Polyphenolic Metabolites Research Articles

Mitophagy disorder mediates cardiac deterioration induced by severe hypoglycemia in diabetic mice

Severe hypoglycemia is closely related to adverse cardiovascular outcomes in patients with diabetes; however, the specific mechanism remains unclear. We previously found that severe hypoglycemia aggravated myocardial injury and cardiac dysfunction in diabetic mice, and that the mechanism of damage was related to mitochondrial oxidative stress and dysfunction. Based on the key regulatory role of mitophagy in mitochondrial quality control, this study aimed to further explore whether the myocardial damage caused by severe hypoglycemia is related to insufficient mitophagy and to clarify their underlying regulatory relationship. After severe hypoglycemia, mitochondrial reactive oxygen species increased, mitochondrial membrane potential and ATP content decreased, and pathological mitochondrial damage was aggravated in the myocardium of diabetic mice. This was accompanied by decreased mitochondrial biosynthesis, increased fusion, and downregulated PTEN-induced kinase 1 (PINK1)/Parkin-dependent mitophagy. Treating diabetic mice with the mitophagy activator and polyphenol metabolite urolithin A activated PINK1/Parkin-dependent mitophagy, reduced myocardial oxidative stress and mitochondrial damage associated with severe hypoglycemia, improved mitochondrial function, alleviated myocardial damage, and ultimately improved cardiac function. Thus, we provide insight into the prevention and treatment of diabetic myocardial injury caused by hypoglycemia to reduce adverse cardiovascular outcomes in patients with diabetes.

Exploring the Effects of Solid-State Fermentation on Polyphenols in Acanthopanax senticosus Based on Response Surface Methodology and Nontargeted Metabolomics Techniques

In order to optimize the process of solid-state fermentation and understand the changes of active ingredients during fermentation of A.senticosus, we used response surface methodology to optimize the solid-state fermentation process of A.senticosus and analyzed the effect of fermentation on the active components of A.senticosus by nontargeted metabolomics techniques. The effects of fermentation conditions on polyphenol content were studied in terms of fermentation time, fermentation temperature, water content, and the inoculum level through Plackett–Burman design and response surface experiments. The optimized fermentation conditions were a fermentation time of 60 h, a fermentation temperature of 37°C, a water content of 55%, and an inoculum level of 12.5%, and the polyphenol content reached 10.25 ± 0.05 mg·g−1, which was 40% higher than that before fermentation. Furthermore, the metabolites and metabolic pathways of A. senticosus were analyzed before and after fermentation using nontargeted metabolomics techniques, and differences in metabolites were investigated based on the analysis of the principal components. The results showed that A.senticosus contained 57 phenolics, and a total of 12 polyphenolic metabolites were significantly different before and after fermentation (including phenols and isoflavonoids), among which the content of caffeic acid and its derivatives with antioxidant capacity was significantly increased, which may improve the antioxidant capacity of fermented A.senticosus. Therefore, solid-state fermentation opens new avenues for the clinical development and application of A. senticosus.

Chemodiversity and bioactivity assessment of phlorotannins from some Phaeophyta species from the Red Sea

AbstractPhlorotannins are a unique and diverse category of secondary polyphenolic metabolites biosynthesized by brown seaweeds. They have revealed a huge potential for food and medicinal applications. In this study, five brown seaweed species were investigated: Polycladia myrica, Sirophysalis trinodis, Dictyota spiralis, Sargassum euryphyllum, and Turbinaria decurrens. All seaweed species contained considerable amounts of phlorotannins with P. myrica recording the highest content (as mg PGEs g−1 DW), followed by S. euryphyllum and then S. trinodis. The presence of phlorotannins was detected using UV–Vis spectroscopy analysis in the characterized range of 280 nm to 300 nm. All species exhibited highly significant antioxidant activity using four different techniques compared to ascorbic acid. For antidiabetic activity, the maximum α-amylase and α-glucosidase activity inhibition were recorded for P. myrica (68.79 ± 0.7%; 66.73 ± 0.5%), followed by T. decurrens (66.38 ± 0.6%; 61.34 ± 0.4%) and then D. spiralis (65.99 ± 0.5%; 60.58 ± 0.4%) compared to the acarbose standard drug (73.76 ± 0.6%; 68.38 ± 0.6%), which nominated these extracts as candidates for antidiabetic drugs. Moreover, the obtained results showed effective anti-inflammatory arthritis effects, with the maximum activity value of 86.02 ± 1.3% recorded for S. euryphyllum, followed by D. spiralis (86.23 ± 1.1%), and then P. myrica (85.94 ± 1.4%). On the other side, a low inhibition percentage of acetyl cholinesterase (AChE) activity was recorded for different phlorotannin extracts, indicating low potentiality as anti-alzheimer materials. Moreover, the P. myrica phlorotannins’ extract showed no toxicity on the WISH normal cell line by using the MTT assay. The same extract comprised a variety of phlorotannins, viz fucophlorethol, fuhalol, and phlorethol compounds, as revealed by UPLC-MS/MS analysis. Graphical Abstract

Metabolomics-Based Analyses of Dynamic Changes in Flavonoid Profiles in the Black Mulberry Winemaking Process.

To overcome the fruit's perishability, mulberry wine has been developed as a method of preservation. However, dynamic changes in metabolites during mulberry wine fermentation have not been reported yet. In the present investigation, UHPLC-QE-MS/MS coupled with multivariate statistical analyses was employed to scrutinize the metabolic profiles, particularly the flavonoid profiles, throughout the process of vinification. In general, the major differential metabolites encompassed organic heterocyclic compounds, amino acids, phenylpropanoids, aromatic compounds, and carbohydrates. The contents of total sugar and alcohol play a primary role that drove the composition of amino acids, polyphenol, aromatic compound, and organic acid metabolites based on the Mantel test. Importantly, among the flavonoids, abundant in mulberry fruit, luteolin, luteolin-7-O-glucoside, (-)-epiafzelechin, eriodictyol, kaempferol, and quercetin were identified as the differential metabolic markers during blackberry wine fermentation and ripening. Flavonoid, flavone and flavonol biosynthesis were also identified to be the major metabolic pathways of flavonoids in 96 metabolic pathways. These results will provide new information on the dynamic changes in flavonoid profiles during black mulberry winemaking.

UHPLC-MS/MS phytochemical screening, polyphenolic content and antioxidant potential of Diplorhynchus condylocarpon (Müll.Arg.) Pichon (Apocynaceae), a medicinal plant

Diplorhynchus condylocarpon (Müll.Arg.) Pichon (Apocynaceae) leaves, stem bark, and roots are commonly used as popular folk medicine in Zambia and other African countries. This work aimed to find out the broad categories of phytocompounds present in the plant, screen the polyphenols, and assess the total polyphenolic content and the antioxidant activity of methanolic extracts of leaf, stem bark, and roots. Maceration was used to extract secondary metabolites for preliminary phytochemical screening. QuEChERS (quick, easy, cheap, effective, rugged, and safe), based technique was used to recover polyphenols for liquid chromatography with tandem mass spectrometry (LC-MS/MS) screening. Standard chemical tests were used for preliminary phytochemical screening. Total phenolic content (TPC) was evaluated using the Folin-Ciocalteu (FC) method at 765 nm. Total flavonoid content (TFC) was evaluated by the aluminum chloride colorimetric assay at 510 nm. Antioxidant activity was determined using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging method at 517 nm. The preliminary phytochemical screening revealed the presence of antioxidants, polyphenols, and other valuable phytocompounds such as alkaloids, saponins, and terpenoids. The LCMS/MS polyphenolic screening revealed the presence of mainly polyphenolic metabolites. TPC values were higher in the leaf (171.099±0.515 mg GAE/g) and root (88.8093±3.156 mg GAE/g) than in the stem bark (71.061±0.515 mg GAE/g) extracts. Further, the leaf extract contained 129.402±0.407, the root contained 64.672±0.813, and the stem bark had 37.643±0.704 mg QE/g total flavonoids. The leaf extract exhibited in a dose-dependent manner higher DPPH radical scavenging activities (34.250, 50.625, 66.562, 81.406, and 97.344%), followed by the root (16.406, 31.406, 50.781, 65.625, and 82.188%), and the stem bark extract only had the least DPP quenching activities (15.469, 27.969, 40.469, 52.500, and 68.590%) for the concentration of 20, 40, 60, 80 and 100 µg/mL respectively. Further, the results from the DPPH assay show that the leaf extract had the best IC50 value of 19.973 µg/mL, followed by the root extract with 60.867 µg/mL, and the stem bark extract with 107.150 µg/mL. These antioxidant activities support the traditionally claimed therapeutic benefits of D. condylocarpon leaves, stem bark, and roots in the treatment of oxidative stress-related disorders such as diabetes mellitus, chronic wounds, and diarrhea. This study may lead to the production of new herbal medicines using D. condylocarpon.

The Antioxidant Effect of Dietary Bioactives Arises from the Interplay between the Physiology of the Host and the Gut Microbiota: Involvement of Short-Chain Fatty Acids.

The maintenance of redox homeostasis is associated with a healthy status while the disruption of this mechanism leads to the development of various pathological conditions. Bioactive molecules such as carbohydrates accessible to the microbiota (MACs), polyphenols, and polyunsaturated fatty acids (PUFAs) are food components best characterized for their beneficial effect on human health. In particular, increasing evidence suggests that their antioxidant ability is involved in the prevention of several human diseases. Some experimental data indicate that the activation of the nuclear factor 2-related erythroid 2 (Nrf2) pathway-the key mechanism in the maintenance of redox homeostasis-is involved in the beneficial effects exerted by the intake of PUFAs and polyphenols. However, it is known that the latter must be metabolized before becoming active and that the intestinal microbiota play a key role in the biotransformation of some ingested food components. In addition, recent studies, indicating the efficacy of the MACs, polyphenols, and PUFAs in increasing the microbial population with the ability to yield biologically active metabolites (e.g., polyphenol metabolites, short-chain fatty acids (SCFAs)), support the hypothesis that these factors are responsible for the antioxidant action on the physiology of the host. The underlying mechanisms through which MACs, polyphenols, and PUFAs might influence the redox status have not been fully elucidated, but based on the efficacy of SCFAs as Nrf2 activators, their contribution to the antioxidant efficacy of dietary bioactives cannot be excluded. In this review, we aimed to summarize the main mechanisms through which MACs, polyphenols, and PUFAs can modulate the host's redox homeostasis through their ability to directly or indirectly activate the Nrf2 pathway. We discuss their probiotic effects and the role played by the alteration of the metabolism/composition of the gut microbiota in the generation of potential Nrf2-ligands (e.g., SCFAs) in the host's redox homeostasis.

Combined metabolome and transcriptome analysis reveal the mechanism of eugenol inhibition of Aspergillus carbonarius growth in table grapes (Vitis vinifera L.)

During storage, Aspergillus carbonarius (A. carbonarius) can easily infect grape berries, resulting in a pronounced decline in nutritional value and substantial economic loss for the grape industry. Characterised by broad-spectrum antibacterial activity, eugenol is proven to significantly inhibit A. carbonarius and ochratoxin A (OTA) in vitro. In this study, the potential mechanism of eugenol against A. carbonarius in grapes (‘Kyoho’) was evaluated using integrative transcriptomic and metabolomics analyses. After eugenol treatment at 50 mM, the inhibition of OTA was reduced by 100%, despite a 56.2% inhibition of A. carbonarius. In the meantime, mycelial growth was completely inhibited by 100 mM eugenol in grape berries. The application of eugenol to grapes stimulated the activity of several enzymes involved in disease resistance, namely catalase (CAT), peroxidase (POD), superoxide dismutase (SOD), chitinase (CHI), β-1,3-glucanase (GLU), cinnamate-4-hydroxylase (C4H), phenylalanine ammonia-lyase (PAL), 4-coumarate-CoA ligase (4CL) and glutathione (GSH) content. In addition, the contents of abscisic acid (ABA), jasmonic acid (JA) and salicylic acid (SA) in eugenol-treated grapes were higher after A. carbonarius inoculation. Combined transcriptomic and metabolomic analysis revealed that in phenylpropane biosynthesis, there were a variety of differentially expressed metabolites (DEMs) and differentially expressed genes (DEGs), and the plant hormone signalling pathway changed significantly. Among these, the levels of 47 polyphenol metabolites significantly increased in eugenol-treated grape berries compared to noneugenol-treated berries. Meanwhile, we investigated the transcript levels of 39 genes in 6 phytohormones signalling in response to eugenol-treated grape berries followed by A. carbonarius inoculation. These results suggest that eugenol positively improved the disease resistance of grapes and might be potentially beneficial for the prevention and treatment of A. carbonarius-caused disease.

Changes in Polyphenols and Anthocyanin Pigments during Ripening of Vitis vinifera cv Maratheftiko: A Two-Year Study

The vineyard of Cyprus is comprised largely of native Vitis vinifera varieties, which are rather underexploited with regard to wine production to date. Although empirical observations concur that several of these varieties may possess a high potential for the production of quality wines, analytical data pertaining to their polyphenolic composition are scarce. This study was undertaken with the aim of providing a detailed picture of the evolution patterns of several important polyphenolic constituents during the last stages of ripening of Maratheftiko, which is one of the major native grape varieties. This study included monitoring of representative simple phenolics, flavonoids and anthocyanin pigments for two consecutive years, 2021 and 2022, to obtain a more integrated portrayal of changes occurring during the critical period prior to harvest. It was revealed that there was a very high difference in the content of almost all polyphenols considered for the harvests in 2021 and 2022. The grapes harvested in 2022 had a much higher content in catechin, but most importantly, the content in total anthocyanins was 3.91-fold higher in 2022 compared to 2021. On the other hand, trans-resveratrol was the only polyphenolic metabolite whose difference was rather marginal. In seeds, the predominant substance was catechin, which displayed pronounced fluctuations during the period examined. It was concluded that the contents of major polyphenolic metabolites in Maratheftiko grapes might exhibit large variations during the period prior to harvest, most possibly reflecting differences in the average temperature and rainfall. Thus, tight monitoring of technologically important constituents, e.g., anthocyanins, is recommended to ensure the harvest of grapes with optimal maturity.

Abstract 5342: Assessment of polyphenolic secondary metabolites and small molecules against the xenobiotic metabolic and cell cycle regulatory proteins in prostate cancer

Abstract Background: Prostate cancer (PCa) is the second most frequent kind of cancer in males globally after Lung Cancer. In clinical practice, medicines that act as antagonists/partial agonists of hormone receptors against prostate tissue are employed in PCa treatment. Cyproterone acetate, Flutamide, and Bicalutamide are prominent medications that induce acute and long-term toxicity and create drug resistance in patients and remission. We concentrated on flavonoids since they are non-cytotoxic and have substantial showing inhibitory action. Methodology: We selected 560 flavonoids and small compounds along with 3 targets from the extensive literature review. Three-dimensional (3D) structures of selected proteins were obtained from Protein Data Bank, docked with 560 flavonoids and small molecules 3D structures, obtained from PubChem and CHEMBL database using Gold Docking Software. ADME characteristics were used to determine their bioactivities in the human body and drug-like investigations by using SwissADME and Zinc database, while Lipinski's rule of five was used to evaluate the flavonoids' anti-prostate cancer efficacy. Additionally, we have performed molecular simulation at 100ns and furthermore, we will perform cytotoxicity analysis. Results: Diosmetin (58.72), Lapatinib Ditosylate (121.61), and Estramustine Phosphate Sodium (143.38) has the highest binding affinity for CDKN2 (4EK3), CYP17A1(3RUK), and CYP19A1(3S79), respectively, and are stable throughout 100ns simulation studies. At present, we are working on cytotoxicity studies on PC3 cell lines. As per the literature review by Ansar et al. 2022 quercetin and thymoquinone induce cytotoxicity in breast, lung, and prostate cancer cells effectively; MCF-7 cells were the most sensitive cells to quercetin with an IC50 value of 50 μM and PC3 cells were more sensitive to thymoquinone with an IC50 value of 20 μM. Conclusion: As a result of our findings, these four Flavonoids may be viable candidates for additional research into PCa prevention or management.Keywords: Diosmetin, Lapatinib Ditosylatye, Prostate cancer, In-silico, Simulation Citation Format: Sumit Sheoran, Swati Arora, Tanmay Basu, Naidu Subbarao, Atul Kumar Upadhyay, Sugunakar Vuree. Assessment of polyphenolic secondary metabolites and small molecules against the xenobiotic metabolic and cell cycle regulatory proteins in prostate cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5342.

Paraburkholderia tropica PKI7 and Kosakonia arachidis PKI8: Two newly reported tannase producing bacteria isolated from forest soil and study of their tannase producing potentiality

Tannins are the polyphenolic secondary metabolites of plants and having antimicrobial properties due to their protein precipitation abilities and other toxic effects towards microbes. However, with the help of an inducible enzyme called tannase, a variety of microbes including bacteria can resist tannin toxicity. Tannase catalyses the dissociation of ester bonds in gallotannins like tannic acid, resulting in release of gallic acid and glucose. Because of its vast industrial applications and ease of manipulation, interest in identifying and applying bacteria as tannase producers has grown in recent years. The bacterial strains reported in the present work were isolated from soil and identified as Paraburkholderia tropica PKI7 and Kosakonia arachidis PKI8 through morphological, biochemical, and 16s rDNA molecular approach. Simultaneous tannase and gallic acid production by these two bacterial strains were observed through submerged fermentation. This is the first report of Paraburkholderia tropica PKI7 and Kosakonia arachidis PKI8 strains as tannase producing bacteria. The initial tannase production were 0.75 U/ml and 1.49 U/ml respectively for P. tropica PKI7 and K. arachidis PKI8 after 24 h of submerged fermentation while gallic acid release was 8.4 µg/ml and 10.74 µg/ml respectively. There is a potential scope in higher tannase and gallic acid biosynthesis by the two strains.

Strawberry, Blueberry, and Strawberry-Blueberry Blend Beverages Prevent Hepatic Steatosis in Obese Rats by Modulating Key Genes Involved in Lipid Metabolism.

There is an increasing interest in developing natural herb-infused functional beverages with health benefits; therefore, in this study, we aimed to evaluate the effect of strawberry, blueberry, and strawberry-blueberry blend decoction-based functional beverages on obesity-related metabolic alterations in high-fat and high-fructose diet-fed rats. The administration of the three berry-based beverages for eighteen weeks prevented the development of hypertriglyceridemia in obese rats (1.29-1.78-fold) and hepatic triglyceride accumulation (1.38-1.61-fold), preventing the development of hepatic steatosis. Furthermore, all beverages significantly down-regulated Fasn hepatic expression, whereas the strawberry beverage showed the greatest down-regulation of Acaca, involved in fatty acid de novo synthesis. Moreover, the strawberry beverage showed the most significant up-regulation of hepatic Cpt1 and Acadm (fatty acid β-oxidation). In contrast, the blueberry beverage showed the most significant down-regulation of hepatic Fatp5 and Cd36 (fatty acid intracellular transport). Nevertheless, no beneficial effect was observed on biometric measurements, adipose tissue composition, and insulin resistance. On the other hand, several urolithins and their derivatives, and other urinary polyphenol metabolites were identified after the strawberry-based beverages supplementation. In contrast, enterolactone was found significantly increase after the intake of blueberry-based beverages. These results demonstrate that functional beverages elaborated with berry fruits prevent diet-induced hypertriglyceridemia and hepatic steatosis by modulating critical genes involved in fatty acid hepatic metabolism.

Stabilization of Labile Lysozyme-Ligand Interactions in Native Electrospray Ionization Mass Spectrometry.

Flavonoids are polyphenolic secondary metabolites with extensive biological activities and pharmacological effects. Exploring the interactions of flavonoids with proteins may be helpful for understanding their biological processes. Electrospray ionization mass spectrometry (ESI-MS) is a powerful tool to characterize the noncovalent protein-ligand (PL) complexes. However, some protein-flavonoid complexes are labile during electrospray ionization. Here, the labile lysozyme-flavonoid (rutin, icariin, and naringin) complexes were determined by direct ESI-MS without derivation. It has been found that low amounts of N-methylpyrrolidinone and dimethylformamide can protect labile lysozyme-flavonoid complexes away from dissociation during electrospray ionization process. The intact lysozyme-flavonoid complexes were specifically observed in mass spectra, and the measured binding affinities by ESI-MS were matched with the fluorescence data. The effects of additives on the analysis of lysozyme-flavonoid complexes were investigated by ESI-MS, combined with the molecular docking and fluorescence. This strategy was helpful to investigate the labile PL interactions by direct ESI-MS.

Supplementation of syringic acid-rich Phrynium pubinerve leaves imparts protection against allergic inflammatory responses by downregulating iNOS, COX-2, and NF-κB expressions

BackgroundThe present study was designed to characterize the role of ethanolic leaf extract of Phrynium pubinerve Blume (EPP) supplement in attenuating allergic inflammation, encouraged by the presence of syringic acid in it, as this phenolic acid is reportedly promising in suppressing serum immunoglobulin E (IgE) and inflammatory cytokine levels. Materials and methodsHPLC-DAD dereplication analysis was performed to determine the presence of the vital polyphenolic metabolites. The efficacy of EPP against lipopolysaccharide (LPS)-induced inflammation in RAW 264.7 cells was evaluated by measuring its inhibitory effects on NO and ROS/RNS production. The expressions of major inflammation-associated molecules (iNOS, COX-2, NF-κB, IL-6, and TNF-α) in RAW 264.7 cells were assessed through Western blot. Physiological and behavioral changes, BMI, and different biochemical parameters in mice blood serum were investigated in the toxicological assays. Formaldehyde-induced paw edema test in mice was conducted using established animal model. TDI-induced allergic model in mice was carried out to determine different allergy-like symptoms, and differential white blood cell (WBC) counts in blood and bronchoalveolar lavage (BAL) fluid. The intermolecular interaction analysis of the identified major metabolite of EPP with H1R and iNOS was studied by molecular docking. ResultsHPLC-DAD analysis showed the presence of syringic acid (89.19 mg/100 g EPP) and a few other compounds. LPS-induced NO generation was reduced by EPP in a concentration-dependent manner, showing IC50 of 28.20 ± 0.27 μg/mL. EPP exhibited a similar inhibitory effect on ROS/RNS production with IC50 of 29.47 ± 2.19 μg/mL. Western blotting revealed that EPP significantly downregulated the expressions of iNOS, COX-2, NF-κB, IL-6, and TNF-α in RAW 264.7 cells when challenged with LPS. The toxicological assays confirmed the dosage and organ-specific safety of EPP. In the formaldehyde-induced paw edema test, EPP caused a 66.41% reduction in mice paw volume at 500 mg/kg dose. It ameliorated TDI-induced allergy-like symptoms and decreased different inflammatory WBCs in mice's blood and BAL fluid in a dose-dependent manner. Finally, syringic acid demonstrated mentionable intermolecular binding affinity towards H1R (−6.6 Kcal/moL) and iNOS (−6.7 Kcal/moL). ConclusionsCollectively, considerable scientific reasoning was obtained in favor of the suppressive potential of EPP against allergic inflammatory responses that are proposed to be exerted via the downregulation of iNOS, COX-2, and NF-κB expressions, H1R antagonism and suppression of cytokines, such as IL-6, and TNF-α.

Effect of ultrasound combined with exogenous GABA treatment on polyphenolic metabolites and antioxidant activity of mung bean during germination

Mung bean seeds were treated by a combination of ultrasound and γ-aminobutyric acid (GABA). Effect of these treatments on the free polyphenols content, antioxidant activity, and digestibility of mung bean sprouts was evaluated. Additionally, phenolic compounds were analyzed and identified using a metabolomics approach. The combined ultrasound and GABA treatments significantly enhanced the free polyphenols and flavonoids content (P < 0.05) of mung bean sprouts depending on sprouting duration. Besides, a positive correlation (P < 0.05) was found between the polyphenols content and in vitro antioxidant activity of mung bean sprouts. Moreover, a total number of 608 metabolites were detected, and 55 polyphenol compounds were identified, including flavonoids, isoflavones, phenols, and coumarins. Also, the KEGG metabolic pathway analysis revealed 10 metabolic pathways of phenols, including flavonoid, isoflavone, and phenylpropanoid biosynthesis. Powder of 48 h sprouted mung bean released polyphenols during simulated gastric digestion and possessed antioxidant activity.

Analysis of Empetrum nigrum L. lipophilic secondary metabolites, their metabolomic profiles and antioxidant activity

ABSTRACT Fourteen hexane-soluble polyphenolic secondary metabolites were previously isolated as individual compounds from Empetrum nigrum L. and identified as three bibenzyls, four 9,10-dihydrophenanthrenes, two chalcones, four dihydrochalcones and one flavanone. In this study, the mass-spectra and retention indexes (RI) of compounds 1-14 without prior derivatization were obtained and the resulting fragmentation pathways rationalized in accordance with literary data and the compounds structures. Preliminary differences in metabolite composition were assessed by comparative profiling using GC-MS chromatography combined with multivariate data analysis for a limited amount of E. nigrum n-hexane extracts obtained from plants growing in three different geographic locations. To characterize antioxidant capacity of isolated compounds 1-14 we used our well-established model based on reactive oxygen species (ROS) production by activated human platelets and showed that most of the examined polyphenols act as antioxidants by inhibition of ROS production.

Effects of pretreatment with a combination of ultrasound and γ-aminobutyric acid on polyphenol metabolites and metabolic pathways in mung bean sprouts.

Polyphenols play an important role in human nutrition, therefore, how to improve its content with innovative approach is important, and understanding the metabolic pathys is necessary. Mung beans are rich in polyphenols, which made them have physiological functions such as hypoglycemia, antioxidant, and hypotension. However, the content of polyphenols in natural mung bean is relatively low, and it needs to be increased. The methods of increasing polyphenol content in grains and beans by enrichment include physical stress, such as ultrasonic stress, hypoxia stress and ultraviolet radiation, and single exogenous substance stress, such as exogenous amino acids, exogenous sugars. But, the enrichment of polyphenols using exogenous substances in combination with physical stress is less applied. Therefore, this study innovated the use of exogenous γ-aminobutyric acid (GABA) combined with ultrasonic stress to enrich mung bean sprouts polyphenols and enhance their content. The metabolic pathways of the enrichment process were also analyzed to provide a reference for studies related to the enrichment of polyphenols. Mung bean seeds were pretreated with a combination of ultrasound and GABA under different conditions. Single-factor test and response surface methodology were used for optimizing pretreatment conditions of mung bean. Effects of combined pretreatments on the polyphenols content and antioxidant activity of sprouted mung beans were investigated. Additionally, metabolites were identified, and metabolic pathways were analyzed using non-targeted metabolomics techniques. Optimal conditions of mung bean pretreatment were found to be 370 W for ultrasound power, 40 min for ultrasonication time, 10 mmol/L for GABA concentration, and 8 h for the soaking duration. Under these conditions, the predicted polyphenol content was found to be 4.52 mg GAE/g DW. The pretreatment of mung beans with a combination of ultrasound and exogenous GABA resulted in mung bean sprouts with enhanced polyphenol content and antioxidant activity compared to mung beans germinated without pretreatment. A significant increase in the content of six polyphenols [Genistein, (-)-Epigallocatechin, Epicatechin, Nobiletin, Naringenin, Biochanin A] in the pretreated and germinated mung beans was found, and six metabolic pathways (flavonoid biosynthesis, isoflavones biosynthesis, biosynthesis of phenylpropanoids, anthocyanin biosynthesis, biosynthesis of secondary metabolites, and metabolic pathways) were significantly activated. The obtained results suggest that a combination of ultrasound and exogenous GABA treatment can be used to produce mung bean sprouts with enriched polyphenols content and enhanced antioxidant activity.

Zebrafish: A Model Deciphering the Impact of Flavonoids on Neurodegenerative Disorders.

Over the past century, advances in biotechnology, biochemistry, and pharmacognosy have spotlighted flavonoids, polyphenolic secondary metabolites that have the ability to modulate many pathways involved in various biological mechanisms, including those involved in neuronal plasticity, learning, and memory. Moreover, flavonoids are known to impact the biological processes involved in developing neurodegenerative diseases, namely oxidative stress, neuroinflammation, and mitochondrial dysfunction. Thus, several flavonoids could be used as adjuvants to prevent and counteract neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. Zebrafish is an interesting model organism that can offer new opportunities to study the beneficial effects of flavonoids on neurodegenerative diseases. Indeed, the high genome homology of 70% to humans, the brain organization largely similar to the human brain as well as the similar neuroanatomical and neurochemical processes, and the high neurogenic activity maintained in the adult brain makes zebrafish a valuable model for the study of human neurodegenerative diseases and deciphering the impact of flavonoids on those disorders.

Optimization of microwave-assisted extraction on polyphenol metabolite from Eleutherine bulbosa (Mill.) urb. bulbs using response surface methodology.

Eleutherine bulbosa bulbs, an endemic plant in Indonesia, have enormous potential as raw materials for pharmaceutical products. Therefore, it is necessary to strengthen and develop extraction methods that are easy, rapid, and efficient to enrich targeted secondary metabolites. This study aims to optimize the microwave-assisted extraction (MAE) method conditions for polyphenol metabolite from E. bulbosa bulbs. The MAE method (with different conditions) was applied to extract total polyphenol content (TPC) from E. bulbosa bulbs. TPC values were determined using a 96-well microplate reader spectrophotometry method and Folin-Ciocalteu reagent. The variables of MAE, as an experimental design-independent variable, were involved. The MAE method condition was optimized using response surface methodology (RSM) and Box-Behnken design based on the TPC value. The MAE condition was optimized with 60% ethanol, sample-solvent ratio of 1:10 g/mL, and 50% Watts of microwave power for 10 min. The quadratic regression analysis was achieved to predict the TPC value using the equation: TPC value = 28.63-5.545A +2.211B -0.741C +1.995D - 4.045AB +0.856AC -7.541BC +1.961CD -8.342A2-0.071B2 +1.840C2-1.535D2. For the scale-up confirmation test, a 50-g sample was used to prove the validity of the equation to predict the TPC value, yielding 35.33 ± 2.13 mg gallic acid equivalent/g samples. The optimum of the MAE condition recommended based on the results of RSM analysis can be applied directly to the enrichment of polyphenols metabolite constituent of E. bulbosa easily, cheaply, quickly, and efficiently.

Molecular mechanisms for polyphenol functionality

Polyphenols are found in a wide variety of vegetables, fruits, and teas that we regularly consume. "Polyphenol" is a general term for a family of compounds with multiple phenolic hydroxyl groups (hydroxyl groups attached to the benzene ring), and about 8,000 species have been identified so far. Polyphenols are becoming widely recognized in society due to their promising health benefits, such as their preventive effects against obesity and cardiovascular diseases. To understand how polyphenols exert their health benefits from a molecular viewpoint, researchers in the food and nutrition fields have been elucidating the various biochemical and molecular biological activities exhibited by polyphenols themselves. It has been pointed out that polyphenols are generally poorly absorbable and therefore unlikely to be taken up by the body or to reach various organs in their native form. The molecular mechanisms by which polyphenols express their functions in vivo include direct interaction with receptor proteins, action of polyphenol metabolites, and effects on intestinal bacterial fermentation. In this paper, I will not only outline the types and chemical characteristics of polyphenols, but also explain their molecular behavior along with their potential health-promoting effects.

Metabolomics signatures of plant protein intake: effects of amino acids and compounds associated with plant protein on cardiometabolic health.

An increase in the plant-based characteristics of the diet is now recommended for human and planetary health. There is growing evidence that plant protein (PP) intake has beneficial effects on cardiometabolic risk. However, proteins are not consumed isolated and the protein package (lipid species, fiber, vitamins, phytochemicals, etc) may contribute, besides the protein effects per se, to explain the beneficial effects associated with PP-rich diets. Recent studies have shown the potential of nutrimetabolomics to apprehend the complexity of both the human metabolism and the dietary habits, by providing signatures associated to the consumption of PP-rich diets. Those signatures comprised an important proportion of metabolites that were representative of the protein package, including specific amino acids (branched-chain amino acids and their derivates, glycine, lysine), but also lipid species (lysophosphatidylcholine, phosphatidylcholine, plasmalogens) and polyphenol metabolites (catechin sulfate, conjugated valerolactones and phenolic acids). Further studies are needed to go deeper in the identification of all metabolites making part of the specific metabolomic signatures, associated to the large range of protein package constituents and their effects on the endogenous metabolism, rather than to the protein fraction itself. The objective is to determine the bioactive metabolites, as well as the modulated metabolic pathways and the mechanisms responsible for the observed effects on cardiometabolic health.