Search

The influence of the composition of the functional used for density functional theory computations on one structural parameter (a dihedral angle) and a spectroscopic parameter (absorption wavelength) is assessed in this study on the basis of two molecules (flavonols). In this kind of molecules, these two parameters should be correlated according to the nature of the electronic transition involved. However, it is shown herein that by varying the proportion of true exchange and correlation while building a functional, it is possible to obtain independently a large range of values for these parameters without any relation with the underlying real values. Therefore, it is concluded that the choice of a functional after a benchmark, especially using user‐defined functionals, should be carried out with great care to avoid such effects. [ABSTRACT FROM AUTHOR]

Summary: Sea buckthorn (SB) is used in cuisines and herbal remedies due to its remarkable nutritional composition and health‐enhancing properties. The phenolic compounds present in SB plant include phenolic acids (gallic, p‐coumaric, protocatechuic and ferulic acids), flavonols (isorhamnetin, quercetin and kaempferol), flavan‐3‐ols and polymeric procyanidins. The highest content of these compounds was reported in branches and leaves than corresponding edible parts of the plant. The antioxidant properties of SB are related to content and composition of phenolic compounds in different plant parts. The studies reported SB flavonoids (isorhamnetin and quercetin) as main phenolic compounds with medicinal potential and health‐promoting effects. The present review summarises information available in recent studies on phenolic composition, phenolic content, flavonoid content, antioxidant activity and health‐promoting activities (anti‐oxidant, hepatoprotective, cardioprotective, anti‐inflammatory, anti‐diabetic and obesity management) of SB that can be used in curtailing various acute and chronic maladies. SB can be projected as a promising source of bioactive constituents with the potential to be used in healthy foods for beneficial effects on human health. [ABSTRACT FROM AUTHOR]

In plants, salicylic acid (SA) hydroxylation regulates SA homoeostasis, playing an essential role during plant development and response to pathogens. This reaction is catalysed by SA hydroxylase enzymes, which hydroxylate SA producing 2,3‐dihydroxybenzoic acid (2,3‐DHBA) and/or 2,5‐dihydroxybenzoic acid (2,5‐DHBA). Several SA hydroxylases have recently been identified and characterised from different plant species, but no such activity has yet been reported in maize. In this work, we describe the identification and characterisation of a new SA hydroxylase in maize plants. This enzyme, with high sequence similarity to previously described SA hydroxylases from Arabidopsis and rice, converts SA into 2,5‐DHBA; however, it has different kinetic properties to those of previously characterised enzymes, and it also catalysers the conversion of the flavonoid dihydroquercetin into quercetin in in vitro activity assays, suggesting that the maize enzyme may have different roles in vivo to those previously reported from other species. Despite this, ZmS5H can complement the pathogen resistance and the early senescence phenotypes of Arabidopsis s3h mutant plants. Finally, we characterised a maize mutant in the S5H gene (s5hMu) that has altered growth, senescence and increased resistance against Colletotrichum graminicola infection, showing not only alterations in SA and 2,5‐DHBA but also in flavonol levels. Together, the results presented here provide evidence that SA hydroxylases in different plant species have evolved to show differences in catalytic properties that may be important to fine tune SA levels and other phenolic compounds such as flavonols, to regulate different aspects of plant development and pathogen defence. Summary statement: Maize plants express an enzyme of the 2‐oxoglutarate‐dependent oxygenase family with unique kinetic properties, having salicylic acid hydroxylase activity but it can also convert flavonols from dihydroflavonols. Zm2‐ODD7 confers increased resistance against pathogens and regulates senescence. [ABSTRACT FROM AUTHOR]

Flavonoids are usually present in forms of glucosides in plants, which could be catabolized by β‐glucosidase (BGLU) to form their corresponding flavonoid aglycones. In this study, we isolated three abiotic‐responsive BGLU genes (MtBGLU17, MtBGLU21 and MtBGLU22) from Medicago truncatula, and found only the recombinant MtBGLU17 protein could catalyse the hydrolysis of flavonoid glycosides. The recombinant MtBGLU17 protein is active towards a variety of flavonoid glucosides, including glucosides of flavones (apigenin and luteolin), flavonols (kaempferol and quercetin), isoflavones (genistein and daidzein) and flavanone (naringenin). In particular, the recombinant MtBGLU17 protein preferentially hydrolyses flavonoid‐7‐O‐glucosides over their corresponding 3‐O‐glucosides. The content of luteoin‐7‐O‐glucoside was reduced in the MtBGLU17 overexpression plants but increased in the Tnt‐1 insertional mutant lines, whereas luteoin content was increased in the MtBGLU17 overexpression plants but reduced in the Tnt‐1 insertional mutant lines. Under drought and salt (NaCl) treatment, the MtBGLU17 overexpression lines showed relatively higher DPPH content, and higher CAT and SOD activity than the wild type control. These results indicated that overexpression lines of MtBGLU17 possess higher antioxidant activity and thus confer drought and salt tolerance, implying MtBGLU17 could be potentially used as a candidate gene to improve plant abiotic stress tolerance. Summary statement: MtBGLU17 gene from Medicago truncatula encodes a β‐glucosidase that is able to hydrolyse a variety of flavonoid glucosides. Both gain‐of‐function and loss‐of‐function studies in M. truncatula demonstrated that MtBGLU17 is involved in drought and salt tolerance by balancing the accumulation of flavonoid aglycones with ROS scavenging activity. [ABSTRACT FROM AUTHOR]

Summary: In the present study, the effect of microwave roasting on the total phenolic quantities, antioxidant activities, phenolic constituents, fatty acids and tocopherol amounts of the pistachio kernel and oil was revealed. The moisture, oil, total phenolic amounts and antioxidant capacity value of raw and roasted pistachio nuts were assessed as 31.13%, 28.58%, 34.79 mgGAE/100 g and 0.75%–3.18%, 56.91%, 18.80 mgGAE/100 g and 2.26%, respectively. The raw pistachio nut contains 1.90 gallic acid, 0.22 3,4‐dihydroxybenzoic acid, 0.87 (+)‐catechin, 0.15 1,2‐dihydroxybenzene, 0.15 rutin trihydrate, 0.16 resveratrol, 0.1 quercetin, 0.19 kaempferol and 0.24 mg/100 g isorhamnetin. In addition, microwave‐roasted nuts contained 0.75 gallic acid, 0.62 3,4‐dihydroxybenzoic acid, 0.83 (+)‐catechin, 0.47 1,2‐dihydroxybenzene, 0.21 syringic acid, 0.17 caffeic acid and 0.17 mg/100 g quercetin. The raw and roasted pistachio nut oils contained 74.12% and 71.16% oleic, 13.76% and 15.23% linoleic, 8.16% and 8.92% palmitic and 2.09% and 2.10% stearic acids, respectively. The oil samples of the raw and roasted kernels contained 8.15 and 0.00 α‐tocopherol, 63.78 and 7.60 β‐tocopherol, 8.72 and 7.40 ɣ‐tocopherol and 5.61 and 6.77 mg g−1 δ‐tocopherols, respectively. The total phenolic quantity of the pistachio kernel roasted by microwave decreased significantly. Phenolic compounds of the pistachio kernel showed partial differences depending on microwave heating. Differences were monitored in the fatty acid profiles of Pistachio kernel oils. β‐tocopherol quantity of the oil of the pistachio kernel heated by microwave significantly decreased. [ABSTRACT FROM AUTHOR]

SUMMARY: Skin color is an important trait that determines the cosmetic appearance and quality of fruits. In cucumber, the skin color ranges from white to brown in mature fruits. However, the genetic basis for this important trait remains unclear. We conducted a genome‐wide association study of natural cucumber populations, along with map‐based cloning techniques, on an F2 population resulting from a cross between Pepino (with yellow‐brown fruit skin) and Zaoer‐N (with creamy fruit skin). We identified CsMYB60 as a candidate gene responsible for skin coloration in mature cucumber fruits. In cucumber accessions with white to pale yellow skin color, a premature stop mutation (C to T) was found in the second exon region of CsMYB60, whereas light yellow cucumber accessions exhibited splicing premature termination caused by an intronic mutator‐like element insertion in CsMYB60. Transgenic CsMYB60c cucumber plants displayed a yellow‐brown skin color by promoting accumulation of flavonoids, especially hyperoside, a yellow‐colored flavonol. CsMYB60c encodes a nuclear protein that primarily acts as a transcriptional activator through its C‐terminal activation motif. RNA sequencing and DNA affinity purification sequencing assays revealed that CsMYB60c promotes skin coloration by directly binding to the YYTACCTAMYT motif in the promoter regions of flavonoid biosynthetic genes, including CsF3′H, which encodes flavonoid 3′‐hydroxylase. The findings of our study not only offer insight into the function of CsMYB60 as dominantly controlling fruit coloration, but also highlight that intronic DNA mutations can have a similar phenotypic impact as exonic mutations, which may be valuable in future cucumber breeding programs. Significance Statement: Genome‐wide association study and map‐based cloning revealed that CsMYB60 regulates mature cucumber fruit skin coloring, which is promising for cucumber breeding. Two loss‐of‐function mutations of CsMYB60 provided color variations in the natural cucumber population. [ABSTRACT FROM AUTHOR]

The repurposing of therapeutic and preventive strategies against Alzheimer's disease (AD) is progressing rapidly. Pancratium aegyptiacum has been found to possess considerable anticholinesterase potential attributed to its alkaloid contents. In this study, the potential anti‐Alzheimer's activity of isolated flavonoids from P. aegyptiacum was investigated through computational analysis, focusing on the flavonoids rather than their well‐known alkaloids. Molecular docking was performed against three crucial targets involved in the development of AD, and the isolated phytoconstituents were analysed against these targets. Pathway enrichment analyses were also established, additionally, ADMETlab and PASS web servers predicted the pharmacological properties and potential biological functions of the isolated flavonoids. The phytochemical analysis of P. aegyptiacum aerial parts revealed the isolation and identification of eleven flavonoids. They were identified as derivatives of kaempferol (Km), quercetin (Qn) and isorhamnetin (Is). Our investigation revealed that these phytoconstituents potentially act against AD, with several phytochemicals showing superior binding affinity against essential AD targets. The Kyoto Encyclopaedia of Genes and Reactome pathway enrichment database revealed that isolated phytochemicals may have a role in regulating the immune pathway directly correlated to AD. Additionally, these phytochemicals exhibited lower toxicity with pleiotropic biological activities, including dementia treatment and neurotrophic factor enhancement. [ABSTRACT FROM AUTHOR]

SUMMARY Flavonols are widely synthesized throughout the plant kingdom, playing essential roles in plant physiology and providing unique health benefits for humans. Their glycosylation plays significant role in improving their stability and solubility, thus their accumulation and function. However, the genes encoding the enzymes catalyze this glycosylation remain largely unknown in apple. This study utilized a combination of methods to identify genes encoding such enzymes. Initially, candidate genes were selected based on their potential to encode UDP‐dependent glycosyltransferases (UGTs) and their expression patterns in response to light induction. Subsequently, through testing the in vitro enzyme activity of the proteins produced in Escherichia coli cells, four candidates were confirmed to encode a flavonol 3‐O‐galactosyltransferase (UGT78T6), flavonol 3‐O‐glucosyltransferase (UGT78S1), flavonol 3‐O‐xylosyltransferase/arabinosyltransferase (UGT78T5), and flavonol 3‐O‐rhamnosyltransferase (UGT76AE22), respectively. Further validation of these genes' functions was conducted by modulating their expression levels in stably transformed apple plants. As anticipated, a positive correlation was observed between the expression levels of these genes and the content of specific flavonol glycosides corresponding to each gene. Moreover, overexpression of a flavonol synthase gene, MdFLS, resulted in increased flavonol glycoside content in apple roots and leaves. These findings provide valuable insights for breeding programs aimed at enriching apple flesh with flavonols and for identifying flavonol 3‐O‐glycosyltransferases of other plant species. [ABSTRACT FROM AUTHOR]

Myricetin can be found in the traditional Chinese medicinal plant, Myrica rubra. Myricetin is a flavonoid that is present in many vegetables, fruits, and plants and is considered to have strong antioxidant properties as well as a wide range of therapeutic applications. Growing interest has been piqued by its classification as a polyphenolic molecule because of its potential therapeutic benefits in both the prevention and management of numerous medical conditions. To clarify myricetin's traditional medical uses, modern research has investigated various pharmacological effects such as antioxidant, anticancer, anti‐inflammation, antiviral, antidiabetic, immunomodulation, and antineurodegenerative effects. Myricetin shows promise as a nutritional flavonol that could be beneficial in the prevention and mitigation of prevalent health conditions like diabetes, cognitive decline, and various types of cancer in humans. The findings included in this study indicate that myricetin has a great deal of promise for application in the formulation of medicinal products and nutritional supplements since it affects several enzyme activities and alters inflammatory markers. However, comprehensive preclinical studies and research studies are necessary to lay the groundwork for assessing myricetin's possible effectiveness in treating these long‐term ailments. This review summarizes both in vivo and in vitro studies investigating myricetin's possible interactions through the nuclear factor‐E2‐related factor 2 (Nrf2) as well as PI3K (phosphatidylinositol 3‐kinase)/AKT (protein kinase B) signaling pathways in an attempt to clarify the compound's possible clinical applicability across a range of disorders. [ABSTRACT FROM AUTHOR]

Carrier‐free nanodrugs that integrate chemodrugs and other therapeutic agents demonstrate good efficacy and minimized side effects, showing promise for combined therapy. However, a key challenge lies in enhancing the bioavailability and therapeutic potential of the nanodrugs through a controllable assembly process. Herein, a carrier‐free photothermal nanodrug (ZPQ NPs) is constructed through flavonol‐driven assembly with amine‐substituted perylene diimide for enhanced chemo‐photothermal combined cancer therapy. The flavonol, particularly quercetin, facilitates J‐aggregation of perylene diimide derivatives within the nanodrug and contributes to multiple improvements, including red‐shifted absorption, enhanced fluorescence intensity, improved photothermal conversion efficiency as well as excellent photostability. Moreover, the nanodrug also demonstrates enhanced cellular uptake and intracellular reactive oxygen species scavenging capability. The combination of quercetin and photothermal effect effectively kills cancer cells, as well as alleviates inflammation following photothermal therapy. Guided by in vivo fluorescence imaging, the application of ZPQ NPs results in complete tumor elimination and effectively inhibits tumor recurrence through chemo‐photothermal combined therapy. This work presents a straightforward strategy for constructing carrier‐free nanodrugs that exhibit simultaneous enhancements in both photophysical properties and biological activity. [ABSTRACT FROM AUTHOR]

Herein an enzyme‐assisted supercritical fluid extraction (EA‐SFE) was developed using the enzyme mix snailase to obtain flavonols and dihydrochalcones, subgroups of flavonoids, from globally abundant waste product apple pomace. Snailase, a commercially available mix of 20–30 enzymes, was successfully used to remove the sugar moieties from quercetin glycosides, kaempferol glycosides, phloridzin and 3‐hydroxyphloridzin. The resulting flavonoid aglycones quercetin, kaempferol, phloretin and 3‐hydroxyphloretin were extracted using supercritical carbon dioxide (scCO2) and minimum amounts of polar cosolvents. A sequential process of enzymatic hydrolysis and supercritical fluid extraction was developed, and the influence of the amount of snailase, pre‐treatment of apple pomace, the time for enzymatic hydrolysis, the amount and type of cosolvent and the time for extraction, was studied. This revealed that even small amounts of snailase (0.25 %) provide a successful cleavage of sugar moieties up to 96 % after 2 h of enzymatic hydrolysis followed by supercritical fluid extraction with small amounts of methanol as cosolvent, leading up to 90 % of the total extraction yields after 1 h extraction time. Ultimately, a simultaneous process of EA‐SFE successfully demonstrates the potential of snailase in scalable scCO2 extraction processes for dry and wet apple pomace with satisfactory enzyme activity, even under pressurized conditions. [ABSTRACT FROM AUTHOR]

Flavonoids are a diverse group of naturally occurring plant compounds that are primarily composed of phenols in their free form or glycosides. Flavonoid medicines are primarily composed of 2‐phenyl‐g‐benzopyrone. This family consists of monomeric flavanols, flavanones, anthocyanidins, flavones, isoflavonoids, and flavonols. The study's main objective is to review the newly discovered natural flavones and flavanols, as well as the biological and pharmacological actions of these essential flavonoids. As per the available data, 3‐hydroxy flavone plays a vital role in the prevention of a range of diseases. Research studies have confirmed that 3‐hydroxyflavone has a broad range of pharmacological properties like therapeutic effects against pain, inflammation, oxidative stress; hepatotoxicity, hypertension, ulcerogenesis, allergy, platelet dysfunction, microbes, fungi, viruses, rhinovirus, malaria, and carcinogens. 3‐Hydroxy flavone has limited utility because of their poor solubility and bioavailability. This has led to the search for new drug delivery methods, such as nanoparticles. To get over these problems, it would be preferable to administer 3‐hydroxyflavone via the biocompatible nanoparticles. It is expected that nanoparticles will improve the solubility of 3‐hydroxyflavone, enhance its therapeutic properties and facilitate its transport to the brain. [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]

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]

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]

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]

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]

SUMMARY: Bougainvillea is a typical tropical flower of great ornamental value due to its colorful bracts. The molecular mechanism behind color formation is not well‐understood. Therefore, this research conducted metabolome analysis, transcriptome analysis, and multi‐flux full‐length sequencing in two color bracts of Bougainvillea × buttiana 'Chitra' to investigate the significantly different metabolites (SDMs) and differentially expressed genes (DEGs). Overall, 261 SDMs, including 62 flavonoids and 26 alkaloids, were detected, and flavonols and betalains were significantly differentially accumulated among the two bracts. Furthermore, the complete‐length transcriptome of Bougainvillea × buttiana was also developed, which contained 512 493 non‐redundant isoforms. Among them, 341 210 (66.58%) displayed multiple annotations in the KOG, GO, NR, KEGG, Pfam, Swissprot, and NT databases. RNA‐seq findings revealed that 3610 DEGs were identified between two bracts. Co‐expression analysis demonstrated that the DEGs and SDMs involved in flavonol metabolism (such as CHS, CHI, F3H, FLS, CYP75B1, kaempferol, and quercetin) and betacyanin metabolism (DODA, betanidin, and betacyanins) were the main contributors for the canary yellow and red bract formation, respectively. Further investigation revealed that several putative transcription factors (TFs) might interact with the promoters of the genes mentioned above. The expression profiles of the putative TFs displayed that they may positively and negatively regulate the structural genes' expression profiles. The data revealed a potential regulatory network between important genes, putative TFs, and metabolites in the flavonol and betacyanin biosynthesis of Bougainvillea × buttiana 'Chitra' bracts. These findings will serve as a rich genetic resource for future studies that could create new color bracts. [ABSTRACT FROM AUTHOR]

Glechoma longituba has been frequently used in treating urolithiasis and cholelithiasis due to the presence of flavonoids, which are its major bioactive constituents. However, research on the molecular background of flavonoid biosynthesis in G. longituba is limited. In this study, we used single‐molecule real‐time combined with next‐generation sequencing technologies to construct the complete transcriptome of G. longituba. We identified 404,648 non‐redundant transcripts, including 249,697 coding sequences, 197,811 simple sequence repeats, 174,846 long noncoding RNA, and 176,554 coding RNA. Moreover, we functionally annotated 346,218 isoforms (85.56%) and identified 86,528 differentially expressed genes. We also identified 55 non‐redundant full‐length isoforms related to the flavonoid biosynthetic pathway. Pearson correlation analysis revealed that the expression levels of some key genes of the flavonoid biosynthesis pathway were significantly positively correlated with the flavonoid metabolites. Furthermore, we performed bioinformatics analysis (sequence and structural) of isoform_47029 (encoding flavanone 3‐hydroxylase) and isoform_53692 (encoding flavonol synthase) to evaluate their potential biological functions. Finally, we validated gene expression levels of 12 flavonoid‐related key enzyme genes using quantitative real‐time PCR. Overall, this study provides full‐length transcriptome information on G. longituba for the first time and valuable molecular resources for further research on the medicinal properties of this plant. [ABSTRACT FROM AUTHOR]

Background: The design and synthesis of hybrid molecules will explore finding new drugs. Objectives: The synthesized hybrid molecules to evaluate their biological properties. Methods: Apply click chemistry to tether flavonols and benzenesulfonamide. Results: Two drug candidates show potential against lung cancer. Conclusions: Two drug candidates did not affect the normal cells and provided a new drug design route. [ABSTRACT FROM AUTHOR]

Family 1 UDP‐glycosyltransferases (UGTs) are known to glycosylate multiple secondary plant metabolites and have been extensively studied. The increased availability of plant genome resources allows the identification of wide gene families, both functional and organizational. In this investigation, two MpUGT isoforms were cloned and functionally characterized from liverworts marchantia polymorpha and had high glycosylation activity against several flavonoids. MpUGT735A2 protein, in particular, tolerates a wide spectrum of substrates (flavonols, flavanones, flavones, stilbenes, bibenzyls, dihydrochalcone, phenylpropanoids, xanthones, and isoflavones). Overexpression of MpUGT735A2 and MpUGT743A1 in Arabidopsis thaliana enhances the accumulation of 3‐O‐glycosylated flavonol (kaempferol 3‐O‐glucoside‐7‐O‐rhamnose), consistent with its in vitro enzymatic activity. Docking and mutagenesis techniques were applied to identify the structural and functional properties of MpUGT735A2 with promiscuous substrates. Mutation of Pro87 to Ser, or Gln88 to Val, substantially altered the regioselectivity for luteolin glycosylation, predominantly from the 3′‐O‐ to the 7‐O‐position. The results were elucidated by focusing on the novel biocatalysts designed for producing therapeutic flavonoids. This investigation provides an approach to modulate MpUGT735A2 as a candidate gene for diverse glycosylation catalysis and a tool to design GTs with new substrate specificities for biomedical applications. [ABSTRACT FROM AUTHOR]

BACKGROUND: The ultraviolet‐B (UV‐B) radiation can alter grape metabolism during berry development, but little is known on the effect of postharvest UV‐B exposure. In this study, we evaluated the effect of postharvest UV‐B exposure on berry primary and secondary metabolites in four grapevine varieties (Aleatico, Moscato bianco, Sangiovese, and Vermentino) in order to evaluate the possibility to increase the grape quality and its nutraceutical properties. RESULTS: The treatment did not significantly affect the berry primary metabolism in terms of organic acids, carbohydrates, and amino acids profile, regardless of the variety. UV‐B exposure reduced the total anthocyanin content, particularly the tri‐substituted and di‐substituted forms in Aleatico and Sangiovese, respectively. An overall negative effect of UV‐B irradiation on the flavonols profile of Aleatico, Moscato bianco, and Vermentino berries was found, whereas it enhanced the quercetin, myricetin and kaempferol concentration in Sangiovese. The free fraction of berry volatile organic compounds increased in UV‐B‐treated Aleatico and Moscato bianco berries, especially C13‐norisoprenoids and volatile phenols, as well as key monoterpenes, such as the linalool derivatives. However, higher concentrations of glycosylated monoterpenes and C13‐norisoprenoids were measured in Sangiovese and Vermentino berries treated with UV‐B. CONCLUSION: This study provides new insights on the effect of postharvest UV‐B radiation on berry secondary metabolism, highlighting a different modulation between varieties and suggesting the potential use of this technique to increase some nutraceutical and quality characteristics of grape berry. © 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Blackcurrant possesses various health‐endorsing attributes owing to its polyphenol profile. Recent studies have demonstrated its therapeutic potential against various health disorders. Various bioactives present in blackcurrants have different functional and pharmacological aspects including anti‐inflammatory, antioxidant, and antimicrobial properties. The most dominant and important bioactive include anthocyanins, flavonols, phenolic acids, and polyunsaturated fatty acids. Food formats derived from blackcurrants comprise pomace, juice, powder, and extracts. All these food formats have industrial, prebiotic, and pharmacological benefits. In the current article, the nutritional composition, industrial applications, and therapeutic potential are discussed in the recent literature. Moreover, novel extraction techniques for the extraction of bioactive compounds present in blackcurrants and their safety concerns have been elaborated. [ABSTRACT FROM AUTHOR]

Summary: In angiosperms, the timely delivery of sperm cell nuclei by pollen tube (PT) to the ovule is vital for double fertilization. Penetration of PT into maternal stigma tissue is a critical step for sperm cell nuclei delivery, yet little is known about the process. Here, a male‐specific and sporophytic mutant xt6, where PTs are able to germinate but unable to penetrate the stigma tissue, is reported in Oryza sativa. Through genetic study, the causative gene was identified as Chalcone synthase (OsCHS1), encoding the first enzyme in flavonoid biosynthesis. Indeed, flavonols were undetected in mutant pollen grains and PTs, indicating that the mutation abolished flavonoid biosynthesis. Nevertheless, the phenotype cannot be rescued by exogenous application of quercetin and kaempferol as reported in maize and petunia, suggesting a different mechanism exists in rice. Further analysis showed that loss of OsCHS1 function disrupted the homeostasis of flavonoid and triterpenoid metabolism and led to the accumulation of triterpenoid, which inhibits significantly α‐amylase activity, amyloplast hydrolysis and monosaccharide content in xt6, these ultimately impaired tricarboxylic acid (TCA) cycle, reduced ATP content and lowered the turgor pressure as well. Our findings reveal a new mechanism that OsCHS1 modulates starch hydrolysis and glycometabolism through modulating the metabolic homeostasis of flavonoids and triterpenoids which affects α‐amylase activity to maintain PT penetration in rice, which contributes to a better understanding of the function of CHS1 in crop fertility and breeding. [ABSTRACT FROM AUTHOR]

SUMMARY: Flavonols are health‐promoting bioactive compounds important for human nutrition, health, and plant defense. The transcriptional regulation of kaempferol and quercetin biosynthesis has been studied extensively, while little is known about the regulatory mechanisms underlying myricetin biosynthesis, which has strong antioxidant, anticancer, antidiabetic, and anti‐inflammatory activities. In this study, the flavonol‐specific MrMYB12 in Morella rubra preferred activating the promoter of flavonol synthase 2 (MrFLS2) (6.4‐fold) rather than MrFLS1 (1.4‐fold) and upregulated quercetin biosynthesis. Furthermore, two SG44 R2R3‐MYB members, MrMYB5 and MrMYB5L, were identified by yeast one‐hybrid library screening using the promoter of flavonoid 3′,5′‐hydroxylase (MrF3′5′H), and transcript levels of these R2R3‐MYBs were correlated with accumulation of myricetin derivatives during leaf development. Dual‐luciferase and electrophoretic mobility shift assays demonstrated that both MrMYB5 and MrMYB5L could bind directly to MYB recognition sequence elements in promoters of MrF3′5′H or MrFLS1 and activate their expression. Protein–protein interactions of MrMYB5 or MrMYB5L with MrbHLH2 were confirmed by yeast two‐hybrid and bimolecular fluorescence complementation assays. MrMYB5L‐MrbHLH2 showed much higher synergistic activation of MrF3′5′H or MrFLS1 promoters than MrMYB5‐MrbHLH2. Studies with Arabidopsis thaliana homologs AtMYB5 and AtTT8 indicated that similar synergistic regulatory effects occur with promoters of MrF3′5′H or MrFLS1. Transient overexpression of MrMYB5L‐MrbHLH2 in Nicotiana benthamiana induced a higher accumulation of myricetin derivatives (57.70 μg g−1 FW) than MrMYB5‐MrbHLH2 (7.43 μg g−1 FW) when MrMYB12 was coexpressed with them. This study reveals a novel transcriptional mechanism regulating myricetin biosynthesis with the potential use for future metabolic engineering of health‐promoting flavonols. [ABSTRACT FROM AUTHOR]

Arsenic (As) toxicity negatively impacts plant development, limits agricultural production, and, by entering the food chain, endangers human health. Studies on the use of natural and bioactive molecules in increasing plants' resistance to abiotic stressors, such as As, have gained increasing attention in the last few years. Flavonols are plant secondary metabolites with high potential in stress tolerance due to their roles in signal transmission. Therefore, the focus of this study was to examine the effects of two flavonols, quercetin (Q, 25 μM) and kaempferol (K, 25 μM), on growth parameters, photosynthesis, and chloroplastic antioxidant activity in wheat leaves under As stress (100 μM). As stress reduced the relative growth rate by 50% and relative water content by 25% in leaves. However, applying Q and/or K alleviated the As‐induced suppression of growth and water relations. Exogenous phenolic treatments reversed the effects of As toxicity in photochemistry and maintained the photochemical quantum efficiency of the Photosystem II (Fv/Fm). As exposure increased, the H2O2 content in wheat chloroplasts by 42% and high levels of H2O2 accumulation were also observed in guard cells in confocal microscopy images. Analysis of the chloroplastic antioxidant system has shown that Q and K applications increase the activity of antioxidant enzymes, including superoxide dismutase, peroxidase, and ascorbate peroxidase. Phenolic applications have induced the ascorbate–glutathione (AsA‐GSH) cycle in charge of the protection of the cellular redox balance in different ways. It has been determined that Q triggers the AsA renewal, and K maintains the GSH pool. As a result, Q and K applications provide tolerance to wheat plants under As stress by increasing the chloroplastic antioxidant system activity and protecting photosynthetic reactions from oxidative damage. This study reveals the potential use of plant phenolic compounds in agricultural systems as a biosafe strategy to enhance plant stress tolerance, hence increasing yield. [ABSTRACT FROM AUTHOR]

Ranunculus japonicus Thunb. is a traditional Chinese herb. Plants in the genus Ranunculus are generally rich in flavonoids, which have antibacterial, anti‐infective, and other pharmacological effects. However, owing to the lack of reference genomes, little is known about the flavonoid biosynthetic pathway in R. japonicus. In this study, PacBio isoform sequencing (PacBio iso‐seq) and DNA nanoball sequencing (DNB‐seq) were combined to build a full‐length transcriptome database for three different tissues of R. japonicus. A total of 395,402 full‐length transcripts were obtained, of which 308,474 were successfully annotated. A Kyoto Encyclopedia of Genes and Genomes analysis identified 29 differentially expressed genes encoding nine key enzymes for flavonoid biosynthesis. Correlation analysis indicated that flavanone 3‐hydroxylase and flavonol synthase genes might have key roles in the accumulation of flavonoid substances in the different tissues of R. japonicus. The structures of chalcone synthase and chalcone isomerase enzymes were spatially modeled. Reverse‐transcription quantitative PCR was used to verify gene expression levels of key enzymes associated with flavonoid biosynthesis. In addition, 22 MYB transcription factors involved in flavonoid biosynthesis and phenylpropanoid biosynthesis were discovered. The reliable transcriptomic data from this study provide genetic information about R. japonicus as well as insights into the molecular mechanism of flavonoid biosynthesis. The results also provide a basis for developing the medicinal value R. japonicus. [ABSTRACT FROM AUTHOR]

Inflammation is an innate reaction of the body of an individual when subjected to the noxious factors repeatedly. Pharmacological approaches focused at disrupting cytokine signaling networks have become significant therapeutic alternatives for the treatment of inflammatory illnesses, cancer and autoimmune disorders. High levels of inflammatory mediators, particularly interleukin IL‐1, IL‐6, IL‐18, IL‐12, and tumor necrosis factor alpha leads to a cytokine storm in the body. Among all the released cytokines in a patient suffering from inflammatory disorder, IL‐6 mediator has a pivotal role in this inflammatory cascade which progresses to a cytokine storm. Therefore, the blockage of the IL‐6 inflammatory mediator could be a promising treatment option for the patients with hyper inflammatory conditions. The phytochemicals could provide the new lead compounds against the IL‐6 mediator. Ficus carica has been the ideal plant of research and investigation due to its commercial, economic and medical importance. The anti‐inflammatory properties of F. carica were further investigated by in silico and in vivo approaches. The docking scores of Cyanidin‐3,5‐diglucoside, Kaempferol‐7‐O‐rutinoside, Cyanidin‐3‐rhamnoglucoside, and Rutin are −9.231, −8.921, −8.840, and −8.335 Kcal/mole respectively. The free energy of binding and stability of the docked complexes of these top four phytochemicals with the IL‐6 were further analyzed by Molecular Mechanics‐Generalized Born Surface Area and Molecular Dynamic simulations, respectively. The in vivo anti‐inflammatory carrageenan‐induced rat paw edema model was used for the validation of in silico results. The maximum percentage paw edema inhibition with petroleum ether and ethyl acetate was 70.32% and 45.05%, respectively. The in vivo anti‐inflammatory activity confirms the anti‐inflammatory potential of F. carica. Therefore, it is predicted that Cyanidin‐3,5‐diglucoside, Kaempferol‐7‐O‐rutinoside, Cyanidin‐3‐rhamnoglucoside, and Rutin have the potential to inhibit the IL‐6 mediator which will aid in mitigating the cytokine storm in patients with acute inflammations. Significance statement: The Ficus carica plant has been included in traditional alternative systems of medicine for the treatment of various ailments since the ancient times. Plant leaves and fruits have profound chemical constituents possessing anti‐inflammatory activity reported in numerous research publications. The current study is designed to evaluate and investigate further, the anti‐inflammatory (IL‐6 inhibitory) potential of F. carica from both computational (in silico) and in vivo methods for discovery of new and potentially better treatment. Both in vivo and in silico studies justify the IL‐6 inhibitory activity of F. carica phytochemicals and show that they can prevent the hyper‐inflammatory condition known as "cytokine storm" in the patients. The most effective IL‐6 inhibitor phytochemicals include Cyanidin‐3,5‐diglucoside, Kaempferol‐7‐O‐rutinoside, Cyanidin‐3‐rhamnoglucoside, and Rutin. In the future, these phytochemicals will require further pharmacokinetic and toxicity studies along with clinical trials to provide a new treatment option for patients with acute inflammatory conditions. [ABSTRACT FROM AUTHOR]

Eucommiae Folium (Duzhongye) is a traditional Chinese medicine with a long history of use in China. However, its quality‐marker in Chinese Pharmacopoeia is poorly defined nowadays. The study, therefore, conducted an ultra‐high‐performance liquid chromatography coupled with hybrid quadrupole‐orbitrap tandem mass spectrometry analysis to obtain accurate data. The obtained data were then compared with the authentic standards library using Xcalibur 4.1 software package and TraceFinder General Quan. Through the comparison, the study has putatively identified 26 bioactive compounds, which include 17 flavonoid derivatives (catechin, quercetin 3‐gentiobioside, quercetin 3‐O‐β‐D‐glucose‐7‐O‐β‐D‐gentiobioside, taxifolin, myricetin 3‐O‐galactoside, myricitrin, hyperoside, rutin, isoquercitrin, quercetin 3‐O‐β‐xylopyranoside, quercitrin, isorhamnetin 3‐O‐β‐D‐glucoside, quercetin, kaempferol, S‐eriodictyol, S‐naringenin, and phloridzin), four caffeoylquinic acids (neochlorogenic acid, chlorogenic acid, isochlorogenic acid A, and isochlorogenic acid C), two alkaloids (vincamine and jervine), one lignan (pinoresinol), one xanthone (cowaxanthone B), and one steroid (cholesteryl acetate). Of these, flavonoid isoquercitrin is recommended as the new and additional pharmacopeia quality‐marker candidate, which can not only overcome the unreliability of old quality‐marker but also recognize the possible counterfeit. [ABSTRACT FROM AUTHOR]

Astringency and more generally mouthfeel perception are relevant to the overall quality of the wine. However, their origin and description are still uncertain and are constantly updating. Additionally, the terminology related to mouthfeel properties is expansive and extremely diversified, characterized by common traditional terms as well as novel recently adopted descriptors. In this context, this review evaluated the mention frequency of astringent subqualities and other mouthfeel attributes in the scientific literature of the last decades (2000–August 17, 2022). One hundred and twenty‐five scientific publications have been selected and classified based on wine typology, aim, and instrumental–sensorial methods adopted. Dry resulted as the most frequent astringent subquality (10% for red wines, 8.6% for white wines), while body—and related terms—is a common mouthfeel sensation for different wine types, although its concept is still vague. Alongside, promising analytical and instrumental techniques investigating and simulating the in‐mouth properties are discussed in detail, such as rheology for the viscosity and tribology for the lubrication loss, as well as the different approaches for the quantitative and qualitative evaluation of the interaction between salivary proteins and astringency markers. A focus on the phenolic compounds involved in the tactile perception was conducted, with tannins being the compounds conventionally found responsible for astringency. Nevertheless, other non‐tannic polyphenolic classes (i.e., flavonols, phenolic acids, anthocyanins, anthocyanin‐derivative pigments) as well as chemical–physical factors and the wine matrix (i.e., polysaccharides, mannoproteins, ethanol, glycerol, and pH) can also contribute to the wine in‐mouth sensory profile. An overview of mouthfeel perception, factors involved, and its vocabulary is useful for enologists and consumers. [ABSTRACT FROM AUTHOR]

Summary: Elicitation is an efficient strategy for enhancing the phytochemical content by inducing various physiological changes in plants and sprouts. In the present study, citric acid, ascorbic acid, sodium chloride and mannitol at different concentrations were used as elicitors for enhancing the content of bioactive compounds in buckwheat sprouts obtained from hydroponically cultivated seeds. The phenolic content, flavonoids, flavonols, antioxidant activity, sugar, chlorophyll and carotenoids were estimated. The influence of elicitation on phenolic acids like ferulic acid, vanillic acid, gallic acid, rutin and quercetin was also determined by Ultra Performance Liquid Chromatography (UPLC). Our results show that most of the phytochemical compounds are markedly higher in sprouts treated with citric acid (10 mm), ascorbic acid (1.5 mm) and sodium chloride (150 mm). The antioxidant activity is highest when the sprouts are treated with citric acid (10 mm) followed by NaCl (150 mm). A positive correlation is observed among antioxidant activity, phenolic content, flavonoids, tannins, rutin and ferulic acid. Our findings suggest that citric acid and sodium chloride can be recommended for effectively enhancing the phytochemical profile of buckwheat sprouts. [ABSTRACT FROM AUTHOR]

As a major public health issue, cutaneous leishmaniasis (CL) has a number of complications, including drug resistance and poor response to conventional treatments. Over the last decade, research on natural sources for finding new antileishmanial agents has been a critical part of tropical disease research. Natural products also should be regarded as one of the most valuable applications for CL infection drug development. In this study, we assessed the in vitro and in vivo antileishmanial potential of Carex pendula Huds. (hanging sedge) methanolic extract and its fractions against Leishmania major produced cutaneous infection. Although the methanolic extract and its fractions exhibited suitable activity, the ethyl acetate fraction showed the best activity (with the half maximal inhibitory concentration IC50 = 1.627 ± 0.211 mg/mL). The toxicity and selectivity indices (SI) of all samples were determined in murine peritoneal macrophage cells (J774A.1) using the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) test. The flavonoid components of the ethyl acetate fraction were identified using liquid chromatography electrospray ionization mass spectrometry (LC‐ESI MS/MS). Nine chemical compounds were identified in this fraction, including three flavonols, four flavanonols, and two flavan derivatives. L. major‐infected mice were used as an in vivo model because the methanolic extract was effective against L. major promastigotes in the mammalian cell line J774A.1 with SI = 2.514 (tail lesion size model). In silico analysis of identified compounds also revealed a favorable interaction between compounds 2–5 and L. major protein targets (3UIB, 4JZX, 4JZB, 5L4N, and 5L42). According to the findings of this study, the ethyl acetate fraction (as flavonoid fraction) exhibited considerable in vitro antileishmanial activity. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder worldwide, and the treatment focuses on delivering L‐DOPA. In this work, we isolated and tested several compounds against α‐synuclein and the hydrophobic peptide 71VTGVTAVAQKTV82 including flavonols (kaempferol, quercetin, and isorhamnetin), isoflavone (genistein) and flavone (luteolin), and compounds with α, β unsaturated carbonyl moieties such as chlorogenic acid and the depsidone fumarprotocetraric acid. Most compounds inhibit both α‐synuclein and hydrophobic peptide fibrillization. Moreover, ITC experiments showed a Kd varying from 9 to 20 μM, and ΔH values vary from −1.94 to −10.5 among the compounds. Docking experiments showed the intermolecular interactions within the sites 2, 9, and 3/13 of α‐synuclein, and with the hydrophobic peptide. In cultured cells, the presence of the compounds showed that most of them can promote cell proliferation and differentiation. Considering that treatments for neurodegenerative disorders, including PD, is only palliative the evaluation of these compounds that can prevent the fibrillization of α‐synuclein and stimulate the catecholamines pathway is promising. [ABSTRACT FROM AUTHOR]

Summary: Seeds slowly accumulate damage during storage, which ultimately results in germination failure. The seed coat protects the embryo from the external environment, and its composition is critical for seed longevity. Flavonols accumulate in the outer integument. The link between flavonol composition and outer integument development has not been explored.Genetic, molecular and ultrastructural assays on loss‐of‐function mutants of the flavonoid biosynthesis pathway were used to study the effect of altered flavonoid composition on seed coat development and seed longevity.Controlled deterioration assays indicate that loss of function of the flavonoid 3′ hydroxylase gene TT7 dramatically affects seed longevity and seed coat development. Outer integument differentiation is compromised from 9 d after pollination in tt7 developing seeds, resulting in a defective suberin layer and incomplete degradation of seed coat starch. These distinctive phenotypes are not shared by other mutants showing abnormal flavonoid composition. Genetic analysis indicates that overaccumulation of kaempferol‐3‐rhamnoside is mainly responsible for the observed phenotypes. Expression profiling suggests that multiple cellular processes are altered in the tt7 mutant.Overaccumulation of kaempferol‐3‐rhamnoside in the seed coat compromises normal seed coat development. This observation positions TRANSPARENT TESTA 7 and the UGT78D1 glycosyltransferase, catalysing flavonol 3‐O‐rhamnosylation, as essential players in the modulation of seed longevity. [ABSTRACT FROM AUTHOR]

SUMMARY: In this work, we identified and functionally characterized the strawberry (Fragaria × ananassa) R2R3 MYB transcription factor FaMYB123. As in most genes associated with organoleptic properties of ripe fruit, FaMYB123 expression is ripening‐related, receptacle‐specific, and antagonistically regulated by ABA and auxin. Knockdown of FaMYB123 expression by RNAi in ripe strawberry fruit receptacles downregulated the expression of enzymes involved in the late steps of anthocyanin/flavonoid biosynthesis. Transgenic fruits showed a parallel decrease in the contents of total anthocyanin and flavonoid, especially malonyl derivatives of pelargonidin and cyanidins. The decrease was concomitant with accumulation of proanthocyanin, propelargonidins, and other condensed tannins associated mainly with green receptacles. Potential coregulation between FaMYB123 and FaMYB10, which may act on different sets of genes for the enzymes involved in anthocyanin production, was explored. FaMYB123 and FabHLH3 were found to interact and to be involved in the transcriptional activation of FaMT1, a gene responsible for the malonylation of anthocyanin components during ripening. Taken together, these results demonstrate that FaMYB123 regulates the late steps of the flavonoid pathway in a specific manner. In this study, a new function for an R2R3 MYB transcription factor, regulating the expression of a gene that encodes a malonyltransferase, has been elucidated. Significance Statement: FaMYB123 is a fruit‐specific transcription factor whose expression is regulated by the two major hormones related to the control of strawberry (Fragaria × ananassa) ripening, ABA and auxins. FaMYB123‐RNAi fruits showed its implication in the final steps of anthocyanin/flavonoid biosynthesis, revealing a newly identified malonyltransferase, FaMT1. The metabolite analysis showed a concomitant decrease in the contents of total anthocyanin and flavonoid, particularly malonyl derivates. Furthermore, FaMYB123 physically interacts with FabHLH3, and together they transactivate FaMT1 expression. [ABSTRACT FROM AUTHOR]

BACKGROUND: Pruned vine shoots prepared as toasted fragments (SEGs) have recently been proposed as enological additives capable of producing differentiated quality wines. In this work, the composition of phenolic and volatile compounds of SEGs, before and after contact with wines, has been studied. RESULTS: SEGs from Tempranillo and Cabernet Sauvignon were used, which were kept in contact for 30 days with red wines made with the same varieties. Phenolic compounds were the ones with the highest sorption in SEGs, but a variety‐dependent behavior was observed in anthocyanins and flavonols, with an increase in some malvidin derivatives only in Tempranillo wine and an increase in (−)‐epicatechin in SEGs and Cabernet Sauvignon wine. trans‐Resveratrol was transferred from SEGs to wine but also increased in SEGs regardless of the variety used. The volatile compounds that were most retained in SEGs were phenylethyl alcohol and ethyl lactate, but in lower proportions than the phenolic compounds and without important changes in wines. CONCLUSION: The high content of phenolic compounds in SEGs after their use as enological additives suggests that they could be considered as a source of anthocyanins and as raw materials for phenolic compounds with recognized antioxidant properties. © 2022 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

In the present research, we encapsulated a flavonoid called kaempferol into nanoliposomal structures and the health‐promoting effects of synthesized nanoliposome‐loaded kaempferol (NLK) were evaluated in mice challenged by cadmium‐induced. The NLK characteristics, such as size, zeta potential, and polydispersity index, were 218.4 nm, −28.55 mV, and 0.29, respectively. The in vivo experiment revealed that the mice receiving water containing cadmium (2 mg/kg body weight/day) showed significant (p < 0.05) weight loss, an increase in liver enzyme activities, and hepatic oxidative stress. Dietary supplementation with NLK at concentrations of 2.5 and 5 mg/kg mice body weight notably (p < 0.05) improved the body weight, liver enzyme activities, hepatic oxidative stress, and antioxidant potential of the liver. Our findings elucidated that NLK could alleviate the toxicity of cadmium in mice challenged by cadmium‐induced toxicity. [ABSTRACT FROM AUTHOR]

Summary: Due to their sessile nature, plants cannot escape adverse environmental conditions and evolved mechanisms to cope with sudden environmental changes. The reaction to variations in abiotic factors, also summarized as acclimation response, affects all layers of cellular functions and involves rapid modification of enzymatic activities, the metabolome, proteome and transcriptome on different timescales. One trait of plants acclimating to high light (HL) is the rapid transcriptional activation of the flavonoid biosynthesis (FB) pathway resulting in the accumulation of photoprotective and antioxidative flavonoids, such as flavonols and anthocyanins, in the leaf tissue. Although enormous progress has been made in identifying enzymes and transcriptional regulators of FB by forward and reverse genetic approaches in the past, the signals and signalling pathways permitting the conditional activation of FB in HL are still debated. With this Tansley Insight, we summarize the current knowledge on the proposed signals and downstream factors involved in regulating FB and will discuss their contribution to, particularly, HL‐induced accumulation of anthocyanins. [ABSTRACT FROM AUTHOR]

BACKGROUND Enzymatic catalyzed grafting of oligosaccharides with polyphenols is a safe and environmentally friendly approach to simultaneously enhance the bioactivity of oligosaccharides and the solubility of polyphenols. In this study, chitosan oligosaccharide (COS) was grafted with three different flavonols including myricetin (MYR), quercetin (QUE) and kaempferol (KAE) by horseradish peroxidase (HRP) catalysis. The structures, antioxidant activity and edible coating application of COS–flavonol conjugates were investigated. RESULTS: The total phenol content of COS–MYR, COS–QUE and COS–KAE conjugates was 59.89, 68.37 and 53.77 mg gallic acid equivalents g−1, respectively. Thin layer chromatography showed the conjugates did not contain ungrafted flavonols. COS–flavonol conjugates showed ultraviolet absorption peak at about 294 nm, corresponding to the A‐ring of flavonols. Fourier‐transform infrared spectra of conjugates confirmed the formation of Schiff‐base and Michael‐addition products. The proton‐nuclear magnetic resonance spectrum of COS–KAE conjugate exhibited phenyl proton signals of KAE. X‐ray diffraction patterns of conjugates showed some diffraction peaks of flavonols. COS–flavonol conjugates presented rough and porous morphologies with sheet‐like and/or blocky structures. The conjugates showed higher water solubility, free radical scavenging activity and reducing power than flavonols. Moreover, fish gelatin/COS–flavonol conjugate coatings effectively prolonged the shelf life of refrigerated largemouth bass (Micropterus salmoides) fillets from 5 days to 7–8 days. CONCLUSION: COS–flavonol conjugates prepared by HRP catalysis have great potentials as novel antioxidant agents. © 2022 Society of Chemical Industry. Chitosan oligosaccharide (COS) was grafted with three different flavonols including myricetin, quercetin and kaempferol by horseradish peroxidase catalysis. The obtainedCOS‐flavonol conjugates showed higher water solubility, free radical scavenging activity and reducing power than flavonols. Moreover, fish gelatin/COS‐flavonol conjugate coatings effectively prolonged the shelf life of refrigerated large mouth bass (Micropterus salmoides) fillets from 5 days to 7–8 days. [ABSTRACT FROM AUTHOR]

Environmental stress can induce changes in organismal traits and in resulting intraspecific variation. The nature of such effects will depend on the plasticity of trait expression and on any ecological constraints to such expression. Plants can mitigate abiotic stress, like drought, by changing their chemistry, but the ability to induce costly metabolites may be under strong local selection and ecologically constrained. Here, we asked whether climate at the seed source predicts plant chemical plasticity in response to water stress and what the consequences are for intraspecific variation in phytochemical traits. To this end, we used common gardens of two widespread species of western milkweed (Asclepias fascicularis and Asclepias speciosa) that had been collected from sites across an aridity gradient. Both species produce high concentrations of leaf flavonols, which are hypothesized to mitigate water stress by functioning as antioxidants. These compounds were found in higher constitutive concentrations in plants sourced from drier sites, and both species responded to water stress in the common garden by increasing leaf flavonol concentrations. Interestingly, flavonol plasticity was higher in plants sourced from wetter sites in A. fascicularis, with similar, but weaker, patterns in A. speciosa. These opposing patterns in constitutive and induced flavonol expression reduced the variation between populations in leaf flavonol concentrations under water stress. These results suggest that local adaptation in plants can shape phytochemical strategies for water limitation but that the cost of metabolite production may ultimately limit the range of phytochemical variation. [ABSTRACT FROM AUTHOR]

Flavonol glycosides are bioactive compounds important for plant defence and human nutrition. Glycosylation and methylation play an important role in enriching the diversity of flavonols in response to the environment. Peach flowers and fruit are rich in flavonol diglycosides such as isorhamnetin 3‐O‐rutinoside (I3Rut), kaempferol 3‐O‐rutinoside and quercetin 3‐O‐rutinoside, and flavonol monoglycosides such as I 3‐O‐glucoside and Q 3‐O‐galactoside. UV‐B irradiation of fruit significantly induced accumulation of all these flavonol glycosides. Candidate biosynthetic genes induced by UV‐B were identified by genome homology searches and the in vitro catalytic activities of purified recombinant proteins determined. PpUGT78T3 and PpUGT78A2 were identified as flavonol 3‐O‐glucosyltransferase and 3‐O‐galactosyltransferase, respectively. PpUGT91AK6 was identified as flavonol 1,6‐rhamnosyl trasferase catalysing the formation of flavonol rutinosides and PpFOMT1 was identified as a flavonol O‐methyltransferase that methylated Q at the 3'‐OH‐OH to form isorhamnetin derivatives. Transient expression in Nicotiana benthamiana confirmed the specificity of PpUGT78T3 as a flavonol 3‐O‐glucosyltransferase, PpUGT78A2 as a 3‐O‐galactosyltransferase, PpUGT91AK6 as a 1,6‐rhamnosyltrasferase and PpFOMT1 as an O‐methyltransferase. This study provides new insights into the mechanisms of glycosylation and methylation of flavonols, especially the formation of flavonol diglycosides such as I3Rut, and will also be useful for future potential metabolic engineering of complex flavonols. [ABSTRACT FROM AUTHOR]

Saffron production from Crocus sativus flowers produces large amounts of by‐products that may represent an excellent source of polyphenols. The aim of this work was to evaluate infusions originating from different brewing processes and from different saffron flower portions, in terms of both functional and sensory traits. For this aim, total polyphenols and total flavonoids, in vitro antioxidant assays and an untargeted phenolic profiling were applied. In general, tepals showed higher polyphenol and flavonoid content than stamen infusions, and their bioactive content depended more on brewing temperature than brewing time. These findings were consistent with both antioxidant capacity and phenolic profiling. Multivariate statistics highlighted polyphenols discriminating 'boiled' vs. 'cold' infusions, being mainly flavonoids, phenolic acids and the alkylphenol 5‐pentadecylresorcinol (showing a strong down‐accumulation at the higher brewing temperatures). Positive correlations could be highlighted between anthocyanins, flavones, flavonols and lignans, and the in vitro antioxidant assays. In general, cold brewing was successful in extracting phenolic compounds and provided better sensory properties, thus indicating that this may represent a valuable strategy to develop saffron‐based functional beverages with better consumers' acceptability. [ABSTRACT FROM AUTHOR]

In a microgravity environment, without any gravitropic signal, plants are not able to define and establish a longitudinal growth axis. Consequently, absorption of water and nutrients by the root and exposure of leaves to sunlight for efficient photosynthesis is hindered. In these conditions, other external cues can be explored to guide the direction of organ growth. Providing a unilateral light source can guide the shoot growth, but prolonged root exposure to light causes a stress response, affecting growth and development, and also affecting the response to other environmental factors. Here, we have investigated how the protection of the root from light exposure, while the shoot is illuminated, influences the direction of root growth in microgravity. We report that the light avoidance mechanism existing in roots guides their growth towards diminishing light and helps establish the proper longitudinal seedling axis in simulated microgravity conditions. This process is regulated by flavonols, as shown in the flavonoid‐accumulating mutant transparent testa 3, which shows an increased correction of the root growth direction in microgravity, when the seedling is grown with the root protected from light. This finding may improve the efficiency of water and nutrient sourcing and photosynthesis under microgravity conditions, as they exist in space, contributing to better plant fitness and biomass production in space farming enterprises, necessary for space exploration by humans. [ABSTRACT FROM AUTHOR]

BACKGROUND During the storage and processing of Lilium bulbs, the phenomenon of violet‐red colour change in Lilium bulbs which is different from enzymatic browning often exists, but the specific mechanism is not clear. RESULTS: In this study, we chose six‐year‐old Lilium davidii var. unicolor to study. Bulb scales which were sealed in polyethylene film plastic bags were exposed to room temperature (20 ± 2 °C) treatment for 5 days (12 h of sunshine and 12 h of sun shading). Metabolomics and transcript omics were conducted to elucidate the mechanism of violet‐red color change in Lilium bulbs. The results showed that the color of Lilium bulb scales was obvious violet‐red in 5 days; chromaticity value measuring showed the a values had the most significant upward trend. Metabolomics analysis showed many metabolites produced from the flavonoid biosynthesis pathway showed an upward trend. Transcriptome revealed that flavonoid biosynthesis pathway was significantly enriched, of which 20 synthesis genes were highly regulated expression. Metabolome and transcriptome co‐analysis that up‐regulated expression of flavonoids synthesis genes including ten chalcone synthase, two anthocyanidin reductase, and chalcone isomerase, 3′‐hydroxylase, 3‐hydroxylase, dihydroflavonol 4‐reductase, anthocyanin synthase, anthocyanidin 3‐O‐glucosyltransferase and flavonol synthase were highly positive correlated with epicatechin, rutin and cyanidin 3‐rutinoside. CONCLUSION: Phenotypic, metabolomic and transcriptomic analysis indicated that the up‐related expression levels of genes and accumulated flavonoids related to flavonoid metabolism contributed greatly to the violet‐red colour change in Lilium bulbs. The results of this study will deepen our understanding of the color formation of violet‐red Lilium bulbs and provide the basis for future storage and preservation of Lilium bulbs. © 2021 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Summary: A purification and fractionation process of the edible flowers of Tibouchina mollis and Tibouchina urvilleana followed by the first attempt to the anthocyanin and flavonol characterisation and identification by UHPLC‐DAD‐ESI‐MS were developed. T. urvilleana exhibited a higher monomeric anthocyanin content, mainly due to the presence of the 3‐O‐(6′‐p‐coumaroyl)‐glucoside derivatives of malvidin and petunidin. Quercetin‐3‐O‐hexoside was the major flavonol identified in T. urvilleana, and the lack of myricetin derivatives was also exhibited. The anthocyanin and flavonol profile of T. mollis was more miscellaneous, characterised by the occurrence of cyanidin‐3‐O‐glucoside followed by the 3‐O‐(6′‐p‐coumaroyl)‐glucoside and 3‐O‐glucoside derivatives of malvidin and petunidin as anthocyanins, and myricetin, quercetin, and 3‐O‐hexosides of kaemperol and quercetin as flavonol compounds. Therefore, the anthocyanin and flavonol profile, through a process based on purification and fractionation, could be a useful tool to ensure the authenticity of the Tibouchina. Furthermore, the purification process made the antioxidant activity increase, which is greatly correlated to the reduction capacity. [ABSTRACT FROM AUTHOR]

BACKGROUND Red light withering significantly improves the sensory flavor qualities of tea, although changes in metabolites during this process have not been systematically studied until now. The present study comprehensively analyzes metabolites in withered tea leaves at 2‐h intervals up to 12 h under red light (630 nm) and dark conditions using ultra performance liquid chromatography‐high resolution mass spectrometry (untargeted metabolomics). RESULTS: Ninety‐four non‐volatile compounds are identified and relatively quantified, including amino acids, catechins, dimeric catechins, flavonol glycosides, glycosidically‐bound volatiles, phenolic acids and nucleosides. The results show that amino acids, catechins and dimeric catechins are most affected by red light treatment. Ten free amino acids, theaflavins and theasinensin A increase after red light irradiation, whereas epigallocatechin gallate and catechin fall. CONCLUSION: The present study provides a comprehensive and systematic profile of the dynamic effects of red light on withering tea and a rationale for its use in tea processing quality control. © 2021 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

The extract of Ginkgo biloba leaf is a popular herbal product or dietary supplement in the world to treat various diseases, and flavonol glycosides are considered as the main bioactive constituents. In this study, 37 flavonol glycosides were rapidly screened out by precursor ion scanning in positive ion mode with production ions at m/z 287.05, 303.05, and 317.06. Subsequently, a reliable and sensitive ultra‐high‐performance liquid chromatography coupled with triple quadrupole‐linear ion trap mass spectrometry approach was established and validated to quantify the 20 prototype flavonol glycosides in rat plasma. Calibration curves showed good linearity (R2 ≥ 0.9894) over the corresponding concentration range. The precision, accuracy, extraction recovery, matrix effect, and stability were also satisfactory. The validated method was successfully applied to a pharmacokinetic study of prototype flavonol glycosides in rat after oral administration of the extract of G. biloba leaf. As a result, the Tmax of flavonol glycosides was short at 0.11–0.60 h. Quercetin‐3‐O‐(2",6″‐di‐O‐rhamnosyl)‐glucoside, kaempferol‐3‐O‐(2′',6′'‐di‐O‐rhamnosyl)‐glucoside, quercetin‐3‐O‐rutinoside, quercetin‐ 3‐O‐glucosyl‐(1‐2)‐O‐rhamnoside, and kaempferol‐3‐O‐glucoside presented relatively high systemic exposure levels with AUC0‐∞ > 500 μg h/L and Cmax > 100 μg/L. This study would provide the valuable information for further scientific research and clinical application of the extract of G. biloba leaf. [ABSTRACT FROM AUTHOR]

In this study, neutral loss scan and high‐resolution MS/MS were used in combination to detect and tentatively identify various flavonoid and limonoid glycosides in navel orange albedo, juice, peel and pulp. These compound classes are of research interest due to their flavour and bioactive properties, and although flavonoid glycosides have been previously studied in other food matrices, to the best of our knowledge, neutral loss scans have not been used for the elucidation of limonoid glycosides. Neutral loss masses of 120, 162 and 308 Da were selected for the detection of hexose, rutinose and neohesperidose‐substituted flavonoids, whereas 197 Da was explored for limonoid glycosides due to their tendency to form ammonium adducts. Fragmentation patterns obtained from targeted MS/MS were then used to differentiate rutinose and neohesperidose substituents as well as flavonoid subclasses of flavones, flavanones and flavonols. Additionally, high‐resolution MS/MS was also used for the identification of aglycones by accurate mass (to four decimal places), allowing for the differentiation of aglycones with similar unit masses but different chemical formulas. In total, 19 flavonoid glycosides and six limonoid glycosides were detected. This workflow allows for a rapid screening of flavonoid and limonoid glycosides in citrus, which can be further extended to other food products such as tea. [ABSTRACT FROM AUTHOR]