Search Results (1,372)

Background/Objectives: The prebiotic effect of resistant potato starch (RPS) has been demonstrated, but the antioxidant properties associated with this ingredient have not been explored. Methods: We performed post hoc analysis of serum metabolomic data from a clinical trial evaluating 3.5 g RPS per day consumption (n = 24) versus a placebo (n = 24) for 4 weeks in a randomized clinical trial (NCT05242913). Results: Levels of the exogenous antioxidants all-trans retinol and α-tocopherol increased in the RPS-consuming group. Among endogenous antioxidants, the concentration of coenzyme Q10 (CoQ10) increased in both treatment groups, while uric acid was unaffected. Hippuric acid, a marker of polyphenol metabolism, was unaffected by treatment, as was the abundance of the tryptophan metabolites kynurenine and 3-hydroxyanthranillic acid. However, levels of 3-hydroxykynurenine were decreased in both treatment groups. Levels of the advanced glycation end products NƐ-(1-carboxymethyl)-L-lysine and NƐ-(1-carboxyethyl)-L-lysine, markers of chronically elevated oxidative stress, were unaffected by treatment. Notably, increases in serum all-trans retinol were correlated with increases in Akkermansia. Conclusions: RPS enhances the absorption of antioxidants all-trans retinol and α-tocopherol from the diet and also influences CoQ10 levels and tryptophan metabolism. Future studies assessing the physiological consequences of enhanced antioxidant absorption in people consuming RPS over a longer duration are warranted. Full article

Urinary tract infections (UTIs) are common and create significant clinical challenges. Most UTIs are caused by uropathogenic Escherichia coli (UPEC) and affect 50 to 70% of women at some point in their lives. Of this population, 25% will have a recurrent urinary tract infection (rUTI) within 3 to 12 months of the first episode. High rates of rUTIs may occur because UPEC can enter a non-proliferative or quiescent state within the urothelium of the bladder. This state allows UPEC to evade the host’s immune response and antibiotic treatment. We utilized a library of plant extracts derived from the URI Heber W. Youngken Jr. Medicinal Garden to determine if they reversed UPEC quiescence with a novel in vitro quiescence assay using the classic UPEC endemic lineage ST73 strain CFT073. We found an overall active extract hit rate of 69% (79/114 active) and that active extracts contained high levels of polyphenolic compounds. Further testing showed that polyphenols with adjacent hydroxyl groups on a benzene ring (catechol moiety) were the most effective and potent in reversing quiescence. The ability to reverse quiescence was also linked to the compound’s ability to bind iron (e.g., epigallocatechin gallate and rosmarinic acid were the most potent reversing agents—0.1 mM—and they both had the strongest iron-binding activity as determined via CAS assay). These findings reveal a new class of metabolites that can reverse quiescence in UPEC strains. Full article

The hybrid Sechium edule H387 07, commonly known as chayote, has shown potential as an antiproliferative, cytotoxic, and pro-apoptotic agent in the murine leukemia cell lines P388 (macrophagic) and J774 (monocytic) and in the myelomonocytic leukemia cell line WEHI-3. However, despite these reported bioactivities, its pharmacokinetic profile remains largely unexplored. Understanding the absorption, distribution, and elimination of this hybrid is critical for addressing unmet therapeutic needs and for advancing the development of natural product-based therapies. These effects are attributed to the presence of phenols, flavonoids, and cucurbitacins in its organic extracts. In this study, the pharmacokinetic parameters of secondary metabolites from methanolic extracts of Sechium H387 07 were evaluated after oral administration in mice, while its segregant H387 M16 was subjected to complementary phytochemical characterization. Methanolic extracts of Sechium edule H387 07 were orally administered to mice at doses of 8, 125, and 250 mg/kg, and plasma, liver, and urine samples were collected at 1, 6, 24, and 48 h post-treatment. High-performance liquid chromatography (HPLC) identified polyphenols and cucurbitacins, notably cucurbitacin B (CuB) and cucurbitacin IIA (CuIIA), in the biological samples, and pharmacokinetic variables such as the maximum plasma concentration (C_max), time to reach maximum concentration (T_max), half-life (T_1/2), and volume of distribution (V_d) were determined. For instance, CuB exhibited a C_max of 37.56 µg/mL at 1 h post-dose after oral administration of 125 mg/kg, confirming its rapid absorption and systemic distribution. Notably, the presence of CuIIA in plasma was documented for the first time, along with the pharmacokinetic profiles of apigenin, phloretin, CuB, CuE, and CuI. In parallel, the segregant H387 M16 was characterized via colorimetric assays, thin-layer chromatography (TLC), HPLC, and antioxidant activity tests, which revealed high levels of flavonoids, phenols, and cucurbitacins, with an antioxidant activity of approximately 75% at the highest tested dose (1 mg/mL), supporting its suitability for future bioassays. Overall, these findings not only provide novel pharmacokinetic data for key metabolites of the H387 07 hybrid but also establish the phytochemical and antioxidant profile of its segregant H387 M16. This dual characterization strengthens the evidence of the therapeutic potential of Sechium genotypes and provides a valuable foundation for future studies aiming to develop standardized protocols and explore translational applications in drug development and natural product-based therapies. Full article

Aging results from the combined effects of oxidative stress, chronic low-grade inflammation, mitochondrial decline, and cellular senescence, which together drive age-related disorders. Natural products ranging from polyphenols and terpenoids to alkaloids, polysaccharides, peptides, and marine metabolites can influence central pathways such as Nrf2/ARE, NF-κB, MAPK, JAK/STAT, AMPK/PGC1-α, mTOR, and SIRT1/FOXO. By doing so, they strengthen antioxidant defenses, temper inflammation, preserve mitochondrial balance, and regulate autophagy. Increasing attention is also being given to synergy, where combinations of bioactives can achieve stronger and more balanced effects than single agents alone. Advances in artificial intelligence are accelerating this discovery process, while greener extraction and smarter delivery systems such as deep eutectic solvents and nanostructured carriers are improving bioavailability and consistency. Together, these developments underscore the promise of natural product-based strategies for healthy aging. Grounded in rigor and reproducibility, this Special Issue aims to inspire translational advances toward healthier and more graceful aging. Full article

Background: Flavor quality in grape berries is shaped by complex metabolic and regulatory networks during development. Methods: In this study, we integrated transcriptomic and LC–MS-based metabolomic analyses to investigate three cultivars (‘Mei Xiangbao’, ‘Adena Rose’, and ‘Kyoho’) at two ripening stages. Results: A total of 491 differentially accumulated metabolites (DAMs) were identified, mainly lipids, organic acids, and heterocyclic compounds. Among them, 33 core metabolites, including LysoPCs, malic acid, and linalool derivatives, were closely linked to aroma, membrane remodeling, and polyphenol biosynthesis. Transcriptome integration revealed 29 transcription factors (TFs) such as AP2/ERF, MYB, and bHLH, which showed strong associations with key metabolites, suggesting their involvement in lipid remodeling and phenylpropanoid-related pathways. Conclusions: These results provide new insights into the molecular regulation of grape flavor metabolism and highlight candidate genes and metabolites for improving berry sensory quality. Full article

Background and Objectives: Anthocyanin-rich barley varieties have recently gained attention due to their high (poly)phenolic content and potential health benefits, yet human data on their bioavailability remain scarce. This study aimed to characterize the absorption, metabolism, and excretion of (poly)phenolic compounds from a novel hull-less purple whole-grain barley (WGB) genotype. Methods: Eleven healthy volunteers consumed 140 g of purple WGB biscuits, and plasma and urine samples were collected over 6 h and 48 h, respectively. Results: UPLC-MS/MS analysis revealed a broad range of metabolites, with 11 (poly)phenolic compounds identified in plasma and 80 in urine. The biscuits were particularly rich in flavones (217 mg/140 g, mainly chrysoeriol derivatives), followed by hydroxycinnamic acids (~54 mg, mainly 4′-hydroxy-3′-methoxycinnamic acid), anthocyanins (44.8 mg), and flavan-3-ols (16.8 mg). In plasma, glycosylated anthocyanins and flavone conjugates (e.g., peonidin-3-O-glucuronide, chrysoeriol-O-glucuronide) were detectable within 1–2 h, consistent with early absorption. In contrast, microbial-derived catabolites—including valerolactones, phenylacetic and benzoic acids—were mainly excreted in urine between 8 and 24 h, reaching concentrations above 1000 nM. Conclusions: These findings provide novel insights into the bioavailability and metabolic fate of barley (poly)phenols, supporting their potential contribution to host and gut health. As a proof-of-concept study, it complements the limited data available from pigmented cereals and underscores the need for validation in larger cohorts. Full article

This study explores the production of nutritious edible mushrooms from mixtures of agave bagasse, an abundant agroindustrial byproduct, through the biotechnological application of solid-state fermentation using the edible mushroom Pleurotus djamor. The ability of the fungus to biotransform different mixtures of agave bagasse and corn stover into secondary metabolites of nutraceutical interest, such as polyphenols, organic acids, and bioactive polysaccharides, was evaluated. Biological efficiency (BE), morphological change, texture, and antioxidant capacity were also assessed, correlating the results with the impact of substrates and fungal developmental stages. The color, size, and margin of P. djamor basidiomas were observed to vary among treatments; BE progressively decreased from T0 (106.5%) to T4 (33.16%). Treatments with higher amounts of agave bagasse (T4) generated firmer fungi, with a fracture toughness of 7.06 ± 3.06 newtons. During fungal development, phenols, flavonoids, and tannins fluctuated. Treatment T0 showed the highest concentration of phenols (5.41 ± 0.92 mg GAE g⁻¹). Treatment T4 stood out for its high antioxidant capacity (DPPH) (61.83 ± 12.16% inhibition). Finally, 17 non-phenolic secondary metabolites were found: L-valine, L-leucine, L-isoleucine, L, D-phenylalanine, L-proline, alanine, L-asparagine, serine, glutamic acid, linoleic acid, palmitic acid, butanoic acid, propanoic acid, pyrimidine, succinic acid, hexanedioic acid, and phosphoric acid. In conclusion, P. djamor can biotransform agroindustrial waste into edible fungi containing nutraceutical compounds. Full article

The use of antioxidants in the dermatocosmetic industry has become increasingly popular to help protect and stabilize other sensitive active ingredients, prolonging the effectiveness and durability of the cosmetic product. Grape pomace, as the main by-product generated through winemaking, and Polygonum cuspidatum, concentrate bioactive metabolites with high antioxidant activity. Hydroalcoholic extracts obtained from grape pomace (Merlot and Feteasca Neagra varieties) and the root and flower of Japanese knotweed, respectively, alone and in mixtures, were characterized, and preliminary assays were conducted for their incorporation in two gel-based cosmetic formulations. The characterization of the extracts revealed the presence of catechin, vanillic acid, caffeic acid, myricetin, resveratrol, and kaempferol. The hydroalcoholic extract of P. cuspidatum flower and root was found to have the highest content of total phenolic compounds (10.920 ± 0.268 mg GAE/mL, respectively, 4.751 ± 0.072 mg GAE/mL), and the highest antioxidant activity (expressed as DPPH Radical Scavenging Capacity, IC₅₀) by 28.04 ± 1.12 µg GAE/mL and 83.91 ± 1.13 µg GAE/mL, respectively. Catechin was the most abundant polyphenol found in pomace extract (687.87 mg/kg). The type and the concentration of the plant extract used in dermatocosmetic gel formulations influenced their antioxidant activity. Encapsulation of P. cuspidatum flower extract in liposomes prior to their incorporation into the gel formulation demonstrated the role of liposomes in enhancing the stability and modulation of phenolic compound delivery. It is worth noting that this dermatocosmetic formulation, which contains the flower extract of P. cuspidatum, was the subject of a pending patent application. Full article

In this study, the cosmeceutical potential of a 70% ethanol extract of Rosa lucieae was investigated as a multifunctional bioactive ingredient. The extract was systematically evaluated for its antioxidant, anti-melanogenic, and anti-aging properties, and was comprehensively phytochemically profiled using ultra-high-performance liquid chromatography–quadrupole time-of-flight mass spectrometry. The analysis tentatively identified 21 metabolites, including phenolic acids (gallic acid, ellagic acid, and corilagin), flavonoids (catechin, rutin, quercetin, hyperoside, and quercitrin), and glycosidic derivatives (e.g., phlorizin), several of which are well-documented for their skin-protective effects. Quantitative measurements confirmed high polyphenol and flavonoid contents, correlating with strong radical-scavenging and reducing capacities in α-diphenyl-β-picrylhydrazyl, 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid, as well as ferric ion reducing antioxidant power assays. Moreover, the extract inhibited tyrosinase activity and 3,4-dihydroxyphenylalanine oxidation, thereby suppressing melanin biosynthesis. In addition, marked inhibitory effects against collagenase, elastase, and hyaluronidase were observed; these enzymes are critically involved in extracellular matrix degradation and skin aging. Taken together, these results indicate that the biological activities of R. lucieae are supported by a diverse polyphenol- and flavonoid-rich chemical profile, highlighting the potential of this plant as a natural multifunctional ingredient for cosmeceutical, nutraceutical, functional food, and preventive healthcare applications. Full article

Polyphenols are an important class of secondary metabolites that possess antioxidant or anti-inflammatory properties and are associated with many health benefits. It has been reported that extracts of fruit juices or the fruit juices themselves are able to influence lipid metabolism. The aims of this study were to establish a reliable analytical method and thereafter investigate the influence of a polyphenol-rich fruit juice during an eight-week intervention on plasma lipid profiles in healthy male subjects. A placebo-controlled intervention study with 36 healthy male subjects was carried out. Volunteers consumed 750 mL of a polyphenol-rich or placebo beverage on a daily basis. With the established untargeted LC-IMS-qTof method, lipids could be identified, and changes in the lipidome could be detected. For the first time, a comparison of the lipidome of the control vs. treatment group allowed for the identification of differences in lipid profiles. The observed changes suggest that polyphenol intake leads to the targeted re-modeling of the lipidome, affecting bioactive lipid mediators and membrane components in particular. In the future, our identified lipid markers may be established as potential biomarker candidates related to health. Full article

In the recent years, the accelerating global demographic shift toward population aging has been accompanied by a marked increase in the prevalence of neurodegenerative disorders, notably Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and multiple sclerosis. Among emerging approaches, dietary interventions targeting the gut–brain axis have garnered considerable attention, owing to their potential to modulate key pathogenic pathways underlying neurodegenerative processes. This review synthesizes current concepts in precision nutrition and elucidates neurohumoral, immune, and metabolic regulatory mechanisms mediated by the gut microbiota, including the roles of the vagus nerve, cytokines, short-chain fatty acids, vitamins, polyphenols, and microbial metabolites. Emerging evidence underscores that dysbiotic alterations contribute to compromised barrier integrity, the initiation and perpetuation of neuroinflammatory responses, pathological protein aggregations, and the progressive course of neurodegenerative diseases. Collectively, these insights highlight the gut microbiota as a pivotal target for the development of precision-based dietary strategies in the prevention and mitigation of neurodegenerative disorders. Particular attention is devoted to key bioactive components such as prebiotics, probiotics, psychobiotics, dietary fiber, omega-3 fatty acids, and polyphenols that critically participate in regulating the gut–brain axis. Contemporary evidence on the contribution of the gut microbiota to the pathogenesis of Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis is systematically summarized. The review further discusses the prospects of applying nutrigenomics, chrononutrition, and metagenomic analysis to the development of personalized dietary strategies. The presented findings underscore the potential of integrating precision nutrition with targeted modulation of the gut–brain axis as a multifaceted approach to reducing the risk of neurodegenerative diseases and preserving cognitive health. Full article

Neuronutrition to improve brain resilience to stress and human health has received considerable attention. The use of specific nutrients is effective in preventing and slowing neurodegenerative and neuropsychiatric disorders. Selective neuronutrients, including polyphenols, short-chain fatty acids (SCFAs), tryptophan, tyrosine, and sulfur metabolites, can modulate the dysregulated nuclear factor erythroid 2 (Nrf2) pathway through neuroepigenetic modifications and altered levels of neurotransmitters such as serotonin, melatonin, and dopamine. In particular, abnormal epigenetic alterations in the promoter function of the NFE2L2/Nrf2 gene may contribute to the onset and progression of various diseases by disrupting cellular homeostasis. Recent evidence has documented that polyphenols are capable of modulating Nrf2 signaling; to do this, they must reverse hypermethylation in the CpG islands of the NFE2L2 gene. This process is achieved by modifying the activity of DNA methyltransferases (DNMTs) and histone deacetylases (HDACs). Furthermore, a diverse group of polyphenolic metabolites can be identified and quantified using innovative mass spectrometry platforms in both in vitro models and human urine samples to investigate redox metabolic homeostasis under physiological and pathophysiological conditions. This review aims to deepen the current understanding of the role of nutrient-derived secondary metabolites. It highlights innovative strategies to effectively prevent, slow, or potentially reverse neuroinflammation and oxidative stress, key drivers of neuronal damage. The targeted application of these metabolites can be considered a novel, personalized neuronutritional approach to promote brain health and neuronal adaptation. Full article

The contents of secondary metabolites such as tea polyphenols, amino acids, caffeine, and volatile metabolites in fresh tea leaves are key factors determining the unique flavor and health attributes of finished tea products. However, differences in varieties, cultivation practices, and environmental conditions often lead to variations in these metabolites among fresh tea leaves, thereby affecting tea quality. In order to clarify the various internal and external factors that influence the formation of the quality of fresh tea leaves and their mechanism of action. This article mainly reviews the research on fresh leaf quality in the past decade. Firstly, it clarifies the molecular basis of metabolic differences among varieties. Then, it summarizes the regulatory mechanisms of underground (soil, microorganisms) and above-ground (light, temperature, humidity) environments on key metabolic pathways, and focuses on evaluating the effects of intercropping, fertilization, and other cultivation measures on improving tea quality. This review found that the specific gene expression of varieties, the transmission of environmental signals, and cultivation interventions jointly drive the synthesis and accumulation of tea polyphenols, amino acids, caffeine, and aroma substances. However, no one has ever systematically reviewed it. Therefore, it provides certain theoretical references for improving the quality of fresh leaves. Full article

The integration of leguminous cover cropping systems (LCR), particularly soybean (LC-S) and cowpea (LC-C), into tea agroecosystem provides a sustainable strategy to enhance soil ecosystem services by promoting beneficial soil microbial communities through the modulation of the rhizosphere microbiome in the tea rhizosphere soil. This study employs 16S rRNA gene sequencing to assess how these leguminous cover crops, when incorporated as green manure within the tea row spaces, influence the microbial community diversity in the rhizosphere soil of tea plants. Compared to conventional monoculture tea plantations (CK), the introduction of LC-S and LC-C significantly reshape the microbial communities in the tea rhizosphere soil. They promote the abundance of copiotrophic and specialized taxa such as Proteobacteria, Actinobacteria, and Mycobacterium, which are crucial for nutrient cycling and organic matter decomposition. Additionally, LC-S and LC-C enrich beneficial microbes including Chloroflexi, Bradyrhizobium, Acidothermus, and Cyanobacteria, supporting processes like nitrogen fixation and pathogen suppression. The metagenomic analysis confirms that leguminous cover crops consistently increase bacterial diversity and enrich beneficial phyla vital for soil nutrient dynamics, organic matter breakdown, and environmental stress resilience. Furthermore, microbial genera linked to nitrogen mobilization and complex organic matter degradation are promoted, underpinning the synthesis of nitrogenous compounds (such as theanine, amino acids), polyphenolic secondary metabolites (like flavonoids), and volatile organic compounds essential for tea quality. Functional pathway analyses revealed that LC-S enhances degradation pathways involved in carbohydrate and aromatic compound metabolism, augmenting precursors for key bioactive constituents such as theanine and catechins. Conversely, LC-C favors glycan biosynthesis and degradation pathways, likely improving root–microbe interactions and micronutrient uptake, both critical for polyphenol biosynthesis. Collectively, these microbiome-driven changes improve tea’s sensory qualities, including flavor, aroma, and antioxidant capacity, by enriching bioactive compounds. This microbiome-mediated agro-ecological approach offers a sustainable alternative to conventional monoculture, enhancing soil functionality, ecological resilience, and the economic viability of tea production systems. Full article

Objectives: This study presents a versatile, AI-guided workflow for the targeted isolation and characterization of prenylated flavonoids from Paulownia tomentosa (Thunb.) Steud. (Paulowniaceae). Methods: The approach integrates established extraction and chromatography-based fractionation protocols with LC-UV-HRMS/MS analysis and supervised machine-learning (ML) custom-trained classification models, which predict prenylated flavonoids from LC-HRMS/MS spectra based on the recently developed Python package AnnoMe (v1.0). Results: The workflow effectively reduced the chemical complexity of plant extracts and enabled efficient prioritization of fractions and compounds for targeted isolation. From the pre-fractionated plant extracts, 2687 features were detected, 42 were identified using reference standards, and 214 were annotated via spectra library matching (public and in-house). Furthermore, ML-trained classifiers predicted 1805 MS/MS spectra as derived from prenylated flavonoids. LC-UV-HRMS/MS data of the most abundant presumed prenyl-flavonoid candidates were manually inspected for coelution and annotated to provide dereplication. Based on this, one putative prenylated (C5) dihydroflavonol (1) and four geranylated (C10) flavanones (2–5) were selected and successfully isolated. Structural elucidation employed UV spectroscopy, HRMS, and 1D as well as 2D NMR spectroscopy. Compounds 1 and 5 were isolated from a natural source for the first time and were named 6-prenyl-4′-O-methyltaxifolin and 3′,4′-O-dimethylpaulodiplacone A, respectively. Conclusions: This study highlights the combination of machine learning with analytical techniques to streamline natural product discovery via MS/MS and AI-guided pre-selection, efficient prioritization, and characterization of prenylated flavonoids, paving the way for a broader application in metabolomics and further exploration of prenylated constituents across diverse plant species. Full article