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8 recordsLinked to original sources
PubMed2026

Orange juice and hesperidin increase flavanone exposure without detectable short-term vascular benefits: a randomized crossover trial.

Orange juice is a major dietary source of hesperidin, a citrus flavanone with vascular protective effects in experimental models. However, whether nutritionally realistic intake levels induce measurable benefits in humans remains unclear. We investigated the effects of orange juice and hesperidin supplementation, at realistic dietary doses, on vascular function, flavanone bioavailability, and molecular responses. Thirty-seven centrally overweight men completed a randomized, double-blind, controlled, three-period crossover trial with three 6-week interventions separated by washout periods. Participants consumed daily 330 mL of 100% orange juice (OJ), an isoenergetic control beverage (CON), or a hesperidin-enriched control beverage (HESP, 210 mg day-1). Fasting vascular, metabolic and anthropometric parameters were assessed before and after each intervention, with flow-mediated dilation (FMD) as the primary endpoint. Postprandial FMD, circulating flavanone metabolites and oxylipin profiles were evaluated following a standardized high-fat meal challenge, and flavanone bioavailability was assessed by 24 h urinary excretion. Whole-blood transcriptomics were performed in a subset (n = 9). Plasma exposure to phase II hesperetin metabolites (AUC0-6 h) and 24 h urinary excretion were comparable after OJ and HESP, indicating effective hesperidin delivery and limited matrix effects on bioavailability. Neither intervention significantly affected fasting or postprandial FMD, vascular, metabolic or anthropometric parameters, or oxylipin profiles versus CON. Marked interindividual variability was observed in vascular responses and flavanone bioavailability, although treatment effects were unrelated to baseline endothelial function or flavanone exposure. Exploratory transcriptomic analyses suggested modulation of pathways involved in vascular biology following OJ and HESP. Under nutritionally realistic conditions, orange juice and hesperidin induced measurable biological engagement without detectable short-term vascular benefits, highlighting the complexity of linking flavanone exposure to functional vascular outcomes in humans.

Humans↗
PubMed2025

Targeting the "bitterness gene" by genome editing abolishes synthesis of bitter flavanones in citrus; prospects for new varieties and extended climates for cultivation.

Bitterness in citrus fruit is conferred by flavanone-neohesperidosides, whose accumulation is catalyzed by a single enzyme flavanone-7-O-glucosides-1,2-rhamnosyltransferase (1,2RhaT), expressed in both leaves and fruit. To eliminate citrus bitterness, we used CRISPR/Cas9 genome editing to inactivate the 1,2RhaT gene in grapefruit (Citrus paradisi) and "Carrizo" citrange (Citrus sinensis × Citrus trifoliata). Edited lines displayed frameshift mutations that introduced premature stop codons, effectively abolishing the synthesis of the bitter neohesperidosides naringin, neohesperidin, and poncirin. Metabolomic analyses in leaves from 1,2RhaT-mutant lines confirmed the absence of bitter flavanone-neohesperidosides and a compensatory increase in the tasteless flavanone-rutinosides hesperidin, didymin, and narirutin. Since 1,2RhaT is encoded by a single gene, our findings in leaves are expected to be identical for fruit and thus demonstrate a strategy for developing non-bitter citrus cultivars while retaining health-benefitting flavonoid levels. Furthermore, cold-hardy citrus species that are currently unacceptably bitter due to high flavanone-neohesperidoside levels may become useful sources for introduction of cold-hardiness following inactivation of the 1,2RhaT gene. This approach thus paves the way for expanding grapefruit markets and breeding cold-hardy, palatable citrus varieties that are better suited to a wider range of climates.

Flavanones↗
PubMed2026

CgMYC2 directly activates jasmonate-induced naringin biosynthesis in Citrus grandis 'Tomentosa'.

CgMYC2 links jasmonate signaling to naringin biosynthesis by binding G-box motifs and activating flavonoid-pathway promoters in Citrus grandis 'Tomentosa' Naringin, the predominant bitter-flavanone glycoside in Citrus grandis 'Tomentosa', has well-characterized biosynthetic enzymes, yet the transcriptional regulators coupling hormonal signals to pathway activation remain poorly understood. We demonstrate that CgMYC2, a jasmonate-responsive bHLH transcription factor, functions as a central activator of naringin biosynthesis. Exogenous methyl jasmonate (MeJA) treatment increased naringin content 3.45-fold in seedlings, coinciding with a rapid 6.6-fold induction of CgMYC2 that preceded the peak transcription of five core biosynthetic genes (CgPAL5, CgCHS, CgFNS, Cg7GlcT, and Cg1,2RhaT). Physical interaction between CgMYC2 and the JAZ protein CgJAZ3 was confirmed by pull-down and Co-IP assays, placing CgMYC2 within the canonical jasmonate signaling cascade. Y1H confirmed CgMYC2 binding to the Cg1,2RhaT promoter, EMSA demonstrated direct G-box-dependent binding to all five pathway promoters, and dual-luciferase assays showed transactivation of all five promoters, with the strongest activation for CgCHS. As complementary chromatin-level support, a single-sample CUT&Tag profile revealed G-box-enriched CgMYC2-associated chromatin regions across jasmonate-responsive and secondary-metabolic loci. Virus-induced gene silencing (VIGS) of CgMYC2 reduced naringin content by ~21% and suppressed biosynthetic gene expression, supporting its positive contribution. Furthermore, heterologous overexpression in tomato activated the flavonoid pathway and elevated 16 flavonoid compounds, consistent with evolutionary conservation of the MYC2-G-box regulatory logic. These findings establish CgMYC2 as a central, JA-responsive activator bridging jasmonate perception and naringin biosynthesis, providing a molecular framework for the targeted improvement of bitter-flavonoid traits in citrus.

Citrus↗
PubMed2026

Flavonoid biosynthesis mediated by GmF3Hs contributes to drought tolerance in soybean.

Flavonoids are central to abiotic stress responses, yet the specific signaling roles and evolutionary dynamics of flavonoid biosynthetic intermediates in crop drought adaptation remain elusive. Here, we demonstrate that dihydrokaempferol (DHK) and dihydroquercetin (DHQ), specific intermediate products of the soybean flavanone 3-hydroxylases GmF3H1/2, function as potent signaling molecules that mitigate drought stress. Exogenous DHK/DHQ promoted abscisic acid-dependent stomatal closure and enhanced drought tolerance across diverse dicot species, including soybean and tobacco, highlighting a broadly conserved stress-mitigating signaling mechanism. CRISPR/Cas9-generated gmf3hs double mutants exhibited severe drought hypersensitivity due to compromised redox homeostasis and defective stomatal regulation, which could be specifically rescued by DHK/DHQ application. Furthermore, the loss of GmF3H triggered a distinct reproductive trade-off under stress, leading to increased pod initiation but severe filling defects. Multiomics network analysis revealed extensive rewiring of broader stress-responsive pathways and identified upstream transcription factors, among which GmPHL11 directly binds to and activates the GmF3H1 promoter; overexpression of GmPHL11 promoted DHK accumulation and enhanced drought stress tolerance in soybean hairy roots. Finally, population genomic analyses demonstrated that the GmF3H1H1 haplotype, which confers superior enzymatic activity and robust root growth under drought stress, might have undergone positive selection during soybean domestication. Collectively, our findings redefine the role of GmF3H-derived specific intermediates as potent signaling molecules, providing comprehensive mechanistic and evolutionary insights into flavonoid-mediated drought resilience, developmental trade-offs, and molecular breeding in crops.

Drought Resistance↗
PubMed2026

Genomic and Molecular Interaction Analysis of NodD1 in a Novel Bradyrhizobium yuanmingense sp. B64 Isolate for Nodulation and Symbiosis of Legume Plants.

Rhizobial bacteria are known for their ability to fix nitrogen for leguminous plants and their essential function for sustainable agriculture. This study characterizes the taxonomic status and functional potential of the Bradyrhizobium B64 isolate using integrated genomic and molecular approaches. The whole genome of the B64 isolate was sequenced via Illumina paired-end technology. Species delimitation was performed using average nucleotide identity (ANI) and digital DNA-DNA Hybridization (dDDH). The NodD1 protein structure was modeled using AlphaFold3 and validated by Ramachandran plot analysis. Molecular docking was then conducted to evaluate interactions between NodD1 and four signaling flavonoids: Apigenin, Daidzein, Genistein, and Naringenin. Genomic analysis revealed a maximum ANI of 94.4% and dDDH values between 51.4 and 62.4%. Since these values fall below the standard prokaryotic thresholds (ANI&#x2009;<&#x2009;95%; dDDH&#x2009;<&#x2009;70%), the B64 isolate is identified as a novel species. Physiological assays confirmed nitrogen fixation (1.97 ppm), IAA production (3.67 ppm), and phosphate solubilization (26.10 ppm). Structural validation showed 100% of NodD1 residues in allowed regions, ensuring high model reliability. Docking simulations demonstrated strong binding affinities across all flavonoids, with binding free energies ranging from -&#x2009;8.8 to -&#x2009;9.0&#xa0;kcal/mol. Daidzein exhibited the highest thermodynamic stability (-&#x2009;9.0&#xa0;kcal/mol), whereas apigenin showed the most extensive residue interaction network. The B64 isolate is a novel Bradyrhizobium species with a high symbiotic capacity. The stable NodD1-flavonoid interactions provide a molecular basis for efficient nodulation, positioning B64 as a promising candidate for developing lipo-chitooligosaccharide (LCO)-based biofertilizers.

Bradyrhizobium↗
PubMed2026

Dietary naringenin modulates antioxidant status and hepatic lipid deposition in marine medaka (Oryzias dancena) fed a high-fat diet.

High-fat diets (HFDs) are widely used in aquaculture to improve growth and feed efficiency; however, prolonged feeding can disrupt lipid metabolism, induce oxidative stress, and impair physiological homeostasis. This study evaluated the protective effects of dietary naringenin against HFD-induced physiological alterations in the marine medaka Oryzias dancena. Fish were randomly assigned to one of four dietary treatments and fed the respective experimental diets for 45&#xa0;days: a normal-fat diet (NFD, 8% crude lipid), a high-fat diet (HFD, 15% crude lipid), or an HFD supplemented with either 0.075% or 0.15% naringenin. Compared with the NFD group, HFD feeding impaired antioxidant status, altered the expression of genes associated with antioxidant defence and lipid metabolism, and promoted hepatic lipid accumulation. Dietary naringenin, particularly at 0.15%, mitigated these adverse effects by restoring muscle superoxide dismutase activity, enhancing total antioxidant capacity, reducing lipid peroxidation, partially normalizing the expression of lipid metabolism-related genes, and alleviating hepatic lipid vacuolation. These findings indicate that dietary naringenin improves antioxidant defence and helps maintain lipid metabolic homeostasis under high-fat feeding conditions, highlighting its potential as a functional dietary additive for aquaculture.

Animals↗
PubMed2023

Discussion on the mechanism of Lingguizhugan Decoction in treating hypertension based on network pharmacology and molecular simulation technology.

To explore the mechanism of Lingguizhugan Decoction in treating hypertension based on network pharmacology and molecular simulation. The active ingredients and potential targets were screened by the Systematic Pharmacological Analysis Platform of Traditional Chinese Medicine (TCMSP). Hypertension-related targets were obtained from OMIM and GeneCards databases. Common targets between drug and hypertension were screened in the Venny platform. A protein-protein interaction (PPI) network was constructed in the STRING database using intersection targets. Key targets in PPI network were analyzed by Cytoscape. R language program was used for Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Finally, the binding abilities of the main active ingredients to critical targets were verified by molecular simulation. Naringenin, quercetin, kaempferol, and &#x3b2;-sitosterol in Lingguizhugan Decoction, and potential targets such as STAT3, AKT1, TNF, IL6, JUN, PTGS2, MMP9, CASP3, TP53, and MAPK3, were screened out. KEGG Enrichment analysis revealed that the common targets of Lingguizhugan Decoction and hypertension are mainly involved in the lipid and atherosclerosis signaling pathway, AGE-RAGE signaling pathway in diabetic complications, fluid shear stress and atherosclerosis, and IL17 signaling pathway. The molecular simulation results showed that naringenin-MAPK3, quercetin-MMP9, quercetin-PTGS2, and quercetin-TP53 were the top four in the docking scores. Naringenin-MAPK3 and quercetin-MMP9 were stable, with binding free energies of -27.97&#x2009;&#xb1;&#x2009;1.41&#x2009;kcal/mol and -21.15&#x2009;&#xb1;&#x2009;3.17&#x2009;kcal/mol, respectively. The possible mechanism of Lingguizhugan Decoction in treating hypertension is characterized of multi-component, multi-target, and multi-pathway.Communicated by Ramaswamy H. Sarma.

Network Pharmacology↗