Search Results (47)

4′-Hydroxymethoxychalcones represent structurally diverse chalcone derivatives that are attractive substrates for microbial functionalization; however, the impact of methoxy substitution position on their cascade biotransformation by fungi remains poorly understood. In this study, three regioisomeric 4′-hydroxymethoxychalcones, featuring ortho-, meta-, or para-methoxy groups on ring B, were transformed using eight entomopathogenic fungal strains belonging to the genera Beauveria, Isaria, and Metarhizium. Metabolic profiles were monitored over a 10-day period using ultra-high-performance liquid chromatography coupled with diode-array detection (UHPLC-DAD), and the structures of the major products were elucidated primarily by one- and two-dimensional nuclear magnetic resonance (NMR) spectroscopy and further supported by high-resolution electrospray ionization quadrupole time-of-flight mass spectrometry (HR-ESI-QTOF-MS). The investigated microorganisms catalyzed multistep transformations encompassing the reduction of the α,β-unsaturated carbonyl system, methylglucosylation, O-demethylation, and the formation of secondary polar metabolites. Although ene-reduction constituted the predominant initial reaction for all substrates, the relative distribution of subsequent metabolites varied depending on both the fungal strain and, to a lesser extent, the position of the methoxy group. The ortho-methoxy derivative exhibited the highest propensity for O-demethylation; the meta-substituted substrate generated the most heterogeneous secondary metabolite profiles, whereas the para-methoxy analogue showed the most consistent accumulation of methylglucosylated dihydrochalcones. These findings indicate that methoxy substitution position does not alter the common core biotransformation pathway, but can modulate the relative efficiency of individual steps and the extent of secondary metabolism. Full article

The aim of this study was to develop novel and sensory-acceptable microgreens–apple juices and characterize them using UHPLC Q-ToF MS-based metabolomic analysis. The obtained juices showed reduced sugar content and mild acidity compared with the control apple juice. Untargeted analysis revealed 71 compounds, including phenolics, betalains, and one glucosinolate. Semi-quantification confirmed a high content of sinapic acid and its derivatives and hydroxybenzoic acid in broccoli–apple juice, as well as a predominant amount of phenolic acid diglycosides and hydroxycinnamoyl–isocitric acid derivatives in amaranth–apple juice. Apigenin C-glycosides were the main phenolics in red beet–apple juice, with the highest content of cytisoside derivatives. All microgreen-based juices contained apple-derived flavan-3-ols, procyanidins, dihydrochalcones, and certain flavonols. The formulated juices exhibited promising antioxidant potential evaluated by several screening assays (TPC, DPPH, ABTS, and FRAP), consistent with their phytochemical profiles, while differences among them may be linked to the amounts of certain bioactive molecules, mainly derived from microgreens. Moreover, these juices showed high overall quality and consumer acceptability, successfully masking typical microgreens flavors. Overall, these cold-pressed microgreen–apple juices can be classified as novel, low-calorie, and highly sensory-acceptable beverages, containing diverse bioactive compounds from both apple and microgreens; however, further in vitro and in vivo evidence is needed to support claims regarding their functionalities. Full article

Weeds are a major cause of crop production losses worldwide, and environmentally friendly chemical control based on natural or semisynthetic compounds has attracted increasing attention. In this study, flavokawains, a class of natural chalcones, and their analogues were converted into dihydrochalcones (1–27) via Pd-catalyzed hydrogenation. The herbicidal activities of these compounds were evaluated against Chinese amaranth (Amaranthus tricolor) and barnyard grass (Echinochloa crus-galli). Several compounds significantly inhibited seed germination and seedling growth in both species. Herbicidal activity was strongly influenced by the type and position of aromatic substituents, with electron-withdrawing groups and meta substitution providing higher activity. The meta-chloro derivative (15) exhibited the highest activity, markedly inhibiting seed germination as well as shoot and root growth. Further investigation of its mode of action revealed that this compound interfered with seed imbibition, inhibited α-amylase activity, and affected membrane integrity and malondialdehyde (MDA) levels in A. tricolor in a concentration-dependent manner. These findings provide valuable insights for the development of natural product-derived herbicides. Full article

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

Whole-cell biocatalysis presents a sustainable and efficient approach for the selective reduction in α,β-unsaturated bonds in flavonoid derivatives. This study investigates the capability of yeast strains from the Yarrowia clade to catalyze the chemoselective reduction of 4′-methoxychalcone (1a) to its dihydro derivative. All tested strains exhibited similarly high hydrogenation activity, indicating a broadly conserved enoate reductase function within the clade. Among them, Yarrowia lipolytica KCh 71, previously reported and well characterized in the literature, was selected for preparative-scale transformation of a diverse series of synthetic methoxychalcones bearing additional methoxy groups in positions C-2, C-3, C-4, C-5, and C-6 of ring B. All derivatives were effectively converted into the corresponding dihydrochalcones, with yields ranging from 62% to 92%. Among the tested derivatives, the 2′,4′,6′-trimethoxy chalcone (7a) did not undergo biotransformation under our conditions, whereas mono- and di-methoxy derivatives (2a–6a) were efficiently reduced. These results confirm the broad substrate tolerance, high efficiency, and potential scalability of Y. lipolytica KCh 71, supporting its potential as a whole-cell biocatalyst for the sustainable synthesis of bioactive dihydrochalcones. The consistently high hydrogenation activity observed across 21 tested strains suggests the involvement of evolutionarily conserved enoate reductases. Bioinformatic analysis supports that the Yarrowia clade possesses a robust complement of Old Yellow Enzymes (OYE), providing a reliable enzymatic basis for the observed chemoselective reductions. All Yarrowia tested strains showed the same general transformation type, although the extent and rate of conversion differed among strains, and Y. lipolytica KCh 71 was one of the most tolerant. The broad reduction in α,β-unsaturated chalcones is consistent with the action of flavoenzymatic ene-reductases, particularly Old Yellow Enzyme (OYE)–like reductases. Bioinformatic analysis of Yarrowia genomes reveals putative OYE homologs, supporting this mechanistic interpretation, although the specific enzymes were not identified in this study. 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

Porphyromonas gingivalis is a key periodontal pathogen whose cysteine proteases, gingipains (Rgp and KGP), are essential for nutrient acquisition and virulence. Targeting gingipains may attenuate bacterial pathogenicity and prevent related systemic diseases. This paper aimed to review advances in food-derived natural products that inhibit P. gingivalis or gingipains, with emphasis on mechanisms, potency, and translational potential. A literature search of several databases identified 64 studies on food-derived compounds demonstrating in vitro, in vivo, or clinical effects against P. gingivalis or gingipains. The results showed that tea polyphenols and dihydrochalcones (e.g., phloretin and phlorizin) inhibited gingipain activity, and a variety of food-derived natural products (especially polyphenols and polysaccharides) suppressed the growth, survival, biofilm formation, and virulence of P. gingivalis. Structure–activity relationships suggest galloyl moieties and dihydrochalcone scaffolds enhance gingipain inhibition. Polysaccharides and alkaloids exhibited anti-adhesion or protease inhibition, though with limited potency data. In summary, food-derived natural products represent promising gingipain inhibitors. These inhibitors have potential structure–activity relationships, indicating that food-derived natural products have considerable research prospects. Future research should prioritize structure-based discovery and structure optimization to realize their therapeutic potential. Full article

The excessive use of synthetic pesticides has not only resulted in increased resistance among weeds and pests, leading to significant economic loss, but has also raised serious health and environmental concerns. Chalcones and their derivatives, known for their herbicidal, fungicidal, bactericidal, and antiviral properties, are emerging as promising bio-based candidates. These naturally occurring compounds have long been recognized for their beneficial health effects and wide-range applications. However, their limited concentration in plants, along with poor solubility and bioavailability, brings challenges for their development. The aim of this study was to examine the properties of a synthetic substance, pinocembrin dihydrochalcone (3-phenyl-1-(2,4,6-trihydroxyphenyl)-1-propanone), including its soil dissipation and adsorption. Additionally, we evaluated its antioxidant activity through the DPPH assay and FRAP experiments. This analysis aims to provide insights into its potential classification as a low risk pesticide. Full article

Annatto (Bixa orellana L.) is cultivated primarily for the extraction of bixin, a natural dye with substantial industrial importance, resulting in the generation of large quantities of residues that remain underutilized. This study provides the first in-depth characterization of annatto byproducts derived through molecular distillation, highlighting their untapped potential for sustainable innovation. Employing state-of-the-art techniques—HS-SPME-GC-MS for volatile compounds and UPLC-MS/QTOF for non-volatile ones—the research identified a remarkable array of bioactive constituents. Over thirty pharmacologically significant compounds were unveiled, many appearing for the first time in annatto byproducts. Notable discoveries include diterpenoid alcohols, oleamide, δ-tocotrienol, n-alkanes, fatty acid methyl esters, and springene among the volatiles. Among the non-volatiles, groundbreaking identifications such as dihydroactinidiolide, dihydrochalcone, 3-phenyl propiofenone, novel tetracosan amides, halisphingosine A, kauranetriols, and phytoene derivatives redefine the chemical profile of this residue. Further amplifying the value of these findings, the study successfully transformed these byproducts into innovative antioxidant packaging materials, demonstrating their high potential for food preservation and sustainable applications. The packaging films, developed from samples devoid of vegetable oil, exhibited robust antioxidant properties, offering a compelling solution to extend shelf life and reduce spoilage. This work underscores the importance of revalorizing agricultural residues like annatto byproducts, turning waste into high-value resources that align with the principles of the circular economy. Full article

Atherosclerosis is caused by injury to the blood arteries and progressive oxidative stress. Blood cells play an important role in its development; thus, their protection is important. Naringenin (N) is documented to possess a protective action against atherosclerosis, and we hypothesize that its derivatives, naringin (Nr) and naringin dihydrochalcone (Nd), with slightly different structures, possess similar or better activity. Therefore, this research aimed to find the mechanism of protective action of N, Nr and Nd in relation to erythrocytes, peripheral blood mononuclear cells (PBMCs) and platelets in terms of their potential anti-atherosclerotic effect. Moreover, their physicochemical properties and the interaction of flavonoids with liposomes were studied. All flavonoids protected erythrocytes from AAPH- and H₂O₂-induced oxidation to varying degrees. None of them had a destructive effect on erythrocyte membrane, and they did not impact the metabolic activity of PBMC and platelets. Nr and Nd inhibited collagen-induced platelet aggregation better in tested concentrations than N. Studied compounds did not induce liposome aggregation, but N and Nd changed their dipole potential. Obtained results show that Nd possesses slightly better activity than N and may have a better potential health effect on blood cells, which is very important in the design of anti-atherosclerotic therapeutics. Full article

Lung cancer stands out as a leading cause of death among various cancer types, highlighting the urgent need for effective anticancer drugs and the discovery of new compounds with potent therapeutic properties. Natural sources, such as the Conamomum genus, offer various bioactive compounds. Adunctin E (AE), a dihydrochalcone derived from Conamomum rubidum, exhibited several pharmacological activities, and its potential as an anticancer agent remains largely unexplored. Thus, this study aimed to elucidate its apoptotic-inducing effect and identify its molecular targets. The network pharmacology analysis led to the identification of 71 potential targets of AE against lung cancer. Subsequent gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Reactome pathway enrichment analyses revealed the involvement of these targets in cancer-associated signaling pathways. Notably, HSP90AA1, MAPK1, and PIK3CA emerged as key players in apoptosis. In silico molecular docking and dynamic simulations suggested a strong and stable interaction between AE and HSP90AA1. In vitro experiments further confirmed a significant apoptotic-inducing effect of AE on lung cancer cell lines A549 and H460. Furthermore, immunoblot analysis exhibited a substantial decrease in HSP90AA1 levels in response to AE treatment. These findings support the potential anticancer activity of AE through the HSP90AA1 mechanism, underscoring its promise as a novel compound worthy of further research and development for anti-lung cancer therapy. Full article

The cider-making industry in Asturias generates between 9000 and 12,000 tons of apple pomace per year. This by-product, the remains of the apple pressing, and made up of peel, flesh, seeds and stems, is a valuable material, containing substantial amounts of antioxidant compounds associated with healthy properties. Polyphenols such as dihydrochalcones and quercetin glycosides, and triterpenic acids, among which ursolic acid is a major compound, are the main antioxidant families described in apple pomace. The simultaneous recovery of those families has been accomplished by low frequency ultrasound-assisted extraction. Working extraction conditions were optimised by response surface methodology (RSM): time, 5.1 min; extractant composition, 68% ethanol in water; solid/liquid ratio, 1/75 and ultrasonic wave amplitude, 90%. This procedure was further applied to analyse those components in the whole apple pomace (WAP), apple peel (AP) and apple flesh (AF). On average, dry WAP contained almost 1300 µg/g of flavonols, 1200 µg/g of dihydrochalcones and 4200 µg/g of ursolic acid. These figures increased in the apple peel to, respectively 2500, 1400 and 8500 µg/g dry matter. Two linear multivariate regression models allowed the antioxidant activity of apple by-products to be predicted on the basis of their bioactive composition. The results derived from this study confirm the potential of industrial cider apple pomace as a source of high-value bioactive compounds, and the feasibility of the ultrasound-assisted extraction technique to recover those components in a simple and efficient way. Full article

The quest for novel therapeutic agents has rekindled interest in natural products, particularly those derived from biotransformation processes. Dihydrochalcones, a class of plant secondary metabolites, exhibit a range of pharmacological properties. Chalcone and dihydrochalcone compounds with the characteristic 4’-hydroxy substitution are present in ‘dragon’s blood’ resin, known for its traditional medicinal uses and complex composition, making the isolation of these compounds challenging. This study investigates the efficient production of 4′-hydroxydihydrochalcones using non-conventional yeast strains. We evaluated the biotransformation efficiency of various 4′-hydroxychalcone substrates utilizing yeast strains such as Yarrowia lipolytica KCh 71, Saccharomyces cerevisiae KCh 464, Rhodotorula rubra KCh 4 and KCh 82, and Rhodotorula glutinis KCh 242. Our findings revealed that Yarrowia lipolytica KCh 71, Rhodotorula rubra KCh 4 and KCh 82, and Rhodotorula glutinis KCh 242 exhibited the highest conversion efficiencies, exceeding 98% within one hour for most substrates. The position of methoxy substituents in the chalcone ring significantly influenced hydrogenation efficiency. Moreover, we observed isomerization of trans-4′-hydroxy-2-methoxychalcone to its cis isomer, catalyzed by light exposure. This study underscores the potential of using yeast strains for the sustainable and efficient production of dihydrochalcones, providing a foundation for developing new therapeutic agents and nutraceuticals. Full article

Saprolegnia sp. is a pathogenic oomycete responsible for severe economic losses in aquaculture. To date, there is no treatment for its control that is effective and does not pose a threat to the environment and human health. In this research, two dihydrochalcones 1 and 2, and three chalcones 3–5, isolated from the resinous plant Adesmia balsamica, as well as their synthesized oxyalkylated derivatives 6–29 already reported and a new synthesized series of oxyalkylchalcones 30–35, were evaluated for their anti-saprolegnia activity and structure–activity relationship as potential control and treatment agents for strains of Saprolegnia parasitica and S. australis. Among the molecules tested, natural 2′,4′-dihydroxychalcone (3) and new oxyalkylchalcone 34 were the most potent antisaprolegnia agents against both strains, even with better results than the commercial control bronopol. On the other hand, the structure–activity relationship study indicates that the contributions of steric and electrostatic fields are important to enhance the activity of the compounds, thus the presence of bulky substituents favors the activity. Full article

Conditions in the gastrointestinal tract and microbial metabolism lead to biotransformation of parent, native phenolic compounds from apples into different chemical forms. The aim of this work was to review current knowledge about the forms of phenolic compounds from apples in the gastrointestinal tract and to connect it to their potential beneficial effects, including the mitigation of health problems of the digestive tract. Phenolic compounds from apples are found in the gastrointestinal tract in a variety of forms: native (flavan-3-ols, phenolic acids, flavonols, dihydrochalcones, and anthocyanins), degradation products, various metabolites, and catabolites. Native forms can show beneficial effects in the stomach and small intestine and during the beginning phase of digestion in the colon. Different products of degradation and phase II metabolites can be found in the small intestine and colon, while catabolites might be important for bioactivities in the colon. Most studies connect beneficial effects for different described health problems to the whole apple or to the amount of all phenolic compounds from apples. This expresses the influence of all native polyphenols from apples on beneficial effects. However, further studies of the peculiar compounds resulting from native phenols and their effects on the various parts of the digestive tract could provide a better understanding of the specific derivatives with bioactivity in humans. Full article