Search

Flavonoids are a large and important group of phytochemicals with a great variety of bioactivities. The addition of methyl groups during biosynthesis of flavonoids and other polyphenols enhances their bioactivities and increases their stability. In a previous study of our research group, we detected a novel flavonoid O-methyltransferase activity in Streptomyces albidoflavus J1074, which led to the heterologous biosynthesis of homohesperetin from hesperetin in feeding cultures. In this study, we identify the O-methyltransferase responsible for the generation of this methylated flavonoid through the construction of a knockout mutant of the gene XNR_0417, which was selected after a blast analysis using the sequence of a caffeic acid 3′-O-methyltransferase from Zea mays against the genome of S. albidoflavus J1074. This mutant strain, S. albidoflavus ∆XNR_0417, was no longer able to produce homohesperetin after hesperetin feeding. Subsequently, we carried out a genetic complementation of the mutant strain in order to confirm that the enzyme encoded by XNR_0417 is responsible for the observed O-methyltransferase activity. This new strain, S. albidoflavus SP43-XNR_0417, was able to produce not only homohesperetin from hesperetin, but also different mono-, di-, tri- and tetra-methylated derivatives on other flavanones, flavones and stilbenes, revealing a broad substrate flexibility. Additionally, in vitro experiments were conducted using the purified enzyme on the substrates previously tested in vivo, demonstrating doubtless the capability of XNR_0417 to generate various methylated derivatives. [ABSTRACT FROM AUTHOR]

Flavonoids are pharmacologically active compounds in flowers of Chrysanthemum morifolium 'Boju' (C. morifolium); however, the molecular regulatory network governing flower development remains largely elusive. Flower samples were collected at four stages, namely budding (BD), bud breaking (BB), early blooming (EB), and full blooming (FB), for omics analysis. We revealed distinct transcriptional regulation patterns at these four stages of the flower from the perspective of differentially expressed unigenes (DEGs). There are 152 DEGs shared among the three comparative groups (BD vs. BB, BB vs EB, EB vs FB), wherein the expression of 44 DEGs (including AtADT6, MDL3, and ROMT) continues to be upregulated, and 85 DEGs (including CYP81E, TPS-Cin-1, and TPS-Cin-2) showed persistent downregulation with flower development. Flavonoid-targeted metabolomics identified 118 differentially abundant metabolites (DAMs) in the FB group compared to the BD stage; the top three upregulated and downregulated metabolites are Cyanidin-3-O-(6″-O-malonyl)glucoside-5-O-glucoside, Luteolin-7-O-(6″-caffeoyl)rhamnoside, Kaempferol-3-O-(6″-p-coumaroyl)glucoside and Chrysoeriol-6,8-di-C-glucoside-7-O-glucoside, Kaempferol, Kaempferol-3,7-O-dirhamnoside, respectively. These DAMs were predominantly enriched in "flavonoid biosynthesis", "isoflavonoid biosynthesis", and "flavone and flavonol biosynthesis" pathways. AtADT6, MDL3, ROMT, CYP81E, TPS-Cin-1, and TPS-Cin-2 were correlated with kaempferol. Our findings provide a new idea for interfering with flavonoid production, especially kaempferol, in flowers. [ABSTRACT FROM AUTHOR]

Taking the yield of total flavonoids as an index, the extraction conditions of total Folium Artemisiae Argyi were optimized by ultrasonic-assisted two-water phase method combined with single factor and response surface method.and on this basis, the antioxidant activity was studied in vitro. The results showed that the optimal extraction conditions were PEG400 mass fraction of 24%, the extraction temperature of 60 ℃, the extraction power of 70 W, the extraction time of 50 min. The established mathematical model was verified by experiments. The verification result is that the predicted value is 17.23%, the actual value is 17.25%. The scavenging rate of total flavonoids from Folium Artemisiae Argyi to DPPH, ABTS and hydroxyl radicals were 89.68%, 99.74% and 99.99%, indicating that total flavonoids of Folium Artemisiae Argyi had good antioxidant activity. Conclusion: the method is simple, high yield of flavonoids, and suitable for the extraction of total flavones [ABSTRACT FROM AUTHOR]

A library of C-3 functionalized flavones was successfully provided via palladium-catalyzed amino- and aryloxycarbonylation reactions of 3-iodoflavone (1), under mild conditions. This methodology showed good functional group tolerance using a variety of amines and phenols, under an atmospheric pressure of carbon monoxide as a carbonyl source. While the flavone-3-carboxamides (2a-t) were produced in 22–79%, the flavone-3-carboxylates (4a′-l′) were obtained in excellent yields (up to 88%), under identical reaction conditions, just by switching N-nucleophiles to O-nucleophiles. The convenient availability of the involved starting materials confers simplicity to this approach to design new C-3-substituted flavones of biological relevance. The solid-state structures of flavone-3-carboxamide (2r) and flavone-3-ester (4f′) were further studied by single-crystal XRD analysis. [ABSTRACT FROM AUTHOR]

This study presents the metabolomic profiles of the four Ribes species (Ribes pauciflorum Turcz., Ribes triste Pall., Ribes dicuscha Fisch., and Ribes aureum Purch.). The plant material was collected during two expeditions in the Russian Far East. Tandem mass spectrometry was used to detect target analytes. A total of 205 bioactive compounds (155 compounds from polyphenol group and 50 compounds from other chemical groups) were tentatively identified from the berries and extracts of the four Ribes species. For the first time, 29 chemical constituents from the polyphenol group were tentatively identified in the genus Ribes. The newly identified polyphenols include flavones, flavonols, flavan-3-ols, lignans, coumarins, stilbenes, and others. The other newly detected compounds in Ribes species are the naphthoquinone group (1,8-dihydroxy-anthraquinone, 1,3,6,8-tetrahydroxy-9(10H)-anthracenone, 8,8′-dihydroxy-2,2′-binaphthalene-1,1′,4,4′-tetrone, etc.), polyhydroxycarboxylic acids, omega-3 fatty acids (stearidonic acid, linolenic acid), and others. Our results imply that Ribes species are rich in polyphenols, especially flavanols, anthocyanins, flavones, and flavan-3-ols. These results indicate the utility of Ribes species for the health and pharmaceutical industry. [ABSTRACT FROM AUTHOR]

Potent antioxidants, like 3-hydroxy flavones, attracted considerable attention due to their excited state intramolecular proton transfer (ESIPT)-based fluorescence behaviour. This article is an interesting demonstration of a series of synthetic 3-hydroxy flavone analogues having high antioxidant activity as molecular rotor-like viscosity probes. Among these flavone analogues, 4′-N,N-dimethylamino-3-hydroxy flavone (3) is the most potent one, showing the twisted intramolecular charge transfer (TICT)-dependent fluoroprobing activity toward the blood viscosity changes associated with diabetes and free fatty acids (FFA)-induced nuclear viscosity changes of MIN6 cells. The TICT dynamics of (3), which instigates its viscosity probing activity, was comprehended with the help of DFT-based computational studies. Abnormal cellular viscosity changes are the pathological traits for various diseases, and non-toxic flavone-based viscosity probes can be useful for diagnosing such pathological conditions. [ABSTRACT FROM AUTHOR]

Ginkgo biloba is a famous economic tree. Ginkgo leaves have been utilized as raw materials for medicines and health products due to their rich active ingredient composition, especially flavonoids. Since the routine measurement of total flavones is time-consuming and destructive, rapid, non-destructive detection of total flavones in ginkgo leaves is of significant importance to producers and consumers. Hyperspectral imaging technology is a rapid and non-destructive technique for determining the total flavonoid content. In this study, we discuss five modeling methods, and three spectral preprocessing methods are discussed. Bayesian Ridge (BR) and multiplicative scatter correction (MCS) were selected as the best model and the best pretreatment method, respectively. The spectral prediction results based on the BR + MCS treatment were very accurate (RTest2 = 0.87; RMSETest = 1.03 mg/g), showing a high correlation with the analytical measurements. In addition, we also found that the more and deeper the leaf cracks, the higher the flavonoid content, which helps to evaluate leaf quality more quickly and easily. In short, hyperspectral imaging is an effective technique for rapid and accurate determination of total flavonoids in ginkgo leaves and has great potential for developing an online quality detection system for ginkgo leaves. [ABSTRACT FROM AUTHOR]

Aluminum (Al) toxicity and low phosphorus availability (LP) are the top two co-existing edaphic constraints limiting agriculture productivity in acid soils. Plants have evolved versatile mechanisms to cope with the two stresses alone or simultaneously. However, the specific and common molecular mechanisms, especially those involving flavonoids and carbohydrate metabolism, remain unclear. Laboratory studies were conducted on two wheat genotypes—Fielder (Al-tolerant and P-efficient) and Ardito (Al-sensitive and P-inefficient)—exposed to 50 μM Al and 2 μM Pi (LP) in hydroponic solutions. After 4 days of stress, wheat roots were analyzed using transcriptomics and targeted metabolomics techniques. In Fielder, a total of 2296 differentially expressed genes (DEGs) were identified under Al stress, with 1535 upregulated and 761 downregulated, and 3029 DEGs were identified under LP stress, with 1591 upregulated and 1438 downregulated. Similarly, 4404 DEGs were identified in Ardito under Al stress, with 3191 upregulated and 1213 downregulated, and 1430 DEGs were identified under LP stress, with 1176 upregulated and 254 downregulated. GO annotation analysis results showed that 4079 DEGs were annotated to the metabolic processes term. These DEGs were significantly enriched in the phenylpropanoid, flavonoid, flavone and flavonol biosynthesis, and carbohydrate metabolism pathways by performing the KEGG enrichment analysis. The targeted metabolome analysis detected 19 flavonoids and 15 carbohydrate components in Fielder and Ardito under Al and LP stresses. In Fielder, more responsive genes and metabolites were involved in flavonoid metabolism under LP than Al stress, whereas the opposite trend was observed in Ardito. In the carbohydrate metabolism pathway, the gene and metabolite expression levels were higher in Fielder than in Ardito. The combined transcriptome and metabolome analysis revealed differences in flavonoid- and carbohydrate-related genes and metabolites between Fielder and Ardito under Al and LP stresses, which may contribute to Fielder's higher resistance to Al and LP. The results of this study lay a foundation for pyramiding genes and breeding multi-resistant varieties. [ABSTRACT FROM AUTHOR]

Citrus fruits are widely consumed for their nutritional and health benefits. They belong to the Rutaceae and have many varieties, such as sweet orange (Citrus sinensis), which is the most popular. Citrus fruits are rich in water (>80%), dietary fiber, and vitamins. They also contain bioactive components, which may modulate energy metabolism and lipid oxidation through various mechanisms. These mechanisms include stimulating β3-adrenergic receptors, increasing mitochondrial biogenesis and thermogenesis, activating AMP kinase and peroxisome proliferator-activated receptor-gamma coactivator-1α pathways, inhibiting lipogenesis and lipid accumulation, and inducing browning of white adipose tissue. This review summarizes the mechanisms and outcomes of citrus fruits and their metabolites on energy metabolism and body weight in different experimental models. The literature was searched for in vitro and in vivo animal and human studies that investigated the effects of citrus consumption on energy expenditure, thermogenesis, adipogenesis, and lipid accumulation. Citrus fruits and their metabolites have shown promising effects on energy metabolism and lipid oxidation in in vitro and in vivo animal studies. However, the evidence from human studies is limited and inconsistent. Possible reasons for the discrepancy are briefly discussed, and knowledge gaps and research needs are identified for future studies. Citrus fruits may have beneficial effects on energy metabolism and body weight, but more rigorous and well-designed human trials are needed to confirm their efficacy and safety. [ABSTRACT FROM AUTHOR]

Context The increase in bacterial resistance to currently available medications, which increases mortality rates, treatment costs is a global problem, and highlights the need for novel classes of antibacterial agents or new molecules that interact synergistically with antimicrobials.Objective The current work explores the potential synergistic effects of certain natural phenylpropanoids and flavonoids on ciprofloxacin (CIP), ampicillin (AMP), gentamicin (GEN), and tetracycline (TET).Materials and methods The adjuvant role of cinnamic acid, p-coumaric acid, caffeic acid, ferulic acid, ferulic acid methyl ester, sinapic acid, apigenin, and luteolin was evaluated by determining the MIC (minimal inhibitory concentration) values of antibiotics in the presence of subinhibitory concentrations (200, 100, and/or 50 µM) of the compounds in Gram-positive and Gram-negative bacterial strains using a 2-fold broth microdilution method. The 96-well plates were incubated at 37 °C for 18 h, and dimethyl sulfoxide was used as a solvent control.Results The combination of luteolin with CIP, reduced the MIC values of the antibiotic from 0.625 to 0.3125 µM and to 0.078 µM in 100 and 200 µM concentration, respectively, in sensitive Staphylococcus aureus. Sinapic acid decreased the MIC value of CIP from 0.625 to 0.3125 µM in S. aureus, from 1.56 to 0.78 µM in Klebsiella pneumoniae, and the MIC of GEN from 0.39 to 0.095 µM in Pseudomonas aeruginosa strains.Discussion and conclusions These findings are useful in delaying the development of resistance, as the required antibacterial effect can be achieved with the use of lower concentrations of antibiotics.

This study aimed to explore the relationship between flavonoids intake and the prevalence and all-cause mortality of depressive symptoms in American adults. Analyzing 2007–2008, 2009–2010, and 2017–2018 NHANES data, we examined the association between dietary flavonoid and depressive symptoms, including specific subclasses assessment and mortality outcomes tracking until December 31, 2019. Our methodology included weighted multivariate logistic regression, weighted cox proportional hazards regression and restricted cubic spline (RCS) models, supported by stratified and sensitivity analyses. Among the 12,340 participants in total, 1129 exhibited depressive symptoms. The multiple logistic regression analysis showed a significant reduction in total flavonoid and subclass intake in individuals with current depressive symptoms. Adjusted odds ratios (ORs) for the highest quartiles were 0.69 for anthocyanidins and 0.63 for flavones. Interaction effects emerged in non-hypertensive, higher-income, and normal-weight groups for flavones intake. The RCS model indicated an L-shaped association between depressive symptoms and total flavonoid intake, with inflection points at 346 mg/day. During a median follow-up of 119 months, 148 deaths occurred among patients with depressive symptoms. Hazard ratios (HRs) for all-cause mortality showed a significant positive correlation between total flavonoid intake and survival in model 1 (HR = 0.56), with an optimal intake range of 45.2–948.3 mg/day according to the RCS model. The study relied on U.S. population survey data, potentially limiting generalizability. Unmeasured confounding factors may exist, and genetic factors were not considered. Adequate intake of flavonoids, especially anthocyanidins and flavones, is associated with reduced odds of depressive symptoms. Additionally, optimal intake ranges of flavonoid intake for mental health benefits were observed for all-cause mortality in population with depressive symptoms. • Flavonoid intake is associated with lower depressive symptoms, particularly from anthocyanidins and flavones, and better survival. • The L-shaped link between total flavonoid intake and depressive symptoms and mortality suggests an optimal intake for mental health. • Interaction effects suggest flavones are more linked to depressive symptoms in non-hypertensive, higher-income, normal-weight individuals. [ABSTRACT FROM AUTHOR]

Background: Flavonoids, an important class of specialized metabolites, are synthesized from phenylalanine and present in almost all plant species. Different branches of flavonoid biosynthesis lead to products like flavones, flavonols, anthocyanins, and proanthocyanidins. Dihydroflavonols form the branching point towards the production of non-colored flavonols via flavonol synthase (FLS) and colored anthocyanins via dihydroflavonol 4-reductase (DFR). Despite the wealth of publicly accessible data, there remains a gap in understanding the mechanisms that mitigate competition between FLS and DFR for the shared substrate, dihydroflavonols. Results: An angiosperm-wide comparison of FLS and DFR sequences revealed the amino acids at positions associated with the substrate specificity in both enzymes. A global analysis of the phylogenetic distribution of these amino acid residues revealed that monocots generally possess FLS with Y132 (FLSY) and DFR with N133 (DFRN). In contrast, dicots generally possess FLSH and DFRN, DFRD, and DFRA. DFRA, which restricts substrate preference to dihydrokaempferol, previously believed to be unique to strawberry species, is found to be more widespread in angiosperms and has evolved independently multiple times. Generally, angiosperm FLS appears to prefer dihydrokaempferol, whereas DFR appears to favor dihydroquercetin or dihydromyricetin. Moreover, in the FLS-DFR competition, the dominance of one over the other is observed, with typically only one gene being expressed at any given time. Conclusion: This study illustrates how almost mutually exclusive gene expression and substrate-preference determining residues could mitigate competition between FLS and DFR, delineates the evolution of these enzymes, and provides insights into mechanisms directing the metabolic flux of the flavonoid biosynthesis, with potential implications for ornamental plants and molecular breeding strategies. [ABSTRACT FROM AUTHOR]

Bovine mastitis is a worldwide disease affecting dairy cattle and causes major economic losses in the dairy industry. Recently, the emergence of microbial resistance to the current antibiotics complicates the treatment protocol which necessitates antibiotic stewardship and further research to find new active compounds. Recently, phytobiotics have gained interest in being used as an alternative to antibiotics in the poultry industry as an antibiotic stewardship intervention. This study evaluated the in vitro antibacterial activity of 16 flavonoids against bovine mastitis pathogens. Two flavones: 2-(4-methoxyphenyl)chromen-4-one (1) and 2-(3-hydroxyphenyl)chromen-4-one (4) showed inhibition of the growth of Klebsiella oxytoca with MIC values range (25–50 µg mL− 1) followed by a structure-activity relationship (SAR) study indicating that the presence of a hydroxyl group at C-3' or methoxy at C-4' increases the activity against Klebsiella oxytoca while the presence of hydroxyl group at C-7 decreases the activity. Furthermore, a structure-based drug development approach was applied using several in silico tools to understand the interactions of active flavones at the active site of the DNA gyrase protein. Compound (4) showed a higher docking score than quercetin (standard) which is known to have antibacterial activity by inhibiting the DNA gyrase. In addition, the structure-based pharmacophores of compound (4) and quercetin showed similar pharmacophoric features and interactions with DNA gyrase. Based on our findings, compounds (1) and (4) are promising for further study as potential anti-microbial phytochemicals that can have a role in controlling bovine mastitis as well as to investigate their mechanism of action further. [ABSTRACT FROM AUTHOR]

Flavonoids play an important role in forming wine grapes and wine quality characteristics. The flavonoids of three winter red wine grapes, Yeniang No. 2 (YN2), Marselan (Mar), and Guipu No. 6 (GP6), were analyzed by ultra-high-performance liquid chromatography–triple quadrupole mass spectrometry (UPLC-QQQ-MS). Furthermore, the flavonoids in GP6 grapevines using two types of training systems, namely, trellis (T) and espaliers (E), were also compared in this study. Overall, 196 flavonoid metabolites, including 96 flavones, 38 flavonols, 19 flavanones, 18 polyphenols, 15 anthocyanins, 7 isoflavones, and 3 proanthocyanidins, were identified. The flavonoid profiles were remarkably different among these three grape varieties, while they did not change much in the GP6 managed on trellis and espaliers. Grape varieties with different genetic backgrounds have their own unique flavonoid profiles. Compared with Mar-T, isoflavones and flavonols presented higher contents in GP6-T and YN2-T, which mainly contain glycitein, genistin, calycosin, kaempferide, isotrifoliin, and ayanin. The anthocyanin content was significantly higher in YN2-T than in the other two varieties. YN2 and GP6-T present a more stable color, with significantly more acetylated diglucosides and methylated anthocyanins in YN2-T and GP6-T than in Mar-T. Notably, GP6 had more varied flavonoids and the better characteristics to its flavonoid profile out of these three varieties, due to it containing a higher number of anthocyanins, flavone, and flavonols and the greatest number of different flavonoid metabolites (DFMs), with higher contents than YN2 and Mar. Compared with the trellis training system, the espaliers training system increased the content of flavonoids detected in GP6 grape berries; however, the composition of flavonoids strictly depends on the grape variety. [ABSTRACT FROM AUTHOR]

Background: To investigate the effects of Isoorientin on the apoptosis, proliferation, invasion, and migration of human gastric cancer cells (HGC27 cells). Methods: We used network pharmacology to predict the targets of drugs and diseases. The CCK-8 assay was used to determine the effects of Isoorientin on the proliferation of HGC27 cells. Flow cytometry was employed to analyze the effects of Isoorientin on cell apoptosis and cell cycle distribution of HGC27 cells. Scratch test and transwell chamber test were conducted to assess the effects of Isoorientin on invasion and migration, respectively. Additionally, qPCR and western blot were performed to examine the impact of Isoorientin on apoptosis-related genes and protein expression, respectively. Results: The Isoorientin significantly inhibited the proliferation, migration, and invasion of HGC27 cells compared to the control group. Furthermore, Isoorientin induced apoptosis in HGC27 cells by upregulating the relative expression of Bax and caspase-3 while downregulating the relative expression of p-PI3K, p-AKT, and Bcl-2 proteins. Conclusion: The Isoorientin exhibits inhibitory effects on the proliferation, invasion, and migration of HGC27 cells, and induces apoptosis in gastric cancer cells. [ABSTRACT FROM AUTHOR]

Context: There are currently no approved specific clinical drugs for non-alcoholic fatty liver disease (NAFLD). Salvia miltiorrhiza Bunge-Reynoutria japonica Houtt. drug pair (SRDP) has been widely used in the treatment of chronic liver diseases. However, the mechanism of SRDP treating NAFLD remains unclear. Objective: Based on network analysis and in vitro experimental verification, we investigated the effect of SRDP on lipid deposition and explored its possible mechanism for the treatment of NAFLD. Methods: The TCMSP platform was used to screen the active metabolites of SRDP and corresponding targets. The GeneCards and OMIM databases were used to screen the NAFLD targets. The drug-disease intersecting targets were extracted to obtain the potential targets. Then the protein–protein interaction (PPI) and drug-active metabolites-target-disease network map was constructed. The DAVID database was performed to GO and KEGG pathway enrichment analysis for the intersecting targets. The core active metabolite and signaling pathway were verified by in vitro experiments. Results: Network analysis predicted 59 active metabolites and 89 targets of SRDP for the treatment of NAFLD. 112 signaling pathways were enriched for KEGG pathways, including PI3K-AKT signaling pathway,etc. It was confirmed that luteolin, the core active metabolite of SRDP, effectively reduced fat accumulation and intracellular triglyceride content in HepG2 fatty liver cell model. Luteolin could inhibit mTOR pathway by inhibiting PI3K-AKT signaling pathway phosphorylation, thereby activating autophagy to alleviate NAFLD. Discussion and conclusion: The results of this study validate and predict the possible role of various active metabolites of SRDP in the treatment of NAFLD through multiple targets and signaling pathways. The core active metabolite of SRDP, luteolin can alleviate NAFLD by acting on the PI3K-AKT-mTOR signaling pathway to induce autophagy. [ABSTRACT FROM AUTHOR]

Mulberry perishes easily due to its high water content and thin skin. It is important to extend the shelf life of mulberry by proper processing methods. In the present study, the influence of three drying techniques, including hot air drying (HAD), vacuum drying (VD), and vacuum freeze-drying (VFD) on the quality maintenance of mulberry was comprehensively evaluated. Bioactive compounds, antioxidant activity, and the sensory and volatile flavor compounds of mulberry have been researched. The results showed that VFD treatment maintained the highest anthocyanins (6.99 mg/g), total flavones (3.18 mg/g), and soluble sugars (2.94 mg/g), and exhibited the best DPPH· (81.2%) and ABTS+· (79.9%) scavenging ability. Mulberry also presented the lowest hardness and the greatest brittleness after VFD. Additionally, VFD maintained the optimal color and presented the best sensory attributes. Furthermore, 30, 20, and 32 kinds of volatile flavor compounds were detected in HAD, VD, and VFD, respectively, among which aldehydes, esters, and ketones were the most abundant compounds. This study indicated the potential application value of VFD for the drying of fruit and vegetable foodstuffs. [ABSTRACT FROM AUTHOR]

Objective To investigate the potential active ingredients and the mechanism of Coreopsis tinctoria Nutt. in the prevention and treatment of hyperlipidemia. Methods Ultra-high performance liquid chromatography-Quadrupole-Exactive Orbitrap mass spectrometry (UPLC-Q-Exactive Orbitrap MS) was used to qualitatively analyze the fractions and blood components of flavones in Coreopsis tinctoria Nutt. The intersection targets of flavones in Coreopsis tinctoria Nutt. and hyperlipidemia were screened, and the protein-protein interaction network was constructed and analyzed by the STRING 12.0 database. Finally, the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used for enrichment analysis. Results A total of 25 compounds were detected from the flavones in Coreopsis tinctoria Nutt., and their structures were identified, including ten chalcones, nine flavanones, four flavonols, one aurone, and one biflavone. The analysis of blood components showed that marein, flavanomarein, okanin, isookanin and 5, 7, 3', 5'-tetrahydroxyflavanone-7-O-β-D-glucopyranoside were the main components of the flavones in Coreopsis tinctoria Nutt. in blood. Network pharmacological GO and KEGG enrichment analysis showed that the flavones in Coreopsis tinctoria Nutt. may regulate phosphatidylinositol 3-kinase/protein kinase B, tumor necrosis factor, hypoxia-inducible factor-1 signaling pathway and other signaling pathways in the regulation and prevention of hyperlipidemia. Conclusion Coreopsis tinctoria Nutt. can prevent and treat hyperlipidemia, and the mechanism may be related to the five blood components of the flavones in Coreopsis tinctoria Nutt., including marein, flavanomarein, okanin, isookanin and 5, 7, 3', 5'-tetrahydroxyflavanone-7-O-β-D-glucopyranoside. [ABSTRACT FROM AUTHOR]

Chronic sinusitis is a persistent inflammatory condition needing better treatment options with fewer side effects to reduce recurrence. Luteolin, a flavonoid found in various plants, exhibits anti-inflammatory and anti-allergic properties. This study explores luteolin's impact on chronic sinusitis. We isolated human nasal epithelial cells from sinusitis patients and used lipopolysaccharide-induced cells as a model. High-mobility group box 1 protein was notably elevated in these patients. Our findings suggest that luteolin can suppress the expression of inflammatory cytokines induced by lipopolysaccharide in these cells. Additionally, luteolin was able to inhibit the epithelial--mesenchymal transition in the treated cells. This inhibitory effect on high-mobility group box 1 expression led to reduced inflammation and transition processes. Overall, luteolin could potentially be an effective treatment for chronic sinusitis, minimizing inflammation and cellular transition in nasal epithelial cells. [ABSTRACT FROM AUTHOR]

To investigate the effects of Cirsilineol on cell viability, pyroptosis, and inflammation in hypoxia/reoxygenation-induced renal tubular cells, we utilized the renal tubular epithelial cell line HK2. The in vitro renal injury model was induced by hypoxia/reoxygenation. Cell viability in hypoxia/reoxygenation-induced HK2 cells was determined using a methylthiazolyldiphenyltetrazolium bromide assay and lactate dehydrogenase releasing kit. The effects of Cirsilineol on inflammation and pyroptosis in HK2 cells were evaluated using enzyme-linked immunosorbent assay, flow cytometry, and immunoblot assays. Our results demonstrated that Cirsilineol promoted survival in hypoxia/reoxygenation-induced tubular cells, inhibited inflammation, and reduced pyroptosis in these cells. Further investigation revealed that the protective effects of Cirsilineol are mediated by the suppression of the Toll-like receptor 4/nuclear factor kappa B pathway, which mitigates the cellular response to hypoxia/ reoxygenation injury. Our study suggests that Cirsilineol protects renal tubular epithelial cells from hypoxia/reoxygenation injury by inhibiting inflammation and pyroptosis, highlighting its potential therapeutic value in renal conditions characterized by ischemic injury. [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]

Herpes viruses (HSV) are among the most common viruses that infect humans. They cause blisters and inflammation of the oral and genital mucosa as well as severe symptoms such as blindness, hearing impairment and fatal encephalitis. Although acyclovir (ACV) and its derivatives are highly effective in treating recurrent lytic infections, the emergence of resistant strains remains a concern. In this study, the in vitro anti-herpetic activity of a hydroalcoholic extract obtained from the brown seaweed Sargassum fluitans, collected from strandings in Cuba, was evaluated. The hydroalcoholic extract was not cytotoxic in Vero cells (CC50 >5000 µg mL-1) and inhibited replication of HSV-1 (ACV-susceptible and -resistant) and HSV-2 (ACV-resistant) strains with EC50 of 271.66, 403.62 and 14.99 µg mL-1 respectively. In addition, first studies about mechanism of action were evaluated with ACV-sensitive HSV-1 model. The extract showed strong inhibition when pre-incubated with the virus and when the extract and virus were added simultaneously on the cells. The protection of Vero cells during the post-infection assay was very effective up to 1 h. A high resolution UPLC/MS-MS analysis detected 139 compounds, of which 44 were identified. In silico analysis was performed to determine the putative interaction sites of two flavones of interest identified in the extract with the viral glycoprotein D (gD). Molecular docking analysis revealed that takakin and tectorigenin mainly interact with the gD protein active center through hydrophobic interactions (Leu44, Pro50, Thr174, Lys169, Tyr208, Gln209) while hydrogen bonding interactions are less abundant (Ser43, Asp46, Lys169, Tyr208). This research represents a contribution to the valorization of S. fluitans as a source of anti-herpetic compounds in the context of recurrent and abundant seaweed strandings. [ABSTRACT FROM AUTHOR]

Background: Chrysanthemum morifolium 'HangBaiJu', a popular medicinal and edible plant, exerts its biological activities primarily through the presence of flavones and caffeoylquinic acids (CQAs). However, the regulatory mechanism of flavone and CQA biosynthesis in the chrysanthemum capitulum remains unclear. Results: In this study, the content of flavones and CQAs during the development of chrysanthemum capitulum was determined by HPLC, revealing an accumulation pattern with higher levels at S1 and S2 and a gradual decrease at S3 to S5. Transcriptomic analysis revealed that CmPAL1/2, CmCHS1/2, CmFNS, CmHQT, and CmHCT were key structural genes in flavones and CQAs biosynthesis. Furthermore, weighted gene co-expression correlation network analysis (WGCNA), k-means clustering, correlation analysis and protein interaction prediction were carried out in this study to identify transcription factors (TFs) associated with flavone and CQA biosynthesis, including MYB, bHLH, AP2/ERF, and MADS-box families. The TFs CmERF/PTI6 and CmCMD77 were proposed to act as upstream regulators of CmMYB3 and CmbHLH143, while CmMYB3 and CmbHLH143 might form a complex to directly regulate the structural genes CmPAL1/2, CmCHS1/2, CmFNS, CmHQT, and CmHCT, thereby controlling flavone and CQA biosynthesis. Conclusions: Overall, these findings provide initial insights into the TF regulatory network underlying flavones and CQAs accumulation in the chrysanthemum capitulum, which laid a theoretical foundation for the quality improvement of C. morifolium 'HangBaiJu' and the high-quality development of the industry. [ABSTRACT FROM AUTHOR]

BACKGROUND: Millet bran (MB), a byproduct of millet production, is rich in functional components but it is underutilized. In recent years, researchers have shown that fermentation can improve the biological activity of cereals and their byproducts. This study used Bacillus natto to ferment millet bran to improve its added value and broaden the application of MB. The bioactive component content, physicochemical properties, and functional activity of millet bran extract (MBE) from fermented millet bran were determined. RESULTS: After fermentation, the soluble dietary fiber (SDF) content increased by 92.0%, the β‐glucan content by 164.4%, the polypeptide content by 111.4%, the polyphenol content by 32.5%, the flavone content by 16.4%, and the total amino acid content by 95.4%. Scanning electron microscopy revealed that the microscopic morphology of MBE changed from complete and dense blocks to loosely porous shapes after fermentation. After fermentation, the solubility, water‐holding capacity, and viscosity significantly increased and the particle size decreased. Moreover, the glucose adsorption capacity (2.1 mmol g−1), glucose dialysis retardation index (75.3%), and α‐glucosidase inhibitory (71.4%, mixed reversible inhibition) activity of the fermented MBE (FMBE) were greater than those of the unfermented MBE (0.99 mmol g−1, 32.1%, and 35.1%, respectively). The FMBE presented better cholesterol and sodium cholate (SC) adsorption properties and the adsorption was considered inhomogeneous surface adsorption. CONCLUSION: Fermentation increased the bioactive component content and improved the physicochemical properties of MBE, thereby improving its hypoglycemic and hypolipidemic properties. This study not only resolves the problem of millet bran waste but also encourages the development of higher value‐added application methods for millet bran. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Inhibiting breast cancer stem cell (BCSC) signaling pathways is a strategic method for successfully treating breast cancer. Nobiletin (NOB) is a compound widely found in orange peel that exhibits a toxic effect on various types of cancer cells, and inhibits the signaling pathways that regulate the properties of BCSCs; however, the effects of NOB on BCSCs remain elusive. The purpose of this study was to determine the target genes of NOB for inhibiting BCSCs using in vitro three-dimensional breast cancer cell culture (mammospheres) and in silico approaches. We combined in vitro experiments to develop mammospheres and conducted cytotoxicity, next-generation sequencing, and bioinformatics analyses, such as gene ontology, the Reactome pathway enrichment, network topology, gene set enrichment analysis, hub genes selection, genetic alterations, prognostic value related to the mRNA expression, and mRNA and protein expression of potential NOB target genes that inhibit BCSCs. Here, we show that NOB inhibited BCSCs in mammospheres from MCF-7 cells. We also identified CDC6, CHEK1, BRCA1, UCHL5, TOP2A, MTMR4, and EXO1 as potential NOB targets inhibiting BCSCs. NOB decreased G0/G1, but increased the G2/M cell population. These findings showed that NOB is a potential therapeutic candidate for BCSCs treatment by regulating cell cycle. [ABSTRACT FROM AUTHOR]

In the present research, the physicochemical properties including electronic and structural properties and antioxidant activity of six fluorinated flavone derivatives have been discussed using of density functional theory calculations. Benchmarking studies of the DFT-B3LYP/6–311 + G(d, p) computational method were done using experimental 1HNMR and 13CNMR data of flavones 2 and 5. The experimental and calculated spectral data are in very good agreement with R2 < 92%. Using the DFT-B3LYP/6–311 + G(d, p) method, bond lengths and bond angles, intramolecular hydrogen interactions, EHOMO and ELUMO, electrophilicity index, and reactivity against active oxygen radicals were investigated. The local electrophilicity indices were calculated for flavones 1–6. Three reactive centers can be considered for nucleophilic attack on flavones 1–6. The data showed that the most active center is C9 on the 4-pyrone ring, conducting the Michael reaction, and the presence of -CF3 group on these compounds increases the electrophilic properties of flavones 1–6. Using three mechanisms of hydrogen atom transfer (HAT), single electron transfer followed by proton transfer (SET-PT), and the sequential proton loss electron transfer (SPLET) mechanisms, antioxidant activity of the studied flavones was investigated and compared with data for phenol. The presence of intramolecular hydrogen bonds strongly affects the antioxidant properties. According to the above-mentioned mechanisms, antioxidant activity of studied flavones 1–6 is higher than that of phenol. The presence of fluorine atom has a significant effect on their physicochemical properties. [ABSTRACT FROM AUTHOR]

Lipotoxicity leads to numerous metabolic disorders such as nonalcoholic steatohepatitis. Luteolin, apigenin, and chrysin are three flavones with known antioxidant and anti‐inflammatory properties, but whether they inhibit lipotoxicity‐mediated NLRP3 inflammasome activation was unclear. To address this question, we used J774A.1 macrophages and Kupffer cells stimulated with 100 μM palmitate (PA) in the presence or absence of 20 μM of each flavone. PA increased p‐PERK, p‐IRE1α, p‐JNK1/2, CHOP, and TXNIP as well as p62 and LC3‐II expression and induced autophagic flux damage. Caspase‐1 activation and IL‐1β release were also noted after 24 h of exposure to PA. In the presence of the PERK inhibitor GSK2656157, PA‐induced CHOP and TXNIP expression and caspase‐1 activation were mitigated. Compared with PA treatment alone, Bcl‐2 coupled to beclin‐1 was elevated and autophagy was reversed by the JNK inhibitor SP600125. With luteolin, apigenin, and chrysin treatment, PA‐induced ROS production, ER stress, TXNIP expression, autophagic flux damage, and apoptosis were ameliorated. Moreover, TXNIP binding to NLRP3 and IL‐1β release in response to LPS/PA challenge were reduced. These results suggest that luteolin, apigenin, and chrysin protect hepatic macrophages against PA‐induced NLRP3 inflammasome activation and autophagy damage by attenuating endoplasmic reticulum stress. [ABSTRACT FROM AUTHOR]

Cestrum parqui L'Herit. (Solanaceae family) is a species of forest shrub, self-incompatible and specialized in pollination, widespread in the subtropical area of the planet, and now widely distributed also in the Mediterranean area. The constituents of its leaves have antimicrobial, anticancer, insecticidal, antifeedant, molluscicidal, and herbicidal properties. The spread of this species represents a valuable source of compounds with high biological value. Various research groups are engaged in defining the chemical composition of the different parts of the plant and in defining its properties in view of important and promising commercial applications. To date, there are only a few incomplete reports on the potential applications of C. parqui extracts as selective natural pesticides and on their potential phytotoxic role. Scientific knowledge and the use of extraction techniques for these components are essential for commercial applications. This article summarizes the research and recent studies available on the botany, phytochemistry, functional properties, and commercial applications of C. parqui. [ABSTRACT FROM AUTHOR]

Background: Heart failure (HF) is a complex cardiovascular syndrome with high mortality. Santalum album L. (SAL) is a traditional Chinese medicine broadly applied for various diseases treatment including HF. However, the potential active compounds and molecular mechanisms of SAL in HF treatment are not well understood. Methods: The active compounds and possible mechanisms of action of SAL were analyzed and validated by a systems pharmacology framework and an ISO-induced mouse HF model. Results: We initially confirmed that SAL alleviates heart damage in ISO-induced HF model. A total of 17 potentially active components in SAL were identified, with Luteolin (Lut) and Syringaldehyde (SYD) in SAL been identified as the most effective combination through probabilistic ensemble aggregation (PEA) analysis. These compounds, individually and in their combination (COMB), showed significant therapeutic effects on HF by targeting multiple pathways involved in anti-oxidation, anti-inflammation, and anti-apoptosis. The active ingredients in SAL effectively suppressed inflammatory mediators and pro-apoptotic proteins while enhancing the expression of anti-apoptotic factors and antioxidant markers. Furthermore, the synergistic effects of SAL on YAP and PI3K-AKT signaling pathways were further elucidated. Conclusions: Mechanistically, the anti-HF effect of SAL is responsible for the synergistic effect of anti-inflammation, antioxidation and anti-apoptosis, delineating a multi-targeted therapeutic strategy for HF. [ABSTRACT FROM AUTHOR]

A transition‐metal‐free protocol is proposed for the selective oxidation of flavones, providing various sulfoxide/sulfone‐flavonoids in excellent yields. This strategy features excellent selectivities, high yields and broad substrate scope. The combination of oxone (2KHSO5 ⋅ KHSO 4⋅ K2SO4) as the sole oxidant and NaHCO3/Na2CO3 as the buffer play an important role in the process, in which the amounts of oxone and reaction temperatures are the key to the outstanding selectivities and high efficiency of the reaction. It should be noteworthy that a class of novel sulfone‐flavonols is also synthesized through triple oxidation. Moreover, the glycosylation of sulfone‐flavonols has been realized. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) incidence has increased in the last decades due to changes in dietary habits. IBDs are characterized by intestinal epithelial barrier disruption, increased inflammatory mediator production and excessive tissue injury. Since the current treatments are not sufficient to achieve and maintain remission, complementary and alternative medicine (CAM) becomes a primary practice as a co-adjuvant for the therapy. Thus, the intake of functional food enriched in vegetal extracts represents a promising nutritional strategy. This study evaluates the anti-inflammatory effects of artichoke, caihua and fenugreek vegetal extract original blend (ACFB) in an in vitro model of gut barrier mimicking the early acute phases of the disease. Caco2 cells cultured on transwell supports were treated with digested ACFB before exposure to pro-inflammatory cytokines. The pre-treatment counteracts the increase in barrier permeability induced by the inflammatory stimulus, as demonstrated by the evaluation of TEER and CLDN-2 parameters. In parallel, ACFB reduces p65NF-κB pro-inflammatory pathway activation that results in the decrement of COX-2 expression as PGE2 and IL-8 secretion. ACFB properties might be due to the synergistic effects of different flavonoids, indicating it as a valid candidate for new formulation in the prevention/mitigation of non-communicable diseases. [ABSTRACT FROM AUTHOR]

Dalbergia odorifera is a natural product rich in pharmacological ingredients, but the comprehensive characterization and rapid profiling of active components remain a challenge. Thus, an integrated data mining and identification strategy was exploited to efficiently identify the chemical constituents and screen acetylcholinesterase inhibitors (AChEIs) through affinity ultrafiltration and ultra‐high‐performance liquid chromatography‐mass spectrometry (AUF‐UHPLC‐MS). As a result, polygonal mass defect filtering, diagnostic product ions, and neutral loss rules were created for rapid structural classification and component identification. A total of 140 flavonoids were tentatively characterized, including 41 isoflavonoids, 23 flavanones, 21 isoflavans, 19 flavones and flavonols, 13 neoflavonoids, 11 isoflavanones, seven flavone glycosides, and five chalcones. Subsequently, six natural AChEIs including tectorigenin, fisetin, dalbergin, pterostilbene, isoliquiritigenin, and biochanin A were screened out using AUF‐UHPLC‐MS and molecular docking. Meanwhile, the AChE inhibitory activities of the six compounds were assessed in vitro, tectorigenin, fisetinand, and dalbergin have moderate inhibitory activity. In conclusion, a novel strategy for systematic characterization and further screening of active compounds in natural products was established, which provides a material basis for quality control of Dalbergia odorifera. [ABSTRACT FROM AUTHOR]

Flavones and their derivatives are biologically and medicinally valuable compounds and have attracted the attention of many chemists. In this research project, we first synthesized the Fe3O4@AMBA-BiPy-Pd(0) nanocomposite through a simple method from the available materials, then we evaluated the application of its catalyst in the three-step synthesis of flavone derivatives. The structure of the synthesized nanocatalyst was well confirmed by several identification methods such as FT-IR, SEM, TEM, EDX, TGA, VSM, XRD and ICP-OES; it should be noted that the stability of the recovered Fe3O4@AMBA-BiPy-Pd(0) catalyst was also confirmed by VSM and ICP-OES techniques. The results confirmed that Fe3O4@AMBA-BiPy-Pd(0) nanocomposite is a highly efficient nanomagnetic catalyst because all flavone products were synthesized with very good yields under mild conditions. Based on the recycling experiments, the Fe3O4@AMBA-BiPy-Pd(0) catalyst was simply separated from the reaction mixture with an external magnet and could be reused 8 times without significantly reducing its efficiency. [ABSTRACT FROM AUTHOR]

Rich in antioxidants with a variety of flavones and anthocyanins, passionflower/fruit has been extensively used in food, beverage, medicinal, and natural dyes industries. The individual components present in passionflower are identified by extracting them in methanol, partitioning them between ethyl acetate and aqueous layers, and recording their ESI mass spectrometric data. The steady‐state absorption and fluorescence spectra of the extract in methanol and dimethyl sulfoxide are recorded and the lifetime of the fluorescing species is reported. The pH dependence of the absorption spectrum confirms the presence of the anthocyanins. [ABSTRACT FROM AUTHOR]

Polygonati rhizoma, known for its distinct yellow rhizomes, is a common therapeutic and culinary plant in Far East Asia. The hue of medicinal plants is closely tied to the flavonoid biosynthesis and content levels. In this research, the fibrous root and taproot of Polygonatum kingianum Coll.et Hemsl. were studied to explore the secondary metabolite expression and flavonoid biosynthesis mechanisms using transcriptomics and metabolomics. Metabolic analysis identified that the differentially accumulated metabolites (DAMs) in the fibrous root and taproot were predominantly flavonoids, steroids, alkaloids, and phenolic acids. Overall, 200 flavonoids were identified in P. kingianum Coll.et Hemsl., with 170 exhibiting variances between the fibrous root and taproot. The transcriptome analysis revealed that a total of 289 unigenes encoding 32 enzymes were annotated into four flavonoid biosynthesis pathways, which include phenylpropanoid biosynthesis pathway, flavonoid biosynthesis pathway, isoflavonoid biosynthesis pathway, and flavone and flavonol biosynthesis pathway. The integration of transcriptomic and metabolomic data elucidated that the 76 differentially expressed genes (DEGs) encoding 13 enzyme genes (HCT, CCOMT, C4H, C3′H, CHI, PGT1, FLS, F3′H, CHS, ANR, DFR, F3′5′H, and LAR) and 15 DAMs preferred to be regulated in the flavonoid biosynthesis pathway. The expression of 10 DEGs was validated by qRT-PCR, agreeing with the same results by RNA-Seq. These findings shed light into the biosynthesis of secondary metabolites in P. kingianum Coll.et Hemsl., offering valuable information for the sustainable utilization and enhancement of this plant species. [ABSTRACT FROM AUTHOR]

The incidence of neurological disorders, particularly age-related neurodegenerative pathologies, exhibits an alarming upward trend, while current pharmacological interventions seldom achieve curative outcomes. Despite their diverse clinical presentations, neurological diseases often share a common pathological thread: the aberrant accumulation of misfolded proteins within the endoplasmic reticulum (ER). This phenomenon, known as ER stress, arises when the cell's intrinsic quality control mechanisms fail to cope with the protein-folding burden. Consequently, misfolded proteins accumulate in the ER lumen, triggering a cascade of cellular stress responses. Recognizing this challenge, researchers have intensified their efforts over the past two decades to explore natural compounds that could potentially slow or even reverse these devastating pathologies. Flavonoids constitute a vast and heterogeneous class of plant polyphenols, with over 10,000 identified from diverse natural sources such as wines, vegetables, medicinal plants, and organic products. Flavonoids are generally divided into six different subclasses: anthocyanidins, flavanones, flavones, flavonols, isoflavones, and flavonols. The diverse family of flavonoids, featuring a common phenolic ring backbone adorned with varying hydroxyl groups and additional modifications, exerts its antioxidant activity by inhibiting the formation of ROS, as evidenced by research. Also, studies suggest that polyphenols such as flavonoids can regulate ER stress through apoptosis and autophagy. By understanding these mechanisms, we can unlock the potential of flavonoids as novel therapeutic agents for neurodegenerative disorders. Therefore, this review critically examines the literature exploring the modulatory effects of flavonoids on various steps of the ER stress in neurological disorders. [ABSTRACT FROM AUTHOR]

Copyright of Farmacia is the property of Societatea de Stiinte Farmaceutice Romania and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The flavonoids in citrus fruits are crucial physiological regulators and natural bioactive products of high pharmaceutical value. Melatonin is a pleiotropic hormone that can regulate plant morphogenesis and stress resistance and alter the accumulation of flavonoids in these processes. However, the direct effect of melatonin on citrus flavonoids remains unclear. In this study, nontargeted metabolomics and transcriptomics were utilized to reveal how exogenous melatonin affects flavonoid biosynthesis in "Bingtangcheng" citrus fruits. The melatonin treatment at 0.1 mmol L−1 significantly increased the contents of seven polymethoxylated flavones (PMFs) and up-regulated a series of flavonoid pathway genes, including 4CL (4-coumaroyl CoA ligase), FNS (flavone synthase), and FHs (flavonoid hydroxylases). Meanwhile, CHS (chalcone synthase) was down-regulated, causing a decrease in the content of most flavonoid glycosides. Pearson correlation analysis obtained 21 transcription factors co-expressed with differentially accumulated flavonoids, among which the AP2/EREBP members were the most numerous. Additionally, circadian rhythm and photosynthesis pathways were enriched in the DEG (differentially expressed gene) analysis, suggesting that melatonin might also mediate changes in the flavonoid biosynthesis pathway by affecting the fruit's circadian rhythm. These results provide valuable information for further exploration of the molecular mechanisms through which melatonin regulates citrus fruit metabolism. [ABSTRACT FROM AUTHOR]

Polyphenols, the important secondary metabolites, consist of multiple phytochemicals and show numerous physiological effects. Flavones play a significant role in various chronic disorders such as diabetes.. In this study, all the flavones were encountered, and it was further filtered based on their drug-likeness properties and pharmacokinetic parameters. Existing literature confirms that flavone-based compounds are suitable as the drug of choice in sarcopenic obesity. A molecular docking study was performed toward the myostatin inhibition profile of the flavones using PDB:3HH2 as a target site. This computer-aided drug design helps select lead molecules in novel drug discovery. [ABSTRACT FROM AUTHOR]

The flavone luteolin and the flavonol quercetin naturally occur in plants, providing some resistance against herbivores. However, despite suggesting the potential use of these compounds for plant protection, research on their relationship with aphids is limited. The aim of our study was to assess the effect of applying two flavonoids, quercetin and luteolin, at different concentrations, in vitro on the feeding behavior of the black bean aphid Aphis fabae Scopoli (Hemiptera: Aphididae). In most events associated with stylet activity, differences in probing behavior did not vary between the control gel and those with flavonoids. Higher concentrations of quercetin increased the number of penetrations, while lower concentrations of luteolin prolonged the first probing. The addition of flavonoids to the gels reduced passive ingestion. At a concentration of 0.1%, luteolin completely stopped salivation, and at 0.01%, it shortened the average duration of this activity. In events associated with active ingestion, differences in feeding behavior were observed between the control gel and those with quercetin at lower concentrations, affecting the time to the first stylet activity and the average time of active ingestion. Lower concentrations of luteolin prolonged the time to the first active ingestion, the duration of the first active ingestion, and the average time of this activity. Increased concentrations of quercetin and luteolin negatively affected aphid feeding behavior. Quercetin was better tolerated by A. fabae. A more noticeable effect was observed with an increase in luteolin concentration on the feeding behavior of A. fabae. These findings could be applied in biotechnological projects aiming to develop plants resistant to aphids and other herbivores. [ABSTRACT FROM AUTHOR]

Flavonoids are an abundant class of naturally occurring compounds with broad biological activities, but their limited abundance in nature restricts their use in medicines and food additives. Here we present the synthesis and determination of the antibacterial and antioxidant activities of twenty-two structurally related flavonoids (five of which are new) by scientifically validated methods. Flavanones (FV1–FV11) had low inhibitory activity against the bacterial growth of MRSA 97-7. However, FV2 (C5,7,3′,4′ = OH) and FV6 (C5,7 = OH; C4′ = SCH3) had excellent bacterial growth inhibitory activity against Gram-negative E. coli (MIC = 25 µg/mL for both), while Chloramphenicol (MIC = 25 µg/mL) and FV1 (C5,7,3′ = OCH3; 4′ = OH) showed inhibitory activity against Gram-positive L. monocytogenes (MIC = 25 µg/mL). From the flavone series (FO1–FO11), FO2 (C5,7,3′,4′ = OH), FO3 (C5,7,4′ = OH; 3′ = OCH3), and FO5 (C5,7,4′ = OH) showed good inhibitory activity against Gram-positive MRSA 97-7 (MIC = 50, 12, and 50 µg/mL, respectively), with FO3 being more active than the positive control Vancomycin (MIC = 25 µg/mL). FO10 (C5,7= OH; 4′ = OCH3) showed high inhibitory activity against E. coli and L. monocytogenes (MIC = 25 and 15 µg/mL, respectively). These data add significantly to our knowledge of the structural requirements to combat these human pathogens. The positions and number of hydroxyl groups were key to the antibacterial and antioxidant activities. [ABSTRACT FROM AUTHOR]

Chalcone synthase (CHS) and chalcone isomerase (CHI) catalyze the first two committed steps of the flavonoid pathway that plays a pivotal role in the growth and reproduction of land plants, including UV protection, pigmentation, symbiotic nitrogen fixation, and pathogen resistance. Based on the obtained X-ray crystal structures of CHS, CHI, and chalcone isomerase-like protein (CHIL) from the same monocotyledon, Panicum virgatum, along with the results of the steady-state kinetics, spectroscopic/thermodynamic analyses, intermolecular interactions, and their effect on each catalytic step are proposed. In addition, PvCHI's unique activity for both naringenin chalcone and isoliquiritigenin was analyzed, and the observed hierarchical activity for those type-I and -II substrates was explained with the intrinsic characteristics of the enzyme and two substrates. The structure of PvCHS complexed with naringenin supports uncompetitive inhibition. PvCHS displays intrinsic catalytic promiscuity, evident from the formation of p-coumaroyltriacetic acid lactone (CTAL) in addition to naringenin chalcone. In the presence of PvCHIL, conversion of p-coumaroyl-CoA to naringenin through PvCHS and PvCHI displayed ~400-fold increased Vmax with reduced formation of CTAL by 70%. Supporting this model, molecular docking, ITC (Isothermal Titration Calorimetry), and FRET (Fluorescence Resonance Energy Transfer) indicated that both PvCHI and PvCHIL interact with PvCHS in a non-competitive manner, indicating the plausible allosteric effect of naringenin on CHS. Significantly, the presence of naringenin increased the affinity between PvCHS and PvCHIL, whereas naringenin chalcone decreased the affinity, indicating a plausible feedback mechanism to minimize spontaneous incorrect stereoisomers. These are the first findings from a three-body system from the same species, indicating the importance of the macromolecular assembly of CHS-CHI-CHIL in determining the amount and type of flavonoids produced in plant cells. [ABSTRACT FROM AUTHOR]

The prevalence of various kidney diseases has become a significant threat to global public health and one of the leading causes of severe morbidity and high mortality. Multiple extrinsic or intrinsic factors, including drug or chemotoxicity, aging biomarkers, and various aging-related disorders, may exacerbate multiple kidney diseases and subsequently lead to end-stage renal disease (ESRD). In addition, the complications of kidney pathologies further pose challenges to current clinical practices. However, amid the development of various novel therapeutic approaches against kidney diseases, the interest in natural products or nutraceutical-based treatments has been growing and active in research on renal disorders. Amongst these, luteolin-a flavone, has been shown to be potent in combatting kidney disorders by effectively preventing and ameliorating the progression of various kidney biomarkers and associated pathologies. Therefore, this systemic review assimilates the evidence of numerous in-vitro and in-vivo studies along with the progress in luteolin-based drug development to enlighten its pharmacological potency in treating kidney disorders. The existing reports strongly support the promising therapeutic benefits of luteolin and thus, the review suggests conducting clinical studies to establish it as a potent therapeutic agent against kidney diseases. [ABSTRACT FROM AUTHOR]

Limited treatment options and emerging resistance necessitate the exploration of novel lung cancer therapeutics. This study investigates the potential of Dandang Gendis (Clinacanthus nutans) leaf extract, a Southeast Asian plant, using a combined in vitro and in silico approach. The in vitro study assessed the extract's cytotoxicity towards A549 lung cancer and TIG-1 fibroblast cells using the WST-1 assay. The in silico analysis identified active compounds, predicted a target protein, performed functional annotation and explored mechanisms through molecular docking and dynamics simulations. The in vitro analysis revealed a significantly higher flavonoid content (177.63 mg QE/g) compared to phenols (45.66 mg GAE/g), suggesting a potential role for flavonoids. Importantly, the extract displayed remarkable selectivity in its cytotoxic effects. It significantly reduced A549 lung cancer cell viability while maintaining high viability in normal TIG-1 fibroblasts, particularly at the 24-hour exposure. While concentrations above 200 μg/ mL significantly decreased the viability of A549 cancer cells, normal TIG-1 fibroblast cells maintained high viability (>50%) at these concentrations. In silico analysis identified isomollupentin 7-O-β-glucoside, isoorientin, and isovitexin, all C-glycosyl flavones, as potential active compounds. These compounds were predicted to act as PD-L1 inhibitors, potentially enhancing T cell-mediated antitumor activity. This aligns with the observed selective cytotoxicity. Overall, this study provides evidence for the potential of the C. nutans extract and its C-glycosyl flavone constituents, particularly the identified compounds, as novel lung cancer therapeutics targeting the PD-L1 pathway for T cell-mediated tumor suppression. [ABSTRACT FROM AUTHOR]

A new flavonolignan, sonyamandin (1), along with other known compounds was isolated from the aerial parts and seeds extracts of Silybum marianum (milk thistle) collected from Jordan. The known ones are ursolic acid (2), oleanolic acid (3), maslinic acid (4), oleic acid (5), β-sitosterol (6), β-, sitosteryl glucoside (7), apigenin (8), kaempferol-3-O-rhamnoside (9), apigenin-7-O-β-D-glycoside (10), isosylibin A (11), isosylibin B (12), and silybin B (13). The absolute stereochemistry of 1 was confirmed by 2D NMR and CD analysis. [ABSTRACT FROM AUTHOR]

Methoxychalcones containing the NMe2, 3,4-(OMe)2, 3,4,5-(OMe)3, and isobornyl substituents in the B ring were synthesized from 1,3-dihydroxy-4-(1,7,7-trimethylbicyclo-[2.2.1]hept-exo-2-yl)benzene and 1,4-dihydroxy-3-(1,7,7-trimethylbicyclo[2.2.1]hept-exo-2-yl)benzene. Oxidative cyclization of the new isobornylchalcones afforded flavones bearing the 1,7,7-trimethylbicyclo[2.2.1]hept-exo-2-yl moiety. The erythrotoxicity, membrane-protective, and antioxidant activity of the synthesized compounds were evaluated in in vitro models including the model of oxidative hemolysis of mammalian erythrocytes initiated by H2O2 or 2,2′-azobis-(2-amidinopropane) dihydrochloride. All the chalcones studied and most flavones possessed good hemocompatibility and high antioxidant activity. The promise of further research into the synthesis of effective pharmacological substances based on the title compounds was demonstrated. [ABSTRACT FROM AUTHOR]

The Musa spp. represents the most commonly produced, transitioned, and consumed fruit around the globe, with several important applications in the biotechnology, pharmaceutical, and food industries. Moko disease is produced by Ralstonia solanacearum—a factor with a high impact on all crops in Ecuador, representing one of the biggest phytosanitary problems. Four of the most common varieties of Musa spp. were tested to identify the metabolic reaction of plants facing Moko disease. The phenolic and flavonoid content has been evaluated as a defense system, and the α-diphenyl-α-picrylhydrazyl free-radical-scavenging method (DPPH), free-radical-scavenging activity (ABTS), ferric-reducing antioxidant power (FRAP) assays, and liquid chromatography and mass spectrometry (LC-MS) have been adapted to analyze the active compounds with the antioxidant capacity necessary to counteract the pathogenic attack. Our results indicate that all the studied varieties of Musa spp. react in the same way, such that the diseased samples showed a higher accumulation of secondary metabolites with antioxidant capacity compared with the healthy ones, with high active compound synthesis identified during the appearance of Moko disease symptoms. More than 40 compounds and their derivatives (from kaempferol and quercetin glycosides) with protective roles demonstrate the implication of the Musa spp. defense system against R. solanacearum infection. [ABSTRACT FROM AUTHOR]