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Seven new glycosides (1 − 7) with galloyl groups and two known kaempferol glycosides (8 and 9) were obtained from the overground parts of Balakata baccata. The structures of the new compounds were determined by comprehensive spectroscopic analyses. The rarely seen allene moiety in compounds 6 and 7 were described by detailed analysis of 1D and 2D NMR data. The antineuroinflammatory effect of all the isolates was assessed through inhibiting nitric oxide (NO) production in lipopolysaccharide (LPS)-induced BV-2 microglial cells. Compounds 1, 2, 6, and 7 showed potent inhibitory activities with IC50 values of 25.7, 17.2, 15.5 and 24.4 μM, respectively, compared with the positive control minocycline (IC50 = 16.1 μM). [ABSTRACT FROM AUTHOR]

Glycosyltransferases (GTs) are pivotal enzymes in the biosynthesis of various biological molecules. This study focuses on the scale-up, expression, and purification of a plant flavonol-specific 3-O glucosyltransferase (Cp3GT), a key enzyme from Citrus paradisi, for structural analysis and modeling. The challenges associated with recombinant protein production in Pichia pastoris, such as proteolytic degradation, were addressed through the optimization of culture conditions and purification processes. The purification strategy employed affinity, anion exchange, and size exclusion chromatography, leading to greater than 95% homogeneity for Cp3GT. In silico modeling, using D-I-TASSER and COFACTOR integrated with the AlphaFold2 pipeline, provided insights into the structural dynamics of Cp3GT and its ligand binding sites, offering predictions for enzyme–substrate interactions. These models were compared to experimentally derived structures, enhancing understanding of the enzyme's functional mechanisms. The findings present a comprehensive approach to produce a highly purified Cp3GT which is suitable for crystallographic studies and to shed light on the structural basis of flavonol specificity in plant GTs. The significant implications of these results for synthetic biology and enzyme engineering in pharmaceutical applications are also considered. [ABSTRACT FROM AUTHOR]

Peumus boldus , a tree native to Chile, is extensively used for medicinal purposes due to its richness in alkaloids and antioxidant polyphenols. A species of galling insect, Dasineura sp. induces structural and chemical changes on P. boldus stems while its galls are established and developed. Taking into account the antioxidant properties of P. boldus polyphenols, it would be expected that Dasineura sp. induces changes in the accumulation sites, chemical profile, and antioxidant activity of the P. boldus stem polyphenols, related to different reactive oxygen species (ROS) production levels during gall development. Dasineura sp. induces changes in the accumulation sites of total polyphenols, flavonols, and lignin, redirecting their accumulation toward the sites of greatest production of H2O2 and O2.−. Although changes in total polyphenol content would be expected, this did not vary significantly between non-galled and galled stems. However, the galling insect induced changes in the profile and concentration of soluble polyphenols, leading to the gall extracts' antioxidant capacity decreasing significantly during the maturation and senescence stages. Additionally, during the maturation stage, lignin deposition increases in the more peripheral gall tissues, which also contributes to ROS dissipation. The differences in the different gall developmental stages' antioxidant activity could be related to the identity and concentration of phenolic compounds in each gall extract, rather than to the total phenol content. Regardless of the mechanisms involved, the dissipation of the ROS generated by Dasineura sp. activity occurs, restoring the redox balance in galls and guaranteeing the success of the inducer. [ABSTRACT FROM AUTHOR]

Diarrhea is among the leading global causes of child morbidity and death worldwide (WHO, 2018), and this disease also kills 1.8 million people yearly. Contaminated food and water resources are the most common causes of diarrhea. 1 out of 10 people still doesn't have improved water sources, leading to people being infected by diarrhea, WHO, 2019. Moreover, this study is aligned with SDG number 3, or good health and well-being, as this study was done to determine the content and the microbial inhibition of Serpentina leaves syrup against Escherichia coli causing diarrhea. Tests were: I. Phytochemical analysis (Alkaloids, Flavonoids, and Tannins) II. Disk Diffusion method on 4 different concentrations. III. Shelf life determination. IV. One-way ANOVA. For phytochemical analyses, serpentina leaves showed chemicals that can inhibit E. coli causing diarrhea, with implications such as pharmacological and microbial inhibition effects. Specifically, it showed the presence of alkaloids, flavonols, a subclass of flavonoids, and tannins. The disk diffusion method showed that serpentina leaves syrup has intermediate to susceptible efficiency against E. coli causing diarrhea (50% to 70% interprets that it's intermediate effective while 75% and above interprets that it's susceptible effective) as results showed that it is 65% effective with 25% and 50% concentrations, 70% effective with 75%concentration, and 80% effective with 100% concentration, which clearly states that the syrup can be used as a potent remedy against diarrhea due to its effective inhibition. After the shelflife determination, it was observed that serpentina syrup could last for up to 2 weeks, as the syrup changes in color on the 13th day and both in color and appearance on the 14th day. Following the one-way ANOVA, the results indicated a significant difference between the 4 concentrations and the positive control group, with F (73.344) > 3.48. [ABSTRACT FROM AUTHOR]

Myricetin is a flavonol with high antioxidant properties. In this research, the fluorescence emission of myricetin powder and its solutions in different solvents were measured and analyzed by comparing with the results of calculations. Comparison of the calculated and measured characteristic wavelengths allowed the identification of all the spectral features in the fluorescence spectra of myricetin powder and solutions with different concentrations. The computation was based on modeling the process of the excited state intermolecular proton transfer, which predicts the formation of tautomeric forms of the flavonol molecule. Characteristic emission wavelengths were obtained using TDDFT/M06-2X/6-31++G(d,p). To understand the influence of the hydroxyl groups in the B-ring of the flavonol molecule on the emission spectrum, we also compared the fluorescence spectra of myricetin with those of kaempferol and quercetin. Moreover, based on the analysis of the changes in the shape of the FL spectra with the concentration of the solution, a criterion for the complete dissolution of the flavonol powders was established, which is important for bioavailability of flavonoids. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate how introducing halophilic sulfur-oxidizing bacteria (SOB) Halothiobacillus halophilus to the growth substrate affects the physiological and biochemical responses of the halophyte Tripolium pannonicum (also known as sea aster or seashore aster) under salt and cadmium stress conditions. This study assessed the plant's response to these stressors and bacterial inoculation by analyzing various factors including the accumulation of elements such as sodium (Na), chloride (Cl), cadmium (Cd) and sulfur (S); growth parameters; levels of photosynthetic pigments, proline and phenolic compounds; the formation of malondialdehyde (MDA); and the plant's potential to scavenge 2,2-Diphenyl-1-picrylhydrazyl (DPPH). The results revealed that bacterial inoculation was effective in mitigating the deleterious effect of cadmium stress on some growth criteria. For instance, stem length was 2-hold higher, the growth tolerance index was 3-fold higher and there was a 20% increase in the content of photosynthetic pigments compared to non-inoculated plants. Furthermore, the SOB contributed to enhancing cadmium tolerance in Tripolium pannonicum by increasing the availability of sulfur in the plant's leaves, which led to the maintenance of an appropriate, about 2-fold-higher level of phenolic compounds (phenylpropanoids and flavonols), as well as chloride ions. The level of MDA decreased after bacterial application in all experimental variants except when both salt and cadmium stress were present. These findings provide novel insights into how halophytes respond to abiotic stress following inoculation of the growth medium with sulfur-oxidizing bacteria. The data suggest that inoculating the substrate with SOB has a beneficial effect on T. pannonicum's tolerance to cadmium stress. [ABSTRACT FROM AUTHOR]

Background: Major depressive disorder (MDD) is a significant cause of disability globally and an emerging body of evidence suggests that dietary components, including flavonoids, may impact depression‐related biochemical pathways. Further research that characterizes dietary intake of flavonoids in diverse population groups, including people with MDD and explores the relationship between flavonoid intake and depression is needed. This study aimed to determine dietary flavonoid and subclass intake and assess the association with depressive symptomatology in a sample of adults with and without MDD. Methodology: Participants with and without MDD (determined using DSM 5) completed the Depression, Anxiety, and Stress Scale‐21 (DASS‐21). Diet history interviews were analyzed using PhenolExplorer to quantify flavonoid subclasses (flavan‐3‐ols, flavonols, anthocyanins, flavones, flavanones, isoflavones), and total flavonoid intake. Independent t‐tests and linear regression, adjusting for age, sex, and BMI were performed. Results: Participants (n = 93; 75% female) had a mean age of 26.0 ± 8.2 years. Participants with MDD had significantly higher DASS‐depression scores (n = 44; DASS‐depression 27.3 ± 9.8) compared to participants without MDD (n = 49; DASS‐depression 3.1 ± 4.4; p <.001). Intakes of total flavonoids and subclasses were similar between groups, except for anthocyanins where participants with MDD reported lower intakes of anthocyanins compared to participants without MDD (median intake: 0.08 mg/day and 11.6 mg/day, respectively; p =.02). In the total sample, higher anthocyanin intake was associated with lower DASS‐depression score (B = ‐4.1; SE = 1.8; 95% CI [−7.7, −0.4]; p =.029). Conclusion: Intake of total flavonoids and most subclasses were similar between people with and without MDD. However, a dietary deficit of anthocyanins (found in purple/red fruits and vegetables) was evident in participants with MDD, and higher anthocyanin intake was associated with lower depressive symptomatology in the total sample. Further research in larger samples is warranted to explore if the documented association is independent of MDD status. [ABSTRACT FROM AUTHOR]

This document is a summary of a special issue of the journal Plants, which focuses on the responses of plants to visible and ultraviolet radiation. The twelve manuscripts included in the special issue cover various aspects of how different wavelengths of light, particularly UV wavelengths, can affect plant organisms. The studies explore topics such as the impact of UV-B radiation on fruit metabolism, the effects of UV-B on pollen viability, the hormonal regulation in different varieties of quinoa exposed to UV-B, and the modulation of bioactive compounds in plants using different light conditions. The findings of these studies have implications for agriculture, the food industry, and human health. [Extracted from the article]

The storage period of tea is a major factor affecting tea quality. However, the effect of storage years on the non-volatile major functional components and quality of green tea remains largely unknown. In this study, a comparative analysis of organic green teas with varying storage years (1–16 years) was conducted by quantifying 47 functional components, using electronic tongue and chromatic aberration technology, alongside an evaluation of antioxidative capacity. The results indicated a significant negative correlation between the storage years and levels of tea polyphenols, total amino acids, soluble sugars, two phenolic acids, four flavonols, three tea pigments, umami amino acids, and sweet amino acids. The multivariate statistical analysis revealed that 10 functional components were identified as effective in distinguishing organic green teas with different storage years. Electronic tongue technology categorized organic green teas with different storage years into three classes. The backpropagation neural network (BPNN) analysis demonstrated that the classification predictive ability of the model based on the electronic tongue was superior to the one based on color difference values and 10 functional components. The combined analysis of antioxidative activity and functional components suggested that organic green teas with shorter storage periods exhibited stronger abilities to suppress superoxide anion radicals and hydroxyl radicals and reduce iron ions due to the higher content of eight components. Long-term-stored organic green teas, with a higher content of substances like L-serine and theabrownins, demonstrated stronger antioxidative capabilities in clearing both lipid-soluble and water-soluble free radicals. Therefore, this study provided a theoretical basis for the quality assessment of green tea and prediction of green tea storage periods. [ABSTRACT FROM AUTHOR]

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The global incidence of recurrent aphthous stomatitis in 2018 reached 5–66 % of the population, while in Indonesia 8 %. Moreover, the prevalence of oral mucosal fibrosis and recurrent aphthous stomatitis among male doctors and nurses in China was 21.24 % and 24.27 %, respectively. Our previous study has shown that the ethanol extract of Kaempferia galanga L. rhizome (EKGR) revealed an accelerated wound-healing effect in the oral mucosa ulcer of Wistar rats. This study aims to explore the effects of EKGR on the expression of NF-kappaB-p65 and COX-2 in the tongue tissue of male Wistar rats by Western blot analysis and immunohistochemistry technique, its safety towards the vascular membrane of the egg chorioallantoic membrane, and its single-dose application on the skin of male rabbits. The rats were randomly assigned into 7 groups: the normal control; the negative control; the positive control (treated with triamcinolone acetonide); and 4 treatment groups of EKGR (0.5 %; 1 %; 2 %; 4 %). Western blot and immunohistochemistry methods were used to measure the expression of NF-kappaB-p65 and COX-2. The hen's egg test-chorioallantoic membrane assay was employed to predict the safety of EKGR towards the vascular membrane. Moreover, the effect of 200 mg/kg BW EKGR application on the dorsal skin of male albino rabbits was also evaluated. EKGR inhibits the expression of NF-kappaB-p65 and COX-2 as proven by WB and IHC results. In the HET-CAM assay, all concentrations of EKGR do not induce irritation responses, which elicits the safety of EKGR. The administration of EKGR causes mild irritation to the dorsal skin of male rabbits but does not induce erythema and edema, no significant changes in BW, no toxic effects on organ macroscopic examination or histopathology, and does not induce abnormalities in the hematological profile of male albino rabbits. EKGR has confirmed its anti-inflammatory activity by suppressing the expression of COX-2 and NF-kappaB-p65 in the oral mucosa ulcer of Wistar rats. EKGR is safe as it does not exhibit irritating potential and harmful effects.

The main purpose of the present study was to determine the effect of associating an optimized ultrasound-assisted extraction (UAE) protocol with enzyme-assisted extraction (EAE) in aqueous media, using the dried berries of Hippophae rhamnoides L. (sea buckthorn) as plant material. A specialized software was used for the determination of potential optimal extraction parameters, leading to the development of four optimized extracts with different characteristics (UAE ± EAE). For these extracts, buffered or non-buffered solutions have been used, with the aim to determine the influence of adjustable pH on extractability. As enzymatic solution, a pectinase, cellulase, and hemicellulase mix (2:1:1) has been applied, acting as pre-treatment for the optimized protocol. The highest extractive yields have been identified for non-buffered extracts, and the E-UAE combination obtained extracts with the highest overall in vitro antioxidant activity. The HPLC-MSn analysis demonstrated a rich composition in different types of isorhamnetin-O-glycosides, as well as some quercetin-O-glycosides, showing a high recovery of specific flavonol-type polyphenolic species. Moreover, we have tentatively identified two flavanols (i.e., catechin and epigallocatechin) and one flavone derivative (i.e., luteolin).

Polyphenolic compounds are a class of phytonutrients that play important roles in plants and contribute to human health when incorporated into our diet through fruit consumption. A large proportion occur as glycoconjugates but the enzymes responsible for their glycosylation are poorly characterized. Here, we report the biochemical and structural characterization of two glycosyltransferases from sweet cherry named PaUGT1 and PaUGT2. Both are promiscuous glucosyltransferases active on diverse anthocyanidins and flavonols, as well as phenolic acids in the case of PaUGT1. They also exhibit weaker galactosyltransferase activity. The expression of the gene encoding PaUGT1, the most active of the two proteins, follows anthocyanin accumulation during fruit ripening, suggesting that this enzyme is the primary glycosyltransferase involved in flavonoid glycosylation in sweet cherry. It can potentially be used to synthesize diverse glycoconjugates of flavonoids for integration into bioactive formulations, and for generating new fruit cultivars with enhanced health-promoting properties using breeding methods.

We aimed to study the obtention of valuable phenolic compounds from tissue by-products of agro-industrial processing of apple (GS) and strawberry (RF) using green solvents and Soxhlet extraction methodology. The effects of solvent type [water (W); 80% ethanol, (EtOH)] and extraction ratio (1:10, 1:20, 1:30, and 1:40 p/v) were determined on total phenolic content (TPC), antioxidant capacity (DPPH), and the profile of phenolic compounds of the GS and RF extracts. The solvent type and the extraction ratio significantly affected TPC and DPPH of GS and RF extracts. Extraction with EtOH and 1:40 ratio produced the highest yields, obtaining an RF extract with 15.8 g GAE/Kg (TPC) and 19 mmol TE/Kg (DPPH). The tetra-galloyl glucose isomer and agrimoniin (0.8-0.4 g/Kg) were the main RF phenolic compounds of the eight identified. GS extract, obtained with EtOH and 1:40 ratio, had 11.9 g GAE/Kg (TPC) and 20.5 mmol TE/Kg (DPPH), having quercetin -3-o-glucuronide (0.43 g/Kg) the highest concentration among the eight phenolic compounds identified. The results highlight the potential of green solvents to obtain valuable compounds from low-cost raw materials, like the high-antioxidant capacity phenolic compound extracts obtained herein. Highlights: • Valuable bioactive compounds can be extracted from strawberry and apple agro-industrial waste. • Extraction parameters affected phenolic compound profile and antioxidant capacity. • Apple and strawberry by-products are low-cost sources of hydrolysable tannins and flavonols. • Green solvents used for biowaste valorisation can help in circular economy transformation.

The growth of antibiotic resistance to antifungal drugs contributes to the search for new ways to enhance their effectiveness and reduce toxicity. The undeniable advantage of polyene macrolide antibiotic amphotericin B (AmB) which ensures low pathogen resistance is its mechanism of action related to the formation of transmembrane pores in target lipid membranes. Here, we investigated the effects of plant flavones, chrysin, wogonin, baicalein, apigenin, scutellarein, luteolin, morin and fisetin on the pore-forming activity of AmB in the sterol-enriched membranes by electrophysiological assays. Сhrysin, wogonin, baicalein, apigenin, scutellarein, and luteolin were shown to decrease the AmB pore-forming activity in the bilayers composed of palmitoyloleylphosphocholine independently of their sterol composition. Morin and fisetin led to the increase and decrease in the AmB pore-forming activity in the ergosterol- and cholesterol-containing bilayers respectively. Differential scanning microcalorimetry of the gel-to-liquid crystalline phase transition of membrane forming lipids, molecular dynamics simulations, and absorbance spectroscopy revealed the possibility of direct interactions between AmB and some flavones in the water and/or in the lipid bilayer. The influence of these interactions on the antibiotic partitioning between aqueous solution and membrane and/or its transition between different states in the bilayer was discussed.

ScopeWhile cocoa flavanol (CF) consumption improves cardiovascular risk biomarkers, molecular mechanisms underlying their protective effects are not understood.ObjectiveTo investigate nutri(epi)genomic effects of CF and identify regulatory networks potential mediating vascular health benefits.Methods and resultsTwenty healthy middle-aged men consume CF (bi-daily 450 mg) or control drinks for 1 month. Microarray analysis identifies 2235 differentially expressed genes (DEG) involved in processes regulating immune response, cell adhesion, or cytoskeleton organization. Distinct patterns of DEG correlate with CF-related changes in endothelial function, arterial stiffness, and blood pressure. DEG profile negatively correlates with expression profiles of cardiovascular disease patients. CF modulated DNA methylation profile of genes implicates in cell adhesion, actin cytoskeleton organization, or cell signaling. In silico docking analyses indicate that CF metabolites have the potential of binding to cell signaling proteins and transcription factors. Incubation of plasma obtained after CF consumption decrease monocyte to endothelial adhesion and dose-dependently increase nitric oxide-dependent chemotaxis of circulating angiogenic cells further validating the biological functions of CF metabolites.ConclusionIn healthy humans, CF consumption may mediate vascular protective effects by modulating gene expression and DNA methylation towards a cardiovascular protective effect, in agreement with clinical results, by preserving integrity of immunological-endothelial barrier functions.

Polyphenols are responsible for wine colour and astringency, and, as antioxidants, they also have beneficial health properties. In this work, we developed a robust full-scan high-resolution mass spectrometry method for the quantification of 90 phenolic compounds in wine samples (either red, rosé, or white wine), using a UHPLC-OrbitrapTM system. With this method, we could conduct a detailed analysis of phenolic compounds in red, rosé, and white wines with great selectivity due to sub-ppm mass accuracy. Moreover, accessing the full-scan spectrum enabled us to monitor all the other compounds detected in the sample, facilitating the adaptability of this method to new phenolic compounds if needed.

Ready-to-eat fresh-cut apples deteriorate rapidly in visual quality due to browning, leading to consumer rejection and food waste. In addition, minimal processing induces tissue damage and releases organic substrates, which could accelerate microbial growth. The present study evaluated the impacts of alkaline and acidic electrolyzed water (AIEW and AEW) on natural microbial load and bioactive compounds on fresh-cut ‘Granny Smith’ apples. Minimally processed apples were dipped for 10 min in AEW and AIEW solutions (200 mg L−1), packed in PET containers with lids, and stored for 9 days at 2 °C. Overall, fresh-cut ‘Granny Smith’ apples treated with AEW significantly (p < 0.05) maintained higher total phenolics (99.4 ± 4.3 mg GAE L−1) and antioxidant capacity (79.5 ± 6.5 mg VitCE L−1) compared to the non-treated control samples (42.9 ± 5.1 mg GAE L−1, 31.9 ± 8.1 mg GAE L−1, respectively). Similarly, pretreatment with AIEW maintained the highest total flavonol content (55.71 ± 1.5 mg QE L−1) compared to the AEW-treated samples and control (p < 0.05). AEW pretreatment led to a 2 Log and a 1 Log decline in total aerobic mesophilic bacteria and yeasts and moulds, respectively. The best visual quality and highest visual score was maintained by AEW and followed by AIEW. This study further demonstrated the effectiveness of electrolyzed water treatments in minimizing browning and enhancing bioactive compounds in fresh-cut ‘Granny Smith’ apples.

Sulla coronaria is indigenous to the Mediterranean region. It is grown as fodder in southern Italy because it contains various secondary metabolites with beneficial activities on animals. Recently, its potential use in cosmeceutical treatments for skin problems was reported. In this scenario, to contribute to a possible cosmeceutical application, we characterized the phytochemical profile of Sulla coronaria flowers’ hydroalcoholic extract by HPLC-DAD, Folin-Ciocalteu, Aluminum Chloride methods, DPPH assay, and, for the first time, we evaluated the antioxidant and anti-inflammatory activities on dermal fibroblasts. The phytochemical analysis confirmed the significant content of phenolic compounds (TPC 69.8 ± 0.6 mg GAE/g extract, TFC 15.07 mg CE/g extract) and the remarkable presence of rutin, quercetin, and isorhamnetin derivatives that give to the phytocomplex a good antioxidant activity as highlighted by the DPPH assay (IC50 of 8.04 ± 0.5 µg/mL). Through the reduction in NO• and ROS levels in human dermal fibroblasts, the biological tests demonstrated both the safety of the extract and its ability to counteract the inflammatory state generated by Interleukin-1β exposure. Our findings indicate that the antioxidant activities of the phytocomplex are strictly related to the anti-inflammatory action of the Sulla coronaria flowers extract, confirming that this plant could be a valuable source of bioactive molecules for cosmeceutical and nutraceutical applications.

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.

We aimed to investigate the combined effects of aerobic exercise (EXE) and cocoa flavanol (COCOA) supplementation on performance, metabolic parameters, and inflammatory and lipid profiles in obese insulin-resistant rats. Therefore, 32 male Wistar rats (230–250 g) were fed a high-fat diet and a fructose-rich beverage for 30 days to induce insulin resistance. Next, the rats were randomized into four groups, orally administered placebo solution or COCOA supplementation (45 mg·kg−1), and either remained sedentary or were subjected to EXE on a treadmill at 60% peak velocity for 30 min, for 8 weeks. Blood samples and peripheral tissues were collected and processed to analyze metabolic and inflammatory parameters, lipid profiles, and morphological parameters. Supplementation with COCOA and EXE improved physical performance and attenuated body mass gain, adipose index, and adipocyte area. When analyzed as individual interventions, supplementation with COCOA and EXE improved glucose intolerance and the lipid profile reduced the concentrations of leptin, glucose, and insulin, and reduced homeostasis assessment index (all effects were p <.001 for both interventions), while ameliorated some inflammatory mediators in examined tissues. In skeletal muscles, both COCOA supplementation and EXE increased the expression of glucose transporter (p <.001 and p <.001), and combined intervention showed additive effects (p <.001 vs. COCOA alone or EXE alone). Thus, combining COCOA with EXE represents an effective nonpharmacological strategy to treat insulin resistance; it could prevent Type 2 diabetes mellitus by improving physical performance, glucose metabolism, neuroendocrine control, and lipid and inflammatory mediators in the liver, pancreas, adipose tissue, and skeletal muscle in obese male insulin-resistant rats. [ABSTRACT FROM AUTHOR]

Using updated National Health and Nutrition Examination Survey (NHANES) follow-up data, and a large nationwide representative sample of adult U.S. citizens, the aim of this study was to explore the relationship between dietary flavonol intake, all-cause and cause-specific mortality risks. In this prospective cohort study based on NHANES (2007–2008, 2009–2010, and 2017–2018), a total of 11,679 participants aged 20 years and above were evaluated. The amount and type of food taken during a 24-h dietary recall were used to estimate dietary flavonol intake, which includes total flavonol, isorhamnetin, kaempferol, myricetin, and quercetin. Each analysis of the weighted data was dealt with in accordance with the NHANES reporting requirements' intricate stratification design. The Cox proportional risk regression model or Fine and Gray competing risks regression model were applied to evaluate all-cause and cause-specific mortality risks, respectively. The follow-up period was calculated using the time interval between the baseline and the death date or December 31, 2019 (whichever occurs first). Each data analysis was performed between October 1, 2023, and October 22, 2023. Dietary flavonol intake included total flavonol, isorhamnetin, kaempferol, myricetin, and quercetin. Up to December 31, 2019, National Death Index (NDI) mortality data were used to calculate mortality from all causes as well as cause-specific causes. A total of 11,679 individuals, which represents 44,189,487 U.S. non-hospitalized citizens, were included in the study; of these participants, 49.78% were male (n = 5816), 50.22% were female (n = 5, 863); 47.56% were Non-Hispanic White (n = 5554), 18.91% were Non-Hispanic Black (n = 2209), 16.23% were Mexican American (n = 1895), and 17.30% were other ethnicity (n = 2021); The mean [SE] age of the sample was 46.93 [0.36] years, with a median follow-up of 7.80 years (interquartile range, 7.55–8.07 years). After adjusting covariates, Cox proportional hazards models and fine and gray competing risks regression models for specific-cause mortality demonstrated that total flavonol intake was associated with all-cause (HR 0.64, 95% CI 0.54–0.75), cancer-specific (HR 0.45, 95% CI 0.28–0.70) and CVD-specific (HR 0.67, 95% CI 0.47–0.96) mortality risks; isorhamnetin intake was associated with all-cause (HR 0.72, 95% CI 0.60–0.86), and cancer-specific (HR 0.62, 95% CI 0.46–0.83) mortality risks; kaempferol intake was associated with all-cause (HR 0.74, 95% CI 0.63–0.86), and cancer-specific (HR 0.62, 95% CI 0.40–0.97) mortality risks; myricetin intake was associated with all-cause (HR 0.77, 95% CI 0.67–0.88), AD-specific (HR 0.34, 95% CI 0.14–0.85), and CVD-specific (HR 0.61, 95% CI 0.47–0.80) mortality risks; quercetin intake was associated with all-cause (HR 0.66, 95% CI 0.54–0.81), cancer-specific (HR 0.54, 95% CI 0.35–0.84), and CVD-specific (HR 0.61, 95% CI 0.40–0.93) mortality risks; there was no correlation observed between dietary flavonol intake and DM-specific mortality. According to the current study, all-cause, AD, cancer, and CVD mortality risks declined with increased dietary flavonoid intake in the U.S. adults. This finding may be related to the anti-tumor, anti-inflammatory, and anti-oxidative stress properties of flavonol. [ABSTRACT FROM AUTHOR]

Background and aims: Flavonoids are a class of secondary plant metabolites that have been shown to have multiple health benefits, including antioxidant and anti-inflammatory. This study was to explore the association between dietary flavonoid consumption and the prevalence of chronic respiratory diseases (CRDs) in adults. Methods and results: The six main types of flavonoids, including isoflavones, anthocyanidins, flavan-3-ols, flavanones, flavones, and flavonols, were obtained from the National Health and Nutrition Examination Survey (NHANES) 2007–2010 and 2017–2018 by the two 24-h recall interviews. The prevalence of CRDs, including asthma, emphysema, and chronic bronchitis, was determined through a self-administered questionnaire. The analysis included 15,753 participants aged 18 years or older who had completed a diet history interview. After adjustment for potential confounders, the inverse link was found with total flavonoids, anthocyanidins, flavanones, and flavones, with an OR (95%CI) of 0.86 (0.75–0.98), 0.84 (0.72–0.97), 0.80(0.69–0.92), and 0.85(0.73–0.98) for the highest group compared to the lowest group. WQS regression revealed that the mixture of flavonoids was negatively linked with the prevalence of CRDs (OR = 0.88 [0.82–0.95], P < 0.01), and the largest effect was mainly from flavanones (weight = 0.41). In addition, we found that flavonoid intake was negatively linked with inflammatory markers, and systemic inflammation significantly mediated the associations of flavonoids with CRDs, with a mediation rate of 12.64% for CRP (P < 0.01). Conclusion: Higher flavonoid intake was related with a lower prevalence of CRDs in adults, and this relationship may be mediated through systemic inflammation. [ABSTRACT FROM AUTHOR]

Dicliptera is a genus belonging to family Acanthaceae. Dicliptera bupleuroides is a small perennial herb commonly known as roxburg's foldwing. It is locally used in folkloric medicines for the treatment of different diseases and as a general tonic for wound healing. The current investigational study was to optimize solvent extraction protocol, to identify quantitative and qualitative biochemical composition, antioxidant and cytotoxic activities of D. bupleuroides and to characterize the gene associated with biosynthesis of flavonol. The plant of D. bupleuroides was collected from district Abbottabad and separated into its four parts including leaf, stem, flower, and root. To extract the biochemical compounds, five different solvents were used such as methanol, acidified methanol, 80 % methanol, ethyl acetate, and n‐butanol. Total phenolic, flavonoids, flavonol, flavanol (catechin), and anthocyanin contents were determined and antioxidant potential of the extracts was evaluated using various antioxidant assays. The methanolic extracts of D. bupleuroides showed promising antioxidant potential towards DPPH, ABTS, H2O2, ferric, phosphomolybdate and hydroxyl radical scavenging capabilities.The extracts obtained from the solvents mentioned above were tested for cytotoxicity using the 3T3 cell line by using mouse fibroblast cells. The results indicated that none of the extracts demonstrated any toxic effects on the cells, suggesting that they are non‐toxic. The RNA was extracted and cDNA was synthesized using reverse transcriptase enzyme. Degenerate primers for dihydroflavonol reductase (DFR) gene were synthesized to amplify the desired product. The high quality of cDNA amplification showed the presence of the DFR gene in the Dicliptera bupleuroides leaf for the first time with a product size of 419 bp respectively. The DFR gene isolated from Dicliptera bupleuroides is involved in flavonol biosynthesis regulation. In addition, Glide molecular docking results proposed that the constituents within the n‐hexanic extract of Dicliptera bupleuroides not only furnish an updated approach to better understand the antioxidant potential of its various constituents to interact with an antioxidant target protein (PDB ID:3MNG) but also ensure promise in addressing these potential therapeutic modalities. The active compounds of D. bupleuroides could be suitable for pharmaceutical industries to develop stress related drugs. [ABSTRACT FROM AUTHOR]

Seed propagation is the main method of mulberry expansion in China, an important economic forest species. However, seed germination is the most sensitive stage to various abiotic stresses, especially salinity stress. To reveal the molecular regulatory mechanism of mulberry seed germination under salt stress, flavonoid metabolomics and transcriptomics analyses were performed on mulberry seeds germinated under 50 and 100 mmol/L NaCl stress. Analysis of the flavonoid metabolome revealed that a total of 145 differential flavonoid metabolites (DFMs) were classified into 9 groups, 40 flavonols, 32 flavones, 16 chalcones and 14 flavanones. Among them, 61.4% (89) of the DFMs accumulated continuously with increasing salt concentration, reaching the highest level at a 100 mmol/L salt concentration; these DFMs included quercetin-3-O-glucoside (isoquercitrin), kaempferol (3,5,7,4'-tetrahydroxyflavone), quercetin-7-O-glucoside, taxifolin (dihydroquercetin) and apigenin (4',5,7-trihydroxyflavone), indicating that these flavonoids may be key metabolites involved in the response to salt stress. Transcriptional analysis identified a total of 3055 differentially expressed genes (DEGs), most of which were enriched in flavonoid biosynthesis (ko00941), phenylpropanoid biosynthesis (ko00940) and biosynthesis of secondary metabolites (ko01110). Combined analysis of flavonoid metabolomic and transcriptomic data indicated that phenylalanine ammonia-lyase (PAL), 4-coumarate-CoA ligase (4CL), chalcone synthase (CHS), flavonol synthase (FLS), bifunctional dihydroflavonol 4-reductase/flavanone 4-reductase (DFR) and anthocyanidin reductase (ANR) were the key genes involved in flavonoid accumulation during mulberry seed germination under 50 and 100 mmol/L NaCl stress. In addition, three transcription factors, MYB, bHLH and NAC, were involved in the regulation of flavonoid accumulation under salt stress. The results of quantitative real-time PCR (qRT‒PCR) validation showed that the expression levels of 11 DEGs, including 7 genes involved in flavonoid biosynthesis, under different salt concentrations were consistent with the transcriptomic data, and parallel reaction monitoring (PRM) results showed that the expression levels of 6 key enzymes (proteins) involved in flavonoid synthesis were consistent with the accumulation of flavonoids. This study provides a new perspective for investigating the regulatory role of flavonoid biosynthesis in the regulation of mulberry seed germination under salt stress at different concentrations. [ABSTRACT FROM AUTHOR]

Galangin is a natural flavonol with high antioxidant properties and has a wide range characteristics of biological activity spectrum. Galangin has low solubility, permeability, and bioavailability, limiting its therapeutic use like many flavonoids. In this study, nano-sized polyelectrolyte liposomes were developed and characterized to overcome the properties that limit the use of galangin. The various parameters (phospholipid/solvent ratio, cholesterol/solvent ratio, time and galangin/solvent ratio) were optimized with a response surface methodology-central composite design to develop liposomes with maximum encapsulation efficiency using the thin-film hydration method. An optimum liposome formulation was developed with 93.77 ± 0.05% encapsulation efficiency, a spherical large unilamellar vesicle with a size of 485.5 ± 128.41 nm, and a zeta potential of − 48 ± 7 mV. The optimum liposome formulation was coated with polyelectrolyte biopolymer chitosan (CH) and gum arabic (GUA) using the layer-by-layer deposition method to improve its stability and drug release profile. The CH-liposome has a size of 208.05 ± 73.04 nm and a zeta potential of + 40 ± 5 mV. The GUA-CH-liposome has a size of 266.60 ± 8.49 nm and a zeta potential of − 6 mV. Fourier transform infrared spectroscopy analysis showed that galangin was encapsulated without disturbing the liposome structure and the polyelectrolyte coated the surface with electrostatic interaction. At the end of the in vitro release study, GUA-CH-liposome released 23.84% of galangin. Regarding stability, drug loading capacity of GUA-CH-liposome, which was 93.77 ± 0.05% on day 0, changed to 92.72 ± 0.51% at + 4 °C, 93.09 ± 0.01% at room temperature and 93.15 ± 0.01% at − 24 °C on day 28. [ABSTRACT FROM AUTHOR]

In searching for compounds with antioxidant and antifungal activity, our study focused on the subshrub species Empetrum rubrum Vahl ex Willd. (Ericaceae). We measured the antioxidant activity of its methanolic extract (MEE) obtained from the aerial parts (leaves and stems) and of its methanolic extract (MEF) obtained from the lyophilized fruits. The antioxidant activity of the MEE and MEF was evaluated in vitro via a 2,2-Diphenyl-1-picrylhydrazyl (DPPH) free radical and 2,2′-Azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) cationic radical. The results were expressed in gallic acid and Trolox equivalents for the DPPH and ABTS assays, respectively. The antioxidant activities, for the DPPH and ABTS assays, were also evaluated by considering the IC50 values. Concerning the antioxidant activity, the total phenolic content (TPC) in the MEE and MEF was determined using the Folin–Ciocalteu method. Polyphenols contained in the leaves, stems, and fruits of E. rubrum were determined qualitatively by employing high-performance liquid chromatography coupled with mass spectrometry (HPLC-MS) analysis. The antifungal activity of the MEE obtained from the aerial parts of E. rubrum was tested against Rhizoctonia solani. The results of IC50 values measured by the DPPH and ABTS methods with MEE were 0.4145 ± 0.0068 mg mL−1 and 0.1088 ± 0.0023 mg mL−1, respectively, and the IC50 values for MEF were 6.4768 ± 0.0218 mg mL−1 and 0.7666 ± 0.0089 mg mL−1 measured by the DPPH and ABTS methods, respectively. The HPLC-MS analysis revealed the presence of anthocyanins, phenolic acids derivatives, and flavonols. In vitro, mycelial growth of this fungus was reduced from 90% to nearly 100% in the presence of MEE. The observed antifungal effect is related to the presence of the abovementioned phenols, detected in the MEE. [ABSTRACT FROM AUTHOR]

In this work, the influence of high-power ultrasound (HPU) followed by pulsed electric field (PEF) in the hurdle concept (HPU + PEF) on the content of biologically active compounds (BACs) and antioxidant activity in strawberry juices stored at 4 °C/7 days was investigated. The HPU was performed with an amplitude of 25% and pulse of 50% during 2.5, 5.0 and 7.5 min, while the PEF was performed with an electric field strength of 30 kV cm−1 and frequency of 100 Hz during 1.5, 3 and 4.5 min. The results obtained indicate that the synergy of the mechanisms of action for technologies in the hurdle concept plays a critical role in the stability of BACs and antioxidant activity. Juices treated with HPU + PEF hurdle technology and kept at 4 °C for 7 days showed a statistically significant decrease in all BACs, antioxidant capacity and pH. Shorter HPU + PEF treatment times favored the preservation of BACs in juices. Regarding total phenolic compounds, flavonols, condensed tannins and antioxidant capacity, optimization of hurdle parameters showed that a shorter HPU treatment time of 2.5 min provided the best yield of these compounds. In summary, by optimizing and adjusting the parameters of the HPU/PEF technology, it is possible to produce functional strawberry juice. [ABSTRACT FROM AUTHOR]

The present study aimed at elucidating the anti-inflammatory, antioxidant, and antibacterial mechanisms of Clematis flammula (CF) leaf extracts. Methodologically, antioxidant activity was evaluated using 2,2-diphenyl-1-picrylhydrazyl and ferric ion reducing antioxidant power assays, and antibacterial activity was assessed using Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) cell cultures. Anti-inflammatory potency was evaluated through cyclooxygenase and trypsin inhibitory activities. Moreover, the anti-inflammatory and antibacterial mechanisms of the active extracts were elucidated using two membrane models: erythrocytes and liposomes. The phenolic compounds in the extracts were identified using high-performance liquid chromatography-mass spectrometry (HPLC-MS). Ethyl acetate extract inhibited S. aureus growth at a minimum inhibitory concentration of 78 µg/mL, possibly due to its lytic activity of liposomes (56.75 ± 0.54%). Additionally, the extract presented the best anti-trypsin activity (IC50 =7.67 ± 0.61 µg/mL) and inhibited cyclooxygenase activity (IC50 = 594.33 ± 11.15 µg/mL), probably related to its high polyphenol content (192.64 ± 1.55 mg GAE/g E). HPLC-MS analysis revealed the presence of flavones and flavonols. Conclusively, the results of this study suggest that CF extracts exert anti-inflammatory and antibacterial effects by inhibiting cyclooxygenase and trypsin activities and altering bacterial cell membrane, suggesting the potential of CF in the treatment of bacterial infections and inflammatory disorders. [ABSTRACT FROM AUTHOR]

Simple Summary: Kaempferol, a natural compound commonly found in fruits, vegetables, and plants, has gained interest within the scientific community because of its anticancer properties against different types of tumors. The results of this review reveal that kaempferol exerts anticancer effects on many types of tumor cells by different mechanisms, providing evidence of its potential as a cancer drug. Given the heterogeneity of different malignant processes, planning cancer treatment is challenging. According to recent studies, natural products are likely to be effective in cancer prevention and treatment. Among bioactive flavonoids found in fruits and vegetables, kaempferol (KMP) is known for its anti-inflammatory, antioxidant, and anticancer properties. This systematic review aims to highlight the potential therapeutic effects of KMP on different types of solid malignant tumors. This review was conducted following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. Searches were performed in EMBASE, Medline/PubMed, Cochrane Collaboration Library, Science Direct, Scopus, and Google Scholar. After the application of study criteria, 64 studies were included. In vitro experiments demonstrated that KMP exerts antitumor effects by controlling tumor cell cycle progression, proliferation, apoptosis, migration, and invasion, as well as by inhibiting angiogenesis. KMP was also able to inhibit important markers that regulate epithelial–mesenchymal transition and enhanced the sensitivity of cancer cells to traditional drugs used in chemotherapy, including cisplatin and 5-fluorouracil. This flavonoid is a promising therapeutic compound and its combination with current anticancer agents, including targeted drugs, may potentially produce more effective and predictable results. [ABSTRACT FROM AUTHOR]

Colorectal cancer is among the well‐known forms of cancer and a prominent cause of cancer demises worldwide. In vitro experiments reinforced by animal studies, as well as epidemiological studies of human colorectal cancer propose that the growth of this disease can be moderated by eating aspects. Dietary intake including green vegetables and fruits may result in the reduction of colon cancer chances. The finding suggests that the combinations of dietary nutrients may deliver additive or synergistic effects and might be a powerful method to avoid or eradicate colon cancer beginning and/or development. Flavonols are one of the most widespread dietary nutrients of the polyphenols‐flavonoids and major constituent of Allium and Brassicaceae vegetables. Flavonols present in vegetables of Allium and Brassicaceae family are kaempferol, myricetin, quercetin, and isorhamnetin. These flavonols are claimed to have antiproliferative activity in vivo and in vitro against colorectal cancer. The objective of this review is to summarize the role of flavonols obtained from dietary sources in the prevention and treatment of colorectal cancer. [ABSTRACT FROM AUTHOR]

Introduction: Huangkui capsule (HKC) is made from the ethanol extract of Abelmoschus manihot (L.) Medik [Malvaceae; abelmoschi corolla] and received approval from the China Food and Drug Administration (Z19990040) in 1999. Currently, HKC is used for treatment of the patients with diabetic nephropathy (DN) in China. The bioactive chemical constituents in HKC are total flavonoids of A. manihot (L.) Medik (TFA). The present study aims to identify the primary flavonoid metabolites in HKC and TFA and their metabolism fates in db/db mice, the animal model for the study of type 2 diabetes and DN. Methods: HKC (0.84 g/kg/d) and TFA (0.076 g/kg/d) or vehicle were respectively administered daily via oral gavage in db/db mice for 4 weeks. The metabolism fate of the main metabolites of HKC in serum, liver, kidney, heart, jejunum, colon, jejunal contents, colonic contents, and urine of db/db mice were analyzed with a comprehensive metabolite identification strategy. Results and Discussion: In db/db mice administered with HKC and TFA, 7 flavonoid prototypes and 38 metabolites were identified. The related metabolic pathways at Phases I and II reactions included dehydroxylation, deglycosylation, hydrogenation, methylation, glucuronidation, sulphation, and corresponding recombined reactions. Quercetin, isorhamnetin, quercetin sulphate, quercetin monoglucuronide, and isorhamnetin monoglucuronide presented a high exposure in the serum and kidney of db/db mice. Thereby, the present study provides a pharmacodynamic substance basis for better understanding the mechanism of A. manihot (L.) Medik for medication of DN. [ABSTRACT FROM AUTHOR]

Numerous onion varieties are cultivated in India, exhibiting variations in antioxidant levels due to genetic and environmental factors. The health benefits associated with these antioxidant compounds motivate breeders to identify genotypes with superior functional properties. In the present study, we have attempted to characterize variations in biochemical compounds in different onion genotypes. Significant variations (p<0.05) were observed in the phenolic content, anthocyanins levels, and activities of biosynthetic enzymes [(phenylalanine ammonia lyase (PAL), tyrosine ammonia lyase (TAL)] among thirty onion genotypes grown under sub-tropical Indian conditions. Among the red genotypes, namely D-305-B, Rec-1404, and PRO-6, high phenolic content, with a mean exceeding 0.7 g/100g DW, was observed. Genotypes Rec-1404 and PRO-6 exhibited the highest mean flavonol and ODH levels. Yellow genotypes POH-4 and POH-5 displayed high quercetin content. Anthocyanins levels were notably high in genotypes PRO-6 and Pb. Naroya. The highest PAL and TAL activities were recorded in the red genotypes D-888-B and Rec-1404, with mean activities exceeding 1.25 units. Total phenols exhibited positive correlations with ODH (r=0.902), flavonols (r=0.862), and anthocyanins (r=0.571). Additionally, TAL enzyme activity showed positive correlations with total flavonols (r=0.493) and anthocyanins (r=0.446). Overall, the red genotype PRO-6 emerges as a promising candidate for breeding programs aimed at developing onion varieties with high phenolics content. By prioritizing antioxidant-rich red genotypes and emphasizing phenolics content as a key parameter, breeders can contribute to the development of onions with enhanced health-promoting properties. [ABSTRACT FROM AUTHOR]

Exogenous application of phytohormones is getting promising results in alleviating abiotic stresses, particularly heavy metal (HMs). Jasmonate (JA) and brassinosteroid (BR) have crosstalk in bamboo plants, reflecting a burgeoning area of investigation. Lead (Pb) is the most common pollutant in the environment, adversely affecting plants and human health. The current study focused on the foliar application of 10 µM JA and 10 µM BR in both single and combination forms on bamboo plants grown under Pb stress (0, 50, 100, 150 µM) with a completely randomized design by four replications. The study found that applying 10 µM JA and 10 µM BR significantly improves growth and tolerance by reducing oxidative stress, reactive oxygen species including hydrogen peroxide (H2O2, 32.91%), superoxide radicals (O2−•, 33.9%), methylglyoxal (MG, 19%), membrane lipoperoxidation (25.66%), and electrolyte leakage (41.5%) while increasing antioxidant (SOD (18%), POD (13%), CAT (20%), APX (12%), and GR (19%)), non-antioxidant (total phenolics (7%), flavonols (12.3%), and tocopherols (13.8%)), and glyoxylate activity (GLyI (13%), GLyII (19%)), proline content (19%), plant metal chelating capacity (17.3%), photosynthetic pigments (16%), plant growth (10%), and biomass (12%). We found that JA and BR, in concert, boost bamboo species' Pb tolerance by enhancing antioxidant and glyoxalase cycles, ion chelation, and reducing metal translocation and accumulation. This conclusively demonstrates that utilizing a BR–JA combination form at 10 µM dose may have the potential to yield optimal efficiency in mitigating oxidative stress in bamboo plants. [ABSTRACT FROM AUTHOR]

Summary: Auxin signaling provides a promising approach to controlling root system architecture and improving stress tolerance in plants. However, how the auxin signaling is transducted in this process remains unclear.The Aux indole‐3‐acetic acid (IAA) repressor IAA17.1 is stabilized by salinity, and primarily expressed in the lateral root (LR) primordia and tips in poplar. Overexpression of the auxin‐resistant form of IAA17.1 (IAA17.1m) led to growth inhibition of LRs, markedly reduced salt tolerance, increased reactive oxygen species (ROS) levels, and decreased flavonol content. We further identified that IAA17.1 can interact with the heat shock protein HSFA5a, which was highly expressed in roots and induced by salt stress. Overexpression of HSFA5a significantly increased flavonol content, reduced ROS accumulation, enhanced LR growth and salt tolerance in transgenic poplar. Moreover, HSFA5a could rescue the defective phenotypes caused by IAA17.1m.Expression analysis showed that genes associated with flavonol biosynthesis were altered in IAA17.1m‐ and HAFA5a‐overexpressing plants. Furthermore, we identified that HSFA5a directly activated the expression of key enzyme genes in the flavonol biosynthesis pathway, while IAA17.1 suppressed HSFA5a‐mediated activation of these genes.Collectively, the IAA17.1/HSFA5a module regulates flavonol biosynthesis, controls ROS accumulation, thereby modulating the root system of poplar to adapt to salt stress. [ABSTRACT FROM AUTHOR]

Study was carried out to examine the influence of plant bioactive compounds [Kaempferol (KAE), Querectin (QUE) and Myricetin (MYR)] on the survival and growth parameters of cultured ovine preantral follicles (PFs) granulosa cells (GCs) and expression of some key developmental genes. Ovine PFs were isolated from slaughterhouse derived ovaries and KAE, QUE and MYR were supplemented to the standard culture medium of GCs and PFs at concentrations of 0, 5, 10, 25, 50 and 100 μM and cultured for 5 and 7 days respectively. PFs morphological and functional parameters [follicle and enclosed oocyte growth rate, viability of follicles, antrum formation rate, oocyte maturation rate, estradiol concentration, reactive oxygen species (ROS) production] and GC growth parameters (metabolic activity, viability rate, cell number increment, ROS production) were measured after culture. Significantly higher PF growth, viability rate and estradiol concentration was observed at 10 μM, 25 μM and 10 μM concentration of KAE, MYR and QUE respectively compared to the control. ROS production was significantly decreased in the PF culture media treated with 10 μM KAE or MYR 25 μM or 10 μM QUE compared to those observed in the control group. Likewise, metabolic activity of GCs, viability rate and cell number increment cultured with KAE, MYR and QUE was significantly higher at 10, 25 and 10 μM concentrations respectively compared to those observed in control group. ROS production was significantly lower in the GC cultured with KAE, MYR and QUE at 10, 25 and 10 μM concentrations respectively compared to the control. Based on the results of the growth parameters, gene expression of PFs and GCs were studied by qPCR at selected concentrations (KAE, MYR and QUE at 10, 25 and 10 μM concentrations respectively) in the cultured PFs and GCs. Gene expression of GDF9, FGF2 , CYP19A1 was significantly higher and Bax , Bcl2 expression was significantly lower in the PFs and GCs cultured with the KAE or QUE at 10 μM concentration. KAE, MYR and QUE have dose dependant responses on PFs and GCs morphological and functional parameters; however, KAE is more potent amongst the three in augmenting the ovarian functions. • Phenolic flavonols have dose-dependent effects on mammalian ovarian functions. • Kaempferol (KAE) was the most potent plant bioactive compound, followed by Quercetin (QUE) and Myricetin (MYR) in improving the proliferation and survival of ovarian cells cultured in vitro at particular doses of 10, 10, and 25 μM respectively. [ABSTRACT FROM AUTHOR]

To elucidate the anti-inflammatory properties and constituents of Agrimonia pilosa Ledeb. (A. pilosa), a comprehensive investigation was conducted employing activity-guided isolation. The anti-inflammatory effects were evaluated through an in vitro nitric oxide (NO) assay on lipopolysaccharide (LPS)-treated RAW 264.7 macrophage cells. Seven bio-active compounds with anti-inflammatory properties were successfully isolated from the butanol fraction and identified as follows: quercetin-7-O-β-d-rhamnoside (1), apigenin-7-O-β-d-glucopyranoside (2), kaempferol-7-O-β-d-glucopyranoside (3), quercetin (4), kaempferol (5), apigenin (6), and apigenin-7-O-β-d-glucuronide-6″-butylester (7). All isolated compounds showed strong NO inhibitory activity with IC50 values ranging from 1.4 to 31 µM. Compound 6 demonstrated the most potent NO inhibition. Compound 7, a rare flavonoid, was discerned as a novel anti-inflammatory agent, ascertained through its inaugural demonstration of nitric oxide inhibition. Subsequently, a comprehensive structure-activity relationship (SAR) analysis was conducted employing eight flavonoids derived from A. pilosa. The outcomes elucidated that flavones exhibit superior NO inhibitory effects compared to flavonols, and the aglycone form manifests greater potency in NO inhibition than the glycone counterpart. These results highlight A. pilosa as a promising source of effective anti-inflammatory agents and indicate its potential as a health-beneficial dietary supplement and therapeutic material. [ABSTRACT FROM AUTHOR]

This study aimed to reduce the bitterness and astringency properties of autumn green tea using different yellowing and drying treatments. The results showed that as the yellowing temperature increased, the contents of tea polyphenols, gallated catechins, flavonol glycosides, and bitter amino acids decreased, while the content of soluble sugar and flavonols increased. The tea sample (YEL35 °C) subjected to yellowing treatment at 35 °C exhibited weak bitterness and astringency intensities and a relatively low content of flavonol glycosides. As the drying temperature increased, the content of gallated catechins decreased. In addition, the tea sample (DRY75 °C) subjected to drying treatment at 75 °C exhibited weak bitterness and astringency intensities, the highest contents of umami amino acids and Thea, and a relatively low content of gallated catechins. Multivariate statistical analysis revealed that vitexin-2-O-rhamnoside, pferol-3-O-rutinoside, myricetin-3-O-galactoside, and quercetin-3-O-glucoside played an important role in the astringency property of the tea. In addition, Asn, Thr, Pro, and Met were positively correlated with umami. Hence, the quality of autumn green tea was improved under optimal yellowing and drying temperatures of 35 and 75 °C, respectively. [ABSTRACT FROM AUTHOR]

Flavonoids have garnered attention because of their beneficial bioactivities. However, some flavonoids reportedly interact with drugs via transporters and may induce adverse drug reactions. This study investigated the effects of food ingredients on organic anion-transporting polypeptide (OATP) 4C1, which handles uremic toxins and some drugs, to understand the safety profile of food ingredients in renal drug excretion. Twenty-eight food ingredients, including flavonoids, were screened. We used ascorbic acid (AA) to prevent curcumin oxidative degradation in our method. Twelve compounds, including apigenin, daidzein, fisetin, genistein, isorhamnetin, kaempferol, luteolin, morin, quercetin, curcumin, resveratrol, and ellagic acid, altered OATP4C1-mediated transport. Kaempferol and curcumin strongly inhibited OATP4C1, and the Ki values of kaempferol (AA(−)), curcumin (AA(−)), and curcumin (AA(+)) were 25.1, 52.2, and 23.5 µM, respectively. The kinetic analysis revealed that these compounds affected OATP4C1 transport in a competitive manner. Antioxidant supplementation was determined to benefit transporter interaction studies investigating the effects of curcumin because the concentration-dependent curve evidently shifted in the presence of AA. In this study, we elucidated the food–drug interaction via OATP4C1 and indicated the utility of antioxidant usage. Our findings will provide essential information regarding food–drug interactions for both clinical practice and the commercial development of supplements. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) is the largest contributor to cancer deaths in women worldwide. Various parts of plants, including fruits, are known for their therapeutic properties and are used in traditional medicine. Fruit species exhibit anticancer activities due to the presence of bioactive natural compounds such as flavonoids and carotenoids. The Vaccinium spp. are fleshy berry-like drupes and are rich in bioactive compounds, with flavonols, flavanols, chalcones, and phenolic acids as the major groups of compounds. While there is clear evidence linking Vaccinium berries with a decreased risk of BC both in in vivo and in vitro experiments, the exact mechanisms involved in the protective effects of Vaccinium spp. rich extracts on BC cells are not fully understood. Thus, the purpose of this review is to highlight the mechanisms of action involved in the therapeutic potential of Vaccinium berries against BC in experimental models. [ABSTRACT FROM AUTHOR]

Mitochondria, a cellular metabolic center, efficiently fulfill cellular energy needs and regulate crucial metabolic processes, including cellular proliferation, differentiation, apoptosis, and generation of reactive oxygen species. Alteration in the mitochondrial functions leads to metabolic imbalances and altered extracellular matrix dynamics in the host, utilized by solid tumors like pancreatic cancer (PC) to get energy benefits for fast‐growing cancer cells. PC is highly heterogeneous and remains unidentified for a longer time because of its complex pathophysiology, retroperitoneal position, and lack of efficient diagnostic approaches, which is the foremost reason for accounting for the seventh leading cause of cancer‐related deaths worldwide. PC cells often respond poorly to current therapeutics because of dense stromal barriers in the pancreatic tumor microenvironment, which limit the drug delivery and distribution of antitumor immune cell populations. As an alternative approach, various natural compounds like flavonoids are reported to possess potent antioxidant and anticancerous properties and are less toxic than current chemotherapeutic drugs. Therefore, we aim to summarize the current state of knowledge regarding the pharmacological properties of flavonols in PC in this review from the perspective of mitigating mitochondrial dysfunctions associated with cancer cells. Our literature survey indicates that flavonols efficiently regulate cellular metabolism by scavenging reactive oxygen species, mitigating inflammation, and arresting the cell cycle to promote apoptosis in tumor cells via intrinsic mitochondrial pathways. In particular, flavonols proficiently inhibit the cancer‐associated proliferation and inflammatory pathways such as EGFR/MAPK, PI3K/Akt, and nuclear factor κB in PC. Overall, this review provides in‐depth evidence about the therapeutic potential of flavonols for future anticancer strategies against PC; still, more multidisciplinary human interventional studies are required to dissect their pharmacological effect accurately. Significance statement: This review provides detailed information regarding the pharmacological properties of flavonols on human cancers with a prime focus on mitochondrial dysfunctions associated with pancreatic cancer cells. It is of utmost importance to target mitochondrial dysfunctions because mitochondria, a crucial metabolic center, regulates various cellular and metabolic processes required for the growth of tumor cells. During pathological conditions such as inflammation, cellular stress, DNA damage, or mutations, the high fission activities promote mitochondrial fragmentation, leading to increased glycolytic flux and reactive oxygen species generation, which support the energy needs of fast‐proliferating cancer cells and promote tumor invasiveness. A potential anticancer drug should efficiently target cancer stem cell populations with a minimum toxic effect on normal host tissue and be capable of removing the senescent cancer cells. As safer natural compounds, bio‐flavonols hold tremendous therapeutic potential as they have reportingly high antioxidant and antiinflammatory properties. Our literature survey indicates that flavonols can efficiently regulate the mitochondrial dysfunctions of cancer cells. [ABSTRACT FROM AUTHOR]

Withstanding extreme cold stress is a prerequisite for alpine treeline trees to persist and survive. However, the underlying mechanism by which treeline trees sense phenological changes and survive hard winters has not been fully elucidated. Here, we investigated the physiology, transcriptome, and metabolome of the subalpine treeline species Larix chinensis to identify the molecular mechanism of phenological and cold resistance. Calcium and antioxidant enzyme activities (e.g., superoxide dismutase and glutathione peroxidase) are essential for coping with winter cold stress in L. chinensis. Transcriptome analysis revealed that circadian rhythm and phytohormone signalling transduction played important roles in regulating L. chinensis phenological changes and cold stress responses. The variations in the transcriptome identified were accompanied by the specific accumulation of flavones, flavonols, and monosaccharides. The flavonoid biosynthesis and phenylpropanoid biosynthesis pathways played important roles in the adaptation of L. chinensis to the extreme winter environment, and flavone and flavonol biosynthesis was an important pathway involved in bud burst. In addition, temperature and photoperiod had synergistic influences on the formation and release of bud dormancy. Thus, our findings provided new insights into the mechanism of subalpine treeline formation. [ABSTRACT FROM AUTHOR]

• Tagetes minuta is a valuable medicinal plant with various uses, such as spice herb, traditional medicine, and a natural herbicide. • The study identified and quantified the secondary metabolites of T. minuta using colorimetric assays and liquid chromatography-mass spectrometry (LCMS). • The major classes of secondary metabolites identified in T. minuta were Phenolic acids, Flavonoids, Fatty acids, and Coumarins. • Ethanol extracts of T. minuta demonstrated higher antioxidant content, activity, and cytotoxicity against HepG2 and Vero cell lines, highlighting their pharmacological potential. The complexity of secondary metabolites in different medicinal plants, including Tagetes minuta , defines the general properties and uses of the plant. Tagetes minuta is reportedly a valuable medicinal plant that has long been used as a spice herb, medicine, a natural herbicide for weeds, and pest control in agriculture. In this study, the secondary metabolite profiles of the water and aqueous ethanol extracts of T. minuta were profiled through identification and quantification using colorimetric assays and a Waters Synapt G2 Quadrupole time-of-flight (QTOF) mass spectrometer (MS) connected to a Waters Acquity ultra-performance liquid chromatograph (UPLC). The antioxidant capacity of the extracts was evaluated with 2,2-Azino-di-3-ethylbenzthiazoline sulfonate and ferric reducing antioxidant power, as well as their toxicity on HepG2 (cancerous) and Vero (non-cancerous) cell lines. The major classes of secondary metabolites identified and quantified were phenolic acids (benzoic acids and hydroxycinnamic acids), flavonoids (chalcones, flavonols, flavanols, and flavones), fatty acids, coumarins and furanocoumarins. The bioavailability of these secondary metabolites is influenced by the polarity of the solvent of extraction. Extracts from aqueous ethanol showed higher secondary metabolites, corresponding to antioxidant content and activity as well as cytotoxicity in HepG2 and Vero cells, compared to the water extract. This study presents a comprehensive phytochemical knowledge of secondary metabolites, primarily phenolic compounds, identified in T. minuta, which can pave the way for future studies on the pharmacological importance and standardisation of the medicinal uses of the plant. [ABSTRACT FROM AUTHOR]

Flower color variations have increasingly been recognized as playing an important role in the adaptation to UV-B radiation; however, the underlying mechanism is poorly understood in perennial fruit trees. Litchi is an important fruit tree, and extremely early maturing (EEM) and middle-to-late-maturing (MLM) cultivars that originated from regions with high and low UV-B radiation have dark brown and light yellow flower buds, respectively, while their hybrid early-maturing (EM) cultivars have an intermediate brown flower bud. This study comprehensively analyzed the metabolome and transcriptome of flower buds of litchi EEM, EM and MLM cultivars to explore the mechanism underlying flower color variation during the adaptation to UV-B radiation for the first time. Metabolomic analysis identified 72 flavonoids in litchi flower buds, among which a higher accumulation of flavonol glycosides was responsible for darker flower buds of EEM cultivars. And transcriptome analysis revealed key structural genes, including LcCHI, LcFLS and seven UGTs, together with two transcription factors (LcMYB12 and LcMYB111), which could be directly up-regulated by UV-B radiation, playing critical roles in regulating the differential accumulation of flavonol glycosides. These results provide new insights into the molecular mechanism underlying adaptation to UV-B radiation and provide a genetic basis for future breeding of stress-tolerant cultivars of litchi. [ABSTRACT FROM AUTHOR]

Mistletoe (Viscum album L.), a semi-parasitic medicinal plant, continues to be of interest, due to its phytochemical composition. The leaves of mistletoe contain phenols, which have a variety of biological effects. The main goal was to characterize the mistletoe that parasitized Robinia pseudoacacia L., (called VAR) in terms of phenolic compounds and to assess the wound healing potential in vitro using the scratch method. Furthermore, the antioxidant capacity was evaluated both by spectrophotometric techniques (DPPH, FRAP, TEAC), as well as by the ability of the mistletoe extract to synthesize green selenium nanoparticles. Among the phenolic acids, dihydroxybenzoic acid is in high level (2.86±0.03 mg/g dw), whereas isorhamnetinglucuronides dominate the flavonol class (0.593±0.03 mg/g dw). The presence of phenolic compounds in the VAR leaves provides antioxidant capacity. The reducing capacity of VAR extract was demonstrated for the first time by the biosynthesis of nanoselenium particles (NSePs) with a regular, spherical shape and a diameter of around 130 nm. The VAR concentrations of 25-200 µg/mL showed no toxic effect on normal human dermal fibroblasts (NHDF), and the concentration of 100 µg/mL exhibited the best percentage of wound surface closure in vitro (94.08%). The results show that mistletoe is a promising plant because of its phytochemical composition and antioxidant capacity, which can modulate the wound repair process in vitro. [ABSTRACT FROM AUTHOR]

Laelia speciosa is an epiphytic orchid endemic to Mexico, enjoying special protected status due to illegal sales and clandestine field extraction. Until now, in vitro cultivation of this plant has not been explored using temporary immersion bioreactor (TIB). L. speciosa seedlings were grown in a TIB, and the presence of bioactive compounds released into the liquid culture medium was determined. Bioactive compounds such as antioxidants, total polyphenols, and flavonoids were identified. The maximum concentration of total polyphenols was 2.29 ± 0.10 mg GAE/g, and the antioxidant capacity reached 33.7 %. Colorimetric tests revealed the presence of flavanones and flavonols. Gas chromatography-mass spectrometry identified components of the culture medium as 1,3- dihydroxyacetone dimer and 5-(hydroxymethyl)-2-furancarbaldehyde. Fourier transform infrared spectroscopy confirmed the presence of polyphenols in the culture medium. This work provides an alternative method for obtaining bioactive compounds while conserving L. speciosa seedlings. [ABSTRACT FROM AUTHOR]

Flavonols are structurally and functionally diverse biomolecules involved in plant biotic and abiotic stress tolerance, pollen development, and inhibition of auxin transport. However, their effects on global gene expression and signaling pathways are unclear. To explore the roles of flavonol metabolites in signaling, we performed comparative transcriptome and targeted metabolite profiling of seedlings from the flavonol-deficient Arabidopsis loss-of-function mutant flavonol synthase1 (fls1) with and without exogenous supplementation of flavonol derivatives (kaempferol, quercetin, and rutin). RNA-seq results indicated that flavonols modulate various biological and metabolic pathways, with significant alterations in camalexin and aliphatic glucosinolate synthesis. Flavonols negatively regulated camalexin biosynthesis but appeared to promote the accumulation of aliphatic glucosinolates via transcription factor-mediated up-regulation of biosynthesis genes. Interestingly, upstream amino acid biosynthesis genes involved in methionine and tryptophan synthesis were altered under flavonol deficiency and exogenous supplementation. Quercetin treatment significantly up-regulated aliphatic glucosinolate biosynthesis genes compared with kaempferol and rutin. In addition, expression and metabolite analysis of the transparent testa7 mutant, which lacks hydroxylated flavonol derivatives, clarified the role of quercetin in the glucosinolate biosynthesis pathway. This study elucidates the molecular mechanisms by which flavonols interfere with signaling pathways, their molecular targets, and the multiple biological activities of flavonols in plants. [ABSTRACT FROM AUTHOR]

Prunus mume is an important medicinal plant with ornamental and edible value. Its flowers contain phenylpropanoids, flavonoids and other active components, that have important medicinal and edible value, yet their molecular regulatory mechanisms in P. mume remain unclear. In this study, the content of total flavonoid and total phenylpropanoid of P. mume at different developmental periods was measured first, and the results showed that the content of total flavonoid and total phenylpropanoid gradually decreased in three developmental periods. Then, an integrated analysis of transcriptome and metabolome was conducted on three developmental periods of P. mume to investigate the law of synthetic accumulation for P. mume metabolites, and the key enzyme genes for the biosynthesis of phenylpropanoids and flavonoids were screened out according to the differentially expressed genes (DEGs). A total of 14,332 DEGs and 38 differentially accumulate metabolites (DAMs) were obtained by transcriptomics and metabolomics analysis. The key enzyme genes and metabolites in the bud (HL) were significantly different from those in the half-opening (BK) and full-opening (QK) periods. In the phenylpropanoid and flavonoid biosynthesis pathway, the ion abundance of chlorogenic acid, naringenin, kaempferol, isoquercitrin, rutin and other metabolites decreased with the development of flowers, while the ion abundance of cinnamic acid increased. Key enzyme genes such as HCT, CCR, COMT, CHS, F3H, and FLS positively regulate the downstream metabolites, while PAL, C4H, and 4CL negatively regulate the downstream metabolites. Moreover, the key genes FLS (CL4312-2, CL4312-3, CL4312-4, CL4312-5, CL4312-6) regulating the synthesis of flavonols are highly expressed in bud samples. The dynamic changes of these metabolites were validated by determining the content of 14 phenylpropanoids and flavonoids in P. mume at different developmental periods, and the transcription expression levels of these genes were validated by real-time PCR. Our study provides new insights into the molecular mechanism of phenylpropanoid and flavonoid accumulation in P. mume. [ABSTRACT FROM AUTHOR]

Nowadays, Camellia sinensis (L.) O. Kuntze is used as a health drink as well as a medication worldwide. Quercetin, kaempferol, and myricetin are different flavonoids present in it. Therefore, it was decided to extract and isolate the flavonoid content of Camellia sinensis with an evaluation of their anticancer activity. In the methodology, the extraction of the dried leaves was performed with the help of the Soxhlet apparatus. The extractives were obtained with different solvents. For the isolation of desired flavonoid column chromatography was applied using solvents of different polarity. Different polarity solvents utilization helped in determining a better medium for the extraction and isolation of flavonols. The flavonol quercetin obtained from Camellia sinensis was subjected to the estimation of anticancer activity. Anticancer ability was determined on the ovarian cancer cell line by in vitro method. The results depicted that the flavonoids especially quercetin, work as a good antineoplastic agent. The outcomes revealed that naturally available anticancer agents having good potential and lesser toxicity can be obtained from easily available natural sources like green tea leaves. Thus, the work in the future may be elaborated to find new targets for quercetin. [ABSTRACT FROM AUTHOR]