Search Results (74)

The development of novel multifunctional emulsifiers using protein–polyphenol interactions is a common strategy. Previously, we investigated the emulsifying properties of the four citrus flavonoids alone. This study investigated how complexing lysozyme (LY) with four citrus-derived flavonoids affects emulsifying properties. Results demonstrated that the emulsification performance was enhanced when flavonoids were complexed with LY, following the order: hesperidin (Hpd) > neohesperidin dihydrochalcone (Neohpddic) > neohesperidin (Neohpd) > hesperetin (Hpt). This enhancement was positively correlated with the intrinsic emulsification abilities of the flavonoids, suggesting that the synergistic effect should not overlook the emulsifying capacity of the flavonoids themselves. The Hpd-LY mixture increased the three-phase contact angle (to near 90°) compared to Hpd alone (51.16° ± 0.58), which helped form high internal phase emulsion (HIPE) gels. Stable HIPEs were achieved at an oil phase fraction φ = 80%, mixture concentration w ≥ 0.8%, and Hpd-to-LY ratio k ≥ 1:1. Droplet size decreased as w increased from 0.6% to 1.2%, but increased with higher φ and k, while gel strength improved. In addition, these HIPEs protected encapsulated lutein and suppressed lipid oxidation. The findings show that flavonoid–protein complexes, especially Hpd-LY, can build stable and functional HIPEs for protecting bioactive compounds. Full article

Background/Objectives: Ludisia discolor, an endangered medicinal orchid, is a vital source of bioactive flavonoids which requires in vitro tissue culture for propagation and metabolite production. While light quality influences metabolic processes, the mechanisms connecting light conditions, phytohormone signaling, and flavonoid biosynthesis remain unclear. This study investigates how specific light qualities trigger secondary metabolism to improve tissue culture and conservation strategies. Methods: L. discolor was cultivated under strictly regulated LED environments (blue, red, yellow, and green). An integrated multi-omics approach, combining transcriptomic sequencing and targeted metabolomic profiling, was employed to analyze leaves, correlating plant hormone changes with flavonoid metabolite levels. Results: LED light qualities significantly altered flavonoid and phytohormone profiles, yielding 80 unique flavonoids. Blue and red light effectively promoted flavonoid accumulation, whereas yellow light suppressed it. Transcriptomics, validated by qRT-PCR, revealed distinct expression patterns in key structural genes (e.g., 4CL, PAL, CYP73A, FLS, CCoAOMT, C12RT1). Ten transcription factors (including MYB93, bZIP36, bHLH4, and bZIP44) with hormone-responsive cis-elements were co-expressed with 16 structural genes. Notably, blue light induced reactive oxygen species (ROS) signaling, activating phytohormone production (IAA, GA, ABA). These hormones subsequently stimulated transcription factors, increasing the biosynthesis of compounds like neohesperidin and hesperetin. Conclusions: We propose a novel regulatory model where light-induced ROS and phytohormone cascades activate specific transcription factors, enhancing structural gene expression in the flavonoid pathway. These findings elucidate the molecular mechanisms of light-driven secondary metabolism, providing valuable insights for the sustainable agriculture and ex situ conservation of endangered medicinal orchids. Full article

Neohesperidin dihydrochalcone (NHDC) has been confirmed to possess excellent nutritional activities as a natural flavonoid low-calorie sweetener, but its practical application in the food industry was greatly limited due to its low water solubility. The potential NHDC activity against oxidative stress (OS) diseases was explored through network pharmacology and molecular docking technology, and a highly water-soluble NHDC-L-arginine complex (NL) was prepared by combining NHDC with L-arginine to overcome this technical bottleneck. Meanwhile, the enhancement of antioxidant capacity markers under non-stressed conditions following NL treatment was systematically investigated in Caenorhabditis elegans (C. elegans), and transcriptomic and metabolomic analyses were integrated to reveal the potential regulatory mechanism at the molecular and metabolic levels. It was found that NHDC could exert potential anti-OS effects by targeting and binding to key proteins such as CYP19A1, TYR, EPHX2, TDP1, ESR1, and SLC5A1. In addition, the MDA level in C. elegans after NL intervention was significantly reduced to 0.65 ± 0.06 nmol/mg prot, while the activities of antioxidant enzymes T-SOD, GSH-Px, and CAT were significantly increased to 48.83 ± 1.75 U/mg prot, 112.95 ± 0.55 U/mg prot, and 6.30 ± 0.16 U/mg prot, respectively. Longevity regulating pathway–worm was identified as a potential key signaling pathway for NL to regulate the enhancement of antioxidant capacity markers under non-stressed conditions of C. elegans at the molecular level, and the pentose phosphate pathway was the core metabolic pathway. These results could offer theoretical support for the potential development of NHDC and NL in the field of antioxidants, as well as their large-scale applications in the functional food and flavored food industries. Full article

Kucha, a unique tea germplasm rich in theacrine, imparts its fresh leaves with a particularly bitter taste and multiple bioactivities. However, systematic studies on processed Kucha—especially white tea—remain limited. In this study, white teas were produced from two Yunnan Kucha accessions (YLKC1, YLKC2) and two conventional cultivars. Their quality characteristics and non-volatile metabolic profiles were systematically compared using sensory evaluation, targeted quantification and widely targeted metabolomics. Results indicated that Kucha white teas displayed pronounced bitterness, with YLKC1 presenting a richer, well-layered flavor, indicating promising quality potential. Targeted quantification demonstrated a remarkably high theacrine content (~30 mg/g) in Kucha white teas, whereas caffeine and several catechin monomers were significantly lower than those in conventional cultivars. Widely targeted metabolomic analysis identified 3376 non-volatile metabolites. PCA and OPLS-DA demonstrated a clear separation in metabolic profiles between Kucha and control groups. In total, 601 significantly differential metabolites were identified. Taste-driven annotation against ChemTastesDB revealed 17 known bitter compounds, 10 of which were significantly accumulated in Kucha white tea—including theacrine, theophylline, theobromine, L-arginine, neohesperidin, pinocembrin, kaempferol-3-O-(6”-malonyl)glucoside, fraxin, adenosine, and xanthine. Among these compounds, theacrine showed the highest upregulation (9.30-fold). In addition, several galloylated flavonoid glycosides also exhibited significant accumulation. KEGG enrichment analysis further indicated that flavonoid biosynthesis and caffeine metabolism were crucial pathways contributing to these metabolic differences. Collectively, these findings demonstrate that the characteristic bitterness of Kucha white tea arises from the coordinated accumulation of a specific set of bitter phytochemicals rather than a single compound and provide a prioritized panel of candidate compounds for flavor-oriented breeding and processing. Full article

Neohesperidin dihydrochalcone (NHDC) is a synthetic sweetener derived from neohesperidin and can improve pathological changes in sepsis-associated acute lung injury (SALI), but the mechanism by which NHDC inhibits SALI remains unclear. We evaluated the therapeutic effect of NHDC (100 mg/kg) and its potential mechanism using bioinformatics approaches with a Lipopolysaccharide (LPS)-induced SALI model (LPS: 10 mg/kg) in mice (n = 6). Bioinformatics analysis identified 176 shared targets between NHDC and SALI, which were enriched in the MAPK signaling pathway. Further screening yielded five key targets (MAPK14, MAPK8, KDR, CASP3, and RHOA) with significant clinical expression differences (p < 0.01). Molecular docking suggested that NHDC could bind to all five targets, with binding energies <−5.0 kJ/mol, and molecular dynamics indicated stable binding between NHDC and MAPK8 (total binding energy ΔG = −181.320 kJ/mol). In vivo, NHDC reversed oxidative stress markers (catalase, superoxide dismutase, glutathione, malondialdehyde, and reactive oxygen species), decreased TNF-α and IL-6 levels, and alleviated lung pathological injury (p < 0.05 vs. model group); it also significantly decreased phosphorylation of mitogen-activated protein kinases(MAPK) pathway proteins (p < 0.001 vs. model group). In summary, our research revealed that NHDC decreased the oxidative stress and inflammatory response of SALI; its specific mechanism is associated with the MAPK pathway. NHDC has a lot of potential as a medication for anti-SALI treatment. Full article

This study investigates the valorisation of sour orange (Citrus aurantium L.) flowers using supercritical antisolvent fractionation (SAF) with CO₂ as an antisolvent. SAF was applied to selectively recover bioactive compounds from ethanolic extracts, using supercritical CO₂ to induce precipitation. Response Surface Methodology (RSM) was employed to optimize operational conditions across a pressure range of 8.7–15 MPa and CO₂ flow rates of 0.6–1.8 kg/h, at a constant temperature of 40 °C. Pressure showed a statistically significant positive effect on precipitate yield, while higher CO₂ flow rates led to reduced recovery. High-performance liquid chromatography (HPLC) analysis identified naringin (33.7%), neohesperidin (21.6%), and synephrine (9.0%) as the main components of the enriched fractions. SAF enabled the selective concentration of these compounds, supporting its application as a green separation technique. As a complementary evaluation, preliminary in silico predictions of ADMET properties and skin permeability were performed. The results indicated favourable absorption, low predicted toxicity, and limited dermal permeation for the major flavonoids. These findings are consistent with available experimental and regulatory safety data. Overall, the study demonstrates the potential of SAF as an effective green technology for the selective extraction and enrichment of high-value bioactive compounds derived from Citrus aurantium flowers, with promising applications in cosmetic, nutraceutical, and pharmaceutical formulations. Full article

Kujingcha (KJC) is a widely consumed substitute tea due to its unique flavor quality and health benefits. However, the biochemical basis for the formation of KJC’s unique flavor quality and health benefits remain unclear. In this study, using Camellia sinensis green tea and its processed fresh leaves as a control, we systematically analyzed the non-volatile and volatile components in KJC and its processed fresh leaves. The results indicate that high levels of flavonoids and water-soluble sugars, and low levels of amino acids and water-soluble proteins, are important biochemical foundations for the formation of taste quality in KJC. High aldehyde, alkene and heterocyclics contents contribute significantly to the aroma of KJC, among which heterocyclics are the key components for the formation of KJC’s rich pan-fried bean-like aroma. Flavonoids such as neohesperidin, hyperoside, rutin, astilbin and morin are important components for the formation of KJC’s health benefits. Full article

Neohesperidin (NH), a bioactive flavanone glycoside, exhibits multifaceted pharmacological properties including antioxidant and anti-inflammatory activities. However, its clinical application is severely constrained by inherent physicochemical limitations such as poor aqueous solubility and instability under physiological conditions. To address these challenges, this study developed a dual-carrier nano-liposomal system through the synergistic integration of phospholipid complexation and hydroxypropyl-β-cyclodextrin (HP-β-CD) inclusion technologies. Two formulations—NH-PC (phospholipid complex) and NH-PC-CD (phospholipid/HP-β-CD hybrid)—were fabricated via ultrasonication-assisted ethanol precipitation. Comprehensive characterization using FTIR and PXRD confirmed the amorphous dispersion of NH within lipid bilayers, with complete elimination of crystalline diffraction peaks, indicative of molecular-level interactions between NH’s hydroxyl groups and phospholipid polar moieties. The engineered nanosystems demonstrated remarkable solubility enhancement, achieving 321.77 μg/mL (NH-PC) and 318.75 μg/mL (NH-PC-CD), representing 2.01- and 1.99-fold increases over free NH. Encapsulation efficiencies exceeded 95% for both formulations, with sustained release profiles revealing 60.81% (NH-PC) and 80.78% (NH-PC-CD) cumulative release over 72 h, governed predominantly by non-Fickian diffusion kinetics. In vitro gastrointestinal simulations highlighted superior bioaccessibility for NH-PC-CD (66.35%) compared to NH-PC (58.52%) and free NH (20.85%), attributed to enhanced stability against enzymatic degradation. Storage stability assessments further validated the robustness of HP-β-CD-modified liposomes, with NH-PC-CD maintaining consistent particle size (<3% variation) and encapsulation efficiency (>92%) over 30 days. Antioxidant evaluations demonstrated concentration-dependent DPPH radical scavenging, wherein nanoencapsulation significantly amplified NH’s activity compared to its free form. This study establishes a paradigm for dual-functional nanocarriers, offering a scalable strategy to optimize the delivery of hydrophobic nutraceuticals while addressing critical challenges in bioavailability and physiological stability. Full article

Acute myeloid leukemia (AML) is a common hematologic malignancy in the elderly with frequent relapse and poor prognosis. Limited treatments highlight the need for novel natural anticancer compounds. Adlay, valued for its medicinal and dietary properties, exhibits anti-inflammatory and anticancer effects. However, research on adlay hulls, particularly their anti-AML bioactive molecules, remains insufficient. This study evaluated the effects of adlay hull ethanol extract (AHE) on AML cell proliferation and apoptosis. AHE was extracted with ethanol and fractionated using n-hexane, ethyl acetate, and n-butanol, followed by silica gel chromatography. Cytotoxicity was assessed via the CCK-8 assay, and mechanisms were analyzed by flow cytometry and Western blotting. The bioactive components were characterized by UPLC-IMS-QTOF-MS. AHE-EA-C (ethyl acetate fraction C) inhibited AML cell proliferation, induced G0/G1 phase arrest, and promoted apoptosis. It suppressed the PI3K/Akt pathway by reducing PI3K and Akt phosphorylation. Using UPLC-IMS-QTOF-MS analysis, a total of 52 compounds with potential anti-AML activity were identified in AHE-EA-C, among which neohesperidin and cycloartanol have been previously reported to exhibit anti-AML activity and thus hold promise as candidates for further development as AML inhibitors. This study is the first to identify adlay hull bioactive components and their anti-AML mechanisms via PI3K/Akt pathway inhibition, providing a foundation for developing natural anti-AML therapies. Full article

In this study, we investigated the inhibitory potential of 60 flavonoids from six distinct subgroups on the programmed cell death ligand 1 (PD-L1) dimer through molecular docking and dynamics simulations. Using AutoDock Vina for docking, the binding poses and affinities were evaluated, revealing an average binding affinity of −8.5 kcal/mol for the flavonoids. Among them, ginkgetin exhibited the highest binding free energy of −46.73 kcal/mol, indicating a strong interaction with PD-L1, while diosmin followed closely, with −44.96 kcal/mol. Molecular dynamics simulations were used to further elucidate the dynamic interactions and stability of the flavonoid–PD-L1 complexes, with the analyses showing minimal root mean square deviation (RMSD) and favorable root mean square fluctuation (RMSF) profiles for several compounds, particularly formononetin, idaein, and neohesperidin. Additionally, contact number and hydrogen bond analyses were performed, which highlighted ginkgetin and diosmin as key flavonoids with significant binding interactions, evidenced by their stable conformations and robust molecular interactions throughout the simulations. Ultimately, a cell-based assay confirmed their ability to inhibit the proliferation of cancer cells. These results, validated through cell-based assays, indicate that the strategy of identifying natural compounds with anticancer activity using computational modeling is highly effective. Full article

Previous research has consistently shown that high-fat diet (HFD) consumption can lead to the development of colonic inflammation. Neohesperidin (NHP), a naturally occurring flavanone glycoside in citrus fruits, has anti-inflammatory properties. However, the efficacy and mechanism of NHP in countering prolonged HFD-induced inflammation remains unclear. In this study, rats on HFD were intragastrically administered (i.g.) with NHP for 12 consecutive weeks. Results indicate that this natural compound is effective in reducing colorectal inflammation at doses of 40–80 mg/kg body weight (BW) by i.g. administration, with significant decreases in inflammation markers such as TNF-α and IL-1β levels. It also improved intestinal mucosal tissue integrity and reduced HFD-stimulated colorectal inflammation via the JAK2/STAT3 pathway. Furthermore, intestinal microbiota sequencing results show that NHP intervention significantly downregulated the Firmicutes/Bacteroidetes ratio. This ratio is closely related to the preventive role in the context of glycolipid metabolism disorder. Compared with fecal cultures of rats from the HFD group, after 48 h in vitro fermentation, those from the NHP group had distinct microbiota composition and notably higher concentrations of SCFAs. Collectively, these observations suggest that 80 mg/kg BW NHP possesses biological activities in downregulating HFD-induced colorectal inflammation by regulating intestinal flora and promoting SCFAs formation. Full article

Twenty-two coumarins and twenty-six flavonoids were quantitated in fingered citron in different growth periods. Limettin was the top coumarin, and diosmin was the highest flavonoid, followed by hesperidin. Antioxidant evaluation by DPPH, ABTS, and FRAP indicated extracts of fingered citron in three growth periods all showed good antioxidant activity, which was positively correlated with the concentration of extracts. The oxidative stress model of RAW264.7 cells indicated extracts from fingered citron effectively reduced the contents of NO, MDA, and ROS in cells and increased the activity of SOD, thereby alleviating cell damage. The antioxidant capacity of fingered citron in November was the highest, followed by July and September. And there was a significantly positive correlation between the total flavonoid content and the antioxidant capacity. Diosmin, hesperidin, and neohesperidin were the main contributors to antioxidation. This study has significance for utilization of fingered citron germplasm resources and development of related functional products. Full article

Habanero pepper (Capsicum chinense) is known for its heat and culinary uses, especially in Mexico’s Yucatán Peninsula. Its leaves, rich in bioactive compounds like polyphenols with antioxidants and anti-inflammatory properties, have been traditionally used in medicinal practices and are gaining interest for health benefits. Efficient green extraction methods, such as natural deep eutectic solvents (NADES), combined with microencapsulation, can improve the stability and application of these compounds in functional foods and nutraceuticals. This study aimed to determine the optimal microencapsulation parameters using response surface methodology, implementing a 2² central composite design with 4 central points of habanero leaf extracts obtained by sonic probe with NADES. The factors evaluated were the percentage of guar gum (5%, 7.5%, and 10%) and the drying temperature (80 °C, 90 °C, and 100 °C). The extracts were spray-dried with maltodextrin (DE17-20), guar gum, and modified starch as encapsulating agents. The total polyphenol content (TPC), polyphenol profile, and antioxidant capacity methods like 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) or ABTS were analyzed. The best results for TPC and ABTS antioxidant capacity were achieved using 7.5% guar gum (GG) at 90 °C. At 104 °C, with the same GG concentration, the microcapsules maintained a high antioxidant capacity. Optimal conditions for TPC, DPPH, and neohesperidin were identified as 7.8% GG/89.4 °C, 8.06% GG/104.1 °C, and 4% GG/75.85 °C, respectively. The resulting powder exhibited high polyphenol content and antioxidant capacity, highlighting successful microencapsulation. Full article

To gain a deeper understanding of the mechanisms by which cushioning packaging preserves the quality of Chinese olive fruits during cold chain transportation and extends their shelf life, this study simulated cold chain conditions and investigated the effects of cushioning packaging on the physiology, antioxidant capacity, and secondary metabolites of fruits during a 20-day shelf life. The results indicated that the decay rate in cushioning-packaging-treated fruit was 75% lower than that in the unbuffered packaging fruit at day 20 of shelf life. Simultaneously, cushioning packaging treatment mitigated the damage severity of the cell membrane structure and kept the cell membrane permeability at a low level, which was 15.34% lower than that in the unbuffered packaging fruit at day 20 of shelf life. Additionally, cushioning packaging effectively restrained the increases in malondialdehyde (MDA) content and alleviated the decline in chlorophyll and total flavonoid contents. It kept a balance among reactive oxygen species (ROS), antioxidant levels, and antioxidant enzyme activities, thereby reducing mechanical-damage-induced decay rates in Chinese olive fruits during the shelf life. Furthermore, metabolome analysis of Chinese olives during the shelf life was performed comparing those without buffered packaging to those with buffered packaging. The metabolome analysis found that the flavonoid biosynthetic pathway exhibited a higher accumulation of chrysin, neohesperidin, naringenin chalcone, sakuranetin, quercetin, catechin, and naringenin metabolites in cushion-packaging treatment compared to those without cushioning treatment. Furthermore, within the phenylalanine metabolic pathway, the accumulation of phenylalanine, p-coumaraldehyde, p-coumaric acid, coniferin and caffeoyl quinic acid metabolites was significantly higher in buffered-packaging groups compared to those without buffering. Together, these findings suggest that cushioning packaging can effectively sustain the integrity of cell membranes and enhance the shelf-life quality of Chinese olive fruits by regulating the balance of ROS and mitigating oxidative stress during cold chain transportation. Full article

Flavonoids derived from plants in the citrus family can have an alleviating effect on allergic asthma. The aim of this study was to provide insights into the mechanisms by which these compounds exert their effects on allergic asthma by combining theoretical and practical approaches. Aurantii Fructus Immaturus flavonoids (AFIFs) were obtained by solvent extraction and were determined by high performance liquid chromatography (HPLC). In vivo and in vitro experiments combined with network pharmacology, Mendelian randomization (MR) analysis and the AutoDock method were applied to study the mechanism of their effects. The main AFIFs were found to be hesperidin (13.21 mg/g), neohesperidin (287.26 mg/g), naringin (322.56 mg/g), and narirutin (19.35 mg/g). Based on the network pharmacology and MR analysis results, five targets Caspase 3 (CASP3), CyclinD1 (CCND1), Intercellular adhesion molecule (ICAM), erb-b2 receptor tyrosine kinase 2 (ERBB2), and rubisco accumulation factor 1 (RAF1) were selected, and the interactions between the AFIFs and the targets were studied using AutoDock Vina. The results indicated that glycosidic bonds play an important role in the interactions between AFIFs and both ERBB2 and RAF1. Full article