Search Results (654)

The present study provides an integrative, targeted phenolic–bioactivity mapping of Hedysarum pestalozzae Boiss., an endemic Fabaceae species from gypsum habitats of Türkiye. Methanolic extracts of flowers, leaves, stems, and roots were comparatively evaluated for their phenolic profiles, antioxidant potentials, and enzyme inhibitory effects. Targeted LC–ESI–MS/MS analysis of selected phenolics revealed organ-dependent chemical profiles, with flowers exhibiting the highest accumulation of flavonols—hyperoside, kaempferol, quercetin—and phenolic acids such as protocatechuic acid, together with the flavanone glycoside hesperidin, while stems and roots were enriched in catechin, verbascoside, vanillin, and eriodictyol. The antioxidant capacities, assessed through multiple assays (CUPRAC, FRAP, DPPH, ABTS, metal chelation), were integrated using the Relative Antioxidant Capacity Index (RACI), ranking flowers as the most active organ, followed by roots, leaves, and stems. Correlation analysis demonstrated strong positive associations between phenolic abundance and electron-transfer assays, whereas metal chelation showed inverse trends, suggesting distinct antioxidant mechanisms. All extracts exhibited moderate inhibition against cholinesterases, tyrosinase, α-amylase, and α-glucosidase, implying multifunctional enzyme-modulating potential. The root extract showed the highest cholinesterase inhibition, and leaf extract was most effective against α-amylase. These findings indicate that H. pestalozzae exhibits organ-dependent chemical diversity and a broad range of biological activities. The present study provides preliminary evidence that H. pestalozzae may represent a promising source of bioactive compounds for future phytochemical and biological investigations, warranting further bioassay-guided fractionation, compound isolation, cellular studies, and in vivo validation. Full article

Peach (Prunus persica) fruit pigmentation is largely associated with anthocyanin accumulation, whereas colorless flavonols such as kaempferol glycosides may reflect alternative use of shared flavonoid precursors. To examine the relationship between anthocyanin and selected kaempferol glycoside accumulation, we analyzed 15 peach accessions classified by red, white, or yellow flesh pigmentation. Skin color was quantified using the a*/b* ratio, where a* represents redness/greenness and b* represents yellowness/blueness. Red-fleshed accessions showed higher skin a*/b* values and accumulated higher levels of total anthocyanins, particularly cyanidin-3-glucoside, than white and yellow accessions. In contrast, kaempferol-3-rhamnoside preferentially accumulated in white-fleshed accessions. Expression analysis of flavonoid pathway genes showed that dihydroflavonol 4-reductase (PpDFR) was more highly expressed in red accessions, whereas flavonol synthase (PpFLS) was more highly expressed in white accessions; chalcone synthase (PpCHS), flavanone 3-hydroxylase (PpF3H), flavonoid 3′-hydroxylase (PpF3′H), and anthocyanidin synthase (PpANS) showed no significant differences among color groups. Heterologous overexpression of PpF3′H in Arabidopsis thaliana, a well-characterized model plant for flavonoid biosynthesis, was associated with increased seed anthocyanin accumulation and a lower kaempferol-to-quercetin ratio, supporting its catalytic capacity to influence flavonoid composition in an exogenous system. Overall, these results indicate that differential anthocyanin and selected kaempferol glycoside accumulation in peach is associated with the relative expression patterns of branch-related flavonoid genes, particularly PpDFR and PpFLS. This study provides targeted metabolic and transcriptional evidence for understanding peach flesh and skin pigmentation and provides mechanistic insight into flavonoid branch competition linking gene expression patterns with metabolite allocation, and identifies candidate genes for improving fruit color and flavonoid-related nutritional quality. Full article

Flavonoids play critical roles in plant adaptation to abiotic stress by acting as potent antioxidants that regulate reactive oxygen species (ROS) homeostasis. In Atriplex canescens (Pursh) Nutt., a halophytic shrub well-adapted to saline and arid environments, transcriptomic analyses revealed that salt stress induces strong upregulation of flavanone 3-hydroxylase (F3H), a key enzyme in the flavonoid biosynthetic pathway. However, the functional role of AcF3H in stress adaptation remains poorly understood. Here, we cloned the AcF3H gene from A. canescens and generated transgenic Arabidopsis thaliana (L.) Heynh. lines constitutively overexpressing this gene. Overexpression of AcF3H significantly enhanced flavonoid accumulation, as confirmed by DPBA staining and total flavonoid quantification, and selectively upregulated the expression of downstream biosynthetic genes AcDFR and AcANS, which encode the dihydroflavonol 4-reductase (DFR) and anthocyanidin synthase (ANS), respectively. Under salt and drought stress, transgenic lines exhibited improved root elongation, increased shoot and root biomass, and higher relative water content compared to wild-type plants. Mechanistic investigations revealed that AcF3H overexpression led to reduced H₂O₂ accumulation and lower plasma membrane permeability under stress conditions, indicating enhanced antioxidative capacity and cellular membrane stability. These results suggest that AcF3H confers enhanced tolerance to abiotic stresses by promoting flavonoid-mediated ROS homeostasis. Our findings highlight AcF3H as a promising genetic target for engineering salt- and drought-tolerant crops. Full article

Ougan (Citrus suavissima Hort. et Tanaka) is valued for its distinctive sweet–bitter flavor and nutritional properties; however, tissue-resolved metabolic differences between two cultivar forms (seeded and seedless) of Ougan (C. suavissima) remains poorly understood. In this study, a comprehensive UPLC-MS/MS-based metabolomic analysis was conducted on peel (SP and NP), pulp (SF and NF), segment membrane (SM and NM) and seed tissues (SS, from seeded fruit only) of seeded and seedless Ougan fruits. A total of 1333 metabolites were annotated, with flavonoids (48.53%) and phenolics (12.25%) representing the predominant compound classes. Tissues specificity was the primary determinant of metabolic variation, with peel and segment membrane tissue showing relatively high abundance (fold change ≥ 2, |Log₂FC| ≥ 1) of phenylpropanoid- and flavonoid-derived metabolites. Comparative analysis between seeded and seedless tissues revealed significant modulation of phenylpropanoid biosynthesis, flavonoid biosynthesis, phenylalanine metabolism, and related secondary metabolite pathways. Seeded tissues showed a higher relative abundance of selected flavonol glycosides (6-hydroxykaempferol-3,6-O-diglucoside), hydroxycinnamic acid derivatives, and santhocyanin-related compounds, whereas seedless tissues showed higher relative abundance of selected flavanones and malonylated flavonoid glycosides. Seeds were characterized by high limonin content, consistent with limonoid-associated bitterness chemistry. Overall, our findings provide a tissue-resolved metabolomic framework for understanding quality-associated secondary metabolite variation in mature Ougan fruit. Full article

Methylated flavonoids are abundant phytochemicals in Eucalyptus and are of interest because methylation can alter flavonoid diversity, bioactivity, and stability. However, the enzymes responsible for flavonoid methylation in eucalypts remain largely uncharacterised. We used comparative leaf transcriptomics of two species with contrasting flavanone profiles, together with protein-structure-guided candidate selection, to identify prospective O-methyltransferases involved in methylated flavonoid biosynthesis. Five candidate methyltransferases from E. eugenioides were cloned, heterologously expressed, and assayed against a panel of flavonoids and a chalcone precursor. The enzymes showed distinct substrate preferences and regioselectivities. EeOMT1 acted as a broad 7-O-methyltransferase, whereas EeOMT3–EeOMT5 preferentially methylated B- and C-ring hydroxyl groups, with differing capacities for sequential methylations at different sites. EeOMT2 was of particular interest because it methylated pinocembrin chalcone to alpinetin chalcone more efficiently than it converted the flavanone pinocembrin to alpinetin. Expression–metabolite analyses across E. eugenioides genotypes were consistent with roles for EeOMT2 and EeOMT1 in the in planta accumulation of 5-O- and 7-O-methylated flavanones, respectively. These findings support a revised model in which alpinetin biosynthesis proceeds, at least in part, through methylation of a chalcone precursor before flavanone formation. This work provides a foundation for elucidating flavonoid methylation pathways in plants and for engineering the production of tailored methylated flavonoids. Full article

The present study describes the phenolic profile of the leaves of 12 different willow species by UPLC^®-RP18-PDA in terms of variability between species, years, harvest month, and among sexes. The analyzed compound classes include salicylic alcohol derivatives (SADs), caffeic acid derivatives (CADs), coumaryl alcohol glucosides (CAGs), flavan-3-ols, flavanones, flavanonols, flavones, and flavonols. Furthermore, the Salix species were chemotaxonomically classified on this basis, and correlations between the constituent classes were analyzed. The investigations indicate that the phenolic spectrum is highly species-specific but reveals no sex-specific variation. The flavan-3-ol content varied substantially among species, ranging from 2.1–36 mg/g DW and S. bicolor was determined to be a species of particular phytochemical interest, as it contained high concentrations of flavanonols (13 mg/g DM) and flavones (24 mg/g DW). Furthermore, at the end of the growth period, the secondary metabolite content was significantly higher and the compound classes CADs and flavan-3-ols were found to be significantly influenced by the harvest year. Chemotaxonomical classification revealed the separation of S. bicolor, S. purpurea, and S. caprea from the other species when compared with the generally accepted classification of the genus. This study contributes to a more comprehensive phytochemical characterization of willow species, which may support the development of willow extracts. Full article

Bergamot (Citrus bergamia Risso et Poiteau), a citrus fruit typically cultivated in the Mediterranean basin, represents a valuable source of bioactive compounds, including polyphenols, flavanone glycosides, and essential oil constituents, which are associated with antioxidant and metabolic effects. Notably, these compounds are highly concentrated not only in the edible fraction but also in industrial by-products, such as peel and pomace, which represent an underexploited resource for sustainable valorisation. This review examines recent advances (2020–2025) in the recovery and application of bioactive compounds from bergamot by-products (BBP), with a focus on green extraction technologies, including ultrasound- and microwave-assisted extraction, enzyme-assisted processes, supercritical fluids, and natural deep eutectic solvents. Particular attention is given to the incorporation of BBP-derived extracts into food systems as natural antioxidants, flavouring agents, and functional ingredients. In addition, current evidence on their nutritional relevance and biological activities, including antioxidants, anti-inflammatory, and lipid-lowering effects, is critically discussed. The integration of green extraction technologies with stabilization strategies, such as microencapsulation, supports the development of clean-label foods enriched with bergamot bioactives, contributing to both product functionality and sustainability. Overall, bergamot by-products (BBP) emerged as a promising model for the circular recovery of natural bioactive compounds and their incorporation into innovative functional food formulations. Full article

(1) Background: Gastric cancer (GC) remains a leading cause of cancer-related mortality worldwide. Aberrant remodeling of the extracellular matrix (ECM) is a hallmark of GC progression; however, the mechanisms by which GC cells sense and exploit ECM cues remain unclear. (2) Methods: ITGA11 was identified through integrative bioinformatic analyses. Its expression, clinical significance, and association with ECM-related signatures were evaluated in GC tissues and public datasets. The function of ITGA11 and its role in regulating the FAK/PI3K/AKT/mTOR pathway were investigated using in vitro and in vivo assays, and the inhibitory effect of Naringenin on ITGA11-associated oncogenic activity was assessed. (3) Results: ITGA11 was upregulated in GC tissues and correlated with an ECM-related gene signature, aggressive clinicopathological features and poor patient survival. ITGA11 promoted malignant phenotypes of GC cells in vitro and in vivo. Importantly, molecular docking and target engagement assays suggested a potential interaction between Naringenin and ITGA11. Functional experiments showed that Naringenin attenuated ITGA11-associated oncogenic activity by reducing ITGA11 levels, suppressing pathway activation, and inhibiting malignant phenotypes. (4) Conclusions: Our findings identify ITGA11 as a potential prognostic biomarker and functional driver of GC progression and suggest that Naringenin may represent a promising bioactive compound for modulating the ITGA11/FAK/PI3K/AKT/mTOR axis in GC. Full article

This study presents the development of a natural hair dye based on Coreopsis tinctoria Nutt. plant extract with and without subsequent mordanting. The dye molecules behind the color development have been investigated to gain better understanding of the relationship between flavonoid structure and color on hair. Yak hair was dyed under different conditions and wash fastness tests were carried out to evaluate the performance of the new hair dye. Analysis of Coreopsis tinctoria Nutt. plant extract was performed to assess the chemical constitution of hair dye. Coreopsis tinctoria Nutt. extract solely led to yellow colors (as represented within L*a*b* color space: L* = 65.5; a* = 0.7; b* = 46.6), whereas the treatment combined with ferrous lactate led to dark brown colors (L* = 26.4; a* = 2.3; b* = 10.0). Wash fastness demonstrated a very good color stability with a maximum loss in color intensity of ΔE = 12.4 after 24 hair washes. Dyeing experiments using the most abundant flavonoids marein, flavanomarein, okanin, and isookanin gave insight into the responsible flavonoids for color outcome. In combination with ferrous lactate, chalcones led to brown colors and flavanones to gray colors. The chalcone okanin presented itself as the most powerful dye, leading to intense colors in combination with ferrous lactate (ΔE = 56.6), at low dye concentrations of 0.1 mg mL⁻¹. Full article

Affective disorders, including anxiety, depression, and bipolar disorder (BD), represent a global mental health burden with complex, multifactorial etiopathogenesis. Increasing evidence implicates neuroinflammation, oxidative stress, and dysregulation of neurotrophic and neurotransmitter systems as central mechanisms driving these conditions. Flavonoids, a structurally diverse class of plant-derived polyphenolic compounds abundantly found in fruits, vegetables, tea, and other dietary sources, have emerged as promising modulators of these pathophysiological pathways. This narrative review synthesizes current preclinical and clinical evidence on the role of flavonoids and related natural compounds in modulating neuroinflammation and affective disorders. We describe the major flavonoid subclasses—flavones, flavonols, isoflavones, anthocyanins, flavanones, and flavan-3-ols—and analyze their mechanisms of action, including inhibition of the NF-κB/NLRP3 axis, reduction in pro-inflammatory cytokines, attenuation of oxidative stress via Nrf2 pathway activation, modulation of monoaminergic and GABAergic neurotransmission, promotion of Brain-Derived Neurotrophic Factor (BDNF)-mediated neuroplasticity, and regulation of the microbiota–gut–brain axis. Preclinical studies consistently demonstrate anxiolytic and antidepressant effects for compounds such as quercetin, luteolin, apigenin, and chrysin; however, clinical evidence remains limited and methodologically heterogeneous. Future research should prioritize bioavailability-enhanced formulations, standardized clinical trials, and biomarker-guided stratification to fully establish the therapeutic potential of flavonoids in affective disorders. Full article

Background: Metabolic syndrome is characterized by dysregulated glucose metabolism and is a major risk factor for type 2 diabetes mellitus and cardiovascular disease. Although glucose-lowering therapies such as glucagon-like peptide-1 receptor (GLP-1R) agonists are effective, their use may be limited by cost, administration route, side effects and tolerability. Bergamot (Citrus bergamia Risso et Poiteau) extract, rich in flavanones, has shown favorable metabolic effects in clinical studies, although its mechanisms of action remain insufficiently defined. This study aimed to investigate the potential glucose-modulating mechanisms of a standardized phospholipid-formulated bergamot extract (BP) (Vazguard™) in vitro. Methods: GLP-1R activation was assessed in a U2OS cell line expressing cyclic adenosine monophosphate (cAMP)-sensitive Nomad Biosensors™. Dipeptidyl peptidase-4 (DPP4) activity was evaluated using a cell-free enzymatic assay, while Glucose transporter type 4 (GLUT4)-mediated glucose uptake was assessed in CHO-K1 cells stably expressing human GLUT4 using an adenosine triphosphate (ATP)-based readout. Cytotoxicity was also using lactate dehydrogenase (LDH), MTT, and nuclei count assays. Results: BP exhibited a dose-dependent (0.31–5 mg/mL) increase in cAMP biosensor fluorescence, consistent with GLP-1R-associated signaling and a maximal response of approximately 60% relative to the positive control (GLP-1R agonist II). No cytotoxic effects were observed. In contrast, BP showed no inhibitory effect on DPP4 activity and did not alter GLUT4-mediated glucose uptake under the experimental conditions tested. Conclusions: These findings provide novel mechanistic evidence that phospholipid-formulated bergamot extract suggests a possible involvement in GLP-1R-associated signaling in vitro, without detectable effects on DPP4 or GLUT4 pathways under the conditions tested. This suggests a mechanism consistent with weak agonist or allosteric modulation of GLP-1R and supports further investigation of bergamot formulated with phospholipids as potential natural adjuncts in metabolic health management. Full article

Flavanones retrieved in the leaves of Glycyrrhiza glabra (licorice), specifically glabranin (GLA), pinocembrin (PIN) and licoflavanone (LIC), represent a valuable source of bioactive natural products, although their isolation and handling are often complicated by their structural similarity and unfavorable physical properties. In this work, crystal engineering strategies were explored both to facilitate the selective separation of licorice flavanones and to improve their solid-state characteristics. Co-crystallization was investigated as a tool for the selective recognition of PIN from a GLA-rich chromatographic fraction. Guided by structural considerations and predictive analyses performed using the Co-Crystal Design and Hydrogen Bond Propensity (HBP) tools in CCDC Mercury (within CCDC-Materials), co-crystallization experiments were performed with pyridinic co-formers. 4,4′-Bipyridine (BPY) selectively formed a new co-crystal with PIN, enabling the capture of traces of this flavanone directly from the GLA-rich fraction. In contrast, nicotinic acid (NIC) did not form a co-crystal with PIN, consistently with the predicted preference for NIC self-association. In addition, a co-amorphous system between LIC and BPY was obtained by quench cooling, yielding a fully amorphous solid with improved handling properties compared to the waxy precursor. These results highlight the potential of crystal engineering approaches for the selective separation and solid-state modification of natural flavanones. Full article

Traditional edible plants such as quelites are an important component of the Mexican diet due to their nutritional and functional value; however, the effects of postharvest and culinary processing on their phytochemical composition remain poorly understood. This study evaluated the impact of oven-drying and freeze-drying, as well as thermal preparation (raw vs. boiled), on the proximal chemical composition, phenolic profile, and antioxidant capacity of leaves and inflorescences of Chenopodium berlandieri subsp. nuttalliae (huauzontle), using an integrated metabolomic approach. Proximal analysis showed that major macronutrients (protein, dietary fiber, lipids, and carbohydrates) were largely preserved across drying methods, whereas moisture and ash contents differed significantly among tissues and treatments (p < 0.05). Raw freeze-dried inflorescences exhibited the highest total phenolic content and antioxidant capacity. UPLC-DAD-ESI-QToF/MS enabled the identification and quantification of 26 phenolic compounds, predominantly glycosylated flavonols derived from quercetin, kaempferol, and isorhamnetin, while naringin was identified as the main flavanone glycoside present. Quercetin glucuronide was the most abundant compound, particularly in inflorescences. Multivariate analyses (principal component analysis [PCA], permutational multivariate analysis of variance [PERMANOVA], and partial least squares discriminant analysis [PLS-DA]) suggested that the drying method was a major source of variability, followed by thermal treatment and tissue type, although these patterns should be interpreted as indicative rather than conclusive. Overall, freeze-drying appeared to be the most effective method for preserving the phytochemical quality of huauzontle under the conditions evaluated, highlighting its potential as a valuable source of bioactive compounds within the genus Chenopodium. Full article

Background/Objectives: Metabolic dysfunction-associated steatohepatitis (MASH) is characterized by severe hepatic steatosis, lobular inflammation, and fibrosis. Although hesperidin, a citrus-derived flavanone, has been reported to exert metabolic and anti-inflammatory effects, its role in severe inflammatory and fibrotic conditions such as MASH remains incompletely understood. This study aimed to evaluate the effects of hesperidin in MASH using integrated in silico and in vivo approaches. Methods: Potential targets of hesperidin were identified using network pharmacology and molecular docking. For in vivo validation, C57BL/6 mice were fed a methionine- and choline-deficient (MCD) diet for five weeks, with oral administration of hesperidin (150 or 300 mg/kg/day) starting from week two. The MCD model induces severe hepatic inflammation and fibrosis but does not fully reflect metabolic features such as obesity and insulin resistance. Hepatic histology, serum transaminases, immune cell populations, and hypothalamic neuroinflammatory markers were assessed. Results: In silico analyses suggested that hesperidin interacts with key regulators associated with MASH, including PPARG, TGFB1, and TNF. In the in vivo MCD-induced model, hesperidin treatment reduced hepatic lipid accumulation and collagen deposition, accompanied by significant decreases in serum ALT and AST levels (by approximately 30–34% and 42–53%, respectively, depending on dose). These effects were associated with downregulation of pro-inflammatory and pro-fibrogenic gene expression and increased expression of antioxidant markers. In addition, hesperidin decreased circulating Ly6C^high monocytes and hepatic Kupffer cells, along with reduced hypothalamic microglial and astrocyte activation. Conclusions: Hesperidin attenuated key pathological features of MASH, including steatosis, inflammation, and fibrosis, and was associated with modulation of peripheral immune responses and central neuroinflammatory markers. These findings suggest that hesperidin may influence the liver–immune–brain axis and warrant further investigation in models that more closely reflect human metabolic conditions. Full article

Phenolic acids and flavonoids remain attractive redox-active scaffolds in medicinal chemistry, where they are widely used for early-stage prioritization and intrinsic reactivity ranking. However, direct comparisons under harmonized conditions remain scarce, limiting structure-based assessment. Here, a structurally diverse panel of hydroxybenzoic acids, hydroxycinnamic acids, flavonoids, a flavanone, and synthetic comparators was profiled using Folin–Ciocalteu response, ABTS radical cation scavenging, DPPH radical scavenging, and reducing power assays. The data reveal pronounced assay dependence alongside clear structure–activity trends. Gallic acid showed the strongest DPPH scavenging (half-maximal inhibitory concentration, IC₅₀ = 4.45 µmol/L) and reducing power (17.26 µmol TE/mg), while quercetin was consistently active across all four endpoints. Eriocitrin (IC₅₀ = 2.47 µmol/L) and rutin (IC₅₀ = 2.66 µmol/L) were particularly effective in the ABTS assay, showing that glycosylation does not abolish cation-radical scavenging. Lipinski’s Rule of Five and Veber oral-bioavailability criteria place these findings within a drug-likeness context. The results also highlight the limitations of the Folin–Ciocalteu assay as a standalone measure of total phenolic content, since its response depends strongly on hydroxylation density. Rather than asserting therapeutic efficacy, this work provides a harmonized comparative dataset identifying phenolic substructures with the strongest and most consistent redox activity, together with the structural drivers underlying these patterns. Full article