Search

Phloretin (PT) belongs to the dihydrochalcones (DHCs) family and is found in apple and rooibos tea. Its glycosides, including phlorizin (PT 2′-O-glucoside), trilobatin (PT 4′-O-glucoside), and nothofagin (NF, PT 3′-C-glucoside), are present in various plants. Phloretin and its related glycosides possess health benefits, including antioxidant, anti-inflammatory, and antibacterial activities. To biosynthesize PT and its glycosides, the relevant pathways in plants were studied and introduced into Escherichia coli. We reconstructed the biosynthetic pathways pertaining to PT and three PT C-glycosides (NF, PT 3′, 5′-di-C-glucoside [PDG], and PT 3′-C-arabinoside [PARA]) in E. coli. To prevent the undesirable synthesis of flavonoids instead of PT, we strategically divided the entire pathway into two parts: the first involved the synthesis of tyrosine to phloretic acid (PA), while the second involved the synthesis of PA to PT and its glycosides. The gene set pertaining to each part was incorporated into a different engineered microbe. We optimized phloretin microbial biosynthesis by improving enzyme affinity, identifying the gene that increased the output, refining the production design to a stepwise culture approach, and analyzing the culture conditions (substrate and yeast extract concentrations and pH) conducive to maximum output and the prevention of product degradation. Using the stepwise culture approach, 12.8 mg/L of PT, 26.1 mg/L of NF, 30.0 mg/L of PDG, and 18.1 mg/L of PARA were synthesized. This study provides valuable information for future approaches in the microbe-based synthesis of PT derivatives. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Among fruits, the apple is unique for producing large amounts of the dihydrochalcone phloridzin, which, together with phloretin, its aglycone, is valuable to the pharmaceutical and food industries for its antidiabetic, antioxidant, and anticarcinogenic properties, as well as its use as a sweetener. We analysed the phloridzin concentration, total phenolic content, and antioxidant activity in the peel, flesh, seeds, juice, and pomace of 13 international and local apple varieties. In the unprocessed fruit, the seeds had the highest phloridzin content, while the highest total phenolic contents were mostly found in the peel. In processed samples, phloridzin and the total phenolic compounds especially were higher mostly in juice than in pomace. Moreover, the total phenolic content was much higher than the phloridzin content. Juice showed the highest antioxidant activity, followed by the peel and flesh. Across all samples, antioxidant activity did not directly correlate with phloridzin concentrations, suggesting that the antioxidant activity ascribed to phloridzin may need re-evaluation. In the Ferric Reducing Antioxidant Power (FRAP) assay, phloridzin only showed antioxidant activity at high concentrations when compared to its aglycone, phloretin. Considering the large amounts of apple juice produced by the juice industry, residual pomace is a promising source of phloridzin. For technical use, processing this phloridzin to phloretin would be advantageous. [ABSTRACT FROM AUTHOR]

BACKGROUND: Green rooibos (Aspalathus linearis (Burm.f.) R.Dahlgren) herbal tea is popular due to its health‐promoting properties. Information on its characteristic sensory profile is scarce and sensory tools to define product variation are needed. The storage conditions and time during its shelf‐life are hypothesized to affect the product quality. RESULTS: Production batches from two producers spanning 5 years (n = 57) were analyzed using descriptive sensory analysis. Primary attributes (>30 median intensity; 100% occurrence frequency) included 'hay/dried grass', 'cooked oats', 'tobacco', 'honey' and 'caramel' aromas, and astringent mouthfeel. 'Cooked vegetables', 'green grass', 'stewed fruit', 'rooibos‐woody', 'marmalade' and 'cardboard' aromas, sweet taste and bitter taste were secondary attributes (10–20 median intensity; 100% occurrence frequency). The same flavor attributes were present, except for sweet‐associated and fruity notes. A sensory lexicon and sensory wheels for aroma and palate attributes were constructed from the data. The shelf‐life stability of green rooibos was evaluated in moisture‐impermeable (pouches) and moisture‐permeable (sachets) packaging at 25 and 40 °C at 60% relative humidity over 24 weeks. Green rooibos samples stored in pouches at 4 °C were also evaluated. Storage in sachets led to moisture uptake (~10 g (100 g)−1 dry basis) and an increase in water activity (>0.6), causing degradation of chlorophyll and dihydrochalcones. Changes in color and sensory profile (decreased vegetal, cereal and cardboard aromas and increased sweet‐associated and fruity aromas) were evident and more pronounced at the higher storage temperature. CONCLUSIONS: Storage at ≤25 °C in moisture‐impermeable packaging material is recommended for green rooibos herbal tea. © 2024 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Apple (Malus domestica) is a reliable source of nutrients to increase the bioactive compounds intake in the human body. In the market, the development of apple is still growing, not only in the hybridization of new cultivars, but also in the functional food products, based on apple's bioactive compounds. In this paper, we review the recent studies about the chemical composition of apples, including carbohydrates, proteins, lipids, dietary fibers, minerals, vitamins, phenolics, and other compounds, from various cultivars, grown in different countries or regions. Among the bioactive compounds in apple, the phenolic compounds, including hydroxybenzoic acids, hydroxycinnamic acids, flavanols and their oligo- and polymeric structure, flavonols, dihydrochalcones, and anthocyanins, majorly contribute to beneficial biological impacts. Therefore, the extraction process might be the most critical step to recover all the phenolics from apple and could be used in various food product developments. In this paper, the comparison of conventional and developed phenolic extraction methods is also reviewed in various apple products (flesh, peel, pomace, pulp, etc.). The selection of food grade and green solvents in the optimal phenolic extraction methods could reduce the environmental issues, thus supports sustainability and can be safer for consumers. To sum up, this paper may help the readers, both at general household and industrial levels, to understand the nutritional composition of various apple cultivars from different regions and to select the optimum conditions for apple's phenolic extraction, based on recent studies. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The present study evaluates the phytotoxic effects of phloretin, a prevalent secondary metabolite of apple trees, on the broadleaf weed Capsella bursa-pastoris (L.) Medik. known for its resistant myxospermous seeds that form a long-lasting soil bank. The results indicate a significant, dose-dependent inhibitory effect of phloretin on the growth and morphological parameters of weed seedlings grown in vitro. Although the applied phloretin concentrations (250–1000 µM) were not lethal to the C. bursa-pastoris seedlings after two weeks, the metabolism of the seedlings was impaired, resulting in an accumulation of lipid droplets in the root tips and root hairs. Histochemical analysis shows deposits of phenols in the root epidermal cells, which are probably aggregates of phloretin or its metabolic derivatives. The accumulation of pectin in the cell walls of root border cells in phloretin-treated seedlings indicates an attempt to reduce the uptake of phloretin and reduce its concentration in the cells. Inhibition of shoot growth associated with chlorosis and reduced photosynthetic pigment content is a consequence of seedling exposure to phloretin. This study provides a basis for further evaluation of phloretin as a new bioherbicidal compound and for elucidating the mechanism underlying its phytotoxic activity. [ABSTRACT FROM AUTHOR]

Herein an enzyme‐assisted supercritical fluid extraction (EA‐SFE) was developed using the enzyme mix snailase to obtain flavonols and dihydrochalcones, subgroups of flavonoids, from globally abundant waste product apple pomace. Snailase, a commercially available mix of 20–30 enzymes, was successfully used to remove the sugar moieties from quercetin glycosides, kaempferol glycosides, phloridzin and 3‐hydroxyphloridzin. The resulting flavonoid aglycones quercetin, kaempferol, phloretin and 3‐hydroxyphloretin were extracted using supercritical carbon dioxide (scCO2) and minimum amounts of polar cosolvents. A sequential process of enzymatic hydrolysis and supercritical fluid extraction was developed, and the influence of the amount of snailase, pre‐treatment of apple pomace, the time for enzymatic hydrolysis, the amount and type of cosolvent and the time for extraction, was studied. This revealed that even small amounts of snailase (0.25 %) provide a successful cleavage of sugar moieties up to 96 % after 2 h of enzymatic hydrolysis followed by supercritical fluid extraction with small amounts of methanol as cosolvent, leading up to 90 % of the total extraction yields after 1 h extraction time. Ultimately, a simultaneous process of EA‐SFE successfully demonstrates the potential of snailase in scalable scCO2 extraction processes for dry and wet apple pomace with satisfactory enzyme activity, even under pressurized conditions. [ABSTRACT FROM AUTHOR]

The fate of phenolic compounds during digestion is important for their bioactive effects in the digestive tract. The aim was to study the various phenolic compounds occurring in the peel and flesh of apples in in vitro simulated gastrointestinal digestion, focusing on the behavior of chlorogenic acids. Additionally, the behavior of individual chlorogenic acids (chlorogenic, neochlorogenic, and cryptochlorogenic) was studied in models of simulated salivary, gastric, and intestinal fluid electrolyte solutions (SSF, SGF, SIF). At the end of the intestinal phase of the digestion of peel and flesh, the amount of recovered dihydrochalcones and flavonols increased or was similar to the amount in the gastric phase, which showed their stability. Anthocyanins and flavan-3-ols decreased, which suggests their biotransformation. Chlorogenic acid isomerized into neochlorogenic and cryptochlorogenic acid: chlorogenic acid from the peel into 22% and 41% of the isomers in the salivary and intestinal phases, respectively; chlorogenic acid from the flesh into 12% of the isomers in the intestinal phase. Similarly, chlorogenic acid isomerized in model solutions (20% and 26% of the isomers in SSF and SIF, respectively). Neochlorogenic and cryptochlorogenic acid isomerized in SSF and SIF into other two forms. They were all stable in SGF. For bioactive effects in the digestive tract, the biotransformation of chlorogenic acids should be considered. [ABSTRACT FROM AUTHOR]

In the search of cytotoxic dihydrochalcones, this investigation led to the isolation of seven compounds (1-7) from Eriosema glomeratum and the preparation of eight derivatives (8-15). The cytotoxicity of samples was evaluated against lung (A549), breast (MCF-7), and cervical (HeLa) human cancer cells. The CH2Cl2/MeOH extract of the aerial part had strong cytotoxicity against all cells [IC50 11.2 (MCF-7), 8.4 (HeLa) and 13.1 (A549) μg/mL]. A strong activity was also displayed by the n-hexane fraction on MCF-7 (IC50 11.2 μg/mL). The precursor 3 and the derivative 8 were specifically found as strong cytotoxic agents toward MCF-7 (7.6 μM) and HeLa (3.1 μM), respectively and were more effective than the positive control. Derivatives 8 (3.1 μM) and 9 (21.3 μM) against HeLa were most potent than their precursor 3 (23.7 μM). This is the first preparation of 8-14 as well as the cytotoxicity of 3, 4, 8-15, fractions, and extract. [ABSTRACT FROM AUTHOR]

Deltamethrin (DEL), a commonly used pyrethroid pesticide, results in higher reactive oxygen species (ROS) levels in aquatic animals, which consequently unbalance the redox state. Phlorizin (PHL) is a flavonoid and a natural product promising to prevent or reduce pesticide-induced oxidative stress. Artemia is a micro-crustacean widely used in marine hatcheries and an experimental aquatic organism for environmental toxicology research. This research aimed to evaluate the toxicity of DEL on Artemia and the antioxidative effect of PHL against the toxicity. Results show that 0.08-mg/mL PHL exerted its antioxidative effects on hatching percentage of the cysts in 24-h incubation and on body length and survival rate of Artemia in 12-d culture. After 12-d culture, 12-, 24-, and 36-h DEL exposure showed significant drops in SOD, CAT, and GSH-Px enzyme activities, and significant increases in ROS and malondialdehyde (MDA) levels in Artemia (P<0.05). On the contrary, 0.08-mg/mL PHL application improved the enzyme activities and decreased the ROS and MDA levels (P<0.05). Moreover, 0.08-mg/mL PHL significantly increased mRNA expression levels of Cu/Zn SOD, CAT, GST, HO-1, NQO1, and Nrf2, and decreased mRNA expression level of Keap1 in the DEL-exposed Artemia (P<0.05). Therefore, DEL is toxic to Artemia, while PHL alleviates DEL-induced oxidative damage by possibly regulating the Nrf2 signaling pathway. This study provided a theoretical basis for PHL to reduce pesticide-induced toxicity in aquatic animals. [ABSTRACT FROM AUTHOR]

Among fruits, the apple is unique for producing large amounts of the dihydrochalcone phloridzin, which, together with phloretin, its aglycone, is valuable to the pharmaceutical and food industries for its antidiabetic, antioxidant, and anticarcinogenic properties, as well as its use as a sweetener. We analysed the phloridzin concentration, total phenolic content, and antioxidant activity in the peel, flesh, seeds, juice, and pomace of 13 international and local apple varieties. In the unprocessed fruit, the seeds had the highest phloridzin content, while the highest total phenolic contents were mostly found in the peel. In processed samples, phloridzin and the total phenolic compounds especially were higher mostly in juice than in pomace. Moreover, the total phenolic content was much higher than the phloridzin content. Juice showed the highest antioxidant activity, followed by the peel and flesh. Across all samples, antioxidant activity did not directly correlate with phloridzin concentrations, suggesting that the antioxidant activity ascribed to phloridzin may need re-evaluation. In the Ferric Reducing Antioxidant Power (FRAP) assay, phloridzin only showed antioxidant activity at high concentrations when compared to its aglycone, phloretin. Considering the large amounts of apple juice produced by the juice industry, residual pomace is a promising source of phloridzin. For technical use, processing this phloridzin to phloretin would be advantageous.

The present study evaluates the phytotoxic effects of phloretin, a prevalent secondary metabolite of apple trees, on the broadleaf weed Capsella bursa-pastoris (L.) Medik. known for its resistant myxospermous seeds that form a long-lasting soil bank. The results indicate a significant, dose-dependent inhibitory effect of phloretin on the growth and morphological parameters of weed seedlings grown in vitro. Although the applied phloretin concentrations (250–1000 µM) were not lethal to the C. bursa-pastoris seedlings after two weeks, the metabolism of the seedlings was impaired, resulting in an accumulation of lipid droplets in the root tips and root hairs. Histochemical analysis shows deposits of phenols in the root epidermal cells, which are probably aggregates of phloretin or its metabolic derivatives. The accumulation of pectin in the cell walls of root border cells in phloretin-treated seedlings indicates an attempt to reduce the uptake of phloretin and reduce its concentration in the cells. Inhibition of shoot growth associated with chlorosis and reduced photosynthetic pigment content is a consequence of seedling exposure to phloretin. This study provides a basis for further evaluation of phloretin as a new bioherbicidal compound and for elucidating the mechanism underlying its phytotoxic activity.

Phenolic compounds are known to degrade and/or undergo changes during food production and storage. Reaction kinetic modeling is generally used to define kinetic parameters of a food system and predict changes during thermal processing and storage. Data for phenolic acids and flavonoids, such as anthocyanins and flavan-3-ols, have been reviewed in detail, but the flavonoid sub-classes, dihydrochalcones and flavanones, have been mostly neglected. Other neglected phenolic classes are xanthones and benzophenones. The stability of these types of compounds is important as they are present in fruits and exposed to heat when processed into juice and jam. Other sources of the compounds are herbal teas, which are also subjected to thermal processing, either during the primary processing of the plant material, or the production of extracts for use as food ingredients. The theoretical background is given to understand the review of literature on these classes/sub-classes. Results of research on kinetic modeling are discussed in detail, while research on compound stability without the application of reaction kinetic modeling is briefly mentioned to provide context. The studies discussed included those focusing on heating during the processing and storage of model solutions, liquid foods, plant material, dried extracts, and extracts formulated with other food ingredients. [ABSTRACT FROM AUTHOR]

Phytosomes consist of a phytochemical bound to the hydrophilic choline head of a phospholipid. Their use in food products is gaining interest. However, literature on the use of food‐grade solvents, crude plant extracts as opposed to pure compounds, and unrefined phospholipids to prepare phytosomes is limited. Furthermore, studies on compound stability are lacking. This study aimed to develop nano‐phytosome vesicles prepared from inexpensive food‐grade ingredients to improve the stability of polyphenolic compounds. Cyclopia subternata extract (CSE) was selected as a source of phenolic compounds. It contains substantial quantities of C‐glucosyl xanthones, benzophenones, and dihydrochalcones, compounds largely neglected to date. The effect of process conditions on the complexation of CSE polyphenols with minimally refined food‐grade fat‐free soybean lecithin (PC) was studied. The PC:CSE ratio, sonication time, and reaction temperature were varied. This resulted in phytosomes ranging in vesicle size (113.7–312.7 nm), polydispersity index (0.31–0.48), and zeta potential (−55.0 to −38.9 mV). Variation was also observed in the yield (93.5%–96.0%), encapsulation efficiency (3.7%–79.0%), and loading capacity (LC, 1.3%–14.7%). Vesicle size and LC could be tailored by adjusting the sonication time and PC:CSE ratio, respectively. Chemical interaction between the lipid and the phenolic compounds was confirmed with nuclear magnetic resonance. Phytosomal formulation protected the compounds against degradation when freeze‐dried samples were stored at 25 and 40°C for 6 months at low relative humidity. The study provided valuable information on the importance of specific process parameters in producing food‐grade phytosomes with improved phenolic stability. [ABSTRACT FROM AUTHOR]

Lithocarpus polystachyus (Wall.) Rehd. (L. polystachyus), a natural resource of herbal tea, has been historically consumed by several ethnic minorities. Modern investigations demonstrated L. polystachyus as a versatile pharmacological agent, with antioxidant, anti-inflammatory, anti-diabetes, anti-tumor, anti-hypertension, anti-obesity, hepatoprotection, and neuroprotection activities, meanwhile, no toxicity. Dihydrochalcones as its major, if not the most abundant, active ingredients, are known for numerous biological properties. Particularly, phloridzin, trilobatin, and phloretin, three prominent members of dihydrochalcones, have attracted attentions as either drug candidates or building blocks in modern drug development. In this review, we've brought together an up-to-date researches on the bioactive constituents, pharmacological effects and emerging mechanisms of L. polystachyus. We hope this review will provide a scientific rationale for understanding the health benefits, and if possible, preclinical assessment of novel applications of L. polystachyus. [ABSTRACT FROM AUTHOR]

Two novel spirolactones, reitziiolide A (1) and reitziiolide B (2), and a new naphthoquinone, 6,7-dimethoxystreptocarpone (3), were isolated from the tubers of Sinningia reitzii (Hoehne) L. E. Skog (Gesneriaceae) from Paraná State, Brazil. In addition, six known compounds were also identified: 6-hydroxy-7-methoxy-α-dunnione (4), 2,4′-dihydroxy-4,6-dimethoxydihydrochalcone (5), loureirin B (6), 8-hydroxy-7-metoxy-2- O -methylstreptocarpone (7), 6,7-dimethoxydunnione (8), and 5-hydroxy-6,7-dimethoxydunnione (9). All compounds were analyzed by NMR 1D and 2D. Additionally, 1 and 2 were analyzed by X-ray diffraction. Compounds 4 - 5 are being reported for the first time in S. reitzii. [Display omitted] • Two novel spirolactones from Sinningia reitzii tubers. • A new naphthoquinone from S. reitzii tubers. • The first record of two known compounds for S. reitzii. [ABSTRACT FROM AUTHOR]

BACKGROUND: The shelf‐life of a functional herbal tea‐based beverage is important not only for consumer acceptability, but also for the retention of bioactive compounds. The present study aimed to clarify the role of common iced tea beverage ingredients (citric and ascorbic acids) on the shelf‐life stability of an herbal tea‐based beverage. A hot water extract of green Cyclopia subternata, also used as honeybush tea, was selected as the main ingredient because it provides different types of phenolic compounds associated with bioactive properties (i.e. xanthones, benzophenones, flavanones, flavones and dihydrochalcones). RESULTS: The model solutions were stored for 180 and 90 days at 25 and 40 °C, respectively. Changes in their volatile profiles and color were also quantified as they contribute to product quality. 3′,5′‐Di‐β‐d‐glucopyranosyl‐3‐hydroxyphloretin (HPDG; dihydrochalcone) and, to a lesser extent, mangiferin (xanthone), were the most labile compounds. Both compounds were thus identified as critical quality indicators to determine shelf‐life. The stability‐enhancing activity of the acids depended on the compound; ascorbic acid and citric acid enhanced the stability of HPDG and mangiferin, respectively. However, when considering all the major phenolic compounds, the base solution without acids was the most stable. This was also observed for the color and major volatile aroma‐active compounds [α‐terpineol, (E)‐β‐damascenone, 1‐p‐menthen‐9‐al and trans‐ocimenol]. CONCLUSION: The addition of acids, added for stability and taste in ready‐to‐drink iced tea beverages, could thus have unwanted consequences in that they could accelerate compositional changes and shorten the shelf‐life of polyphenol‐rich herbal tea beverages. © 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

This study investigated the composition of sugars, organic acids, individual and total phenolic compounds in the pulp, peel, leaves, and bark of a red-fleshed 'Baya Marisa' apple cultivar. As the fruit is known for its red pulp color, the study focused on comparing the profiles of primary and selected secondary metabolites in three sections along the equatorial fruit plane. The analyses were carried out using HPLC–MS system, and compositional differences were compared among fruit segments. Inner fruit segments accumulated higher levels of sorbitol and the sum of sugars and lower levels of citric acid. However, no differences in the sum of organic acids could be determined among segments. The phenolic composition differed among pulp (hydroxycinnamic acids > dihydrochalcones ≈ anthocyanins ≈ flavanols > flavonols), peel (flavanols > anthocyanins > dihydrochalcones > flavonols > hydroxycinnamic acids), leaves (flavonols > dihydrochalcones > hydroxycinnamic acids > anthocyanins), and bark (dihydrochalcones > flavonols > flavanols > anthocyanins > hydroxycinnamic acids). The greatest phenolic diversity was detected in bark (25), followed by leaves (18), peel (17) and finally, pulp (11). Three anthocyanins (cyanidin-3-O-galactoside > cyanidin-3-O-arabinoside > peonidin-3-O-galactoside) were determined in all 'Baya Marisa' tissues with their content highest in the peel. The innermost sections of the fruit were characterized by higher levels of dihydrochalcones and lower levels of most flavanols, flavonols and anthocyanins. These were predominant in the apple pulp nearest to the peel, with cyanidin-3-O-galactoside being the prevalent representative. Accumulation of anthocyanins in pulp is a rare trait in apples, and therefore, the distinct distribution and diversity of metabolites in this cultivar highlights its potential for high-nutrient products such as juices, apple chips or purees. [ABSTRACT FROM AUTHOR]

Carboxylated chalcones and other related flavonoids were synthesized and evaluated as inhibitors of xanthine oxidase, which is a known target for synthetic and herbal drugs used against hyperuricemia, gout, and other diseases. The 4-carboxylated chalcones with hydroxy, methoxy, and ethoxy groups at ring A were found to exhibit in vitro inhibitory activities with IC50 values in the range of 0.057 to 0.26 μM, being 10–60-fold more potent than allopurinol. Structurally related carboxylic acids with Δ3,9-homoisoflavonoid and flavone scaffolds also showed micromolar activity towards xanthine oxidase. At the same time, dihydrochalcone and Δ2,3-homoisoflavonoid carboxylic acids as well as their oxa-analogues were more than two orders of magnitude less effective inhibitors. Kinetic and molecular docking studies indicated that the carboxylated chalcones and Δ3,9-homoisoflavonoids are mixed-type inhibitors, which mostly bind to free enzyme occupying the active site of xanthine oxidase. [ABSTRACT FROM AUTHOR]

Fourteen hexane-soluble polyphenolic secondary metabolites were previously isolated as individual compounds from Empetrum nigrum L. and identified as three bibenzyls, four 9,10-dihydrophenanthrenes, two chalcones, four dihydrochalcones and one flavanone. In this study, the mass-spectra and retention indexes (RI) of compounds 1-14 without prior derivatization were obtained and the resulting fragmentation pathways rationalized in accordance with literary data and the compounds structures. Preliminary differences in metabolite composition were assessed by comparative profiling using GC-MS chromatography combined with multivariate data analysis for a limited amount of E. nigrum n-hexane extracts obtained from plants growing in three different geographic locations. To characterize antioxidant capacity of isolated compounds 1-14 we used our well-established model based on reactive oxygen species (ROS) production by activated human platelets and showed that most of the examined polyphenols act as antioxidants by inhibition of ROS production. [ABSTRACT FROM AUTHOR]

Several studies have shown that apples (Malus domestica Borkh.) in the daily diet are healthy due to their rich content of phytochemicals. The aim of this study was to compare the content of polyphenols in the peels, flesh, seeds and leaves of five apple cultivars ('Antonovka', 'Åkerö', 'Cortland', 'Karksi renett' and 'Krista') grown in Estonia. Of the 21 collected cultivars, these five were selected on the basis of their rich or distinct chemical composition according to the LC-DAD-MS/MS data. In addition, the weight of the fruit, the number of seeds in the fruit and the weight of the seeds were determined. A total of 33 compounds were detected in the peels, 23 in the flesh, 11 in the seeds, and 25 in the leaves. They belong to four groups: 1) flavon-3-ols (quercetin and its derivatives), 2) dihydrochalcones (phloretin and its derivatives), 3) flavan-3-ols (catechin, epicatechin and oligomers), and 4) esters formed between caffeic acid and L-quinic acid (chlorogenic acid). Based on the data presented in this article, the leaves contained the highest measured total polyphenol content (TPGA). The peels contained high amounts of all the major polyphenolic groups mentioned. The apple flesh lacked flavon-3-ols and the seeds flavon-3-ols and flavan-3-ols. In the peels, the major polyphenols were quercetin galactoside (3-342 mg/100 g), procyanidin B1 (18-179 mg/100 g), and (epi)catechin trimer (28-200 mg/100 g); in the flesh chlorogenic acid (77-298 mg/100 g); in the seeds phloridzin (466 mg/100 g in 'Cortland'); and in the leaves chlorogenic acid (147-446 mg/100 g) and quercetin glycosides, especially quercetin rhamnoside (242-350 mg/100 g), quercetin galactoside (39-334 mg/100 g) and quercetin glucoside (91-321 mg/100 g). [ABSTRACT FROM AUTHOR]

In recent years the analysis of natural products has been carried out using a range of approaches, but mainly utilizing liquid chromatography (LC) or gas chromatography (GC). However, alternative approaches with orthogonal selectivity like capillary electrophoresis (CE) and supercritical fluid chromatography (SFC) have increasingly been employed as well, even though they are often considered niche techniques only. In this study, we intended to confirm and compare their suitability as reliable state-of-the-art methods for the analysis of bioactive compounds by developing CE and SFC for the analysis of dihydrochalcones (DHCs) in apple leaves. The analytes were chosen as they have shown interesting pharmacological effects, such as anti-inflammatory, anti-tumor and immunomodulatory activities, and also present an interesting analytical challenge due to their structural similarity and polarity range. Both methods were well capable to separate the five standard compounds within short separation times and fulfilling the demands for an environmentally friendly "green" technology. CE as well as the SFC assay were validated for linearity, sensitivity, accuracy and precision according to ICH guidelines and met all respective requirements. Using the optimized methods, several Malus sp. samples were analyzed whereby a significant difference in the qualitative as well as quantitative DHC profile was revealed, with overall DHC concentrations ranging from 5.47% to 17.24%. [ABSTRACT FROM AUTHOR]

The global overproduction of apples is associated with large amounts of post-production waste, for which new forms of utilization should be sought. Therefore, we aimed to enrich wheat pasta with apple pomace in various percentages (10, 20, 30 and 50%). The content of total polyphenols, individual polyphenols (using UPLC-PDA-MS/MS methods) and dietary fibre, chemical composition and physical properties of the resulting pasta were determined. The addition of apple pomace to pasta resulted in increased levels of pro-health compounds: total polyphenols, phenolic acids, quercetin derivatives, flavon-3-ols and dihydrochalcones as well as dietary fibre. Decreases in hardness and maximum cutting energy were also observed in pasta supplemented with apple pomace compared to control pasta. Water absorption capacity was not influenced by the addition of apple pomace, with the exception of pasta made with 50% apple pomace. [ABSTRACT FROM AUTHOR]

Neuroinflammation is a hallmark of traumatic brain injury (TBI)'s acute and chronic phases. Despite the medical and scientific advances in recent years, there is still no effective treatment that mitigates the oxidative and inflammatory damage that affects neurons and glial cells. Therefore, searching for compounds with a broader spectrum of action that can regulate various inflammatory signaling pathways is of clinical interest. In this study, we determined not only the in vitro antioxidant capacity of apple pomace phenolics, namely, phlorizin and its metabolite, phloretin, but we also hypothesize that the use of these bioactive molecules may have potential use in TBI. We explored the antioxidant effects of both compounds in vitro (DPPH, iron-reducing capacity (IRC), and Folin–Ciocalteu reducing capacity (FCRC)), and using network pharmacology, we investigated the proteins involved in their protective effects in TBI. Our results showed that the antioxidant properties of phloretin were superior to those of phlorizin in the DPPH (12.95 vs. 3.52 mg ascorbic acid equivalent (AAE)/L), FCRC (86.73 vs. 73.69 mg gallic acid equivalent (GAE)/L), and iron-reducing capacity (1.15 vs. 0.88 mg GAE/L) assays. Next, we examined the molecular signature of both compounds and found 11 proteins in common to be regulated by them and involved in TBI. Meta-analysis and GO functional enrichment demonstrated their implication in matrix metalloproteinases, p53 signaling, and cell secretion/transport. Using MCODE and Pearson's correlation analysis, a subcluster was generated. We identified ESR1 (estrogen receptor alpha) as a critical cellular hub being regulated by both compounds and with potential therapeutic use in TBI. In conclusion, our study suggests that because of their vast antioxidant effects, probably acting on estrogen receptors, phloretin and phlorizin may be repurposed for TBI treatment due to their ease of obtaining and low cost. [ABSTRACT FROM AUTHOR]

SUMMARY: Phloridzin is the most abundant polyphenolic compound in apple (Malus × domestica Borkh.), which results from the action of a key phloretin‐specific UDP‐2′‐O‐glucosyltransferase (MdPGT1). Here, we simultaneously assessed the effects of targeting MdPGT1 by conventional transgenesis and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR‐associated protein 9 (Cas9)‐mediated genome editing. To this end, we conducted transcriptomic and metabolic analyses of MdPGT1 RNA interference knockdown and genome‐edited lines. Knockdown lines exhibited characteristic impairment of plant growth and leaf morphology, whereas genome‐edited lines exhibited normal growth despite reduced foliar phloridzin. RNA‐sequencing analysis identified a common core of regulated genes, involved in phenylpropanoid and flavonoid pathways. However, we identified genes and processes differentially modulated in stunted and genome‐edited lines, including key transcription factors and genes involved in phytohormone signalling. Therefore, we conducted a phytohormone profiling to obtain insight into their role in the phenotypes observed. We found that salicylic and jasmonic acid were increased in dwarf lines, whereas auxin and ABA showed no correlation with the growth phenotype. Furthermore, bioactive brassinosteroids were commonly up‐regulated, whereas gibberellin GA4 was distinctively altered, showing a sharp decrease in RNA interference knockdown lines. Expression analysis by reverse transcriptase‐quantitative polymerase chain reaction expression analysis further confirmed transcriptional regulation of key factors involved in brassinosteroid and gibberellin interaction. These findings suggest that a differential modulation of phytohormones may be involved in the contrasting effects on growth following phloridzin reduction. The present study also illustrates how CRISPR/Cas9 genome editing can be applied to dissect the contribution of genes involved in phloridzin biosynthesis in apple. Significance Statement: We applied RNA interference silencing and CRISPR/Cas9‐mediated genome editing to target the key gene MdPGT1 involved in the synthesis of phloridzin, an abundant secondary metabolite naturally occurring in apple. Both approaches caused a reduction in phloridzin but led to contrasting growth phenotypes, along with differential phytohormone profiles following MdPGT1 alteration. The present study provides insight into the key role of brassinosteroids and gibberellins on the effects mediated by MdPGT1. [ABSTRACT FROM AUTHOR]

A novel, efficient route to the first total synthesis of the bioactive isocoumarins aspergisocoumarin A, fusarimarin C and cytogenin is demonstrated. This approach features a groundbreaking single-step synthesis of isocoumarins utilizing a challenging cross-ester coupling of ethyl dimethoxy orsellinate and ethyl glycolate in the presence of a LiBr-LiTMP complex. The process leverages bromide ion-induced aggregation to facilitate a one-pot tandem reaction sequence: lateral lithiation, acylation, enolization, and lactonization. This innovative method directly produces the isocoumarin moiety with high efficiency. Subsequent transformations include selective BBr 3 -mediated demethylation, oxidation, and Wittig reactions. The streamlined synthetic routes demonstrated: a two-step pathway to cytogenin and a four-step sequence to aspergisocoumarin A and fusarimarin C, achieving overall yields of 37 %, 27 %, and 27 % respectively. [Display omitted] [ABSTRACT FROM AUTHOR]

Sweet tea is a popular herbal drink in southwest China, and it is usually made from the shoots and tender leaves of Lithocarpus litseifolius. The sweet taste is mainly attributed to its high concentration of dihydrochalcones. The distribution and biosynthesis of dihydrochaldones in sweet tea, as well as neuroprotective effects in vitro and in vivo tests, are reviewed in this paper. Dihydrochalones are mainly composed of phloretin and its glycosides, namely, trilobatin and phloridzin, and enriched in tender leaves with significant geographical specificity. Biosynthesis of the dihydrochalones follows part of the phenylpropanoid and a branch of flavonoid metabolic pathways and is regulated by expression of the genes, including phenylalanine ammonia-lyase, 4-coumarate: coenzyme A ligase, trans-cinnamic acid-4-hydroxylase and hydroxycinnamoyl-CoA double bond reductase. The dihydrochalones have been proven to exert a significant neuroprotective effect through their regulation against Aβ deposition, tau protein hyperphosphorylation, oxidative stress, inflammation and apoptosis. [ABSTRACT FROM AUTHOR]

Sieboldin is a specialised secondary metabolite of the group of dihydrochalcones (DHC), found in high concentrations only in some wild Malus species, closely related to the domesticated apple (Malus × domestica L.). To date, the first committed step towards the biosynthesis of sieboldin remains unknown. In this study, we combined transcriptomic analysis and a de novo transcriptome assembly to identify two putative 3-hydroxylases in two wild Malus species (Malus toringo (K. Koch) Carriere syn. sieboldii Rehder, Malus micromalus Makino) whose DHC profile is dominated by sieboldin. We assessed the in vivo activity of putative candidates to produce 3-hydroxyphloretin and sieboldin by de novo production in Saccharomyces cerevisiae. We found that CYP98A proteins of wild Malus accessions (CYP98A195, M. toringo and CYP98A196, M. micromalus) were able to produce 3-hydroxyphloretin, ultimately leading to sieboldin accumulation by co-expression with PGT2. CYP98A197-198 genes of M. × domestica, however, were unable to hydroxylate phloretin in vivo. CYP98A195-196 proteins exerting 3-hydroxylase activity co-localised with an endoplasmic reticulum marker. CYP98A protein model from wild accessions showed mutations in key residues close to the ligand pocket predicted using phloretin for protein docking modelling. These mutations are located within known substrate recognition sites of cytochrome P450s, which could explain the acceptance of phloretin in CYP98A protein of wild accessions. Screening a Malus germplasm collection by HRM marker analysis for CYP98A genes identified three clusters that correspond to the alleles of domesticated and wild species. Moreover, CYP98A isoforms identified in M. toringo and M. micromalus correlate with the accumulation of sieboldin in other wild and hybrid Malus genotypes. Taken together, we provide the first evidence of an enzyme producing sieboldin in vivo that could be involved in the key hydroxylation step towards the synthesis of sieboldin in Malus species. [ABSTRACT FROM AUTHOR]

The excessive dietary intake of simple sugars and abnormal metabolism in certain diseases contribute to the increased production of α-dicarbonyls (α-DCs), such as methylglyoxal (MGO) and glyoxal (GO), the main precursors of the formation of advanced glycation end products (AGEs). AGEs play a vital role, for example, in the development of cardiovascular diseases and diabetes. Aspalathus linearis (Burman f.) R. Dahlgren (known as rooibos tea) exhibits a wide range of activities beneficial for cardio-metabolic health. Thus, the present study aims to investigate unfermented and fermented rooibos extracts and their constituents for the ability to trap MGO and GO. The individual compounds identified in extracts were tested for the capability to inhibit AGEs (with MGO or GO as a glycation agent). Ultra-high-performance liquid chromatography coupled with an electrospray ionization mass spectrometer (UHPLC–ESI–MS) was used to investigate α-DCs' trapping capacities. To evaluate the antiglycation activity, fluorescence measurement was used. The extract from the unfermented rooibos showed a higher ability to capture MGO/GO and inhibit AGE formation than did the extract from fermented rooibos, and this effect was attributed to a higher content of dihydrochalcones. The compounds detected in the extracts, such as aspalathin, nothofagin, vitexin, isovitexin, and eriodictyol, as well as structurally related phloretin and phloroglucinol (formed by the biotransformation of certain flavonoids), trapped MGO, and some also trapped GO. AGE formation was inhibited the most by isovitexin. However, it was the high content of aspalathin and its higher efficiency than that of metformin that determined the antiglycation and trapping properties of green rooibos. Therefore, A. linearis, in addition to other health benefits, could potentially be used as an α-DC trapping agent and AGE inhibitor. [ABSTRACT FROM AUTHOR]

Apple (Malus domestica) is widely consumed by consumers from various regions. It contains a high number of phenolic compounds (majorly hydroxybenzoic acids, hydroxycinnamic acids, flavanols, flavonols, dihydrochalcones, and anthocyanins) and antioxidant activity, which are beneficial for human health. The trends on healthy and fresh food have driven the food industry to produce minimally processed apple, such as fresh‐cut, puree, juice, and so on without degrading the quality of products. Enzymatic browning is one of the problems found in minimally processed apple as it causes the undesirable dark color as well as the degradation of phenolics and antioxidant activity, which then reduces the health benefits of apple. Proper inhibition is needed to maintain the quality of minimally processed apple with minimal changes in sensory properties. This review summarizes the inhibition of enzymatic browning of apple products based on recent studies using the conventional and nonconventional processing, as well as using synthetic and natural antibrowning agents. Nonconventional processing and the use of natural antibrowning agents can be used as promising treatments to prevent enzymatic browning in minimally processed apple products. Combination of 2–3 treatments can improve the effective inhibition of enzymatic browning. Further studies, such on as other potential natural antibrowning agents and their mechanisms of action, should be conducted. [ABSTRACT FROM AUTHOR]

One of the most widespread representatives of mosses in the temperate and boreal latitudes of the Northern Hemisphere is common haircap (Polytrichum commune), which is known as the largest moss in the world and widely used in traditional herbal medicine. Polyphenolic compounds constitute one of the most important groups of biologically active secondary metabolites of P. commune, however, the available information on their chemical composition is still incomplete and contradictory. In the present study, a group of dihydrochalcone polyphenolic derivatives that were not previously found in mosses was isolated from P. commune biomass using pressurized liquid extraction with aqueous acetone. The combination of two-dimensional NMR spectroscopy and high-performance liquid chromatography–high-resolution mass spectrometry allowed for identifying them as 3-hydroxyphloretin oligomers formed through a carbon–carbon bond between phloroglucinol and pyrocatechol moieties ("head-to-tail" coupling), with a polymerization degree of 2–5. The individual compounds isolated by preparative reverse-phase HPLC had a purity of 71 to 97% and demonstrated high radical scavenging activity (17.5–42.5% with respect to Trolox) determined by the photochemiluminescence method. Along with the low toxicity predicted by QSAR/QSTR algorithms, this makes 3-hydroxyphloretin oligomers a promising source for the production of biologically active food additives and pharmaceuticals. [ABSTRACT FROM AUTHOR]

Introduction. A number of studies have shown that various genetic and environmental factors can affect the biosynthesis and accumulation of secondary metabolites. In particular, it is known that the local geoclimate, seasonal changes, external conditions such as light, temperature, moisture and soil fertility can affect the chemical composition and, as a result, the therapeutic properties of plants used in the pharmaceutical and food industries. Empetrum nigrum L. is a rich source of various pharmacologically active secondary metabolites – chalcones, dihydrochalcones, bibenzyls, 9,10-dihydrophenanthrenes, flavonoids, and proanthocyanidins. In the scientific literature, there is no data on the variation in the chemical composition of E. nigrum depending on the growing area. The obtained data are necessary for a reasonable choice of the collecting location for the plant, with the aim of its further chemical and pharmacological research for the development of promising drug candidates.Aim. To carry out a comparative analysis of secondary metabolites composition in the aerial parts of Empetrum nigrum growing in different regions of the Russian Federation.Materials and methods. Samples collected in three different areas were used to compare HPLC profiles: sample 1 was collected next to SPCPU nursery garden of medicinal plants (Leningrad region, Vsevolozhsky district, Priozerskoe highway, 38 km) in July 2020, sample 2 was collected on the Kola Peninsula, around the Khibiny mountains in July 2020, sample 3 was collected on the Kamchatka Peninsula, next to Khalaktyrsky beach (Pacific Ocean coast) in July 2020. Extracts were analyzed by analytical high performance liquid chromatography (HPLC) using a Prominence LC-20 device (Shimadzu, Japan) equipped with a diode array detector.Results and discussion. As a result of the research, for the first time, a significant variation in the qualitative chemical composition in the aerial parts of Empetrum nigrum growing in different regions of Russian Federation was established. Sample 3, collected on the Kamchatka Peninsula, in comparison with samples 1 and 2, contain the greatest variety of polar secondary metabolites belonging to the classes of flavonoids, tannins, and phenol carboxylic acids, while in the shoots collected in the Leningrad region, the major metabolites were weakly polar compounds belonging to the classes of chalcones, dihydrochalcones, bibenzyls, and 9,10-dihydrophenanthrenes, and in sample 2, collected in the Khibiny mountains, the lowest qualitative content of secondary metabolites was found. This variation may be caused by various environmental factors (biotic and abiotic).Conclusion. For the first time, the comparison of HPLC profiles of aerial part samples of E. nigrum, collected in different regions of the Russia Federation has been carried out. As a result, significant variations in the secondary metabolites composition of the studied samples were established, depending on the regions and growing conditions of the plants. The data obtained can be used for a reasonable choice of the collection location for the plant, with the aim of its further chemical and pharmacological research for the development of promising drug candidates.

Sieboldin is a specialised secondary metabolite of the group of dihydrochalcones (DHC), found in high concentrations only in some wild Malus species, closely related to the domesticated apple (Malus × domestica L.). To date, the first committed step towards the biosynthesis of sieboldin remains unknown. In this study, we combined transcriptomic analysis and a de novo transcriptome assembly to identify two putative 3-hydroxylases in two wild Malus species (Malus toringo (K. Koch) Carriere syn. sieboldii Rehder, Malus micromalus Makino) whose DHC profile is dominated by sieboldin. We assessed the in vivo activity of putative candidates to produce 3-hydroxyphloretin and sieboldin by de novo production in Saccharomyces cerevisiae. We found that CYP98A proteins of wild Malus accessions (CYP98A195, M. toringo and CYP98A196, M. micromalus) were able to produce 3-hydroxyphloretin, ultimately leading to sieboldin accumulation by co-expression with PGT2. CYP98A197-198 genes of M. × domestica, however, were unable to hydroxylate phloretin in vivo. CYP98A195-196 proteins exerting 3-hydroxylase activity co-localised with an endoplasmic reticulum marker. CYP98A protein model from wild accessions showed mutations in key residues close to the ligand pocket predicted using phloretin for protein docking modelling. These mutations are located within known substrate recognition sites of cytochrome P450s, which could explain the acceptance of phloretin in CYP98A protein of wild accessions. Screening a Malus germplasm collection by HRM marker analysis for CYP98A genes identified three clusters that correspond to the alleles of domesticated and wild species. Moreover, CYP98A isoforms identified in M. toringo and M. micromalus correlate with the accumulation of sieboldin in other wild and hybrid Malus genotypes. Taken together, we provide the first evidence of an enzyme producing sieboldin in vivo that could be involved in the key hydroxylation step towards the synthesis of sieboldin in Malus species.

Apple species are the unique naturally rich source of dihydrochalcones, phenolic compounds with an elusive role in planta, but suggested auto-allelochemical features related to "apple replant disease" (ARD). Our aim was to elucidate the physiological basis of the phytotoxic action of dihydrochalcone phloretin in the model plant Arabidopsis and to promote phloretin as a new prospective eco-friendly phytotoxic compound. Phloretin treatment induced a significant dose-dependent growth retardation and severe morphological abnormalities and agravitropic behavior in Arabidopsis seedlings. Histological examination revealed a reduced starch content in the columella cells and a serious disturbance in root architecture, which resulted in the reduction in length of meristematic and elongation zones. Significantly disturbed auxin metabolome profile in roots with a particularly increased content of IAA accumulated in the lateral parts of the root apex, accompanied by changes in the expression of auxin biosynthetic and transport genes, especially PIN1, PIN3, PIN7, and ABCB1, indicates the role of auxin in physiological basis of phloretin-induced growth retardation. The results reveal a disturbance of auxin homeostasis as the main mechanism of phytotoxic action of phloretin. This mechanism makes phloretin a prospective candidate for an eco-friendly bioherbicide and paves the way for further research of phloretin role in ARD. [ABSTRACT FROM AUTHOR]

Apple species are the unique naturally rich source of dihydrochalcones, phenolic compounds with an elusive role in planta, but suggested auto-allelochemical features related to “apple replant disease” (ARD). Our aim was to elucidate the physiological basis of the phytotoxic action of dihydrochalcone phloretin in the model plant Arabidopsis and to promote phloretin as a new prospective eco-friendly phytotoxic compound. Phloretin treatment induced a significant dose-dependent growth retardation and severe morphological abnormalities and agravitropic behavior in Arabidopsis seedlings. Histological examination revealed a reduced starch content in the columella cells and a serious disturbance in root architecture, which resulted in the reduction in length of meristematic and elongation zones. Significantly disturbed auxin metabolome profile in roots with a particularly increased content of IAA accumulated in the lateral parts of the root apex, accompanied by changes in the expression of auxin biosynthetic and transport genes, especially PIN1, PIN3, PIN7, and ABCB1, indicates the role of auxin in physiological basis of phloretin-induced growth retardation. The results reveal a disturbance of auxin homeostasis as the main mechanism of phytotoxic action of phloretin. This mechanism makes phloretin a prospective candidate for an eco-friendly bioherbicide and paves the way for further research of phloretin role in ARD.

• NGDC/NHDC bound to BSA through a static quenching, and NGDC had stronger binding affinity to BSA compared with NHDC. • Hydrophobic interactions and hydrogen bonds played a major role in the binding of NGDC/NHDC to BSA. • The interaction between NGDC/NHDC and BSA induced some conformational changes of BSA. • NGDC/NHDC showed obvious anti-glycation activities in a dose-dependent manner. The interactions of two dihydrochalcones (naringin dihydrochalcone (NGDC) and neohesperidin dihydrochalcone (NHDC)) with bovine serum albumin (BSA) and their anti-glycation effects were studied utilizing multiple spectral methods and molecular simulation technique. The findings proved that NGDC/NHDC could use a static quenching mechanism to reduce the intrinsic fluorescence of BSA, and the interaction between NGDC/NHDC and BSA was a spontaneous behavior with the binding constant ranging from 104 to 105 M −1. Furthermore, NGDC and NHDC mainly interacted with the site I (subdomain IIA) of BSA via hydrophobic interactions and hydrogen bonds, endorsed by molecular docking study. A conjoint analysis of circular dichroism, three-dimensional fluorescence, dynamic light scattering, and UV-vis absorption spectra confirmed that NGDC/NHDC could induce some alterations in the spatial conformation and microenvironment of BSA. Additionally, NGDC and NHDC inhibited the non-enzymatic glycation of BSA by decreasing the contents of advanced glycation end products (AGEs), trapping methylglyoxal/glyoxal and maintaining the stability of the natural conformation of the protein. Overall, these findings were highly beneficial in disclosing the interaction mechanisms between dihydrochalcones and BSA and providing valuable information for the application of dihydrochalcones as functional food ingredients. [Display omitted] [ABSTRACT FROM AUTHOR]

This study presents a comprehensive analysis of the impact of plasma treatment on the browning inhibition. A 30 min plasma treatment resulted in a pronounced decrease in the concentration of flavan-3-ols, which play a pivotal role in antioxidant defense and browning prevention. This significant reduction is likely due to plasma-induced oxidative stress, which can lead to the breakdown of these compounds or their conversion into other phenolic structures. Simultaneously, a slight increase in dihydrochalcones and flavonols was observed, suggesting a selective effect of plasma on different phenolic classes. The increase in these compounds could be attributed to the plasma's ability to induce specific reactions that generate these phenolics from other precursors present in the apples. The reduction in flavan-3-ols may affect the antioxidant capacity and health benefits associated with the apples, while the increase in dihydrochalcones and flavonols could have a positive impact on the flavor profile and potential health-promoting properties. Moreover, these modifications could contribute to the extension of shelf-life and maintenance of sensory qualities, making plasma treatment a valuable tool in the food industry for enhancing product stability and consumer appeal. [ABSTRACT FROM AUTHOR]

[Display omitted] • Green tea manufacturing process improved Penthorum chinense leaf tea (PLT) flavor for beverages. • Grassy odor reduced due to dodecanal and geranylacetone decrease with 1-hexadecanol increasing. • Bitterness was weakened by flavonols reduction and masked by increased dihydrochalcones. • Increasing of pinocembrins and catechins maintained the NAFLD-alleviation effects of PLT. • New-identified functional agents: norbergenin, gomisin K2, pseudolaric acid B and tanshinol B. The green-tea manufacturing process showed good effect of flavor improving, debittering and shaping in making Penthorum chinense Pursh leaf (PL) tea (PLT), which serves as a polyphenol dietary supplement and beverage raw material. GC–MS results showed that its unpleasant grassy odor decreased by 42.8% due to dodecanal, geranylacetone, and (E)-2-nonenal reduction, coupled with 1-hexadecanol increasing. UPLC-ESI-TOF-MS identified 95 compounds and showed that the debittering effect of green-tea manufacturing process was attributed to decreasing of flavonols and lignans, especially quercetins, kaempferols and luteolins, and increasing of dihydrochalcones which act as sweeteners bitterness-masking agents, while astringency was weakened by reducing delphinidin-3,5- O -diglucoside chloride, kaempferol-7- O -β- d -glucopyranoside, and tannins. The increase of pinocembrins and catechins in aqueous extracts of PLT, maintained its hepatoprotective, NAFLD-alleviation, and hepatofibrosis-prevention activities similar to PL in high fat–diet C57BL/6 mice, with flavonoids, tannins, tannic acids, and some newfound chemicals, including norbergenin, gomisin K2, pseudolaric acid B, tanshinol B, as functional ingredients. [ABSTRACT FROM AUTHOR]

In recent years the analysis of natural products has been carried out using a range of approaches, but mainly utilizing liquid chromatography (LC) or gas chromatography (GC). However, alternative approaches with orthogonal selectivity like capillary electrophoresis (CE) and supercritical fluid chromatography (SFC) have increasingly been employed as well, even though they are often considered niche techniques only. In this study, we intended to confirm and compare their suitability as reliable state-of-the-art methods for the analysis of bioactive compounds by developing CE and SFC for the analysis of dihydrochalcones (DHCs) in apple leaves. The analytes were chosen as they have shown interesting pharmacological effects, such as anti-inflammatory, anti-tumor and immunomodulatory activities, and also present an interesting analytical challenge due to their structural similarity and polarity range. Both methods were well capable to separate the five standard compounds within short separation times and fulfilling the demands for an environmentally friendly “green” technology. CE as well as the SFC assay were validated for linearity, sensitivity, accuracy and precision according to ICH guidelines and met all respective requirements. Using the optimized methods, several Malus sp. samples were analyzed whereby a significant difference in the qualitative as well as quantitative DHC profile was revealed, with overall DHC concentrations ranging from 5.47% to 17.24%.

This research aimed to select yeast strains capable of the biotransformation of selected 2′-hydroxybromochalcones. Small-scale biotransformations were carried out using four substrates obtained by chemical synthesis (2′-hydroxy-2″-bromochalcone, 2′-hydroxy-3″-bromochalcone, 2′-hydroxy-4″-bromochalcone and 2′-hydroxy-5′-bromochalcone) and eight strains of non-conventional yeasts. Screening allowed for the determination of the substrate specificity of selected microorganisms and the selection of biocatalysts that carried out the hydrogenation of tested compounds in the most effective way. It was found that the position of the bromine atom has a crucial influence on the degree of substrate conversion by the tested yeast strains. As a result of the biotransformation of the 2′-hydroxybromochalcones, the corresponding 2′-hydroxybromodihydrochalcones were obtained. The products obtained belong to the group of compounds with high potential as precursors of sweet substances. [ABSTRACT FROM AUTHOR]

Sweet tea (Lithocarpus polystachyus Rehd.) has been consumed as herbal tea to prevent and manage diabetes for a long time. Recent studies indicate that sweet tea is rich in a variety of bioactive compounds, especially a class of nonclassical flavonoids, dihydrochalcones. In order to provide a better understanding of sweet tea and its main dihydrochalcones on human health, this review mainly summarizes related literature in the recent ten years, with the potential molecular mechanisms emphatically discussed. Phlorizin, phloretin, and trilobatin, three natural sweeteners, are the main dihydrochalcones in sweet tea. In addition, sweet tea and its dihydrochalcones exhibit plenty of health benefits, such as antioxidant, anti-inflammatory, antimicrobial, cardioprotective, hepatoprotective, antidiabetic, and anticancer effects, which are associated with the regulation of different molecular targets and signaling pathways. Therefore, sweet tea, as a rare natural source of dihydrochalcones, can be processed and developed into nutraceuticals or functional foods, with the potential application in the prevention and management of certain chronic diseases. [ABSTRACT FROM AUTHOR]

Polyphenols can interact with dietary fibers and these interactions can affect polyphenols bioactivities. The interactions can be studied with the adsorption process, and adsorptions of flavan-3-ols (procyanidin B1, procyanidin B2), dihydrochalcones (phloretin, phloretin-2-glucoside), and anthocyanins (cyanidin-3-glucoside, cyanidin-3-galactoside) onto ß-D-glucan from barley were studied in this work. The intention was to reveal the kinetics of the adsorption process. Adsorption was carried out using model solutions at room temperature. The results showed that in the flavan-3-ol group procyanidin B1 showed higher adsorption capacity than procyanidin B2. Phloretin showed a higher adsorption capacity than phloretin-2-glucoside in the dihydrochalcone group and anthocyanins showed similar adsorption capacities. Parameter k1 for all polyphenols was in the range from 0.30 h-1 to 0.93 h-1. Adsorption capacity qe for all polyphenols ranged from 2.90 mmol g-1 to 9.76 mmol g-1, parameter k2 was in the range 70-225 g mol-1 h-1, and adsorption capacities qe ranged from 3.70 mmol g-1 to 9.90 mmol g-1. [ABSTRACT FROM AUTHOR]

Neuroinflammation is a hallmark of traumatic brain injury (TBI)’s acute and chronic phases. Despite the medical and scientific advances in recent years, there is still no effective treatment that mitigates the oxidative and inflammatory damage that affects neurons and glial cells. Therefore, searching for compounds with a broader spectrum of action that can regulate various inflammatory signaling pathways is of clinical interest. In this study, we determined not only the in vitro antioxidant capacity of apple pomace phenolics, namely, phlorizin and its metabolite, phloretin, but we also hypothesize that the use of these bioactive molecules may have potential use in TBI. We explored the antioxidant effects of both compounds in vitro (DPPH, iron-reducing capacity (IRC), and Folin–Ciocalteu reducing capacity (FCRC)), and using network pharmacology, we investigated the proteins involved in their protective effects in TBI. Our results showed that the antioxidant properties of phloretin were superior to those of phlorizin in the DPPH (12.95 vs. 3.52 mg ascorbic acid equivalent (AAE)/L), FCRC (86.73 vs. 73.69 mg gallic acid equivalent (GAE)/L), and iron-reducing capacity (1.15 vs. 0.88 mg GAE/L) assays. Next, we examined the molecular signature of both compounds and found 11 proteins in common to be regulated by them and involved in TBI. Meta-analysis and GO functional enrichment demonstrated their implication in matrix metalloproteinases, p53 signaling, and cell secretion/transport. Using MCODE and Pearson’s correlation analysis, a subcluster was generated. We identified ESR1 (estrogen receptor alpha) as a critical cellular hub being regulated by both compounds and with potential therapeutic use in TBI. In conclusion, our study suggests that because of their vast antioxidant effects, probably acting on estrogen receptors, phloretin and phlorizin may be repurposed for TBI treatment due to their ease of obtaining and low cost.

One flavonoid (quercetin, 1) and three dihydrochalcones (6''-O-p-hydroxybenzoyl-davidioside, 2, 4'-O-methyl-davidioside, 3, and davidioside, 4) were isolated from the leaves and young branches of Viburnum davidii Franch. All the structures were identified by comparison of their spectroscopic data (NMR and MS) with those present in literature. In addition, compounds 2–4 were evaluated for their cholinesterase inhibitory (ChEI) activity, for the first time. Accordingly, compounds 2 and 4 showed significant inhibition of both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with IC50 values equal to 36.883 and 39.274 µM, respectively for the former and 39.504 and 43.101 µM, respectively for the latter. [ABSTRACT FROM AUTHOR]

Azolla is a genus of floating freshwater ferns. By their high growth and N2 fixation rates, Azolla species have been exploited for centuries by populations of South-east Asia as biofertilizers in rice paddies. The use of Azolla species as a sustainable plant material for diverse applications, such as feeding, biofuel production, and bioremediation, has encountered a growing interest over the last few years. However, high levels of feed deterrent flavonoids in their fronds have discouraged the use of these ferns as a sustainable protein source for animal consumption. Additionally, information on how and to what extent environmental determinants affect the accumulation of secondary metabolites in these organisms remains poorly understood. Moving from these considerations, here, we investigated by an untargeted metabolomics approach the profiles of phenylpropanoid compounds in the fronds of Azolla filiculoides sampled under control and pigment-inducing stress conditions. In parallel, we assayed the expression of essential structural genes of the phenylpropanoid pathway by quantitative RT-PCR. This study provides novel information concerning A. filiculoides phenylpropanoid compounds and their temporal profiling in response to environmental stimuli. In particular, we show that besides the already known 3-deoxyanthocyanidins, anthocyanidins, and proanthocyanidins, this fern can accumulate additional secondary metabolites of outstanding importance, such as chemoattractants, defense compounds, and reactive oxygen species (ROS) scavengers, and crucial as dietary components for humans, such as dihydrochalcones, stilbenes, isoflavones, and phlobaphenes. The findings of this study open an opportunity for future research studies to unveil the interplay between genetic and environmental determinants underlying the elicitation of the secondary metabolites in ferns and exploit these organisms as sustainable sources of beneficial metabolites for human health. [ABSTRACT FROM AUTHOR]

Phytochemical investigation of the methanolic extract of Monodora minor Engl. & Diels (Annonaceae) stem bark yielded a new indole (E)-4-(1H-indol-5-yl)-but-3-en-2-one (1), a known indole 5-formyl-1H-indole (2) and an ubiquitous steroid sitosterol (3). The investigations of the methanolic extract of Uvaria tanzaniae Verdc. (Annonaceae) root bark yielded two previously reported C-benzylated dihydrochalcones namely uvaretin (4) and diuvaretin (5). Structures of the isolated compounds were elucidated based on NMR spectroscopy and high resolution electron ionization mass spectrometry (HR-EI-MS) data. All compounds were tested against Trypanosoma brucei brucei and Plasmodium falciparum. At a single concentration (20 μM) in the antitrypanosomal and antiplasmodial assays, compound 4 exhibited remarkable activities against T. brucei brucei and P. falciparum with percentage inhibition of 97.3% and 83.0% respectively, whereas compounds 1, 2, 3 and 5 were inactive. In a dose response antiplasmodial assay compound 4 exhibited moderate activity against P. falciparum with an IC50 value of 7.20 μM. [ABSTRACT FROM AUTHOR]