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As an important member of innate immunity, macrophages show remarkable plasticity and heterogeneity, and play an important role in immune regulation, tissue development, homeostasis of the internal environment and injury repair. However, the excessive activation of macrophages is closely related to the occurrence and development of many diseases. The prenylated flavonoid structure is one of the characteristic structures isolated from Sophora flavescens , with anti-inflammatory, anti-tumor, anti-allergy and other effects. In this study, the effects of (2 R )-3 β ,7,4'-trihydroxy-5-methoxy-8-prenylflavanone (TMP), a prenylated dihydroflavonol, on the polarization and phagocytosis of macrophages were systematically studied. In LPS-induced M1-type macrophages, TMP dose-dependently inhibited the expression of COX-2, iNOS and the secretion of NO, IL-1β, IL-6 and IL-18, showing an inhibitory effect on M1 polarization. Further experiments revealed that it was related to the inhibition of TLR4-related AKT/mTOR, MAPK and NF-κB signaling pathways; in IL-4-induced M2-type macrophages, TMP down-regulated the expression of M2-related Arg1, IL-10, TGF-β, CD206 and CD163, as well as the phosphorylation levels of AKT1 and STAT6. For macrophages in a physiological state, it was very important for cells to return from a stress state to a phenotypic stability in the M0 state. These results indicated that TMP negatively regulated the M1/M2 polarization of macrophages, and made them tend to M0 homeostasis, which might provide new theoretical and data support for explaining the anti-inflammatory immunoregulatory activity of Sophora flavescens .

Human intestinal bacteria are the primary producers of azo reductase, and the content of azo reductase is closely associated with various intestinal diseases, including ulcerative colitis (UC). The rapid detection of changes in azo reductase levels is crucial for diagnosing and promptly intervening in UC. In this study, a therapeutic agent, FAI , specifically targeting UC, was designed and synthesized. This agent was developed by linking the anti-inflammatory drug indomethacin to flavonols with antioxidant activity via an azo bond (off-on). Breakage of the azo bond breaks results in the release of both fluorophores and drugs, achieving targeted tracing and integrated treatment effects. In vivo and in vitro fluorescence imaging experiments were used to demonstrate the potential of FAI in the diagnosis of UC, together with synergistic therapeutic effects through the release of both fluorophores and anti-inflammatory agents. Therefore, this diagnostic agent shows promise as a potential tool for diagnosing and treating UC.

A series of flavanols were synthesized to assess their biological activity against human non-small cell lung cancer cells (A549). Among the sixteen synthesized compounds, it was observed that compounds 6k (3.14 ± 0.29 µM) and 6l (0.46 ± 0.02 µM) exhibited higher potency compared to 5-fluorouracil (5-Fu, 4.98 ± 0.41 µM), a clinical anticancer drug which was used as a positive control. Moreover, compound 6l (4'-bromoflavonol) markedly induced apoptosis of A549 cells through the mitochondrial- and caspase-3-dependent pathways. Consequently, compound 6l might be developed as a candidate for treating or preventing lung cancer.

Hibiscus rosa-sinensis plants are mainly cultivated as ornamental plants, but they also have food and medicinal uses. In this work, 16 H. rosa-sinensis cultivars were studied to measure their colorimetric parameters and the chemical composition of hydroethanolic extracts obtained from their petals. These extracts were characterized using UHPLC-ESI + -Obitrap-MS, and their antioxidant activity was evaluated using the ORAC assay. The identified flavonoids included anthocyanins derived from cyanidin, glycosylated flavonols derived from quercetin and kaempferol, and flavan-3-ols such as catechin and epicatechin. Cyanidin-sophoroside was the anthocyanin present in extracts of lilac, pink, orange, and red flowers, but was not detected in extracts of white or yellow flowers. The total flavonol concentration in the flower extracts was inversely proportional to the total anthocyanin content. The flavonol concentration varied according to the cultivar in the following order: red < pink < orange < yellow ≈ white, with the extract from the red flower presenting the lowest flavonol concentration and the highest anthocyanin concentration. The antioxidant activity increased in proportion to the anthocyanin concentration, from 1580 µmol Trolox ® /g sample (white cultivar) to 3840 µmol Trolox ® /g sample (red cultivar).

Flavonols are found in plants as aglycones and as glycosides. Antioxidant activity of flavonols may occur via several mechanisms within the cell, and mitochondria as a target may play an important role. There is a lack of information about the influence of the sugar moiety on biological activity of flavonoid glycosides. The aims of study were to investigate the effects of quercetin and its glycosides on mitochondrial respiration rates at various metabolic states, and to evaluate their antioxidant potential using chemical and biological approaches. Mitochondrial function was measured using an oxygraphic method, cytochrome c reduction spectrophotometrically, H 2 O 2 generation in mitochondria fluorimetrically, and antioxidant activity of flavonoids using an HPLC-post column system. Our data revealed that quercetin and its glycosides isoquercitrin, rutin, and hyperoside uncouple kidney mitochondrial respiration (increasing the State 2 respiration rate) and significantly reduce cytochrome c. Moreover, quercetin, and its glycosides decrease the production of mitochondrial H 2 O 2 and possess radical scavenging and ferric reducing capacities. The highest activity was characteristic for quercetin, showing that the sugar moiety significantly diminishes its activity. In conclusion, our results show the efficient radical scavenging, ferric and cytochrome c reducing capacities, and uncoupling properties of quercetin and its glycosides, as well as the importance of the sugar residue and its structure in the regulation of kidney mitochondrial function.

Natural flavonoids, in addition to some of their synthetic derivatives, are recognized for their remarkable medicinal properties. The present study was designed to investigate the in vitro antioxidant and in vivo antistress effect of synthetic flavonoids (flavones and flavonols) in mice, where stress was induced by injecting acetic acid and physically through swimming immobilization. Among the synthesized flavones ( F1-F6 ) and flavonols ( OF1-OF6 ), the mono para substituted methoxy containing F3 and OF3 exhibited maximum scavenging potential against DPPH (2,2-diphenyl-1-picrylhydrazyl) with IC 50 of 31.46 ± 1.46 μg/mL and 25.54 ± 1.21 μg/mL, respectively. Minimum antioxidant potential was observed for F6 and OF6 with IC 50 values of 174.24 ± 2.71 μg/mL and 122.33 ± 1.98 μg/mL, respectively, in comparison with tocopherol. The ABTS scavenging activity of all the synthesized flavones and flavonols were significantly higher than observed with DPPH assay, indicating their potency as good antioxidants and the effectiveness of ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate) assay in evaluating antioxidant potentials of chemical substances. The flavonoids-treated animals showed a significant (* p < 0.05, ** p < 0.01 and *** p < 0.001, n = 8) reduction in the number of writhes and an increase in swimming endurance time. Stressful conditions changed plasma glucose, cholesterol and triglyceride levels, which were used as markers when evaluating stress in animal models. The level of these markers was nearly brought to normal when pre-treated with flavones and flavonols (10 mg/kg) for fifteen days in experimental animals. These compounds also considerably reduced the levels of lipid peroxidation (TBARS: Thiobarbituric acid reactive substances), which was significant (* p < 0.05, ** p < 0.01 and *** p < 0.001, n = 8) compared to the control group. A significant rise in the level of catalase and SOD (super oxide dismutase) was also observed in the treated groups. Diazepam (2 mg/kg) was used as the standard drug. Additionally, the flavonoids markedly altered the weight of the adrenal glands, spleen and brain in stress-induced mice. The findings of the study suggest that these flavonoids could be used as a remedy for stress and are capable of ameliorating diverse physiological and biochemical alterations associated with stressful conditions. However, further experiments are needed to confirm the observed potentials in other animal models, especially in those with a closer resemblance to humans. Toxicological evaluations are also equally important.

Obesity is becoming increasingly common all over the world and global strategies are accordingly being developed to prevent it. In order to support the strategies, the effects of green apple (Golden Delicious) and the consumption of its three major flavonols (quercetin-3-glucoside, quercetin-3-D-galactoside, and quercetin-3-rhamnoside) on body weight; the weight of liver, kidney, and spleen; some lipid parameters in serum; and total lipid ratios of liver and kidney and oxidative stress parameters of obese rats were studied. This study was conducted on two experimental groups: one of which was given an apple, and the other was given flavonols, in addition to their high-energy diet; along with a sham and a control rat group, for 4 weeks. According to results, there was no difference in body and organ weights between groups. The liver and kidney weights increased in obese rats, but there was no difference between the total lipid ratios in these organs. The addition of green apple and selected flavonols to the high-energy diet of rats was not sufficient to prevent the increase in body and organ weights, but it supported the reduction in some lipid fractions and in oxidative stress parameters of obese rats. Moreover, this study supported the argument that obesity causes most of the lipid fractions increase in serum and induces oxidative stress.

In this paper, biological investigations and a high-resolution UPLC-PDA-ESI-qTOF-HRMS technique were employed for Brassica oleracea L. var. capitata f. rubra DC. (red cabbage) of the family Brassicaceae (Cruciferae), cultivated in Egypt, for the first time. The positive ionization mode is usually performed to identify anthocyanins. However, this technique cannot differentiate between anthocyanins and corresponding non-anthocyanin polyphenols. Thus, the negative ionization mode was also used, as it provided a series of characteristic ions for the MS analysis of anthocyanins. This helped in identifying five kaempferol derivatives for the first time in red cabbage, as well as nine-previously reported-anthocyanins. For the biological investigations, the acidified methanolic extract of fresh leaves and the methanolic extract of air-dried powdered leaves were examined for their antioxidant, antimicrobial, and anticancer activities. The freshly prepared phenolic extract was proven to be more biologically potent. Statistical significance was determined for its anticancer activity in comparison with standard doxorubicin.

The inhibition of α-glucosidase is a clinical strategy for the treatment of type 2 diabetes mellitus (T2DM), and many natural plant ingredients have been reported to be effective in alleviating hyperglycemia by inhibiting α-glucosidase. In this study, the α-glucosidase inhibitory activity of fisetin extracted from Cotinus coggygria Scop. was evaluated in vitro. The results showed that fisetin exhibited strong inhibitory activity with an IC 50 value of 4.099 × 10 -4 mM. Enzyme kinetic analysis revealed that fisetin is a non-competitive inhibitor of α-glucosidase, with an inhibition constant value of 0.01065 ± 0.003255 mM. Moreover, fluorescence spectrometric measurements indicated the presence of only one binding site between fisetin and α-glucosidase, with a binding constant (lgKa) of 5.896 L·mol -1 . Further molecular docking studies were performed to evaluate the interaction of fisetin with several residues close to the inactive site of α-glucosidase. These studies showed that the structure of the complex was maintained by Pi-Sigma and Pi-Pi stacked interactions. These findings illustrate that fisetin extracted from Cotinus coggygria Scop. is a promising therapeutic agent for the treatment of T2DM.

Plants are the everlasting source of a wide spectrum of specialized metabolites, characterized by wide variability in term of chemical structures and different biological properties such antiviral activity. In the search for novel antiviral agents against Human Immunodeficiency Virus type 1 (HIV-1) from plants, the phytochemical investigation of Scrophularia trifoliata L. led us to isolate and characterize four flavonols glycosides along with nine iridoid glycosides, two of them, 5 and 13 , described for the first time. In the present study, we investigated, for the first time, the contents of a methanol extract of S. trifoliata leaves, in order to explore the potential antiviral activity against HIV-1. The antiviral activity was evaluated in biochemical assays for the inhibition of HIV-1Reverse Transcriptase (RT)-associated Ribonuclease H (RNase H) activity and HIV-1 Integrase (IN). Three isolated flavonoids, rutin, kaempferol-7- O -rhamnosyl-3- O -glucopyranoside, and kaempferol-3- O -glucopyranoside, 8 - 10 , inhibited specifically the HIV-1 IN activity at submicromolar concentration, with the latter being the most potent, showing an IC 50 value of 24 nM.

Recommendations towards increased consumption of fresh fruit and vegetables are well supported by epidemiological and clinical trials. However, in some specific cases, it is difficult to follow these recommendations and the use of nutraceuticals or, in the present work, a freeze-dried fruits mixture can be recommended in order to afford the optimal consumption of dietary polyphenols naturally present in fruits and vegetables. In this work we have carefully characterized a red-berry mixture in terms of polyphenol composition, encountering mainly anthocyanins, which account for a total of 2.8 mg/g as cyanidin-3-glucoside equivalents. Additionally, we have assayed the red-berry blend in a cell model of neurological damage by differentiating the cells and measuring the effect of red-berry polyphenols on cell viability and redox state by flow cytometry. The berry-fruit extract showed an inhibitory effect on differentiated SH-SY5Y ROS formation at a concentration as low as 250 µg/mL (33% inhibition). The results show the potential of this berry-fruit blend for its nutraceutical use in the prevention of the neurodegeneration associated with age or environmental agents.

Momordica balsamina leaf extracts originating from three different geographical locations were analyzed using reversed-phase liquid chromatography (RP-LC) coupled to travelling wave ion mobility (TWIMS) and high-resolution mass spectrometry (HRMS) in conjunction with chemometric analysis to differentiate between potential chemotypes. Furthermore, the cytotoxicity of the three individual chemotypes was evaluated using HT-29 colon cancer cells. A total of 11 molecular species including three flavonol glycosides, five cucurbitane-type triterpenoid aglycones and three glycosidic cucurbitane-type triterpenoids were identified. The cucurbitane-type triterpenoid aglycones were detected in the positive ionization mode following dehydration [M + H - H 2 O] + of the parent compound, whereas the cucurbitane-type triterpenoid glycosides were primarily identified following adduct formation with ammonia [M + NH 4 ] + . The principle component analysis (PCA) loadings plot and a variable influence on projection (VIP) analysis revealed that the isomeric pair balsaminol E and/or karavilagen E was the key molecular species contributing to the distinction between geographical samples. Ultimately, based on statistical analysis, it is hypothesized that balsaminol E and/or karavilagen E are likely responsible for the cytotoxic effects in HT-29 cells.

In this study, we determined the phytochemical profile of the Spanish "triguero" asparagus landrace "verde-morado" ( Asparagus officinalis L.), a wild traditional landrace, and the improved "triguero" HT-801, together with two commercial green asparagus varieties. For comparison, we used reverse-phase high-performance liquid chromatography coupled with diode array electrospray time-of-flight mass spectrometry (RP-HPLC-DAD-ESI-TOF/MS) followed by a permutation test applied using a resampling methodology valid under a relaxed set of assumptions, such as i.i.d. errors (not necessarily normal) that are exchangeable under the null hypothesis. As a result, we postulate that "triguero" varieties (the improved HT-801 followed by its parent "verde-morado") have a significantly different phytochemical profile from that of the other two commercial hybrid green varieties. In particular, we found compounds specific to the "triguero" varieties, such as feruloylhexosylhexose isomers, or isorhamnetin-3- O -glucoside, which was found only in the "triguero" variety HT-801. Although studies relating the phytochemical content of "triguero" asparagus varieties to its health-promoting effects are required, this characteristic phytochemical profile can be used for differentiating and revalorizating these asparagus cultivars.

The aim of this study was to profile the bioaccessibility and intestinal absorption of epicatechins and flavonols in different forms of green tea and its formulation: loose leaf tea, powdered tea, 35% catechins containing GTE, and GTE formulated with green tea-derived polysaccharide and flavonols (CATEPLUS™). The bioaccessibillity and intestinal absorption of epicatechins and flavonols was investigated by using an in vitro digestion model system with Caco-2 cells. The bioaccessibility of total epicatechins in loose leaf tea, powdered tea, GTE, and CATEPLUS™ was 1.27%, 2.30%, 22.05%, and 18.72%, respectively, showing that GTE and CATEPLUS™ had significantly higher bioaccessibility than powdered tea and loose leaf tea. None of the flavonols were detected in powdered tea and loose leaf tea, but the bioaccessibility of the total flavonols in GTE and CATEPLUS™ was 85.74% and 66.98%, respectively. The highest intestinal absorption of epicatechins was found in CATEPLUS™ (171.39 ± 5.39 ng/mg protein) followed by GTE (57.38 ± 9.31), powdered tea (3.60 ± 0.67), and loose leaf tea (2.94 ± 1.03). The results from the study suggest that formulating green tea extracts rich in catechins with second components obtained from green tea processing could enhance the bioavailability of epicatechins.

Wine is one of the most consumed beverages around the world. It is composed of alcohols, sugars, acids, minerals, proteins and other compounds, such as organic acids and volatile and phenolic compounds (also called polyphenols). Polyphenols have been shown to be highly related to both (i) wine quality (color, flavor, and taste) and (ii) health-promoting properties (antioxidant and cardioprotective among others). Polyphenols can be grouped into two big families: (i) Flavonoids, including anthocyanidins, flavonols, flavanols, hydrolysable and condensed tannins, flavanones, flavones and chalcones; and (ii) Non-flavonoids, including hydroxycinnamic acids, hydroxybenzoic acids, stilbenes, tyrosol and hydroxytyrosol. Each group affects in some way the different properties of wine to a greater or a lesser extent. For that reason, the phenolic composition can be managed to obtain singular wines with specific, desirable characteristics. The current review presents a summary of the ways in which the phenolic composition of wine can be modulated, including (a) invariable factors such as variety, field management or climatic conditions; (b) pre-fermentative strategies such as maceration, thermovinification and pulsed electric field; (c) fermentative strategies such as the use of different yeasts and bacteria; and (d) post-fermentative strategies such as maceration, fining agents and aging. Finally, the different extraction methods and analytical techniques used for polyphenol detection and quantification have been also reviewed.

Previous studies have reported that Hedyotis diffusa Willdenow extract shows various biological activities on cerebropathia, such as neuroprotection and short-term memory enhancement. However, there has been a lack of studies on the inhibitory activity on neurodegenerative diseases such as Alzheimer's disease (AD) through enzyme assays of H. diffusa . Therefore, H. diffusa extract and fractions were evaluated for their inhibitory effects through assays of enzymes related to AD, including acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), and β-site amyloid precursor protein cleaving enzyme 1 (BACE1), and on the formation of advanced glycation end-product (AGE). In this study, ten bioactive compounds, including nine iridoid glycosides 1 - 9 and one flavonol glycoside 10 , were isolated from the ethyl acetate and n -butanol fractions of H. diffusa using a bioassay-guided approach. Compound 10 was the strongest inhibitor of cholinesterase, BACE1, and the formation of AGEs of all isolated compounds, while compound 5 had the lowest inhibitory activity. Compounds 3 , 6 , and 9 exhibited better inhibitory activity than other compounds on AChE, and two pairs of diastereomeric iridoid glycoside structures (compounds 4 , 8 , and 6 , 7 ) showed higher inhibitory activity than others on BChE. In the BACE1 inhibitory assay, compounds 1 - 3 were good inhibitors, and compound 10 showed higher inhibitory activity than quercetin, the positive control. Moreover, compounds 1 and 3 were stronger inhibitors of the formation of AGE than aminoguanidine (AMG), the positive control. In conclusion, this study is significant since it demonstrated that the potential inhibitory activity of H. diffusa on enzymes related to AD and showed the potential use for further study as a natural medicine for AD treatment on the basis of the bioactive components isolated from H. diffusa .

Opuntia ficus-indica (L.) Mill. is the Cactaceae plant with the greatest economic relevance in the world. It can be used for medicinal purposes, animal nutrition, production of biofuels and phytoremediation of soils. Due to its high content of bioactive compounds, the prickly pear has antioxidant, antimicrobial and anticancer properties. The aim of this study was to determine the polyphenolic, fatty acid and amino acid profile and characterize the antioxidant capacity of seeds of seven Spanish prickly pear cultivars. A total of 21 metabolites, mainly phenolic acids and flavonols, were identified using ultraperformance liquid chromatography photodiode detector quadrupole/time-of-flight mass spectrometry (UPLC-PDA-Q/TOF-MS). Significant differences were found in the phenolic concentrations of the investigated varieties. The highest amount of phenolic compounds (266.67 mg/kg dry matter) were found in the "Nopal espinoso" variety, while the "Fresa" variety was characterized by the lowest content (34.07 mg/kg DM) of these compounds. In vitro antioxidant capacity was positively correlated with the amount of polyphenols. The amino acid composition of protein contained in prickly pear seeds was influenced by the variety. Glutamic acid was the predominant amino acid followed by arginine, aspartic acid and leucine, independent of prickly pear variety. Overall, 13 different fatty acids were identified and assessed in prickly pear seeds. The dominant fatty acid was linoleic acid, with content varying between 57.72% "Nopal ovalado" and 63.11% "Nopal espinoso".

This study aimed to isolate, prepare and identify the main flavonoids from a standardized Smilax glabra flavonoids extract (SGF) using preparative HPLC, MS, 1 H NMR and 13 C NMR, determine the contents of these flavonoids using UPLC, then compare their pharmacological activities in vitro. We obtained six flavonoids from SGF: astilbin (18.10%), neoastilbin (11.04%), isoastilbin (5.03%), neoisoastilbin (4.09%), engeletin (2.58%) and (-)-epicatechin (1.77%). The antioxidant activity of six flavonoids were evaluated by determining the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical and 2,2'-Azinobis (3-ethylbenzothiazoline-6-sulphonic acid) diammonium salt (ABTS + ) radical scavenging activity and ferric reducing antioxidant power (FRAP). In addition, the anti-inflammatory activity of six flavonoids were evaluated by determining the production of cytokines (IL-1β, IL-6), nitric oxide (NO) using enzyme linked immunosorbent assay and the NF-κB p65 expression using Western blotting in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. The results showed that (-)-epicatechin, astilbin, neoastilbin, isoastilbin and neoisoastilbin had strong antioxidant activities, not only in DPPH and ABTS + radicals scavenging capacities, but in FRAP system. Furthermore, all the six flavonoids could significantly inhibit the secretion of IL-1β, IL-6, NO ( p < 0.01) and the protein expression of NF-κB p-p65 ( p < 0.01) in LPS-stimulated RAW264.7 cells. This study preliminarily verified the antioxidant and anti-inflammatory activities of six flavonoids in S. glabra .

Flavonol glycosides are important components of tea leaves, contributing to the bioactivities as well as bitterness and astringency of tea. However, the standards of many flavonol triglycosides are still not available, which restricts both sensory and bioactivity studies on flavonol glycosides. In the present study, we established a simultaneous preparation method of seven flavonol triglycoside individuals from tea leaves, which consisted of two steps: polyamide column enrichment and preparative HPLC isolation. The structures of seven flavonol triglycoside isolates were identified by mass and UV absorption spectra, four of which were further characterized by nuclear magnetic resonance spectra, namely, quercetin-3- O -glucosyl-rhamnosyl-glucoside, quercetin-3- O -rhamnosyl-rhamnosyl-glucoside, kaempferol-3- O -glucosyl-rhamnosyl-glucoside and kaempferol- O -rhamnosyl-rhamnosyl-glucoside. The purities of all isolated flavonol triglycosides were above 95% based on HPLC, and the production yield of total flavonol glycosides from dry tea was 0.487%. Our study provides a preparation method of flavonol triglycosides from tea leaves, with relatively low cost of time and solvent but high production yield.

Astilbin and neoastilbin are two flavonoid stereoisomers. In the present study, their solubility, stability, and bioavailability were compared in a rat. The results revealed that the water solubility of astilbin and neoastilbin was 132.72 μg/mL and 217.16 μg/mL, respectively. The oil-water distribution coefficient (log P) of astilbin and neoastilbin in simulated gastric fluid (SGF) was 1.57 and 1.39, and in simulated intestinal fluid (SIF) was 1.09 and 0.98, respectively. In SIF, about 78.6% astilbin remained after 4 h of incubation at 37 °C, while this value was 88.3% for neoastilbin. Most of the degraded astilbin and neoastilbin were isomerized into their cis-trans-isomer, namely neoisoastilbin and isoastilbin, respectively, and the decomposed parts were rare. For bioavailability comparison in a rat, an HPLC method for trace amounts of astilbin and neoastilbin determination in plasma was developed, and the pretreatment of plasma was optimized. A pharmacokinetic study showed that the absolute bioavailability of astilbin and neoastilbin in a rat showed no significant difference with values of 0.30% and 0.28%, respectively.

Sour cherry ( Prunus cerasus L.) is a very important fruit crop for producers as well as consumers. To obtain information on sour cherry fruit, we determined the sugar and organic acid composition and phenolic compound contents of twenty-one cultivars and genotypes of Prunus cerasus L. by HPLC quantification. Antioxidant capacity was determined by DPPH radical scavenging, reducing power (FRAP) and determination of substances reacting with Folin-Ciocalteu reagent (FCRS). The main organic acids in sour cherries were malic and malonic acids, and the main sugars were glucose and fructose. The highest sugar content was found in the "Lucyna" cultivar and the highest organic acids in "Paraszt Meggy" and "Suda Hardy". The richest in phenolic compounds were "Wieluń 17", "Sokówka Nowotomyska", "Grosenkirch" "Sokówka Nowotomyska" "Grosenkirch" (anthocyanins, flavanols and total phenolics), and "Meteor" (phenolic acids). Flavan 3-ols were not quantified in every cultivar. "Dradem, "Turgieniewka", "Wróble", and "Nana" contained the smallest amounts of phenolic compounds. Antioxidant capacity was highly correlated with phenolic compound composition. According to principal component analysis (PCA), it was concluded that cultivars whose harvest maturity was medium to late contained more flavonols and anthocyanins and were characterized by higher antioxidant capacity than those whose harvest maturity was classified as early or early to medium.

Grapevine red blotch disease (GRBD) is a recently identified viral disease that affects grapevines. GRBD has been shown to impact grapevine physiology and grape composition by altering specific ripening events. However, no studies have been reported on the impact of GRBD on wine composition and its sensory attributes. This study evaluated the impact of GRBD on wine primary and secondary metabolites, in addition to its sensory properties, when making wines from Cabernet Sauvignon and Merlot grapes during two seasons. Wines made with GRBD-impacted fruit were lower in ethanol content when compared to wines made with grapes from healthy grapevines. This was attributed to the lower total soluble sugar (TSS) levels of diseased grapes due to delayed ripening at harvest. GRBD impacted wine phenolic composition by decreasing anthocyanin concentrations and increasing flavonol concentrations in some instances. Additionally, proanthocyanidin concentrations were also consistently higher in GRBD wines compared to wines made from healthy fruit. Descriptive analysis demonstrated that GRBD can impact wine style by altering aroma, flavor, and mouthfeel attributes. However, the extent of GRBD impact on wine composition and sensory properties were site and season dependent.

This study investigates the effects of various drying methods applied to leaves of Cistus creticus L. on the contents of polyphenols and the composition of the volatile fraction. The following four drying methods were used: convection drying at a temperature of 40 °C (CD 40 °C), 50 °C (CD 50 °C), and 60 °C (CD 60 °C); vacuum-microwave (VMD 240 W); combined drying, involving convection pre-drying (50 °C) and vacuum-microwave (240 W) finish drying (CPD-VMFD) as well as freeze-drying (FD). Polyphenols in the dried leaves were determined using chromatography-photodiode detector-quadrupole/time of flight-mass spectrometry (UPLC-PDA-Q/TOF-MS). The contents of odoriferous substances in the dry material were determined by means of head space-solid phase microextraction (HS-SPME) with the use of a gas chromatograph (GC). Thirty-seven polyphenol components including 21 flavonols, eight flavan-3-ols, and eight hydrolyzed tannins in dry Pink Rock Rose material were found for the first time. The highest contents of polyphenols, totaling 2.8 g/100 g -1 dry matter (d.m.), were found in the samples subjected to the CPD/VMFD drying method. Pink Rock Rose subjected to this drying method was characterized by large quantities of odoriferous compounds, mainly eugenol, thymol, and carvacrol, which contribute to its antiseptic properties. By using CPD/VMFD methods, it is possible to obtain fine quality dry material from the leaves of C. creticus .

Although the intake of jack bean ( Canavalia ensiformis (L.) DC.), an underutilized tropical legume, can potentially decrease the risk of several chronic diseases, not much effort has been directed at profiling the polyphenolics contained therein. Hence, this work aimed to identify and quantify the dominant jack bean polyphenolics, which are believed to have antioxidant and other bioactivities. Four major compounds were detected and identified as kaempferol glycosides with three or four glycoside units. Their structures were established based on UV-visible, 1d, 2D NMR, and HR-ESI-MS analyses. Specifically, kaempferol 3-O-a-l-rhamnopyranosyl (1®6)- b-d-glucopyranosyl (1®2)-b-d-galactopyranosyl-7-O-[3-O- o -anisoyl]-a-l-rhamnopyranoside was detected for the first time, while the other three compounds have already been described in plants other than jack bean. This new compound was found to have a higher a-glucosidase inhibition activity compared to acarbose.

Raisins are dried grapes mostly obtained from cultivars of Vitis vinifera L. and are extensively consumed worldwide. They are rich in bioactive compounds such as polyphenols, which are associated with a broad range of health benefits. The aim of the present study was to compare the phenolic profiles of three different raisin varieties (Thompson seedless, Muscat, and sultanas). Total polyphenols (TPs) were evaluated by the Folin-Ciocalteu (F-C) assay and significant differences were observed among all raisin varieties. Furthermore, liquid chromatography coupled with electrospray ionization hybrid linear ion trap quadrupole-Orbitrap-mass spectrometry (LC/ESI-LTQ-Orbitrap-MS) was employed for the comprehensive identification of phenolic constituents. A total of 45 compounds were identified, including hydroxybenzoic and hydroxycinnamic acids, flavanoids, flavonoids, flavonols, flavones, and stilbenoids. The three varieties of raisins showed a similar phenolic profile, although the highest number of phenolic compounds was identified in Muscat raisins owing to the proanthocyanidins extracted from their seeds, while stilbenoids were not detected in the Thompson variety.

Green pruning residues (GPRs) and leaves from 16 red and white Vitis vinifera L. cultivars from Piedmont (Italy) were studied. The investigated samples were extracted by ultrasound-assisted extraction optimized by an experimental design, and quali- and quantitatively analyzed by HPLC-PDA-MS/MS. GPRs and leaves show a similar polyphenolic pattern, with quercetin 3- O -glucuronide, caftaric acid, and quercetin 3- O -glucoside as the main components, although in variable proportions. The HPLC results were related to the antioxidant activity, measured as total phenolic content and through DPPH and ABTS assays with similar results. Colorimetric in vitro assays, offline combined with HPLC-PDA analysis, determine which compounds contribute to the antioxidant activity in terms of radical scavenging abilities. Valorization of GPRs is a potential source of natural compounds that could be of interest in the health field, increasing their economic value together with a positive effect on the environment., Competing Interests: The authors declare no conflict of interest.

Climate models predict an increase in the frequency and duration of heatwaves with an increase in intensity already strongly evident worldwide. The aim of this work was to evaluate the effect of two heatwave-related parameters (intensity and duration) during berry ripening and identify a threshold for berry survival and flavonoid accumulation. A Doehlert experimental design was used to test three temperature intensities (maxima of 35, 46, and 54 °C) and five durations (3 to 39 h), with treatments applied at the bunch level shortly after véraison. Berry skin and seeds were analysed by liquid chromatography-triple quadrupole-mass spectrometry (LC-QqQ-MS) for flavonoids (flavonols, anthocyanins, free flavan-3-ols, and tannins). Berries exposed to 46 °C showed little difference compared to 35 °C. However, berries reaching temperatures around 54 °C were completely desiccated, and all flavonoids were significantly decreased except for skin flavonols on a per berry basis and seed tannins in most cases. Some compounds, such as dihydroxylated flavonoids and galloylated flavan-3-ols (free and polymerised), were in higher proportion in damaged berries suggesting they were less degraded or more synthesised upon heating. Overall, irreversible berry damages and substantial compositional changes were observed and the berry survival threshold was estimated at around 50-53 °C for mid-ripe Shiraz berries, regardless of the duration of exposure.

Halophytic grasses have been recently targeted as possible sources of nutraceutical and medicinal compounds. Nonetheless, few studies have been conducted on the phytochemistry and biological activities of metabolites produced by these plants. Among these, Spartina maritima (Curtis) Fernald, Spartina patens (Aiton.) Muhl., and Puccinellia maritima (Hudson) Parl. are three halophytic grasses whose chemical composition and bioactivities are unknown. The present work broadens the knowledge on the polyphenolic and chlorophyll composition of these species identifying for the first time hydroxycinnamic acids and their derivatives, flavones, flavonols, lignans, as well as chlorophylls and xantophylls. The extracts were particularly rich in caffeic and ferulic acids as well as in trihydroxymethoxyflavone, apigenin and tricin derivatives. Interestingly, several of the identified compounds are relevant from a medicinal and nutraceutical point of view putting in evidence the potential of these species. Thus, the antioxidant, anti-acetylcholinesterase, antibacterial, and antifungal activities of the polyphenolic extracts were assessed as well as the photophysical properties of the chlorophyll-rich extracts. The results, herein presented for the first time, reinforce the nutritional and the medicinal potential of these halophytic grasses.

Leaves of Vitis vinifera cv. Greco di Tufo, a precious waste made in the Campania Region (Italy), after vintage harvest, underwent reduction, lyophilization, and ultrasound-assisted maceration in ethanol. The alcoholic extract, as evidenced by a preliminary UHPLC-HR-MS analysis, showed a high metabolic complexity. Thus, the extract was fractionated, obtaining, among others, a fraction enriched in flavonol glycosides and glycuronides. Myricetin, quercetin, kaempferol, and isorhamnetin derivatives were tentatively identified based on their relative retention time and TOF-MS 2 data. As the localization of saccharidic moiety in glycuronide compounds proved to be difficult due to the lack of well-established fragmentation pattern and/or the absence of characteristic key fragments, to obtain useful MS information and to eliminate matrix effect redundancies, the isolation of the most abundant extract's compound was achieved. HR-MS/MS spectra of the compound, quercetin-3- O -glucuronide, allowed us to thoroughly rationalize its fragmentation pattern, and to unravel the main differences between MS/MS behavior of flavonol glycosides and glycuronides. Furthermore, cytotoxicity assessment on the (poly)phenol rich fraction and the pure isolated compound was carried out using central nervous system cell lines. The chemoprotective effect of both the (poly)phenol fraction and quercetin-3- O -glucuronide was evaluated., Competing Interests: The authors declare no conflicts of interest.

A series of 7-halogeno- (X = F, Cl, Br) and 7-methoxy-substituted acetylated 6-iodo-3- O -flavonol glycosides were prepared, and evaluated for inhibitory effect in vitro against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities. 7-Bromo-2-(4-chlorophenyl)-6-iodo-4 H -chromen-4-one-3- O -2,3,4,6 -O -tetraacetyl-β- d -glucopyranoside ( 2k ) and 7-bromo-6-iodo-2-(4-methoxyphenyl)-4 H -chromen-4-one-3- O -2,3,4,6- O -tetraacetyl-β- d -glucopyranoside ( 2l ) exhibited significant inhibitory effect against AChE activity when compared to the activity of the reference standard, donepezil. Compound 2k was found to be selective against AChE and to exhibit reduced inhibitory effect against BChE activity. 6-Iodo-7-methoxy-2-(4-methoxyphenyl)-4 H -chromen-4-one-3- O -2,3,4,6- O -tetraacetyl-β- d -glucopyranoside ( 2p ) was found to exhibit increased activity against BChE, more so than the activity of donepezil. The most active compounds were also evaluated for inhibitory effect against β-secretase activity and for potential radical scavenging activities. The experimental data were complemented with molecular docking (in silico) studies of the most active compounds into the active sites of these enzymes.

Plum pomace, an agro-industrial waste product has received attention due to the worldwide popularity of plums. During convection, the content of flavan-3-ols decrease, except drying at 90 °C, whereas the content of i.e., chlorogenic, 3- p - and 4- p -coumaroylquinic acids, quercetin rutinoside, and galactoside was observed to increase along with the increase in process temperature. The highest content of all identified polyphenols was found in plum pomace powders obtained using a combination of convective at 90 °C and microwave vacuum drying (MVD) at 120 W, whereas the highest retention of the group consisted of phenolic acids, flavonols, and anthocyanins was noted when CD 70 °C/MVD 120 W was used, pointing to a strong influence of the type of polyphenols on their changes caused by drying. The correlations between TEAC ABTS and the sum of flavonoids ( r = 0.634) and anthocyanins ( r = 0.704) were established. The multiple regression analysis showed that polyphenol content was more strongly affected by drying time than by maximum temperature, whereas antioxidant capacity was more influenced by maximum temperature of sample than by drying time.

The inhibition of recombinant CpLIP2 lipase/acyltransferase from Candida parapsiolosis was considered a key model for novel antifungal drug discovery and a potential therapeutic target for candidiasis. Lipases have identified recently as potent virulence factors in C. parapsilosis and some other yeasts. The inhibition effects of orlistat and four flavonols (galangin, kaempferol, quercetin and myricetin) characterized by an increasing degree of hydroxylation in B-ring, were investigated using ethyl oleate hydrolysis as the model reaction. Orlistat and kaempferol (14 µM) strongly inhibited CpLIP2 catalytic activity within 1 min of pre-incubation, by 90% and 80%, respectively. The relative potency of flavonols as inhibitors was: kaempferol > quercetin > myricetin > galangin. The results suggested that orlistat bound to the catalytic site while kaempferol interacted with W294 on the protein lid. A static mechanism of interactions between flavonols and CpLIP2 lipase was confirmed by fluorescence quenching analyses, indicating that the interactions were mainly driven by hydrophobic bonds and electrostatic forces. From the Lehrer equation, fractions of tryptophan accessibility to the quencher were evaluated, and a relationship with the calculated number of binding sites was suggested., Competing Interests: The authors declare no conflict of interest

Dihydromyricetin (DMY) has recently attracted increased interest due to its considerable health-promoting activities but there are few reports on its antibacterial activity and mechanism. In this paper, the activity and mechanisms of DMY from Ampelopsis grossedentata leaves against food-borne bacteria are investigated. Moreover, the effects of pH, thermal-processing, and metal ions on the antibacterial activity of DMY are also evaluated. The results show that DMY exhibits ideal antibacterial activity on five types of food-borne bacteria ( Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Salmonella paratyphi, and Pseudomonas aeruginosa ). The activities of DMY against bacteria are extremely sensitive to pH, thermal-processing, and metal ions. The morphology of the tested bacteria is changed and damaged more seriously with the exposure time of DMY. Furthermore, the results of the oxidative respiratory metabolism assay and the integrity of the cell membrane and wall tests revealed that the death of bacteria caused by DMY might be due to lysis of the cell wall, leakage of intracellular ingredients, and inhibition of the tricarboxylic acid cycle (TCA) pathway.

To explore the optimum conditions for the extraction of anthocyanins and flavonols from bog bilberry ( Vaccinium uliginosum L.) marc on a single-factor experimental basis, a response surface methodology was adopted for this intensive study. The extraction procedure was carried out in a Waring blender and followed an ultrasonic bath, and the natural antioxidant carnosic acid was added to inhibit oxidation. The optimum extraction conditions were as follows: a volume fraction of ethanol of 70%, an antioxidant content of 0.02% (the mass of sample) carnosic acid, a liquid-solid ratio of 16 mL/g, a homogenization time of 3 min, a reaction temperature of 55 °C, an ultrasound irradiation frequency of 80 kHz, an ultrasound irradiation power of 200 W, and an ultrasound irradiation time of 40 min. Satisfactory yields of anthocyanins (13.95 ± 0.37 mg/g) and flavonols (3.51 ± 0.16 mg/g) were obtained. The experimental results showed that the carnosic acid played an effective antioxidant role in the extraction process of anthocyanins and flavonols with a green and safety guarantee.

Carcinogenesis is the process whereby a normal cell is transformed into a neoplastic cell. This action involves several steps starting with initiation and followed by promotion and progression. Driving these stages are oxidative stress and inflammation, which in turn encompasses a myriad of aberrant gene expressions, both within the transforming cell population and the cells within the surrounding lesion. Chemoprevention of cancer with bioreactive foods or their extracted/purified components occurs via normalizing these inappropriate gene activities. Various foods/agents have been shown to affect different gene expressions. In this review, we discuss whereby the chemoprevention activities of the red beetroot itself may disrupt carcinogenesis and the activities of the water-soluble betalains extracted from the plant.

Inflammation is related to many diseases. Lindera akoensis Hayata was often used in folktherapy in Taiwan for inflammation. In this study, three new flavonol acyl glycosides, namelykaempferol-3-O--D-4",6"-di-(E)-p-coumaroylglucoside (1), 3"-(E)-p-coumaroylafzelin (2) and 40-Omethyl-2",4"-di-(E)-p-coumaroylquercitrin (3), and three components, 3-dodecyl-4-hydroxy-5-methyldihydrofuran-2-one (4), 2-acetoxyclovan-9-ol (5), (1,4,6)-trihydroxyeudesmane(6) that were isolated from the natural product for the first time were obtained along with 25 knowncompounds from L. akoensis. Their structures were determined by comprehensive spectroscopicanalyses (1D and 2D NMR, EI-, ESI- and HRESI-MS). The ability of 1 to decrease the LPS-stimulatedproduction of nitrite in RAW264.7 cell was evaluated, showing an IC 50 value of 36.3 ± 3.2 μM.This result supports the value of L. akoensis as a traditional medicine resource.

Streptococcus mutans ( S. mutans ) is the primary etiological agent of dental caries. The S. mutans enzyme sortase A (SrtA) is responsible for anchoring bacterial cell wall surface proteins involved in host cell attachment and biofilm formation. Thus, SrtA is an attractive target for inhibiting dental caries caused by S. mutans -associated acid fermentation. In this study, we observed that astilbin, a flavanone compound extracted from Rhizoma Smilacis Glabrae , has potent inhibitory activity against the S. mutans SrtA, with an IC 50 of 7.5 μg/mL. In addition, astilbin was proven to reduce the formation of biofilm while without affecting the growth of S. mutans . The results of a molecular dynamics simulation and a mutation analysis revealed that the Arg213, Leu111, and Leu116 of SrtA are important for the interaction between SrtA and astilbin. The results of this study demonstrate the potential of using astilbin as a nonbactericidal agent to modulate pathogenicity of S. mutans by inhibiting the activity of SrtA.

A hitherto unknown polyoxygenated flavonol robinobioside (gossypetin-3- O - β -d-robinobioside) was isolated from the leaves of Caesalpinia gilliesii along with thirteen known phenolic secondary metabolites. The isolated compounds were characterized using spectroscopic analysis, including 1D and 2D NMR and mass spectrometry (MS) analyses. The extract reduced the level of liver damage in CCl₄-induced liver injury in rats. A decrease of the liver biomarkers-aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and an increase of total antioxidant capacity (TAC) levels-were observed similar to the liver protecting drug silymarin. In addition, the extract showed promising activity against carrageenan-induced paw edema in rats and protected their stomachs against ethanol-induced gastric ulcers in a concentration dependent fashion. The observed activities could be attributed to the high content of antioxidant polyphenols. Our results suggest that the C. gilliesii has the capacity to scavenge free radicals and can protect against oxidative stress, and liver and stomach injury.

Six new flavonols ( 6a ⁻ f ) were synthesized with Claisen⁻Schmidt and Suzuki reactions and they were fully characterized by spectroscopic methods. In order to evaluate their antioxidant activities, their oxygen radical absorption capacity and ferric reducing antioxidant power were measured, along with their free radical scavenging activity against 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) and 2,2-diphenyl-1-picrylhydrazylradicals. In addition, their cytotoxicity on H9c2 cardiomyoblast cells was also assessed by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Compounds bearing the phenyl- N,N -dimethylamino group ( 6a , 6c , and 6e ) exhibited promising antioxidant potency and did not have any cytotoxic effect. After a consideration of these data, the oxidative transformation of the 6c compound was investigated in vitro with a chemical Fenton reaction and the identification of the formed oxidation products was performed by mass spectrometry. Two potential metabolites were detected. Based on these results, compound 6c can be a model compound for future developments. Overall, this work has proved the involvement of the phenyl- N,N -dimethylamino group in the antioxidant activity of flavonols., Competing Interests: The authors declare no conflict of interest.

To clarify the role of the B -ring in antioxidant flavonols, we performed a comparative study between galangin with a null B -ring and 3,5,7-trihydroxychromone without a B -ring using five spectrophotometric assays, namely, • O₂ - -scavenging, 1,1-diphenyl-2-picrylhydrazyl radical (DPPH • )-scavenging, 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide radical-scavenging, 2,2'-azino-bis(3-ethylbenzo-thiazoline-6-sulfonic acid) radical-scavenging, and Fe 3+ -reducing activity. The DPPH • -scavenging reaction products of these assays were further analyzed by ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UPLC-ESI-Q-TOF-MS/MS) technology. In the five spectrophotometric assays, galangin and 3,5,7-trihydroxychromone dose-dependently increased their radical-scavenging (or Fe 3+ -reducing) percentages. However, galangin always gave lower IC 50 values than those of 3,5,7-trihydroxychromone. In the UPLC-ESI-Q-TOF-MS/MS analysis, galangin yielded galangin-DPPH adduct MS peaks ( m / z 662, 434, 301, 227,196, and 151) and galangin-galangin dimer MS peaks ( m / z 538, 385, 268, 239, 211, 195, and 151). 3,5,7-Trihydroxychromone, however, only generated m / z 3,5,7-trihydroxychromone-DPPH adduct MS peaks ( m / z 586, 539, 227, 196, and 136). In conclusion, both galangin and 3,5,7-trihydroxychromone could similarly undergo multiple antioxidant pathways, including redox-dependent pathways (such as electron transfer (ET) and ET plus proton transfer (PT)) and a non-redox-dependent radical adduct formation (RAF) pathway; thus, the null B -ring could hardly change their antioxidant pathways. However, it did improve their antioxidant levels in these pathways. Such improvement of the B -ring toward an antioxidant flavonol is associated with its π-π conjugation, which can provide more resonance forms and bonding sites.

Pancreatic lipase, a key enzyme for lipid absorption, is one of the most important targets for the treatment of obesity, while natural compounds have recently attracted much interest as potential inhibitors of this enzyme. Here, in an attempt to find new effective agents, the methanolic extract from Moricandia arvensis (L.) DC. and its sub-extracts were investigated for their potential inhibitory activity. The ability to inhibit pancreatic lipase was verified through the in vitro evaluation of the prevention of p -nitrophenyl caprylate hydrolysis. The antioxidant activity was also verified by means of DPPH and β-carotene bleaching tests. Compositional profiling revealed that flavonoid glycosides were the main specialized metabolites present in the methanolic extract from the aerial parts of the plant with kaempferol and quercetin representing the two O -glycosylated aglycones. Kaempferol-3- O -β-(2″- O -glucosyl)-rutinoside and kaempferol-3- O - a- arabinosyl-7- O -rhamnoside were the most abundant flavonols. The crude methanolic extract and the dichloromethane and ethyl acetate sub-extracts showed a strong lipase inhibitory activity, with IC 50 values of 2.06 ± 0.02, 1.52 ± 0.02 and 1.31 ± 0.02 mg/mL, respectively. The best capacity to scavenge DPPH radical was detected for the ethyl acetate sub-extract (IC 50 = 171.9 ± 1.0 µg/mL), which was also effective in protecting linoleic acid from peroxidation (IC 50 = 35.69 ± 2.30 µg/mL). Obtained results support the hypothesis that M. arvensis can be a source of bioactive phytochemicals for the pharmacological inhibition of dietary lipids absorption.

Anthocyanins in red grape musts may evolve during the winemaking process and wine aging for several different reasons; colour stability and evolution is a complex process that may depend on grape variety, winemaking technology, fermentative yeast selection, co-pigmentation phenomena and polymerization. The condensation of flavanols with anthocyanins may occur either with the flavylium ion or with the hemiacetal formation in order to produce oligomers and polymers. The kinetics of the reaction are enhanced by the presence of metabolic acetaldehyde, promoting the formation of pyranoanthocyanin-type dimers or flavanol-ethyl-anthocyanin structures. The experimental design carried out using white must corrected with the addition of malvidin-3- O -glucoside and flavanols, suggests that non- Saccharomyces yeasts are able to provide increased levels of colour intensity and larger polymeric pigment ratios and polymerization indexes. The selection of non- Saccharomyces genera, in particular Lachancea thermotolerans and Schizosaccharomyces pombe in sequential fermentation, have provided experimental wines with increased fruity esters, as well as producing wines with potential pigment compositions, even though there is an important reduction of total anthocyanins.

Recently, there is a growing interest in fortifying food products with flavonoids to enhance health benefits. Naringenin, naringin, hesperetin, and dihydromyricetin are four typical flavonoids constituting a natural part of our diet. In the present work, they were fortified into a chia oil cookie model to evaluate their thermal stability during baking as well as their impact on antioxidant capacity and toxicant formation. Among them dihydromyricetin was the most unstable one (only 36.1% of which was left after baking at 180 °C for 20 min) and led to a loss of brightness in cookie. However, the antioxidant capacity of cookie fortified with dihydromyricetin was significantly enhanced compared with untreated cookie; on the other hand, dihydromyricetin showed the strongest effect to attenuate lipid and protein oxidation as well as decrease the level of fluorescent advanced glycation endproducts and carboxymethyl lysine in cookie model. Overall, among the four selected flavonoids, dihydromyricetin might be the most promising functional bakery additive enhancing the antioxidant capacity while decreasing the formation of toxicants.

Dipeptidyl peptidase IV (DPP-IV), a new target for the treatment of type 2 diabetes mellitus, degrades incretins such as glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide. DPP-IV inhibitors shorten the inactivation of GLP-1, permitting the incretin to stimulate insulin release, thereby combating hyperglycemia. In our ongoing search for new DPP-IV inhibitors from medicinal plants and foods, three flavonol glycosides ( 1 ⁻ 3 ) were isolated from the seeds of Lens culinaris Medikus (Fabaceae) and tested for their DPP-IV⁻inhibitory activity. We demonstrated for the first time, that compounds 1 ⁻ 3 inhibited DPP-IV activity in a concentration-dependent manner in our in vitro bioassay system. In addition, molecular docking experiments of compounds 1 ⁻ 3 within the binding pocket of DPP-IV were conducted. All investigated compounds readily fit within the active sites of DPP-IV, in low-energy conformations characterized by the flavone core structure having optimal electrostatic attractive interactions with the catalytic triad residues of DPP-IV.

Anthocyanin-flavanol pigments, formed during red wine fermentation and storage by condensation reactions between anthocyanins and flavanols (monomers, oligomers, and polymers), are one of the major groups of polyphenols in aged red wine. However, knowledge of their biological activities is lacking. This is probably due to the structural diversity and complexity of these molecules, which makes the large-scale separation and isolation of the individual compounds very difficult, thus restricting their further study. In this study, anthocyanins (i.e., malvidin-3-glucoside, cyanidin-3-glucoside, and peonidin-3-glucoside) and (⁻)-epicatechin were first isolated at a preparative scale by high-speed counter-current chromatography. The condensation reaction between each of the isolated anthocyanins and (⁻)-epicatechin, mediated by acetaldehyde, was conducted in model wine solutions to obtain ethyl-linked anthocyanin-flavanol pigments. The effects of pH, molar ratio, and temperature on the reaction rate were investigated, and the reaction conditions of pH 1.7, molar ratio 1:6:10 (anthocyanin/(⁻)-epicatechin/acetaldehyde), and reaction temperature of 35 °C were identified as optimal for conversion of anthocyanins to ethyl-linked anthocyanin-flavanol pigments. Six ethyl-linked anthocyanin-flavanol pigments were isolated in larger quantities and collected under optimal reaction conditions, and their chemical structures were identified by HPLC-QTOF-MS and ECD analyses. Furthermore, DPPH, ABTS, and FRAP assays indicate that ethyl-linked anthocyanin-flavanol pigments show stronger antioxidant activities than their precursor anthocyanins.

Myrcia bella Cambess., Myrcia fallax (Rich.) DC. and Myrcia guianensis (Aubl.) DC. (Myrtaceae) are trees found in Brazilian Cerrado. They have been widely used in folk medicine for the treatment of gastrointestinal disorders, hemorrhagic and infectious diseases. Few reports have been found in the literature connecting their phenolic composition and biological activities. In this regard, we have profiled the main phenolic constituents of Myrcia spp. leaves extracts by ESI(−)Q-TOF-MS. The main constituents found were ellagic acid ( M. bella ), galloyl glucose isomers ( M. guianensis ) and hexahydroxydiphenic (HHDP) acid derivatives ( M. fallax ). In addition, quercetin and myricetin derivatives were also found in all Myrcia spp. extracts. The most promising antioxidant activity, measured by 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity, was found for M. fallax extracts (EC 50 8.61 ± 0.22 µg·mL −1 ), being slightly less active than quercetin and gallic acid (EC 50 2.96 ± 0.17 and 2.03 ± 0.02 µg·mL −1 , respectively). For in vitro antiproliferative activity, M. guianensis showed good activity against leukemia (K562 TGI = 7.45 µg·mL −1 ). The best antimicrobial activity was observed for M. bella and M. fallax to Escherichia coli (300 and 250 µg·mL −1 , respectively). In conclusion, the activities found are closely related to the phenolic composition of these plants.

Tea ( Camellia sinensis ) is an important crop, and its leaves are used to make the most widely consumed beverage, aside from water. People have been using leaves from tea plants to make teas for a long time. However, less attention has been paid to the flowers of tea plants, which is a waste of an abundant resource. In the past 15 years, researchers have attempted to discover, identify, and evaluate functional molecules from tea flowers, and have made insightful and useful discoveries. Here, we summarize the recent investigations into these functional molecules in tea flowers, including functional molecules similar to those in tea leaves, as well as the preponderant functional molecules in tea flowers. Tea flowers contain representative metabolites similar to those of tea leaves, such as catechins, flavonols, caffeine, and amino acids. The preponderant functional molecules in tea flowers include saponins, polysaccharides, aromatic compounds, spermidine derivatives, and functional proteins. We also review the safety and biological functions of tea flowers. Tea flower extracts are proposed to be of no toxicological concern based on evidence from the evaluation of mutagenicity, and acute and subchronic toxicity in rats. The presence of many functional metabolites in tea flowers indicates that tea flowers possess diverse biological functions, which are mostly related to catechins, polysaccharides, and saponins. Finally, we discuss the potential for, and challenges facing, future applications of tea flowers as a second resource from tea plants., Competing Interests: The authors declare no conflict of interest.

Scutellaria baicalensis Georgi is a traditional Chinese herbal medicine mainly containing flavonoids that contribute to its bioactivities. In this study, the distributions and dynamic changes of flavonoid levels in various organs of S. baicalensis at different development stages were investigated by UHPLC-QTOF-MS/MS and HPLC-DAD methods. The results indicated that the metabolic profiles of S. baicalensis changed with growth and development. During the initial germination stage, the seeds mainly contained flavonols. With growth, the main kinds of flavonoids in S. baicalensi s changed from flavonols to flavanones and flavones. The results also revealed that the accumulation of flavonoids in S. baicalensis is organ-specific. The flavones without 4'-OH groups mainly accumulate in the root and the flavanones mainly accumulate in aerial organs. Dynamic accumulation analysis showed that the main flavonoids in the root of S. baicalensis accumulated rapidly before the full-bloom stage, then changed to a small extent. The results suggested the proper harvest time for the aerial parts was at the initial stage of reproductive growth and the flower buds should be collected before flowering. This study deepening the knowledge of S. baicalensis should provide valuable information for guiding the scientific cultivation of this plant and the development and utilization of S. baicalensis ., Competing Interests: The authors declare no conflict of interest.

Anthocyanins and flavones are important pigments responsible for the coloration of fruits. Mulberry fruit is rich in anthocyanins and flavonols, which have multiple uses in traditional Chinese medicine. The antinociceptive and antibacterial activities of total flavonoids (TF) from black mulberry (MnTF, TF of Morus nigra ) and non-black mulberry (MmTF, TF of Morus mongolica ; and MazTF, TF of Morus alba 'Zhenzhubai') fruits were studied. MnTF was rich in anthocyanins (11.3 mg/g) and flavonols (0.7 mg/g) identified by ultra-performance liquid chromatography-tunable ultraviolet/mass single-quadrupole detection (UPLC-TUV/QDa). Comparatively, MmTF and MazTF had low flavonol contents and MazTF had no anthocyanins. MnTF showed significantly higher antinociceptive and antibacterial activities toward Escherichia coli , Pseudomonas aeruginosa and Staphylococcus aureus than MmTF and MazTF. MnTF inhibited the expression of interleukin 6 (IL-6), inducible nitric oxide synthase (iNOS), phospho-p65 (p-p65) and phospho-IκBα (p-IκBα), and increased interleukin 10 (IL-10). Additionally, mice tests showed that cyanidin-3- O -glucoside (C3G), rutin (Ru) and isoquercetin (IQ) were the main active ingredients in the antinociceptive process. Stronger antinociceptive effect of MnTF was correlated with its high content of anthocyanins and flavonols and its inhibitory effects on proinflammatory cytokines, iNOS and nuclear factor-κB (NF-κB) pathway-related proteins., Competing Interests: The authors declare no conflict of interest.

This work provides an optimized extraction approach intended to maximize the recovery of dihydromyricetin (DHM) from Chinese vine tea ( Ampelopsis grossedentata ) leaves. The presented work adopts a Box-Behnken design as a response surface methodology to understand the role and influence of specific extraction parameters including: time, temperature, and solvent composition/ethanol (%) on DHM final yields. Initially, single factor experiments were used to delineate the role of above factors (temperature, time, and solvent composition) before proceeding with three factors-three levels Box-Behnken design with 17 separate runs to assess the effect of multifactorial treatments on DHM recovery rates. The collected data shows that independent variables (solvent composition, time, and temperature) can significantly affect DHM recovery rates with maximum yields resulting from a combined 60 °C, 60% aqueous ethanol, and 180 min treatment. From the empirical point of view, the above optimized extraction protocol can substantially enhance processing and profitability margins with a minimum need of interventions or associated costs., Competing Interests: The authors declare no conflict of interest.