in a cellular model of chronic colonic inflammation. In this case, improved barrier function was associated with modulation of tight junction expression.

The Polyphenol-Rich Extract from Chokeberry (Aronia melanocarpa L.) Modulates Gut Microbiota and Improves Lipid Metabolism in Diet-Induced Obese Rat

Preprint

Full-text available

Mar 2020

The gut microbiota plays a critical role in obesity and lipid metabolism disorder. Chokeberry ( Aronia melanocarpa L.) are rich in polyphenols with various physiological and pharmacological activities. We determined serum physiological parameters and fecal microbial components by using related kits, liquid chromatography-mass spectrometry (LC-MS) and 16S rRNA gene sequencing every 10 days. Real-time PCR analysis was used to measured gene expression of bile acids (BAs) and lipid metabolism in liver and adipose tissues. We analyzed the effects of different Chokeberry polyphenol (CBPs) treatment time on obesity and lipid metabolism in high fat diet (HFD)-fed rat. The results indicated that CBPs treatment prevents obesity, liver steatosis and improves dyslipidemia in HFD-fed rat. CBPs modulated the composition of the gut microbiota with the extended treatment time, reducing the Firmicutes / Bacteroidetes ratio (F/B ratio) and increasing the relative abundance of Bacteroides , Prevotella , Akkermansia and other bacterial species associated with anti-obesity properties. We found that CBPs treatment gradually decreased the total BAs pool and particularly the reduced the relative content of cholic acid (CA), deoxycholic acid (DCA) and enhanced the relative content of chenodeoxycholic acid (CDCA). These changes were positively correlated Bacteroides , Prevotella and negatively correlated with Clostridium , Eubacterium , Ruminococcaceae . In liver and white adipose tissues, the gene expression of lipogenesis, lipolysis and BAs metabolism were regulated after CBPs treatment in HFD-fed rat, which was most likely mediated through FXR and TGR-5 signaling pathway to improve lipid metabolism. In addition, the mRNA expression of PPARγ, UCP1 and PGC-1α were upregulated markedly in interscapular brown adipose tissue (iBAT) after CBPs treatment. We confirmed that CBPs could reduce the body weight of HFD-fed rat by accelerating energy homeostasis and thermogenesis in iBAT. Finally, the fecal microbiota transplantation (FMT) experiment results demonstrated that FMT from CBPs-treated rat failed to reduce the weight of HFD-fed rat. However, FMT from CBPs-treated rat improved dyslipidemia and reshaped gut microbiota in HFD-fed rat. In conclusion, CBPs treatment improved obesity and complications by regulating gut microbiota in HFD-fed rat. The gut microbiota plays a important role in BAs metabolism after CBPs treatment, and BAs have therefore emerged as major effectors in microbe-host signaling events that influence host lipid metabolism, energy metabolism and thermogenesis.

Assessment of Hepatoprotective Effect of Chokeberry Juice in Rats Treated Chronically with Carbon Tetrachloride

Article

Full-text available

Mar 2020
MOLECULES

The aim of this study was to compare the protective effects of chokeberry juice and silymarin against chemical-induced liver fibrosis in rats. Liver fibrosis was induced by CCl4 administered two days a week for six weeks. Two groups of rats were co-treated with chokeberry juice, 10 mL/kg/day. or silymarin as a positive control, 100 mg/kg/day for six weeks. Hepatic lipid peroxidation was suppressed by 50% and the activity of hepatic antioxidant enzymes was increased by 19%−173% in rats co-treated with CCl4 and substances tested as compared to rats administered CCl4 alone. Hepatic hydroxyproline was decreased by 24% only in rats treated with silymarin. The messenger RNA (mRNA) expression levels of fibrosis-related molecules, procollagen I, α-SMA, TIMP-1, TGFβ, and TNFα, which were significantly increased in the liver of CCl4-treated rats, were not modulated by substances tested. Histological evaluation revealed a slight protective effect of silymarin against fibrosis. However, in CCl4 + chokeberry-treated rats, the density of vacuolated hepatocytes was significantly lower than that in silymarin administered animals. Chokeberry juice did not demonstrate an antifibrotic effect in the applied experimental model of fibrosis, and the effect of the known antifibrotic agent, silymarin, was very limited.

Bioavailability and Metabolic Pathway of Phenolic Compounds

Chapter

Full-text available

Sep 2019

As potential agents for preventing different oxidative stress-related diseases, phenolic compounds have attracted increasing attention with the passage of time. Intake of fruits, vegetables and cereals in higher quantities is linked with decreased chances of chronic diseases. In plant-based foods, phenolic compounds are very abundant. However, bio-accessibility and biotransformation of phenolic compound are not reviewed in these studies; therefore, a detailed action mechanism of phenolic compounds is not recognized. In this article, inclusive concept of different factors affecting the bioavailability of phenolic compounds and their metabolic processes is presented through which phenolic compounds go after ingestion.

Nutritional and bioactive value of Rubus berries

Article

Jul 2019

Rubus L. (Rosaceae) berries have received worldwide attention, mainly for their nutritional and bioactive value. The raspberries and blackberries of this genus contain nutrients and bioactive compounds such as vitamins, minerals, proteins, sugars, and polyphenols. This review summarizes available data on the physical-chemical characteristics, nutritional composition, biologically active compounds, and biological activities of Rubus raspberries (Rubus idaeus L., R. ellipticus Smith, R. niveus Thunb., R. coreanus Miquel and R. occidentalis L.) and blackberries (R. ulmifolius Schott, R. fruticosus L., R. adenotrichus Schltdl., R. glaucus Benth). The composition and the antioxidant, anti-inflammatory, chemopreventive, and antimicrobial activities, as well as the positive effects on blood lipids and atherosclerosis of the Rubus berries showed that these fruits are important sources of biologically active compounds, and their biological effects suggest potential uses for human health.

Differences Between Aronia Medik. Taxa on the Morphological and Biochemical Characters

Article

Full-text available

Jan 2019

Useful wild plants usually decrease the content of biologically active substances in culture. However, there are no studies on the reverse process and no evidence whether the level of biologically active compounds increases in plants escaping from culture and becoming invaded in natural communities (invasive species). We studied Aronia melanocarpa, A. arbutifolia, A. × prunifolia, 2 samples of cultivated A. mitschurinii in the arboretum of the Main Botanical Garden (Moscow, Russia) and one sample of invasive A. mitschurinii from the Moscow region. The task of the study was to determine the degree of heritability of macro-and micromorphological characters of North American plants introduced to Europe. The identification of the samples most promising for further broad cultivation by their antioxidant activity and the content of microelements in leaves was also our research purpose. The diagnostic features of the introduced North American Aronia were found to be inherited under culture conditions. The mass of fruits increases in this order: A. arbutifolia → naturalised A. mitschurinii → A. × prunifolia → A. melanocarpa → cultivated A. mitschurinii. An original table was compiled to compare the studied taxa on 21 biomorphological features. Naturalising plants have a higher antioxidant activity of alcohol extracts than cultivated plants, and, on the contrary, lower antioxidant activity of water extracts. The leaves of A. mitschurinii have the highest content of 10 microelements: Fe, Mn, Sr, Zn, Se, Cu, Mo, Cr, As and Sb; A. × prunifolia has the highest content of 6 microelements: Ni, Co, V, Cd, Pb, and Sn; and A. arbutifolia has the highest content of B. Our observations suggest that naturalising plants of Aronia have a potential source of useful bioactive compounds.

Development of Kefir Products Using Aronia or Elderberries and the Impacts of Fermentation on the Health-promoting Characteristics of Aronia Polyphenols

Article

Aug 2018

Xue Du

Diabetes is a global health problem. The consumption of dietary polyphenols may help to decrease the risk of type 2 diabetes and slow the progression of diabetic complications. Aronia (Aronia melanocarpa) and elderberry (Sambucus nigra L. ssp. canadensis) fruits are rich in polyphenols and exhibit health-promoting properties, but they are underutilized. Aronia and elderberries are rarely consumed raw due to the astringent mouth feel. New food products are needed to increase their consumption. Kefir, a fermented dairy beverage, was chosen to be the matrix for incorporating berries due to: 1) the protein matrix can help mask the astringency; 2) an acidic environment is beneficial for the stability of phenolic compounds; 3) fermentative microorganisms may be able to increase the bioavailability of polyphenols. The first objective of this research was to develop new palatable products using underutilized berries and different sweeteners (sucrose, stevia and monk fruit extracts). Sensory evaluations were conducted to assess consumer acceptability of berry-containing kefirs. The results showed that aronia and elderberry kefirs sweetened with stevia or sucrose were all accepted by consumers where sucrose was the best-accepted sweetener. The second objective was to assess the health-promoting characteristics of the berry-containing kefirs. Aronia kefirs contained high levels of total phenolics and anthocyanins. Elderberry kefirs were moderate in total phenolics. All kefirs exhibited antioxidant capacity. The third objective was to evaluate the diabetes-beneficial properties of aronia kefir using an in-vitro digestion model. The impacts of fermentation on aronia polyphenols were also assessed. The results showed that the levels of bioaccessible polyphenols were elevated during digestion and the antioxidant capacity increased. Fermentation enhanced the inhibitory activity of aronia kefir on α-glucosidase but did not alter its weak inhibition on pancreatic α-amylase. Specific inhibition of α-glucosidase may decrease the absorption of carbohydrates and contribute to blood glucose control without side effects compared to pharmaceutical agents, such as acarbose. In conclusion, new berry-containing kefirs were well-accepted by the consumers and the consumption of berry-containing kefirs may help to reduce oxidative stress and aid in blood glucose control. In addition, fermentation may be a good strategy to increase the bioavailability of dietary polyphenols.

Anti-tumor properties of anthocyanins from Lonicera caerulea 'Beilei' fruit on human hepatocellular carcinoma: In vitro and in vivo study

Article

May 2018

In this study, the anthocyanin from Lonicera caerulea 'Beilei' fruit (ABL) was extracted and purified. The purified component (ABL-2) was then evaluated for its anti-tumor properties on human hepatoma cells (SMMC-7721) in vitro and the murine hepatoma cells (H22) in vivo. In vitro, ABL-2 not only significantly inhibited the growth of SMMC-7721 cells, but also remarkably blocked the cells' cycle in G2/M phase, inducing DNA damage and eventually leading to apoptosis. In vivo, ABL also killed tumor cells, inhibited tumor growth, and improved the survival status of H22 tumor-bearing mice. These effects were associated with an increase in the activities of antioxidase and a decrease in the level of lipid peroxidation, as evidenced by changes in SOD, GSH-Px, GSH, and MDA levels. In addition, ABL-2 also regulated the levels of immune cytokines including IL-2, IFN-γ, and TNF-α. These results revealed that ABL-2 exerts an effective anti-tumor effect by dynamically adjusting the REDOX balance and improving the immunoregulatory activity of H22 tumor-bearing mice. High performance liquid chromatography (HPLC) analysis revealed that cyanidin-3,5-diglucoside (8.16 mg/g), cyanidin-3-glucoside (387.60 mg/g), cyanidin-3-rutinoside (23.62 mg/g), and peonidin-3-glucoside (22.20 mg/g) were the main components in ABL-2, which may contribute to its anti-tumor activity.

Preparative Purification of Polyphenols from Aronia melanocarpa (Chokeberry) with Cellular Antioxidant and Antiproliferative Activity

Article

Full-text available

Jan 2018
MOLECULES

The aim of this study was the purification process of polyphenols from Aronia melanocarpa (chokeberry), and the purification parameters were optimised by adsorption and desorption tests. By comparing adsorption and desorption ability of polyphenols from chokeberry on six kinds of macroporous resin, XAD-7 resin was selected. Experiments prove that the best purification parameters of static adsorption and desorption were sample pH = 4.0 with 4 h of adsorption; and desorption solvent is 95% ethanol (pH = 7.0) with 2 h of desorption. The best dynamic parameters were 9.3 bed volume (BV) of sample loading amount at a feeding flow rate of 2 BV/h, and washing the column with 5.8 BV of water, followed by subsequent elution with an eluent volume of 5.0 mL at an elution flow rate of 2 BV/h. Next the antioxidant and antiproliferative activity of polyphenols from chokeberry, blueberries, haskap berries was studied on HepG2 human liver cancer cells. The results show that polyphenol from chokeberry has a strong antioxidant effect. Taking into account the content of polyphenols in fruit, polyphenols from chokeberry represent a very valuable natural antioxidant source with antiproliferative products.

Fruits of Black Chokeberry Aronia melanocarpa in the Prevention of Chronic Diseases

Article

Full-text available

Jun 2017
MOLECULES

In recent years, growing attention has been focused on the utilization of natural sources of antioxidants in the prevention of chronic diseases. Black chokeberry (Aronia melanocarpa) represents a lesser known fruit species utilized mainly as juices, purees, jams, jellies and wine, as important food colorants or nutritional supplements. The fruit is valued as a great source of antioxidants, especially polyphenols, such as phenolic acids (neochlorogenic and chlorogenic acids) and flavonoids (anthocyanins, proanthocyanidins, flavanols and flavonols), particularly cyanidin-3-galactoside and cyanidin-3-arabinoside, as well as (−)-epicatechin units. The berries of A. melanocarpa, due to the presence and the high content of these bioactive components, exhibit a wide range of positive effects, such as strong antioxidant activity and potential medicinal and therapeutic benefits (gastroprotective, hepatoprotective, antiproliferative or anti-inflammatory activities). They could be also contributory toward the prevention of chronic diseases including metabolic disorders, diabetes and cardiovascular diseases, because of supportive impacts on lipid profiles, fasting plasma glucose and blood pressure levels.

The Effect of Black Chokeberry (Aronia melanocarpa) on Human Inflammation Biomarkers and Antioxidant Enzymes: A Systematic Review of Randomized Controlled Trials

Article

Nov 2024
NUTR REV

Context: Consuming antioxidant-rich foods has been associated with potential benefits in managing chronic diseases by reducing oxidative stress and inflammation. Objective: This systematic review aimed to evaluate the effects of Aronia melanocarpa (aronia berry or chokeberry) on human inflammation biomarkers and antioxidant enzymes. Data sources: A systematic search was conducted across multiple databases, including PubMed, Scopus, Science Direct, and Web of Science, to identify relevant studies investigating the potential effects of aronia on human inflammation biomarkers and antioxidant enzymes between April 2022 and November 2023. Data extraction: The selection of studies followed the PRISMA guidelines, data screening was conducted by 4 independent reviewers, and data extraction and risk-of-bias assessments were performed by 2 independent reviewers using the Cochrane Risk of Bias 2 tool. Data analysis: A total of 1986 studies were screened, and 18 studies that met the inclusion criteria were included in a systematic review that investigated the anti-inflammatory effects of aronia on various health parameters. These studies primarily focused on the effects of aronia on cardiometabolic diseases, performance in sport, and other health parameters. Conclusions: This study examined the effects of Aronia intervention on human health outcomes using aronia juice, extract, or oven-dried powder for a period of 4 to 13 weeks. The primary health parameters considered were C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), interleukin-8 (IL-8), interleukin-10 (IL-10), interleukin-1ß (IL-1ß), superoxide dismutase (SOD), catalase (CAT), and reduced glutathione peroxidase (GSH-Px). The results showed that aronia had a beneficial effect on several inflammatory cytokines, including reductions in CRP, TNF-α and IL-6 concentrations, as well as elevated IL-10 levels. Moreover, positive changes have been observed in antioxidant enzyme systems, including; elevated SOD, GSH-Px and CAT activity. The findings of the presented studies provide evidence that Aronia melanocarpa may have beneficial effects on inflammatory markers. Systematic review registration: PROSPERO registration No. CRD42022325633.

Aronia melanocarpa extract extends lifespan and health-span in Caenorhabditis elegans via mitogen-activated protein kinase 1

Article

Oct 2024

Aging is a highly complex process and one of the largest risk factors for many chronic diseases. Aronia melanocarpa (AM) is rich in bioactive phytochemicals with antioxidant, anti-inflammatory, and anticancer...

Biogenic Synthesis of Silver Nanoparticles Mediated by Aronia melanocarpa and Their Biological Evaluation

Article

Full-text available

Sep 2024

In the present study, two A. melanocarpa berry extracts were used for the synthesis of silver nanoparticles (AgNPs). After the optimization of synthesis, the AgNPs were characterized using UV–Vis, FTIR, EDX, DLS, and STEM analyses. The stability in different media, phytotoxicity, as well as antimicrobial and antioxidant activities were also evaluated. The ideal synthesis conditions were represented by a 3 mM AgNO3 concentration, 1:9 extract:AgNO3 volume ratio, alkaline medium, and stirring at 40 °C for 120 min. The synthesis was confirmed by the surface plasmon resonance (SPR) peak at 403 nm, and the strong signal at 3 keV from the EDX spectra. FTIR analysis indicated that polyphenols, polysaccharides, and amino acids could be the compounds responsible for synthesis. Stability tests and the negative zeta potential values showed that phytocompounds also play a role in the stabilization and capping of AgNPs. The preliminary phytotoxicity studies on T. aestivum showed that both the extracts and their corresponding AgNPs had an impact on the growth of roots and shoots as well as on the microscopic structure of leaves. The synthesized AgNPs presented antimicrobial activity against S. aureus, E. coli, and C. albicans. Moreover, considering the results obtained in the lipoxygenase inhibition, the DPPH and hydroxyl scavenging activities, and the ferrous ion chelating assay, AgNPs exhibit promising antioxidant activity.

β-Escin and Chokeberry Fruit Extract Supplementation in Smokers as Potential anti-Inflammatory Protection-a Pilot Proof-of-Concept Study

Article

Sep 2024
J MED FOOD

Chemical Composition, Nutritional, and Biological Properties of Extracts Obtained with Different Techniques from Aronia melanocarpa Berries

Article

Full-text available

May 2024
MOLECULES

This study investigates the chemical composition, nutritional, and biological properties of extracts obtained from A. melanocarpa berries using different extraction methods and solvents. Hydrodistillation and supercritical fluid extraction with CO 2 allowed us to isolate fruit essential oil (HD EX) and fixed oil (SFE EX), respectively. A phenol-enriched extract was obtained using a mild ultrasound-assisted maceration with methanol (UAM M). The HD EX most abundant component , using gas chromatography-mass spectrometry (GC/MS), was italicene epoxide (17.2%), followed by hexadecanoic acid (12.4%), khusinol (10.5%), limonene (9.7%), dodecanoic acid (9.7%), and (E)-anethole (6.1%). Linoleic (348.9 mg/g of extract, 70.5%), oleic (88.9 mg/g, 17.9%), and palmitic (40.8 mg/g, 8.2%) acids, followed by α-linolenic and stearic acids, were the main fatty acids in SFE EX determined using high-performance liquid chromatography coupled with a photodi-ode array detector and an evaporative light scattering detector (HPLC-DAD/ELSD). HPLC-DAD analyses of SFE EX identified β-carotene as the main carotenoid (1.7 mg/g), while HPLC with flu-orescence detection (FLU) evidenced α-tocopherol (1.2 mg/g) as the most abundant tocopherol isoform in SFE EX. Liquid chromatography-electrospray ionization-MS (LC-ESI-MS) analysis of UAM M showed the presence of quercetin-sulfate (15.6%, major component), malvidin 3-O-(6-O-p-coumaroyl) glucoside-4-vinylphenol adduct (pigment B) (9.3%), di-caffeoyl coumaroyl spermidine (7.6%), methyl-epigallocatechin (5.68%), and phloretin (4.1%), while flavonoids (70.5%) and phenolic acids (23.9%) emerged as the most abundant polyphenol classes. UAM M exerted a complete inhibition of the cholesterol oxidative degradation at 140 • C from 75 µg of extract, showing 50% protection at 30.6 µg (IA 50). Furthermore, UAM M significantly reduced viability (31-48%) in A375 melanoma cells in the range of 500-2000 µg/mL after 96 h of incubation (MTT assay), with a low toxic effect in normal HaCaT keratinocytes. The results of this research extend the knowledge of the nutritional and biological properties of A. melanocarpa berries, providing useful information on specific extracts for potential food, cosmetic, and pharmaceutical applications.

Profile of biologically active substances of Aronia mitschurinii leaves growing in the conditions of the Central Black Earth region

Article

Apr 2024

Polyphenol-rich blue honeysuckle extract alleviates silica particle-induced inflammatory responses and macrophage apoptosis via NRF2/HO-1 and MAPK signaling

Article

Jul 2018

The purification of dominant spoilage fungi on Lonicera Caeruleum and the inhibitory effects of composite essential oils against these fungi

Article

Jun 2023

ML BASED PYTHON IMPLEMENTATION FOR DETECTION OF LUNG CANCER

Conference Paper

Full-text available

Aug 2022

Vaibhav Kant Singh

The Paper is a Continuation of the Work done by the Author in the Field of Machine Learning, Artificial Intelligence, Artificial Neural Network and so on in the Area of Computer Science and Engineering. In the Current Paper beside of the Reference Section there are Six More Sections. In Section One which is Introduction the Author gave a brief description on the disease that is Cancer. In the Next Section that which is Literature Survey we made inroads on the previous work done in the field discussed in the Paper. Next we elaborate the Statement on which we are actually focused in the Paper. Next the Proposed Algorithm is formulated after which we will have a discussion on the Results Obtained and the Conclusion. In the Introduction Section we basically discussed the Disease Cancer and also made a small Introduction of Python Programming Language. The Conclusion Section Comprise of the Classification Report Obtained for the Model Used for the Purpose of Detection and From the Classification Report it could be concluded that the Approach that we adopted gives us a very high degree of Efficiency in terms of the metrics used for assessment. The work done by the Author is Another Work in the Field of Medical Science. The Author had already done some work in the past which is discussed in the Literature Survey Part that is portraying that the Author has done a good amount of work in the field of Machine Learning and used the Machine Learning Approach in various Medical Fields. From the Research Article it could be easily identified that Python is a very useful Programming Language and the Results Shown Could be easily taken as a benchmark for going on for the Research work in various other field using the Programming Tool Python.

A STUDY ON ARTIFICIAL NEURAL NETWORK WHEN VIEWED AS A DIRECTED GRAPH

Conference Paper

Full-text available

Aug 2022

Vaibhav Kant Singh

This is a Continuation to what the Author has done in the Field of Artificial Neural Network. In this Paper the Author Gave a Study Report of the Basic Methodologies Adopted for the Representation of the Artificial Neural Network. After Presenting the Basic Techniques the Author Gave a Detailed Description of the Basic Techniques. Out of the Techniques Presented the Author is more keen on the Technique Presented by Mason and the Author Gave a Detailed Description of the Technique. The Basic Properties that are shown when Neural Network is represented as a Directed Graph is Discussed. The Author gave a Description of the Rules that Guide the Portrayal of the Representation Technique. The Limitations of the Artificial Neural Network when viewed as a Directed Graph is discussed as well as the Advantages is also Discussed. The Paper Comprises of Sections namely Introduction where an Introduction to the Artificial Neural System Technology is Discussed. In the Next Section that is Literature Survey we made a Detailed Analysis of works done in the Past. Then in the Problem Statement we discussed the Problem for which we are actually going for the Techniques. In the Next Section the Survey Report of the Models is discussed and then comes the Result and Conclusion Sections.

A COMPUTERIZED APPROACH FOR THYROID DISEASE HAVING THE USAGE OF ML TECHNIQUE

Conference Paper

Full-text available

Aug 2022

Vaibhav Kant Singh

The work is a essentially a continuation of the work done by the author in the field of Medical Science, Artificial Intelligence, Machine Learning and Computer Science. In the current world we are suffering from the critical issue of COVID. The pandemic has a great impact on some of the countries of the world. The pandemic has affected the whole world. Apart of COVID in the current time the world is suffering from diseases like thyroid, diabetes etc. which is also a major challenge for the People in the World. In the current work the author is interested in the study and elaboration of ways to face the disease named Thyroid. In the current paper the author made study and implementation of the ML paradigm to prepare a System that can detect Thyroid. In the current paper the author made a usage of the Programming Language named Python. The author made effective usage of the libraries available in Python. In the current research article the author studied and created System that used the algorithms namely Light Gradient Boosting Machine, Gradient Boosting Classifier, Decision Tree Classifier, Extra Tree Classifier, Dummy Classifier, Logistic Regression, KNeighbors Classifier, ADA Boost Classifier, SVM-Linear Kernel, Linear Discriminant Analysis, Ridge Classifier, Naïve Bayes and Quadratic Discriminant Analysis. The work done by the author is an approach that still is lagging in some vital areas like the output user interface is not that interactive which would have made the research work more popular among the end users. The dataset used for Experimentation purpose is taken from Kaggle. The availability of rows and columns in the dataset of Kaggle is not that wealthy although the accuracies that are generated after execution of the implemented code is extremely nice. At this point from the Experiment Carried it would be said that the approach would have been more efficient if the data set that was Considered for Doing the Experimental Analysis and had some limitation would have been more effective and efficient from the point of Early Diagnosis if the Data-Set would be having more number of Records and might have Considered some more Features in the Landscape.

A STUDY ON FEEDBACK IN AN ARTIFICIAL NEURAL SYSTEM

Conference Paper

Full-text available

Aug 2022

Vaibhav Kant Singh

This Research Article is basically a continuation of the Work done by the Author in the Field of Artificial Neural Network. In this work the Author Presented a Mathematical Derivation of the Relation between the Input Signal and Output Signal for Artificial Neural Network Having Feedback. As the people those who are having proficiency in the Field of Artificial Neural Network are Aware of the Basic Elements of the Artificial Neural Network. Out the Basic Elements of the Artificial Neural Network one Basic Element is the Network Topology. In Network Topology there is a Concept of Recurrent Networks. So this Paper is a Research Article which basically presents a Survey Report on the Mathematical Representation between the Input Signal and the Output Signal. The paper comprises of Section Titled Introduction where we make a brief Discussion on the Artificial Neural System Technology. Next we come to the Literature Survey Part where we made a Discussion on the various work done in the Past in the Area. Next we will be discussing the Problem Statement after which we will be Discussing the Mathematical Derivation than we will Observe the Result and Conclusion Section where the Mathematical Derivation Perspectives are Discussed.

A STUDY ON ELEMENTARY NEUROPHYSIOLOGY OF HUMAN BRAIN

Conference Paper

Full-text available

Aug 2022

Vaibhav Kant Singh

This Paper is a Continuation of the Work done by the Author in the Field of Artificial Neural Network and Computer Science and Engineering. In the Current Research Article the Author is engaged in the Study of the Biological Neuron and its Basic Working. In the Paper the Author Gave a Detailed Portrayal of the Major Constituents Present in the Biological Neuron, Working of Each of the Constituents of the Biological Neuron. Biological Neural Network Functioning is discussed in Detail in the Research Work. The Association between the Artificial Neural Network and Biological Neural Network is found so that we can form a bridge and can portray how Computer Science and Engineering and Working of Human Brain go Hand in Hand. The Research Article Comprises of Section named Introduction where we will discuss the constituents of the Biological Neuron. Next Comes the Literature Survey where we will discuss the Work done in the Past in the Field. Next Comes the Problem Statement After which come the Survey Report as to How the Brain Works. In this Section we will discuss the Major Organelles of the Biological Neuron. We will also be discussing the Major Parts that are going to be used as the basis for forming a bridge between the ANN and the BNN. Then in the Next Section that is Conclusion we will discuss the Bridge between the Artificial Neural Network and the Central Nervous System. The Research Article is a Collection of Figures that Explain the overall Working. Also the Na+ and K+ pump is Discussed in Detail.

Comparative Phytochemical Analysis of Aronia melanocarpa L. Fruit Juices on Bulgarian Market

Article

Full-text available

Jun 2022

Aronia melanocarpa L. (black chokeberry), belonging to the Rosaceae family, contains high amounts of polyphenolics and therefore exhibits one of the highest antioxidant and anti-inflammatory activities among berry fruits. Chokeberries are used in the food industry for juice, nectar, and wine production and as colorants. We aimed to compare the phytochemical composition of three chokeberry juices commercially available in the local market as sources of beneficial phytochemicals. Using GC-MS and LC-MS/MS, we performed the identification and quantitation of polar compounds and polyphenolics. The concentrations of 13 amino acids, including 6 essential amino acids, 10 organic acids, 20 sugar alcohols and derivatives, 14 saccharides, 12 fatty acids and esters, and 38 polyphenols, were estimated. One of the analyzed juices had the highest polyphenolic content (5273.87 ± 63.16 µg/mL), possibly due to 2.9 times higher anthocyanin concentration compared to anthocyanins in other tested juices. This study provides new data concerning phytochemical composition in terms of amino acids, organic acids, sugar acids, fatty acids and their esters, and polyphenols as phytocomponents of commercially available chokeberry juices. Results show that after all processing techniques and possibly different plant growth conditions, chokeberry juices are a valuable source of health-promoting phytochemicals such as phenolic acids, pro-anthocyanins, and anthocyanins, thus considering them as functional foods. We demonstrated a diversity of the active substances in bioactive foods marketed as "same"; therefore, the standardized therapeutic effect could be expected only by the utilization of food supplements with guaranteed constant content.

Radical Scavenging Actions and Immunomodulatory Activity of Aronia melanocarpa Propylene Glycol Extracts

Article

Full-text available

Nov 2021

Researchers are attracted to the wide-ranging, useful components in Aronia melanocarpa berries. They are searching for the most effective ways to extract the active substances that can enhance the body’s protective properties. The current study presents detailed information about the extracts from A. melanocarpa fruits frozen and dried under mild conditions and their chemical composition. In Wistar rats with induced immunosuppression, the effect of chokeberry fruit extracts on the leukocyte formula, phagocytic activity, and cytokine system was studied. It was shown that the A. melanocarpa frozen fruit extract contains more anthocyanins, sugars, and ascorbic acid, and has a more pronounced antioxidant activity determined by the ability to bind APPH-radicals. Moreover, the extract showed membrane-protective and cytoprotective properties against RPMI-1788 cell line. The extract from dried raw material shows a higher antioxidant activity due to the ability to bind DPPH-radicals. It was revealed that extracts from A. melanocarpa fruits promote rapid immune system recovery in rats, normalize the leukocyte count, and improve monocyte and neutrophil phagocytic indicators. Research on the cytokine profile revealed that the anti-inflammatory properties in A. melanocarpa extracts were more pronounced in dried extracts. For several cytokines, a normalization of quantity was noted.

Aronia melanocarpa Extract Fermented by Lactobacillus plantarum EJ2014 Modulates Immune Response in Mice

Article

Full-text available

Aug 2021

The present study aimed to assess the immunomodulatory effects of fermented Aronia melanocarpa extract (FAME) on RAW 264.7 cells and BALB/c mice. Aronia melanocarpa fruit was fermented with Lactobacillus plantarum EJ2014 by adding yeast extract and monosodium glutamate for 9 days at 30 °C to produce γ-aminobutyric acid (GABA). After fermentation, significant GABA production was noted, along with minerals, polyphenols, and flavonoids (p < 0.05). The polyphenol content was confirmed by liquid chromatography with tandem mass spectrometry (LC–MS/MS) analysis. RAW 264.7 cells were stimulated with lipopolysaccharide (LPS, 1 μg/mL) in the presence or absence of FAME, and proinflammatory cytokine contents were measured by qPCR. In the in vivo experiment, female BALB/c mice were administered 125, 250, and 500 mg/kg of FAME for 21 days. FAME treatment increased neutrophil migration and phagocytosis (p < 0.05). It also increased splenocyte proliferation, CD4+ and CD8+ T-cell expression, and lymphocyte proliferation. Furthermore, it increased IFN-γ, IL-2, and IL-4 cytokine levels in a dose-dependent manner (p < 0.05). However, it decreased TNF-α and IL-6 levels (p < 0.05). These results indicate that FAME fortified with GABA including bioactive compounds exerts anti-inflammatory effects by inhibiting proinflammatory cytokines in RAW 264.7 cells and modulates immune response in mice. Thus, FAME could be a potential therapeutic agent for inflammatory disorders.

Preferential ammonium: Nitrate ratio of blueberry isregulated by nitrogen transport and reduction systems

Article

Oct 2021
SCI HORTIC-AMSTERDAM

Blueberry (Vaccinium spp., Vc) is inefficient in uptake and utilizing a single nitrogen (N) form (ammonium or nitrate), and prefers the presence of both N forms; however, its the preferential ammonium: nitrate ratios and the underlying molecular mechanism remains elusive. To reveal the mechanism of blueberry preference in the composition of N forms, blueberries had grown over three months in pure coconut bran irrigated with modified Hoagland nutrient solution contained ammonium N (NH4⁺-N) alone or nitrate N (NO3⁻-N) alone at two pHs (5.0 and 7.5), and NH4⁺-N:NO3⁻-N ratios of 4:1, 2:1 and 1:1 at pH 5.0. After three months, the physiological responses and the expression of key genesinvolved in N metabolism were analyzed. Afterwards, the genes were then genetically transformed into Arabidopsis thaliana for functional verification. The results showed that (i) plants grew better at pH 5.0 than pH 7.5; (ii) at pH 5.0, when NH4⁺-N:NO3⁻-N ratio was applied at 2:1, plant growth was at the best performance (i.e., 11% higher in the crown width compared to the control(nil-N applied). In the presence of both NH4⁺ and NO3⁻, the transcriptional levels of VcAMT3, VcNRT1.5, VcNRT2, VcNR and VcNiR were significantly upregulated. Its highest value appeared in the 2:1 of NH4⁺-N:NO3⁻-N ratio where, VcAMT3 and VcNRT2 were raised by 4 and 5 times, respectively. Hence, the results suggested that the mixed N forms at 2:1 NH4⁺-N:NO3⁻-N ratio at pH 5.0 induced the expression of the related gene, which may have increased root absorption and transportation of NH4⁺-N and NO3⁻-N, resulting in the better plant growth; and (iii) under NH4⁺-N alone treatments, the transgenic VcNiR Arabidopsis thaliana plants was the only survival; under NO3⁻-N alone treatments, compared to the wild-type (WT) plants, the transgenic VcAMT3 Arabidopsis thaliana had 11 and 2 times higher in the plant height and leaf disc size. The results showed that VcAMT3, VcNRT2, VcNiR gene could improve the nitrogen absorption ability of Arabidopsis thaliana plants. Our study improved the understanding of the underlying molecular mechanism of N speciation preference of blueberry, and the findings can be a great guidance for better N fertilizer management to promote blueberry productivity.

Cyanidin 3-O-galactoside: A Natural Compound with Multiple Health Benefits

Article

Full-text available

Feb 2021
INT J MOL SCI

Cyanidin 3-O-galactoside (Cy3Gal) is one of the most widespread anthocyanins that positively impacts the health of animals and humans. Since it is available from a wide range of natural sources, such as fruits (apples and berries in particular), substantial studies were performed to investigate its biosynthesis, chemical stability, natural occurrences and content, extraction methods, physiological functions, as well as potential applications. In this review, we focus on presenting the previous studies on the abovementioned aspects of Cy3Gal. As a conclusion, Cy3Gal shares a common biosynthesis pathway and analogous stability with other anthocyanins. Galactosyltransferase utilizing uridine diphosphate galactose (UDP-galactose) and cyanidin as substrates is unique for Cy3Gal biosynthesis. Extraction employing different methods reveals chokeberry as the most practical natural source for mass-production of this compound. The antioxidant properties and other health effects, including anti-inflammatory, anticancer, antidiabetic, anti-toxicity, cardiovascular, and nervous protective capacities, are highlighted in purified Cy3Gal and in its combination with other polyphenols. These unique properties of Cy3Gal are discussed and compared with other anthocyanins with related structure for an in-depth evaluation of its potential value as food additives or health supplement. Emphasis is laid on the description of its physiological functions confirmed via various approaches.

Comparative analysis of antioxidant activity and phenolic compounds in the fruits of Aronia spp.

Article

Full-text available

May 2020

Chokeberry (Aronia Medik.) is a non-traditional fruit plant known as a rich source of biologically active compounds and inhibits the numerous biological activities. We compared the antioxidant activity and phenolic compounds of fruits between widely cultivated Aronia mitschurinii (AM-TCH, from Tchekhov district; AM-D, from Dmitrov district; AM-OZ, from Orekhovo-Zuevsky district of Moscow region, Russia) and introduced North American Aronia species (Aronia arbutifolia (AA-M), A. melanocarpa (AML-M), A. × prunifolia (AP-M), which have not been planted yet in the arboretum of Main Botanical Garden of the Russian Academy of Sciences (Moscow). Studying samples were collected in their secondary distribution range. Ethanolic extracts were determined for antioxidant capacity (antioxidant activity by DPPH and phosphomolybdenum methods, the total content of polyphenols, flavonoids, phenolic acids) and measured spectrophotometrically. As standards were used Trolox (TE) for antioxidant activities, gallic acid (GAE) for polyphenol content, quercetin (QE) for flavonoid content, caffeic acid (CAE) for phenolic acid content. The antioxidant activity by DPPH method in ethanol extracts of investigated plants was from 6.96 (AM-D) to 8.89 (AM-OZ) mg TE.g-1 DW. Reducing the power of investigated extracts exhibited activity from 151.47 (AM-OZ) to 297.8 (AA-M) mg TE.g-1 DW. The content of polyphenol compounds determined from 25.98 (AM-TCH) to 54.39 (AA-M) mg GAE.g-1 DW, phenolic acids content was from 7.76 (AP-M) to 11.87 (AM-D) mg CAE.g-1 DW and the content of flavonoids detected from 8.12 (AM-OZ) to 16.62 (AM-D) mg QE .-1 DW. Obtained data showed a strong correlation between the content of polyphenol compounds and reducing the power of extracts (r = 0.700), between flavonoids and phenolic acids (r = 0.771) and also between phenolic acids and reducing power (r = 0.753) in Aronia ethanol extracts. Fruits of investigated species of Aronia can be propagated as a source of polyphenol compounds with antioxidant activity and obtained results may use for farther pharmacological study.

Dietary Prevention of Colitis by Aronia Berry is Mediated Through Increased Th17 and Treg

Article

Dec 2018

Scope: Increased fruit consumption is associated with reduced risk of colitis. We investigated whether the anti‐colitic effects of the polyphenol‐rich aronia berry (Aronia mitschurinii ‘Viking’) were mediated through Th17 and Treg. Methods and results: Colitis was induced in recombinase activating gene‐1 deficient mice injected with syngeneic CD4⁺CD62L⁺ naïve T cells. Mice consumed either 4.5% w/w aronia berry‐supplemented or a control diet concurrent with T cell transfer. The extent of colitis and immunocyte populations were evaluated at weeks 3 to 7 after transfer. Aronia consumption prevented colitic wasting and reduced colon weight/length ratios relative to the control diet at weeks 5 and 7. Compared to the control diet, aronia feeding increased Treg in mesenteric lymph node at all colitis stages. Treg and regulatory Th17 subpopulations (IL‐17A⁺IL‐10⁺ and IL‐17A⁺IL‐22⁺) were increased in lamina propria and spleen at week 5 in aronia‐fed mice. Aronia feeding also decreased total CD4⁺ cells but increased colonic Tregs. The ability of aronia to modulate colonic cytokines was associated with functional T cell IL‐10 and increased diversity of microbiota. Conclusions: Aronia berry consumption inhibits adoptive transfer colitis by increasing Treg and regulatory Th17 cells. Dietary modulation of T cells is dynamic and precede colitic wasting. This article is protected by copyright. All rights reserved

Morphological characteristics for fruits of Aronia mitschurinii A.K. Skvortsov & Maitul

Article

Full-text available

Jan 2017

The aim of this study was to determine morphometric characteristics of fruits within some phenotypes of Aronia mitschurinii A.K. Skvortsov & Maitul. Their morphometric parameters were following: weight from 0.75 g (AM-03) to 1.52 g (AM-04), length from 9.46 mm (AM-03) to 12.73 mm (AM-04), diameter from 10.49 mm (AM-03) to 13.73 mm (AM-04), fruits number in the corymb from 11.33 (AM-07) to 20.13 (AM-03), cumulative weight of fruits in the corymb from 10.42 g (AM-07) to 21.73 g (AM-04), volume of fruits from 0.55 (AM-03) to 1.26 (AM-04) cm³. The shape index of the fruits was found in the range of 0.87 (AR-01, AR-05, AR-07) to 0.93 (AM-02). The analysis of coefficient of variation showed the difference of variability in morphological characteristics between Aronia mitschurinii samples. Data showed that the most variability of important selection characteristics are the average cumulative mass of fruits in a corymb - from 12.34 (AM-03) to 38.61 (AM-02) % and fruit number of fruits in the corymb - from 14.56 (AM-03) to 36.88 (AM-02) %. The other characteristics are more or less stable. The introduction population of the Aronia mitschurinii, was created in the M.M. Gryshko National Botanical Garden in Kyiv, has a sufficient potential for successful selection work. © 2017 Potravinarstvo Slovak Journal of Food Sciences, License.

Identification of Anthocyanins from Four Kinds of Berries and Their Inhibition Activity to α-Glycosidase and Protein Tyrosine Phosphatase 1B by HPLC-FT-ICR MS/MS

Article

Jul 2017

The polyphenolic profiles of four berries (blueberry, bilberry, mulberry, and cranberry) in China were investigated using Fourier transform-ion cyclotron resonance mass spectrometry (FT-ICR MS). Thirty-nine polyphenols including 26 anthocyanins, 9 flavonoids, and 4 phenolic acids were identified accurately. Cyanidin aglycones are common in four berries, and malvidin aglycones are the main compounds found in bilberry and cranberry. The anthocyanin level in blueberry are the highest with 739.6 ± 17.14 mg/g DW and presented the strongest antioxidant capacity in DPPH, ABTS, FRAP, and ORAC assay. In α-glycosidase, the inhibition activity was in the following order: mulberry > bilberry > blueberry > cranberry. For the PTP1B inhibition assay, blueberry demonstrated the highest inhibitory effect with IC50 3.06 ± 0.02 µg/mL, followed by bilberry, mulberry, and cranberry. Molecular docking results showed that cyanidin aglycones had the highest inhibition activity to PTP1B.

Aronia Berry Extract Ameliorates the Severity of Dextran Sodium Sulfate-Induced Ulcerative Colitis in Mice

Article

Jul 2017

Inflammatory bowel disease, including Crohn's disease and ulcerative colitis (UC), is a group of inflammatory conditions of the colon and small intestine. UC is a chronic inflammatory disorder of the colon and rectum that includes intervals of acute exacerbation. Although recent studies have suggested that proinflammatory cytokines might have initiated the inflammatory responses in UC, its etiology remains unclear. Aronia berries are rich in dietary polyphenols such as phenolic acids, anthocyanins, flavonoids, and proanthocyanidins with various health benefits, including antioxidant, anti-inflammatory, and antiaging activities. The objective of this study was to determine whether Aronia berry can be an effective intervention for the treatment of UC. BALB/c mice were administered 5% dextran sulfate sodium (DSS) to induce UC. They were then given Aronia berry extracts at concentrations of 10 or 100 mg/kg. During the induction of UC, the expression levels of nuclear factor-kappa B were increased in colonic epithelial cells and immune cells, leading to increased proinflammatory cytokine levels. Aronia berry extract significantly improved the clinical signs of DSS-induced UC, including body weight loss, colon length shortening, and disease activity index increase, with histological markers of colon injury. Furthermore, oral administration of Aronia berry extract inhibited prostaglandin E2 production in DSS-induced colitis and decreased the levels of nitric oxide, interleukin-6, and tumor necrosis factor-α in lipopolysaccharide-stimulated macrophages. These results suggest that Aronia berry extract could efficiently ameliorate clinical signs and inflammatory mediators of UC. Therefore, Aronia berry might be a promising natural treatment for UC.

Chokeberry pomace valorization into food ingredients by enzyme-assisted extraction: Process optimization and product characterization

Article

Jun 2017

Currently berry juice pressing residues are used inefficiently due to a lack of innovative processes of their valorisation. This study reports valorization of chokeberry pomace via combined high pressure fractionation and enzyme-assisted extraction (EAE), utilizing commercially available cellulolytic and xylanolytic enzyme preparations, namely Viscozyme L and CeluStar XL. The results obtained indicate that optimized enzyme treatment (E/S 6% v/w, 40 °C, pH 3.5, 7 hours), especially using Viscozyme L, facilitates pomace cell-wall breakdown and: (1) increases the yield of water-soluble fraction by 44-113%, monosaccharide content by 12-140%, total phenolic content by 29-41%, radical scavenging capacity by 20-39%; (2) promotes some alterations in phenolic acid and flavonol profiles of EAE-derived supernatants. For the first time antioxidant potential of solid residues from enzyme-treated berry pomaces was evaluated too, indicating that all fractions could be utilized as a low-cost source of high added value functional ingredients with various scientific and commercial applications.

Effects of Lonicera caerulea berry extract on lipopolysaccharide-induced toxicity in rat liver cells: Antioxidant, anti-inflammatory, and anti-apoptotic activities

Article

Jun 2017

Lonicera caerulea L. berry extract has antioxidant and anti-inflammatory properties. The mechanism underlying the inhibitory effect of L. caerulea berry extract on lipopolysaccharide (LPS)-induced toxicity in BRL-3A cells was investigated in this study. It was observed that post-treatment with L. caerulea berry extract inhibited LPS-elicited decreases in catalase and superoxide dismutase activities, total antioxidant capacity, acetylcholinesterase activity, the mRNA expression levels of interleukin-10, and the protein expressions of poly (ADP-ribose) polymerase (PARP) and B-cell lymphoma-2. Furthermore, the extract significantly reduced LPS-induced increases in the activities of aspartate aminotransferase and alanine aminotransferase, the mRNA expressions of nuclear factor-kappa B and tumour necrosis factor-alpha, and the protein expressions of caspase-3, cleaved caspase-3, cleaved PARP, and Bax. Moreover, the extract suppressed LPS-induced apoptosis of BRL-3A cells. Taken together, the L. caerulea berry extract attenuates LPS-induced liver toxicity via antioxidant, anti-inflammatory, and anti-apoptotic pathways. Additionally, cyanidin-3-glucoside contributes more to these activities of the extract.

The polyphenolic-rich Aronia melanocarpa juice kills teratocarcinomal cancer stem-like cells, but not their differentiated counterparts

Data

Full-text available

Jul 2013

A diet rich in plant-derived products is expected to have anticancer chemopreventive effects by acting on the appearance and growth of cancer stem cells (CSCs). Thus the effects of Aronia melanocarpa juice (AMJ) on the mouse embryonal carcinoma (EC) stem cell line P19 were investigated. AMJ inhibited cell proliferation, induced cell cycle arrest in S phase and triggered apoptosis. A pronounced upregulation of tumour suppressors p53 and p73 was observed in association with caspase-3 activation and a downregulation of the anti-apoptotic protein UHRF1 and the stemness factor Oct-4. Overall the results strongly suggest that AMJ is functionally able to counteract the carcinogenesis process by targeting CSCs. Interestingly AMJ selectively kills undifferentiated EC cells, without sig-nificant effects on normal restricted pluripotent cells (i.e. NIH/3T3 fibroblasts) or even dif-ferentiated EC cells. This argues that a differentiation therapy might normalize the pathological phenotype of a CSC which becomes insensitive to further plant-derived phar-macological treatment.

Attenuation of iNOS and COX2 by blueberry polyphenols is mediated through the suppression of NF-KB activation

Article

Full-text available

Jul 2009

Treatment of BV2 microglial cells with blueberry extracts has been shown to be effective in reducing lipopolysaccharide (LPS)-induced proinflammatory mediators such as nitric oxide (NO), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), inducible NO synthase (iNOS), and cyclooxygenase 2 (COX2). The current study explored the possibility that the down-regulation of iNOS and COX2 by blueberry extracts was mediated through NF-κB signaling pathway. A column-purified fraction of polyphenol-enriched blueberry extract (PC18) was used to treat LPS-activated BV2 cells. The results thus far showed that blueberry polyphenols significantly suppressed iNOS and COX2 promoter activities. In addition, blueberry polyphenols inhibited NF-κB nuclear translocation in LPS-activated BV2 cells. These findings suggested that the beneficial effects of blueberries may involve direct modulation of oxidative stress and/or inflammatory signaling cascades.

The Role of the Immune System in Obesity and Insulin Resistance

Article

Full-text available

Jan 2013
J Obes

The innate immune system provides organisms with rapid and well-coordinated protection from foreign pathogens. However, under certain conditions of metabolic dysfunction, components of the innate immune system may be activated in the absence of external pathogens, leading to pathologic consequences. Indeed, there appears to be an intimate relationship between metabolic diseases and immune dysfunction; for example, macrophages are prime players in the initiation of a chronic inflammatory state in obesity which leads to insulin resistance. In response to increases in free fatty acid release from obese adipose depots, M1-polarized macrophages infiltrate adipose tissues. These M1 macrophages trigger inflammatory signaling and stress responses within cells that signal through JNK or IKK β pathways, leading to insulin resistance. If overnutrition persists, mechanisms that counteract inflammation (such as M2 macrophages and PPAR signaling) are suppressed, and the inflammation becomes chronic. Although macrophages are a principal constituent of obese adipose tissue inflammation, other components of the immune system such as lymphocytes and mast cells also contribute to the inflammatory cascade. Thus it is not merely an increased mass of adipose tissue that directly leads to attenuation of insulin action, but rather adipose tissue inflammation activated by the immune system in obese individuals that leads to insulin resistance.

The Immunomodulation Effect of Aronia Extract Lacks Association with Its Antioxidant Anthocyanins

Article

Full-text available

Apr 2013
J MED FOOD

Abstract Polyphenols comprise a diverse group of molecules with antioxidative and anti-inflammatory activities. To compare the antioxidative and anti-inflammatory capacity of Aronia melanocarpa berries (chokeberries), recognized for their high content of anthocyanins, a noncytotoxic isolation method was developed to obtain high-purity anthocyanins in the extract. The antioxidative activity of the extract, the anthocyanin-rich fraction (AF) was determined by 1,1-diphenyl-2-picrylhydrazyl radical and ferric-reducing ability of plasma along with resveratrol as a reference. The immunomodulation properties were assessed in lipopolysaccharide (LPS)-stimulated human monocytes mono mac 6. The isolated AF, containing six different anthocyanins, exhibited a stronger antioxidative capacity compared to resveratrol. Resveratrol enhanced tumor necrosis factor-α and reduced interleukin-10 (IL-10) production by LPS, whereas AF only had a slight effect in reducing IL-10. These results demonstrated that there was no major relationship between the antioxidative effect and immunomodulation capacities of AF and resveratrol. The immunomodulatory activity of the extract is associated with bioactive compounds in Aronia other than its anthocyanins.

Bioassay-guided isolation of anti-inflammatory and antinociceptive principles from a folk remedy, Rhododendron ponticum L. leaves

Article

Full-text available

Sep 2008
J ETHNOPHARMACOL

Rhododendron ponticum L. (Ericaceae) is used for the treatment of inflammatory diseases and to alleviate rheumatic pain and against toothache in Turkish traditional medicine. To evaluate the anti-inflammatory and antinociceptive effects of Rhododendron ponticum leaves using in vivo models, and isolation and chemical characterization of the biologically active constituents through bioassay-guided fractionation procedures. Carrageenan-induced hind paw edema model was used for anti-inflammatory activity and p-benzoquinone induced abdominal contractions model for the antinociceptive activity assessment. The ethylacetate fraction displayed marked anti-inflammatory (28.4-40.7% inhibition) and antinociceptive (50.7% inhibition) effects as compared to reference compounds. Through bioassay-guided fractionation and isolation procedures flavonol glycosides [a mixture of hyperoside and isoquercitrin (1) and quercitrin (2)] along with one flavanone glycoside [6-C-glycosylnaringenin (3)] were isolated as the active ingredients of ethylacetate extract against carrageenan-induced edema and p-benzoquinone-induced writhes and their structures were elucidated by spectral techniques. 1 and 2 also showed a significant anti-inflammatory activity against 12-O-tetradecanoyl-13-acetate (TPA)- induced mouse ear edema model. Results of the present study supported the utilization of the plant in Turkish folk medicine and revealed that flavones are the major anti-inflammatory and antinociceptive principles of the leaves.

The neuropathological basis of clinical progression in multiple sclerosis

Article

Full-text available

May 2011
ACTA NEUROPATHOL

Multiple sclerosis is the major inflammatory condition affecting the central nervous system (CNS) and is characterised by disseminated focal immune-mediated demyelination. Demyelination is accompanied by variable axonal damage and loss and reactive gliosis. It is this pathology that is thought to be responsible for the clinical relapses that often respond well to immunomodulatory therapy. However, the later secondary progressive stage of MS remains largely refractory to treatment and it is widely suggested that accumulating axon loss is responsible for clinical progression. Although initially thought to be a white matter (WM) disease, it is increasingly apparent that extensive pathology is also seen in the grey matter (GM) throughout the CNS. GM pathology is characterised by demyelination in the relative absence of an immune cell infiltrate. Neuronal loss is also seen both in the GM lesions and in unaffected areas of the GM. The slow progressive nature of this later stage combined with the presence of extensive grey matter pathology has led to the suggestion that neurodegeneration might play an increasing role with increasing disease duration. However, there is a paucity of studies that have correlated the pathological features with clinical milestones during secondary progressive MS. Here, we review the contributions that the various types of pathology are likely to make to the increasing neurological deficit in MS.

The WSX-1 pathway restrains intestinal T-cell immunity

Article

Full-text available

Feb 2011
INT IMMUNOL

Mechanisms regulating intestinal T-cell accumulation during inflammation have considerable therapeutic value. In this study, LPS increased Staphylococcus aureus enterotoxin A-specific T cells in the gut through induction of IL-12 family members. Mice deficient in IL-12 (p35(-/-)) favored T(h)17 differentiation in lamina propria, whereas mice lacking both IL-12 and IL-23 (p40(-/-)) produced significantly fewer T(h)17 cells. However, serum analysis revealed that IL-27p28 was much higher and sustained following LPS injection than other IL-12 family cytokines. Strikingly, WSX-1 (IL-27Rα) deficiency resulted in log-fold increases in lamina propria T(h)17 cells without affecting T(h)1 numbers. These results may be explained by increased expression of α4β7 on WSX-1-deficient T cells after immunization. WSX-1-deficient regulatory T cells (Tregs) were also perturbed, producing more IL-17 and less IL-10 than wild-type Tregs. Thus, IL-27 blockade may provide a new pathway to improve mucosal vaccination.

Aronia Plants: A Review of Traditional Use, Biological Activities, and Perspectives for Modern Medicine

Article

Full-text available

Feb 2010
J MED FOOD

The Aronia genus (Rosaceae family, Maloideae subfamily) includes two species of native North American shrubs: Aronia melanocarpa (Michx.) Ell. (black chokeberry) and Aronia arbutifolia (L.) Pers. (red chokeberry). The fruits of A. melanocarpa have been traditionally used by Potawatomi Native Americans to cure colds. In the first half of the 20(th) century, cultivars of black chokeberry were introduced to the Soviet Union and other European countries, providing fruits used by food industry. At present, it is used mainly for juice, jam, and wine production, as well as an ornamental plant. Among other substances, the berries of A. melanocarpa contain anthocyanins and procyanidins, possessing strong antioxidative potential. Numerous health-promoting activities-namely, antioxidative, antimutagenic, anticancer, cardioprotective, hepatoprotective, gastroprotective, antidiabetic, anti-inflammatory, antibacterial, antiviral, radioprotective, and immunomodulatory-have been demonstrated for black chokeberry extracts by both in vitro and in in vivo studies. The presented review summarizes the information concerning botany, cultivation, chemical composition, and pharmacological activities of Aronia plants.

Aronia: Native Shrubs With Untapped Potential

Article

Jan 2010

Mark H Brand

Anti-inflammatory effects of chlorogenic acid in lipopolysaccharide-stimulated RAW 264.7 cells

Article

Oct 2013
INFLAMM RES

Chlorogenic acid, which belongs to the polyphenols, is an anti-oxidant and anti-obesity agent. In this study, we investigated the role of chlorogenic acid in inflammation. Anti-inflammatory effects of chlorogenic acid were examined in lipopolysaccharide (LPS)-stimulated murine RAW 264.7 macrophages and BV2 microglial cells. We observed the level of various inflammation markers such as nitric oxide (NO), inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and chemokine (C-X-C motif) ligand 1 (CXCL1) under LPS treatment with or without chlorogenic acid. To clarify the specific effect of chlorogenic acid, we evaluated the adhesion activity of macrophages and ninjurin1 (Ninj1) expression level in macrophages. Finally, we confirmed the activation of the nuclear factor-κB (NF-κB) signaling pathway, which is one of the most important transcription factors in the inflammatory process. Chlorogenic acid significantly inhibited not only NO production but also the expression of COX-2 and iNOS, without any cytotoxicity. Chlorogenic acid also attenuated pro-inflammatory cytokines (including IL-1β and TNF-α) and other inflammation-related markers such as IL-6 in a dose-dependent manner. Additionally, endotoxin-induced adhesion of macrophages and the expression level of ninjurin1 (Ninj1) were decreased by chlorogenic acid. Finally, chlorogenic acid inhibited the nuclear translocation of NF-κB. Chlorogenic acid may be beneficial for the prevention and treatment of anti-inflammatory diseases.

Lingonberry, cranberry and blackcurrant juices affect mRNA expressions of inflammatory and atherothrombotic markers of SHR in a long-term treatment

Article

Apr 2012

Cyanidin 3-O-β-D-glucoside-rich blackberries modulate hepatic gene expression, and anti-obesity effects in ovariectomized rats

Article

Apr 2012

Estrogen loss predisposes postmenopausal women to a 60% greater risk of developing metabolic syndrome. We examined the dose dependent effects of whole blackberries containing 87% cyanidin-3-O-β-d-glucoside (C3G), a powerful antioxidative and anti-inflammatory anthocyanin, in ovariectomized rats. Nine-month-old female Sprague–Dawley rats were either sham-operated or ovariectomized (OVX) and divided four groups, Sham + control diet, OVX + control diet, OVX + 5% blackberry and OVX + 10% blackberry (OVX-BB10%). After 100 days of treatment, serum, liver lipids, insulin and C-reactive protein, serum antioxidant capacity, low density lipoprotein oxidation and gene expression of inflammatory markers were measured. Final body weights of blackberry treatments were lower than the OVX controls, and BB10% (w/w) diet decreased hepatic nuclear factor-kappa B, and cyclooxygenase-2 expression levels. Thus, consumption of C3G-rich blackberries is protective against weight gain and inflammation associated with ovariectomy-induced menopause in a rat model.

Underutilized Chokeberry (Aronia melanocarpa, Aronia arbutifolia, Aronia prunifolia) Accessions Are Rich Sources of Anthocyanins, Flavonoids, Hydroxycinnamic Acids, and Proanthocyanidins

Article

Aug 2013
J AGR FOOD CHEM

Polyphenols from underutilized black, purple, and red aronia (Aronia melanocarpa, prunifolia, and arbutifolia) and 'Viking' (A. mitschurinii) berries were characterized. Anthocyanin and non-anthocyanin flavonoids were quantitated by UHPLC-DAD-MS, and proanthocyanidins by normal-phase HPLC. On a dry weight basis, anthocyanins were mainly cyanidin-3-galactoside, highest in black aronia (3.4 to 14.8 mg/g) and lowest in red aronia (0.5 to 0.8 mg/g) as cyandin-3-galactoside equivalents. Berries from 'Viking' and the red accession UC021 had substantially more proanthocyanidins than the other accessions, with 3.3 and 3.8 mg catechin equivalents/g, respectively. Chlorogenic acids and quercetin glycosides were most abundant in purple UC047 berries, at 17.3 and 1.3 mg/g, respectively. In contrast to anthocyanin content, total phenol values were highest in berries from red and purple accessions, and attributed to phenolic acid and proanthocyanin content. Thus, red, purple, and black aronia berries are rich sources of polyphenols with varying levels of polyphenol classes.

Blood pressure-lowering properties of chokeberry (Aronia mithurinii, var. Viking)

Article

Apr 2010

The blood pressure-lowering properties of lyophilized chokeberry juice and polyphenols were monitored using in vitro angiotensin-converting enzyme (ACE) inhibition measurement and a 10day in vivo study with spontaneously hypertensive rats (SHR). Juice and polyphenols indicated weak ACE-inhibitory activity. The IC50 values for polyphenols and juice were 1.5–2.5 and 4.5mg dry matter/ml, respectively. In the SHR study the blood pressure-lowering effects of juice and polyphenol extract seemed to be short-term and were generally highest after 3h from administration (50mg/kg/day) when mean reductions in systolic blood pressure were 20±8 and 15±7mmHg, respectively. Corresponding mean decreases in diastolic blood pressure were 23±6 and 13±2mm Hg in juice and polyphenol groups, respectively. It was concluded that both chokeberry juice and polyphenols had blood pressure-lowering effects. We hypothesize that chokeberry polyphenols enhance endothelial nitric oxide production with an ACE-independent mechanism, e.g. by activation of endothelial nitric oxidase enzyme; this is yet to be verified.

Aronia melanocarpa (chokeberry) polyphenol-rich extract improves antioxidant function and reduces total plasma cholesterol in apolipoprotein E knockout mice

Article

May 2013

Effects of a citrus based juice on biomarkers of oxidative stress in metabolic syndrome patients

Article

Apr 2013

Polyphenol-rich black chokeberry (Aronia melanocarpa) extract regulates the expression of genes critical for intestinal cholesterol flux in Caco-2 cells

Article

Mar 2013

Black chokeberry (Aronia melanocarpa) is a rich source of polyphenols. The hypolipidemic effects of polyphenol-rich black chokeberry extract (CBE) have been reported, but underlying mechanisms have not been well characterized. We investigated the effect of CBE on the expression of genes involved in intestinal lipid metabolism. Caco-2 cells were incubated with 50 or 100 μg/ml of CBE for 24 h for quantitative realtime polymerase chain reaction analysis. Expression of genes for cholesterol synthesis (3-hydroxy-3-methylglutaryl coenzyme A reductase and sterol regulatory element binding protein 2), apical cholesterol uptake (Niemann-Pick C1 Like 1 and scavenger receptor class B Type 1) and basolateral cholesterol efflux [ATP-binding cassette transporter A1 (ABCA1)] was significantly decreased by CBE compared with control. Western blot analysis confirmed that CBE inhibited expression of these proteins. In contrast, CBE markedly induced mRNA and/or protein levels of ABCG5 and ABCG8 that mediate apical cholesterol efflux to the intestinal lumen. Furthermore, CBE significantly increased mRNA and protein levels of low-density lipoprotein (LDL) receptor, and cellular LDL uptake. Expression of genes involved in lipid metabolism and lipoprotein assembly, including sterol regulatory element-binding protein 1c, fatty acid synthase and acyl-CoA oxidase 1, was significantly decreased by CBE in a dose-dependent manner. Concomitantly, CBE significantly increased sirtuin 1, 3 and 5 mRNA levels, while it decreased SIRT-2. Our data suggest that hypolipidemic effects of CBE may be attributed, at least in part, to increased apical efflux of LDL-derived cholesterol and to decreased chylomicron formation in the intestine; and specific isoforms of SIRT may play an important role in this process.

Quercetin and quercetin-3- O -glucuronide are equally effective in ameliorating endothelial insulin resistance through inhibition of reactive oxygen species-associated inflammation

Article

Jun 2013
MOL NUTR FOOD RES

Quercetin represents antioxidative/antiinflammatory flavonoids widely distributed in the human diet. Quercetin is efficiently metabolized during absorption to quercetin-3-O-glucuronide. This study aims to parallelly investigate whether quercetin and quercetin-3-O-glucuronide exert protection against palmitate (PA)-induced inflammation and insulin resistance in the endothelium. Human umbilical vein endothelial cells were pretreated with quercetin and quercetin-3-O-glucuronide for 30 min, and then incubated with 100 μM PA for 30 min or 12 h with or without insulin. PA stimulation led to reactive oxygen species (ROS) production with collapse of mitochondrial membrane potential (Δψm). Quercetin and quercetin-3-O-glucuronide inhibited ROS overproduction and effectively restored Δψm, demonstrating their chemorpotection of mitochondrial function through antioxidative actions. Also, quercetin and quercetin-3-O-glucuronide inhibited ROS-associated inflammation by inhibition of interleukin-6 and tumor necrosis factor-α production with suppression of IKKβ/NF-κB phosphorylation. Inflammation impaired insulin PI3K signaling and reduced insulin-mediated nitric oxide (NO) production. Quercetin and quercetin-3-O-glucuronide facilitated PI3K signaling by positive regulation of serine/tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) and restoration of downstream Akt/eNOS activation, leading to an increased insulin-mediated NO level. The above-mentioned evidence indicates that quercetin and quercetin-3-O-glucuronide are equally effective in inhibiting ROS-associated inflammation and ameliorating insulin resistant endothelial dysfunction by beneficial regulation of IRS-1 function.

Quercetin negatively regulates TLR4 signaling induced by lipopolysaccharide through Tollip expression

Article

Jan 2013
BIOCHEM BIOPH RES CO

Polyphenolic compounds have been regarded as one of the most promising dietary agents for the prevention and treatment of inflammation-related chronic diseases; however, the anti-inflammatory activities of flavonoids, such as quercetin, are not completely characterized, and many features remain to be elucidated. In this study, we showed the molecular basis for the downregulation of TLR4 signal transduction by quercetin. Quercetin markedly elevated the expression of the Toll-interacting protein, a negative regulator of TLR signaling. Lipopolysaccharide-induced expression of cell surface molecules (CD80, CD86, and MHC class I/II) and production of pro-inflammatory cytokines (tumor necrosis factor-α, IL-1β, IL-6, and IL-12p70) were inhibited by quercetin, and this action was prevented by Toll-interacting protein silencing. In addition, quercetin-treated macrophages inhibited lipopolysaccharide-induced activation of mitogen-activated protein kinases, such as extracellular signal-regulated kinase 1/2, p38, and c-Jun N-terminal kinase, and the translocation of nuclear factor-κB and p65 through Toll-interacting protein. Treatment with quercetin resulted in a significant decrease in prostaglandin E(2) and cyclooxygenase-2 levels as well as inducible nitric oxide synthase-mediated nitric oxide production induced by lipopolysaccharide. Taken together, these findings represent new insights into the understanding of negative regulatory mechanisms of the TLR4 signaling pathway and effective therapeutic intervention for the treatment of inflammatory disease.

Neutralizing Tumor-Promoting Chronic Inflammation: A Magic Bullet?

Article

Jan 2013
SCIENCE

A Shift in Cancer's Inflammatory Balance One of the many factors that contribute to the initiation and progression of cancer is inflammation. Inflammation can support tumor development, both directly and indirectly, and tumors can promote a chronic inflammatory environment that results in immunosuppression, which benefits the tumor. Coussens et al. (p. 286 ) review the components of the immune system that contribute to the chronic inflammation seen in tumors. Potential therapies might shift this inflammatory environment toward one more characteristic of an acute, resolving inflammation, similar to what is observed during a pathogenic infection. Such a shift would relieve immunosuppression and drive antitumor immunity that, when combined with other therapies, may ultimately result in tumor cell clearance.

Shi H, Dong L, Jiang J, Zhao J, Zhao G, Dang X, Lu X, Jia MChlorogenic acid reduces liver inflammation and fibrosis through inhibition of toll-like receptor 4 signaling pathway. Toxicology 303: 107-114

Article

Nov 2012

Chlorogenic acid (CGA) is a type of polyphenol with anti-inflammatory, antioxidant activities. Our previous studies showed CGA could efficiently inhibit carbon tetrachloride (CCl(4))-induced liver fibrosis in rats. However, the specific underlying mechanism remains unclear. The aim of this study is to investigate the effects of CGA on liver inflammation and fibrosis induced by CCl(4) and whether they are related to inhibition of toll-like receptor 4 (TLR4) signaling pathway. Male Sprague-Dawley (SD) rats were administrated CCl(4) together with or without CGA for 8 weeks. Histopathological and biochemical analyses were carried out. The mRNA and protein expression levels of proinflammatory and profibrotic mediators were detected by RT-PCR and Western blot, respectively. The levels of serum proinflammatory cytokines were detected by ELISA. CGA significantly attenuated CCl(4)-induced liver damage and symptoms of liver fibrosis, accompanied by reduced serum transaminase levels, collagen I and α-smooth muscle actin (α-SMA) expression. As compared with the CCl(4)-treated group, the expression levels of TLR4, myeloid differentiation factor 88 (MyD88), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were reduced in the treatment group of CCl(4) and CGA, whereas bone morphogenetic protein and activin membrane-bound inhibitor (Bambi) expression was increased. CGA also suppressed CCl(4) induced nuclear factor-κB (NF-κB) activation. Moreover, the hepatic mRNA expression and serum levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) were significantly increased in CCl(4)-treated rats and attenuated by co-treatment with CGA. Our data indicate that CGA can efficiently inhibit CCl(4)-induced liver fibrosis in rats and the protective effect may be due to the inhibition of TLR4/MyD88/NF-κB signaling pathway.

Analysis of Total Phenols and Other Oxidation Substrates and Antioxidants by Means of Folin-Ciocalteu Reagent

Article

Dec 1999

Publisher Summary This chapter discusses the analysis of total phenols and other oxidation substrates and antioxidants by means of Folin-Ciocalteu reagent. Analyses of the Folin-Ciocalteu (FC) type are convenient, simple, and require only common equipment and have produced a large body of comparable data. Under proper conditions, the assay is inclusive of monophenols and gives predictable reactions with the types of phenols found in nature. Because different phenols react to different degrees, expression of the results as a single number—such as milligrams per liter gallic acid equivalence—is necessarily arbitrary. Because the reaction is independent, quantitative, and predictable, analysis of a mixture of phenols can be recalculated in terms of any other standard. The assay measures all compounds readily oxidizable under the reaction conditions and its very inclusiveness allows certain substances to also react that are either not phenols or seldom thought of as phenols (e.g., proteins). Judicious use of the assay—with consideration of potential interferences in particular samples and prior study if necessary—can lead to very informative results. Aggregate analysis of this type is an important supplement to and often more informative than reems of data difficult to summarize from various techniques, such as high-performance liquid chromatography (HPLC) that separate a large number of individual compounds .The predictable reaction of components in a mixture makes it possible to determine a single reactant by other means and to calculate its contribution to the total FC phenol content. Relative insensitivity of the FC analysis to many adsorbents and precipitants makes differential assay—before and after several different treatments—informative.

Characterisation of the pigment components in red cabbage (Brassica oleracea L. var.) juice and their anti-inflammatory effects on LPS-stimulated murine splenocytes

Article

Aug 2008
FOOD CHEM

To determine anti-inflammatory effects of pigments from red cabbage, red cabbage (Brassica oleracea L. var.) juice was prepared, characterized by UV-vis absorption spectra, partially purified by Sephadex LH-20 column, analyzed by HPLC, and administered to lipopolysaccharide (LPS)-stimulated murine splenocyte cultures. The study showed that red cabbage juice (RC) exhibited anti-inflammatory effects against LPS-induced inflammation of splenocytes via increasing anti-inflammatory cytokine interleukin (IL)-10 and decreasing pro-inflammatory cytokine IL-6 secretions. The maximum absorption peaks of RC and its heated products, but not activated charcoal-adsorbed products, appeared at 280nm with a small shoulder around 310-330nm while there existed a minor peak at 560nm (range from 480 to 630nm), reflecting red cabbage juice included phenolics, flavonoids, and anthocyanins. The lyophilized powder of chromatographic fractions F2, F3, and F4 through Sephadex LH-20 column were rich in phenolics (5.9±0.2%, 4.4±0.0%, and 3.9±0.0%, respectively) and flavonoids (1.8±0.3%, 1.8±0.3%, and 1.1±0.3%, respectively). The results suggest that anti-inflammatory pigment compounds in red cabbage juice were heat stable. Further analysis of chromatograms from HPLC suggests malvidin glycosides including malvidin 3-glucoside (oenin), malvidin 5-glucoside and malvidin 3,5-diglucoside in red cabbage juice could inhibit IL-6 secretion of LPS-stimulated splenocytes. Copyright © 2008 Elsevier Ltd. All rights reserved.

Role of Interleukin 10 Transcriptional Regulation in Inflammation and Autoimmune Disease

Article

Jan 2012
CRIT REV IMMUNOL

Interleukin 10 (IL-10) is a cytokine with potent anti-inflammatory properties that plays a central role in limiting host immune response to pathogens, thereby preventing damage to the host and maintaining normal tissue homeostasis. Dysregulation of IL-10 is associated with enhanced immunopathology in response to infection as well as increased risk for development of many autoimmune diseases. Thus a fundamental understanding of IL-10 gene expression is critical for our comprehension of disease progression and resolution of host inflammatory response. In this review, we discuss modes of regulation of IL-10 gene expression in immune effector cell types, including signal transduction, epigenetics, promoter architecture, and post-transcriptional regulation, and how aberrant regulation contributes to immunopathology and disease progression.

Variations on cardiovascular risk factors in metabolic syndrome after consume of a Citrus-based juice

Article

Dec 2011

Inflammation and oxidative stress plays a critical role in cardiovascular disease and metabolic syndrome often occurs with these two variables. The aim of the study is to estimate variations on cardiovascular risk factors in Metabolic Syndrome patients after consume of a citrus-based juice compared with control groups. The study comprised 20 healthy subjects and 33 patients with Metabolic Syndrome. 18 patients consume daily 300 mL of a citrus-based juice during 6 month and 15 patients consume 300 mL of a placebo beverage. The control group consumes a citrus-based juice. Before, at fourth month and at sixth month after treatment the following parameters were determined: lipid profile, oxidized LDL, C-Reactive Protein and Homocysteine. The study was carried out in accordance with the Helsinki Declaration, and the Ethical Committee of the San Antonio Catholic University and approved the protocol (6 November 2006, register number: 1424). After six months of citrus-based juice consuming, there is significant differences at 95% confidence in oxidized LDL, C-Reactive Protein, and Homocysteine in Metabolic Syndrome patients who consume citrus-based juice. We have not found significant differences in other groups. Consume of citrus-based juice improve lipid profile and inflammation markers in Metabolic Syndrome patients.

Conjugated quercetin glucuronides as bioactive metabolites and precursors of aglycone in vivo

Article

Jan 2011

Quercetin is a typical anti-oxidative flavonoid ubiquitously distributed in vegetables. It is likely to act as a bioactive compound by exerting reactive oxygen species (ROS)-scavenging activity and/or binding to specific proteins such as oxidative enzymes and transcriptional factors in signal transduction pathways. Its absorption and metabolism (as well as its molecular targets) have been extensively explored from the viewpoint of its potential for disease prevention. It is known that glucuronide and/or sulfate conjugates with or without O-methylation exclusively circulate in the human bloodstream after intake of a quercetin-containing diet. We propose that glucuronide conjugates of quercetin function not only as detoxified metabolites but hydrophilic bioactive agents to various ROS-generating systems and precursors of hydrophobic aglycone. Quercetin aglycone is assumed to emerge in the target site by the action of β-glucuronidase activity under oxidative stress such as inflammation. The cardiovascular system and central nervous system seem to be the major targets of conjugated quercetin glucuronides circulating in the human bloodstream.

Effects of Flavonoids and other Polyphenols on Inflammation

Article

Apr 2011
CRIT REV FOOD SCI

Flavonoids are a family of polyphenolic compounds which are widespread in nature (vegetables) and are consumed as part of the human diet in significant amounts. There are other types of polyphenols, including, for example, tannins and resveratrol. Flavonoids and related polyphenolic compounds have significant antiinflammatory activity, among others. This short review summarizes the current knowledge on the effects of flavonoids and related polyphenolic compounds on inflammation, with a focus on structural requirements, the mechanisms involved, and pharmacokinetic considerations. Different molecular (cyclooxygenase, lipoxygenase) and cellular targets (macrophages, lymphocytes, epithelial cells, endothelium) have been identified. In addition, many flavonoids display significant antioxidant/radical scavenging properties. There is substantial structural variation in these compounds, which is bound to have an impact on their biological profile, and specifically on their effects on inflammatory conditions. However, in general terms there is substantial consistency in the effects of these compounds despite considerable structural variations. The mechanisms have been studied mainly in myeloid cells, where the predominant effect is an inhibition of NF-κB signaling and the downregulation of the expression of proinflammatory markers. At present there is a gap in knowledge of in vitro and in vivo effects, although the pharmacokinetics of flavonoids has advanced considerably in the last decade. Many flavonoids have been studied for their intestinal antiinflammatory activity which is only logical, since the gastrointestinal tract is naturally exposed to them. However, their potential therapeutic application in inflammation is not restricted to this organ and extends to other sites and conditions, including arthritis, asthma, encephalomyelitis, and atherosclerosis, among others.

Inflammatory Mechanisms in Obesity

Article

Apr 2010
ANNU REV IMMUNOL

The modern rise in obesity and its strong association with insulin resistance and type 2 diabetes have elicited interest in the underlying mechanisms of these pathologies. The discovery that obesity itself results in an inflammatory state in metabolic tissues ushered in a research field that examines the inflammatory mechanisms in obesity. Here, we summarize the unique features of this metabolic inflammatory state, termed metaflammation and defined as low-grade, chronic inflammation orchestrated by metabolic cells in response to excess nutrients and energy. We explore the effects of such inflammation in metabolic tissues including adipose, liver, muscle, pancreas, and brain and its contribution to insulin resistance and metabolic dysfunction. Another area in which many unknowns still exist is the origin or mechanism of initiation of inflammatory signaling in obesity. We discuss signals or triggers to the inflammatory response, including the possibility of endoplasmic reticulum stress as an important contributor to metaflammation. Finally, we examine anti-inflammatory therapies for their potential in the treatment of obesity-related insulin resistance and glucose intolerance.

Grape seed proanthocyanidin extract (GSPE) differentially regulates Foxp3(+) regulatory and IL-17(+) pathogenic T cell in autoimmune arthritis

Article

Oct 2010

Grape seed proanthocyanidin extract (GSPE), which is the antioxidant derived from grape seeds, has been reported to possess a variety of potent properties. We have previously shown that GSPE attenuates collagen-induced arthritis. However the mechanism by which GSPE regulates the immune response remains unclear, although it may involve effects on the regulation of pathogenic T cells in autoimmune arthritis. To clarify this issue, we have assessed the effects of GSPE on differential regulation of Th17 and regulatory T (Treg) cells subsets in vitro in mouse and human CD4(+) T cells. We observed that GSPE decreased the frequency of IL-17(+)CD4(+)Th17 cells and increased induction of CD4(+)CD25(+)forkhead box protein 3 (Foxp3)(+) Treg cells. In vivo, GSPE effectively attenuated clinical symptoms of established collagen-induced arthritis in mice with concomitant suppression of IL-17 production and enhancement of Foxp3 expression (type II collagen-reactive Treg cells) in CD4(+) T cells of joints and splenocytes. The presence of GSPE decreased the levels of IL-21, IL-22, IL-26 and IL-17 production by human CD4(+) T cells in a STAT3-dependent manner. In contrast, GSPE induces Foxp3(+) Treg cells in humans. Our results suggest that GSPE possesses a reciprocal control over IL-17 and Foxp3. By potently regulating inflammatory T cell differentiation, GSPE may serve as a possible novel therapeutic agent for inflammatory and autoimmune diseases, including rheumatoid arthritis.

Effect of quercetin and its metabolites isorhamnetin and quercetin-3-glucuronide on inflammatory gene expression: Role of MIR-155

Article

Mar 2011

In the present study the effect of quercetin and its major metabolites quercetin-3-glucuronide (Q3G) and isorhamnetin on inflammatory gene expression was determined in murine RAW264.7 macrophages stimulated with lipopolysaccharide. Quercetin and isorhamnetin but not Q3G significantly decreased mRNA and protein levels of tumor necrosis factor alpha. Furthermore a significant decrease in mRNA levels of interleukin 1β, interleukin 6, macrophage inflammatory protein 1α and inducible nitric oxide synthase was evident in response to the quercetin treatment. However Q3G did not affect inflammatory gene expression. Anti-inflammatory properties of quercetin and isorhamnetin were accompanied by an increase in heme oxygenase 1 protein levels, a downstream target of the transcription factor Nrf2, known to antagonize chronic inflammation. Furthermore, proinflammatory microRNA-155 was down-regulated by quercetin and isorhamnetin but not by Q3G. Finally, anti-inflammatory properties of quercetin were confirmed in vivo in mice fed quercetin-enriched diets (0.1 mg quercetin/g diet) over 6 weeks.

Inflammatory Bowel Disease

Article

Nov 2009
NEW ENGL J MED

TLRs and chronic inflammation

Article

Oct 2009

After the discovery of Toll-like receptors (TLRs), innate immune mechanisms came back in the focus of scientific research. With more and more mechanisms of TLR biology known, it has become clear that these and also other innate immune receptors are not only of crucial importance in the immune response to invading pathogens, but also play a role in the homeostasis of commensal flora and in the response to stress and danger signals. In this respect, increasing evidence is found that inappropriate quantity or quality of TLR ligands or aberrant response to TLR activation plays a role in a variety of chronic inflammatory diseases. In this review, an overview of the currently known TLRs and their signaling pathways is given and reports about their expression and activation in chronic inflammatory diseases are recapitulated.

Grape seed proanthocyanidin extract (GSPE) attenuates collagen-induced arthritis

Article

Jun 2009

To examine whether grape seed proanthocyanidin extract (GSPE) which is known to act as an antioxidant has therapeutic effect on collagen-induced arthritis (CIA) in mice, an animal model of rheumatoid arthritis. Mice were treated with an intraperitoneal injection of GSPE (10, 50, or 100 mg/kg) or saline. Clinical, histological, and biochemical parameters were assessed. The effects of GSPE on osteoclastogenesis were determined by tartrate-resistant acid phosphatase (TRAP) staining of the inflamed joints and bone-marrow cells cultured with the receptor activator of nuclear factor B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). Intracellular levels of hydrogen peroxide were determined using carboxy-dichlorodihydrofluorescein diacetate. GSPE treatment significantly attenuated the severity of CIA in a dose-dependent manner and reduced the histology scores for synovial inflammation, cartilage erosion, bone erosion, and the number of TRAP+ osteoclasts. GSPE treatment significantly reduced the numbers of tumor necrosis factor alpha (TNF-alpha)- or interleukin 17 (IL-17)-producing cells in the synovial tissue and the spontaneous production of TNF-alpha and IL-17 by splenocytes compared with those in the control mice. The serum levels of type-II-collagen-specific IgG2a and plasma levels of 8-isoprostane in the GSPE-treated mice were significantly lower than those in the control mice. GSPE dose-dependently suppressed osteoclastogenesis in vitro. GSPE significantly reduced hydrogen peroxide production by anti-CD3-monoclonal-antibody-stimulated CD4+ splenocytes. These results indicate that intraperitoneal injection of GSPE attenuated CIA in mice. GSPE may be useful in the treatment of rheumatoid arthritis.

Suppressive Effects of the Flavonoids Quercetin and Luteolin on the Accumulation of Lipid Rafts after Signal Transduction via Receptors

Article

Sep 2008
IMMUNOPHARM IMMUNOT

Quercetin (QUER) and luteolin (LUTE) are dietary flavonoids capable of regulating the production of cytokines, such as tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6). However, their mechanisms of action are not fully understood. In lipopolysaccharide-triggered (LPS)-triggered signaling via Toll-like receptor 4 (TLR4), QUER and LUTE suppresses not only the degradation of the inhibitor of kappaB (IkappaB), with resultant activation of nuclear factor-kappaB (NF-kappaB), but also the phosphorylation of p38 and Akt in bone marrow-derived macrophages that have been stimulated with LPS. We report here that, in TNF-alpha-induced signaling, QUER and LUTE significantly suppressed the production of IL-6 and activation of NF-kappaB. Accumulation of lipid rafts, the initial step in the signaling pathway, was significantly inhibited when macrophages were treated with QUER or with LUTE prior to exposure to LPS. Similarly, the accumulation of lipid rafts was inhibited by the flavonoids when B cells were activated via the membrane IgM and when T cells were activated via CD3. In contrast, QUER and LUTE did not inhibit the activation of phorbol myristate acetate-induced NF-kappaB in macrophages. Our observations suggest that QUER and LUTE interact with receptors on the cell surface and suppress the accumulation of lipid rafts that occurs downstream of the activation of the receptors.

Anti-inflammatory activity of aronia berry extracts in murine splenocytes

Abstract

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