Search Results (234)

A KGM/CMC/PVA film loaded with a hydroxypropy-β-cyclodextrin/hesperetin (HP-β-CD/HES) inclusion complex was developed for strawberry preservation. The inclusion complex showed an encapsulation efficiency of 70.41 ± 4.01%. Loading the inclusion complex enhanced the barrier and bioactive properties of the films. At the better loading level (KCP-HH3, 1.5%), the film provided nearly complete UV shielding at 200–350 nm and showed a transmittance of approximately 21% at 800 nm. Relative to KCP, KCP-HH3 exhibited lower water vapor permeability (0.69 ± 0.06 g·mm/(m²·h·kPa)) and oxygen permeability (0.066 ± 0.006 g·mm/(m²·h·kPa)). The cumulative HES release from KCP-HH3 reached 82.43 ± 2.19% after 7 days at 98% relative humidity. KCP-HH3 scavenged 78.19 ± 3.71% of DPPH radicals and 88.89 ± 4.30% of ABTS radicals. It also inhibited Escherichia coli (91.18 ± 2.99%), Staphylococcus aureus (79.21 ± 3.45%), and Aspergillus niger (92.85 ± 2.75%). This highest-loading formulation delivered the best overall strawberry-preservation performance. After 12 days of storage, strawberries packaged with KCP-HH3 showed higher firmness (0.89 ± 0.04 N) and total soluble solids (7.96 ± 0.21%), as well as lower weight loss (14.30 ± 0.40%), than the polyethylene control, which showed a firmness of 0.42 ± 0.05 N, total soluble solids of 6.22 ± 0.20%, and weight loss of 16.36 ± 0.66%. These results support the potential of HP-β-CD/HES-loaded KCP films as biodegradable active packaging for fruit preservation. Full article

Naringinase is an enzyme complex composed of α-L-rhamnosidase and β-D-glucosidase, capable of deglycosylating flavonoids such as hesperidin. α-L-rhamnosidase converts hesperidin into rhamnose and hesperetin 7-O-glucoside (Hes-7-G), while β-D-glucosidase further hydrolyses Hes-7-G to hesperetin. Selective inactivation of β-D-glucosidase enables accumulation of Hes-7-G, a compound with higher water solubility and bioavailability than hesperidin or hesperetin, making it valuable for food and biotechnological applications. This study aimed to identify conditions allowing selective inhibition of β-D-glucosidase while preserving α-L-rhamnosidase activity for efficient Hes-7-G production. The effects of pH, temperature, and incubation time were investigated, together with the influence of polyols and sugars, including inositol, sucrose, glycerol, xylose, erythritol, xylitol, and sorbitol, on α-L-rhamnosidase thermostability. Among the tested additives, erythritol significantly improved α-L-rhamnosidase thermostability. The highest selectivity was achieved by incubating the enzyme in 1.4 M erythritol at 70 °C for 10 min, resulting in ~5% residual β-D-glucosidase activity and 50% α-L-rhamnosidase activity. Under these conditions, α-L-rhamnosidase activity exceeded β-D-glucosidase activity by more than 60-fold. Selective thermal inactivation of β-D-glucosidase in the presence of erythritol provides an effective strategy for producing Hes-7-G from hesperidin and may enhance flavonoid bioavailability for industrial applications. Full article

Accumulation of aggregated amyloid beta (Aβ) species is a defining pathological hallmark of Alzheimer’s disease and is associated with extensive neuronal structural abnormalities. Mild cognitive impairment (MCI), a transitional stage between normal aging and the onset of dementia, is thought to represent an early phase of this pathological continuum. Studies at the cellular level suggest that the conditions impair the maintenance of established neuronal processes/networks and restrict their capacity for elongation or re-elongation. They may also attenuate the activation and process extension of quiescent neural progenitor or stem-like cells. These early cellular changes precede overt neurodegeneration in neural tissue and are likely to contribute to cognitive decline. They highlight the importance of in vitro models for identifying molecular targets involved in recovery from disease. In this study, we investigated the effects of aggregated Aβ (25–35) on neuronal process elongation and associated intracellular events in the N1E-115 cell line, a widely used model of neuronal differentiation. Addition of aggregated Aβ to cultured N1E-115 cells attenuated process elongation in a concentration-dependent manner. This morphological impairment was accompanied by decreased expression of neuronal differentiation markers. In contrast, at the half-maximal inhibitory concentration for process elongation, long-term cultured cells did not exhibit apparent process retraction or degenerative morphology. This mild but progressive impairment, without extensive cell death, is consistent with the cellular features of early-stage conditions rather than advanced Alzheimer’s pathologies. Similar results were observed in primary cortical neurons. Aβ also decreased the level of GTP-bound Ras and phosphorylation of the downstream mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK). Furthermore, treatment with hesperetin, a bioactive flavonoid compound, recovered the Aβ-induced inhibition of neuronal process elongation. Hesperetin also restored Ras and MAPK/ERK states, suggesting that its effects are associated, at least in part, with modulation of signaling through Ras and MAPK/ERK. Our findings suggest that hesperetin may serve as a useful molecular probe for modulating early cellular responses associated with Alzheimer’s disease-related pathology. This in vitro model might serve as a useful platform for investigating the molecular target candidates involved in recovery from nervous system disorders. Full article

Lemon processing by-products are rich in flavonoids, limonoids, and phenolic acids, but their direct utilization is limited by glycoside-dominant flavonoid profiles, bitterness-associated limonoids, and insufficiently defined valorization strategies. This study compared eight food-relevant microorganisms, including lactic acid bacteria, Bacillus, yeast, and filamentous fungi, using a common aerobic submerged fermentation framework for lemon by-products. Rather than evaluating fermentation as a single uniform process, the study aimed to determine whether different microbial groups could redirect the same substrate toward distinct functional remodeling profiles. Targeted HPLC analysis of flavonoids, limonoids, and phenolic acids, together with DPPH and ABTS radical-scavenging assays, revealed clear strain-dependent differences in metabolite remodeling and antioxidant outcomes. L. plantarum showed the most consistent antioxidant enhancement profile, characterized by increased hesperetin and phenolic acid responses together with low DPPH and ABTS IC₅₀ values. L. pentosus promoted flavonoid remodeling but showed a more timing-sensitive antioxidant response. S. cerevisiae tended to preserve glycosylated flavonoids and showed a release-oriented phenolic acid profile with strong early ABTS activity. R. stolonifer exhibited the most pronounced limonoid remodeling, including marked limonin reduction and obacunone accumulation, suggesting potential relevance for bitterness-oriented applications. These findings demonstrate that different microorganisms can be functionally classified according to their dominant remodeling tendencies, including antioxidant enhancement, flavonoid conversion, glycosylated flavonoid preservation, phenolic acid release, and limonoid-associated debittering. This functional classification provides a practical basis for selecting microorganisms according to the intended application of lemon by-product valorization. Full article

Citrus flavonoid intake is associated with beneficial effects on endothelial function. Our previous randomized control trial demonstrated that the concentration of Hesperetin-7-O-glucuronide (H7G) was positively correlated with the improvement in endothelial function in overweight and obese participants following blood orange juice consumption. To explore the underlying mechanism by which H7G improves endothelial function, we investigated the regulation of H7G on endothelial function in a permanent human endothelial cell line (EA. hy926 cells) under normal and oxidative conditions treated with high-oxidation low-density lipoprotein. The results indicated that H7G improved the expression of nitric oxide synthase 3 (NOS3), heme oxygenase 1 (HMOX1) ad glutamate cysteine ligase catalytic (GCLC), and inhibited the expression of endothelin-1 (EDN1), through the upregulation of miR-660-5p and inhibition of miR-21-5p. In summary, H7G improves endothelial cell function via the upregulation of miR-660-5p and the inhibition of miR-21-5p. Full article

This study explored the impact of ethanol as a co-solvent in supercritical fluid extraction on the recovery of bioactive compounds from carrot seeds and assessed the resulting extracts for antimicrobial, α-amylase and α-glucosidase, and butyrylcholinesterase inhibitory potential. Ethanol supplementation significantly improved extraction performance, with the yield increasing from 110 mg in the absence of ethanol to 134 mg at 5% ethanol, followed by a slight decrease to 132 mg at 10%. High-performance liquid chromatography (HPLC) revealed pronounced phytochemical enrichment at 5% ethanol, particularly for chlorogenic acid (1541.24 µg/g), gallic acid (1279.27 µg/g), and hesperetin (1513.68 µg/g), indicating enhanced recovery of phenolic and flavonoid constituents. The 5% ethanol extract demonstrated superior antimicrobial activity, producing inhibition zones of 19 mm against Enterococcus faecalis, 26 mm against Klebsiella pneumoniae, 25 mm against Staphylococcus aureus, and 29 mm against Candida albicans. Values of both minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were markedly reduced, while antibiofilm activity reached 93.11% for E. faecalis and 91.00% for K. pneumoniae. The extract also exhibited potent inhibitory effects with IC₅₀ values of 7.74 and 13.37 µg/mL, against α-amylase and α-glucosidase, correspondingly, as well as strong butyrylcholinesterase inhibition (IC₅₀ = 2.51 µg/mL), highlighting promising α-amylase/α-glucosidase and butyrylcholinesterase inhibitory potential. Molecular docking further supported these findings, showing that chlorogenic acid bound more strongly than vanillin to OmpK36, lysosomal acid-α-glucosidase, and butyrylcholinesterase, with docking scores ranging from −6.1 to −6.9 kcal/mol. These findings identify ethanol-modified supercritical fluid extraction as a sustainable and effective green strategy for improving the recovery of carrot seed bioactives and enhancing their multifunctional in vitro biological properties. Notably, this study provides the first comprehensive evidence that 5% ethanol modification selectively enriches key phenolic constituents, including chlorogenic acid, gallic acid, and hesperetin, in carrot seed extracts, with corresponding enhancement of α-amylase, α-glucosidase, and butyrylcholinesterase inhibitory activities. 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

Blueberries are widely consumed due to their richness in nutrients, yet they are also prone to quality deterioration after being harvested, even at cold temperatures. Non-thermal physical technology is an important auxiliary method worth considering for maintaining the quality of this fruit while refrigerated. In this study, a static magnetic field (SMF) was applied as a complementary pretreatment strategy prior to cold storage of blueberries. The optimal SMF parameters were identified as 5 mT exposure for 12 h, as this significantly retarded decay and softening. The contents of ascorbic acid, total polyphenols, flavonoids and proanthocyanidins were elevated by 20.0%, 17.7%, 23.9%, and 9.1%, respectively. Concurrently, DPPH (1,1-diphenyl-2-picrylhydrazyl) radical-scavenging capacity, catalase (CAT), and superoxide dismutase (SOD) activity markedly improved. Targeted metabolomic analysis revealed that SMF pretreatment significantly regulated polyphenol metabolic pathways and redirected polyphenol biosynthesis toward more stable and functional compounds, including three hydroxycinnamic acids, quercetin, dihydromyricetin, glycosylated hesperetin, and acylated delphinidin derivates. The synergistic effect of these SMF-elevated phenolics and the reinforced antioxidant system preserved the overall cold-storage quality of blueberries. These findings underscore the potential of SMF pretreatment as an effective physical technique for reducing postharvest blueberry losses. Full article

Background/Objectives: Natural compounds occupy a pharmacologically rich chemical space, characterized by abundant scaffolds, extensive functional group elaboration, and defined stereochemistry. In this context, Helichrysum italicum, a Mediterranean medicinal plant, represents a valuable source of polyphenols with multiple biological and pharmacological activities. Methods: Here, we introduce an inverse molecular docking fingerprint approach to systematically investigate eight major Helichrysum italicum polyphenols, including $\alpha$-pyrones (arzanol, ethylpyrone), flavonols (gnaphaliin, kaempferol, quercetin), and flavanones (naringenin, pinocembrin, hesperetin). More than 40,000 human protein structures from the Protein Data Bank were screened to generate target-based inverse docking score fingerprints for each compound. Results: Hierarchical clustering of these fingerprints revealed shared binding patterns among structurally related polyphenols and enabled hypothesis generation regarding potential synergistic effects. Notably, favorable interactions were identified with PPARG and CARM1, supporting therapeutic relevance in inflammation and cancer, alongside additional targets associated with neurodegeneration and bone metabolism. Conclusions: This study establishes inverse docking fingerprints as a robust, mechanism-oriented method for natural product research and highlights Helichrysum italicum polyphenols as starting points for medicinal chemistry and drug discovery. Full article

Leaves from California yerba santa (Eriodictyon californicum) have been used historically by indigenous peoples for medicinal purposes. Recent research has ascribed potential pharmaceutical effects to leaf polyphenols, without a consideration of other constituents. Based on prior analyses of polyphenols in leaves sampled in nature, five accessions known to be rich in sterubin and five accessions known to be rich in eriolic acid C were grown from seeds in Ontario, Oregon, and samples of their leaves were harvested and evaluated for their essential oil and polyphenol contents. The major essential oil components in E. californicum were 1,8-cineole (0.6–35.5%), (Z)-β-ocimene (6.8–15.7%), terpinen-4-ol (8.3–16.1%), α-pinene (2.6–13.6%), β-phellandrene (1.9–11.7%), γ-terpinene (4.6–7.9%), ethyl (E)-cinnamate (0.2–8.9%), α-terpineol (1.5–5.2%), p-cymene (2.0–5.3%), and β-pinene (0.6–6.8%). Fifteen polyphenols with a prominence of eriolic acid C, rosmarinic acid, sterubin, homoeriodictyol, 6-methoxynaringenin, hesperetin, and eriodictyol were identified. Essential oils may contribute to the medicinal properties of the leaves of California yerba santa. Results from the ten samples were evaluated for both polyphenols and essential oils; the variations in several essential oils may be correlated to variations in some of the polyphenols. Full article

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

The chemical composition of Iris songarica rhizome extracts was systematically investigated using GC-MS and UHPLC-MS. Their biological activity was further evaluated in vivo. The chloroform rhizome extract contained 33 identified compounds distributed across five main classes. Flavonoids predominated (50.7% of total ionic current), with tectochrysine (42.15%) as the major component, followed by 3,7-dihydroxy-2-(3,4-dimethoxyphenyl)-4H-chromene-4-one (5.18%) and a naringenin derivative (3.99%). Fatty acid esters comprised 30.6%, dominated by linoleic acid ethyl ester (11.05%), ethyl oleate, and hexadecanoic acid ethyl ester. Phenolic and aromatic compounds accounted for 14.24%, including (E)-4-(3-hydroxyprop-1-en-1-yl)-2-methoxyphenol and flamenol. Quantitative HPLC revealed hesperetin (69.72 µg/mL) and fisetin (12.32 µg/mL) as predominant in the 50% aqueous ethanol extract, and cinarin (6.28 µg/mL) in the ethyl acetate root extract. HPLC-MS identified 25 polyphenols, mainly isoflavonoids and flavones, with key markers songaricol, irilin B, tectorigenin, irisflavone A, and irizon B, some reported for the first time in Kazakhstan irises. Biological evaluation demonstrated potent activity: the 50% aqueous ethanol extract inhibited xylene-induced ear oedema in mice by 72.7% at 300 mg/kg, comparable to diclofenac (90.9%), without observable toxicity. These findings confirm I. songarica as a valuable source of bioactive polyphenols with anti-inflammatory potential. Full article

The solubility values of polyphenolic compounds in different extraction solvents are crucial for their recovery from natural matrices. Hansen solubility parameters (HSPs) stand out as a predictive tool for evaluating solute-solvent affinity and thus rational solvent selection for extraction processes. In this study, HSPs of trans-resveratrol and hesperetin were calculated using a semi-empirical method to assess the capability to predict the solubility behavior of both polyphenols in organic binary solvent mixtures. Experimental solubility of both polyphenols was determined in up to 21 monosolvents at 298.15 K and 0.1 MPa and used to classify them to iteratively calculate HSPs. Calculated HSPs were compared and discussed with literature values in terms of molecular interactions, demonstrating a fair agreement. Solubility of trans-resveratrol and hesperetin was then determined in methanol + MEK, ethanol + MEK, methanol + MiBK, ethanol + MiBK, and methanol + ethanol binary solvent mixtures. trans-Resveratrol achieved higher mole fraction solubility than hesperetin in all binary mixtures across the whole molar fraction range except in methanol + MiBK. Both compounds exhibited enhanced solubility in all alcohols + ketone binary mixtures, attributed to synergistic solvent effects. HSP analysis revealed a minimum Hansen distance between solute and solvent mixtures at compositions corresponding to the solubility maximum in synergistic systems. Additionally, calculated HSPs proved to effectively estimate the concentration at which this phenomenon occurs in all tested systems, reaching a robust correlation between maximum solubility and minimum Hansen distance. Overall, insights from this study underscore the effectiveness of experimentally derived HSPs in predicting the solubility behavior of polyphenols and seek to provide valuable guidance on solvent selection strategies for the recovery of bioactive compounds. Full article

Cancer ranks as one of the top causes of death worldwide, and the World Health Organisation (WHO) estimates an increase of up to 55% in cases over the next 15 years, reaching 300 million cases worldwide. Current approaches to the treatment of cancer, such as chemotherapy and radiation therapy, have been used with continuous significant advancements. However, these conventional methods have harmful side effects that can last a lifetime. Today, there is growing interest in developing alternative cancer therapies from natural products or complementary medicine. One of the natural sources that has shown promise as an anticancer agent is honey, which has long been applied as a complementary medicine, and its beneficial health effects on various diseases in both animal and human models have been widely studied. Malaysian honey, such as Tualang, pineapple, Gelam, Kelulut, and Acacia, possesses a rich composition of phytochemicals, including polyphenols and flavonoids, which are reported to have promising anticancer properties. Examples of the phytochemicals highlighted in this review are phenolic acid, syringic acid, salicylic acid, p-coumaric acid, gallic acid, benzoic acid, caffeic acid, chrysin and its derivatives, kaempferol, fisetin, catechin, apigenin, quercetin, acacetin, pinocembrin, pinobanksin, hesperetin, naringenin, vitexin, isoorientin, xanthohumol, and galangin. This review highlights the anticancer mechanisms and molecular pathways of the phytochemicals found in Malaysian honey, focusing on their antioxidant effects, induction of mitochondrial-mediated apoptosis, inhibition of angiogenesis and metastasis, and suppression of cancer cell proliferation. The findings of various studies published in the past five years are collated to understand their mechanisms of action. Full article

Candida auris is a critical emerging pathogen of high priority due to its ability to develop multidrug resistance to various antifungals. Given the increase in cases associated with C. auris, it is essential to evaluate new candidates with antifungal potential. In this context, flavonoids represent a promising source for the development of new therapeutic alternatives. In this study eleven flavonoids were evaluated for their antifungal activity against C. auris strains from clades III and IV. The flavonoids showed dose-dependent inhibition of C. auris growth. Toxicity tests were conducted using the in vivo Tenebrio molitor model. The flavonoids exhibited toxicity levels either comparable to or lower than reference antifungals. Also, the study examined the ability of the flavonoids to inhibit efflux pumps. Some of the flavonoids (quercetin, fisetin, hesperetin, luteolin and apigenin) reduced efflux pump activity, which is an important feature since these pumps actively expel antifungal drugs from the cell, reducing the drug’s effectiveness. This suggests that the flavonoids might inhibit efflux pump activity, potentially enhancing the efficacy of antifungal treatments. The study supports the potential of flavonoids as new therapeutic agents for C. auris. Since they target efflux pumps, which are a significant mechanism of resistance in C. auris, flavonoids could be used either alone or in combination with existing antifungals to improve treatment outcomes. Full article