Search Results (6,772)

The mammalian target of rapamycin pathway, mTOR, is a crucial signaling pathway that regulates cell growth, proliferation, metabolism, and survival. Due to its dysregulation it is involved in several ailments such as cancer or age-related diseases. The discovery of mTOR and the understanding of its biological functions were greatly facilitated by the use of rapamycin, an antibiotic of natural origin, which allosterically inhibits mTORC1, effectively blocking its function. In this entirely computational study, we investigated mTOR’s interaction with seven ligands: two clinically established inhibitors (everolimus and rapamycin) and five lignin-derived oligomers, a renewable natural polyphenol recently used for the drug delivery of everolimus. The seven complexes were analyzed through all-atom molecular dynamics simulations in explicit solvent using a high-performance computing platform. Trajectory analyses revealed stable interactions between mTOR and all ligands, with lignin-derived compounds showing comparable or enhanced binding stability relative to reference drugs. To evaluate the stability of the molecular complex and the behavior of the ligand over time, we analyzed key parameters including root mean square deviation, root mean square fluctuation, number of hydrogen bonds, binding free energy, and conformational dynamics assessed through principal component analysis. Our results suggest that lignin fragments are a promising, sustainable scaffold for developing novel mTOR inhibitors. Full article

Neurodegenerative disorders, including Alzheimer’s disease (AD), Parkinson’s disease (PD), and post-stroke cognitive impairment (PSCI), represent an escalating global health and economic challenge. In the quest for disease-modifying interventions, natural polyphenols—most notably curcumin, the principal bioactive compound of Curcuma longa—have attracted considerable interest due to their pleiotropic neuroprotective effects. This narrative review critically synthesizes findings from a selection of peer-reviewed articles published between 2000 and 2025, chosen for their relevance to curcumin’s molecular mechanisms and translational potential. Curcumin’s complex chemical structure confers antioxidant, anti-inflammatory, and epigenetic modulatory properties; however, its clinical application is limited by poor oral bioavailability. Mechanistically, curcumin attenuates oxidative stress and suppresses key inflammatory mediators, including nuclear factor kappa B (NF-κB), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS). Additionally, it modulates apoptosis, inhibits amyloid-beta aggregation, and enhances cellular quality control processes such as autophagy and mitophagy, while upregulating neurotrophic factors such as brain-derived neurotrophic factor (BDNF). Preclinical studies employing rodent models of AD, PD, and ischemic stroke have demonstrated curcumin’s dose-dependent neuroprotective efficacy, with improved outcomes observed using nanoparticle-based delivery systems. Early-phase clinical trials further support curcumin’s favorable safety profile and potential cognitive benefits, although challenges remain regarding pharmacokinetics, formulation standardization, and therapeutic reproducibility. Future directions include the development of advanced drug delivery platforms, combinatory therapeutic regimens, and personalized medicine approaches integrating curcumin within multifaceted neurotherapeutic strategies. Collectively, this narrative review highlights curcumin as a promising multi-targeted candidate for combating neurodegenerative diseases, while emphasizing the need for further translational and clinical validation. Full article

Sea grape kombucha has been known to exhibit high antioxidant activity due to its elevated total polyphenol content. This study aims to identify and characterize the active microbial community involved in the fermentation of kombucha using sea grapes (C. racemosa) as the primary substrate. Furthermore, it evaluates the effects of different Symbiotic Culture of Bacteria and Yeast (SCOBY) starter concentrations on the physicochemical properties and antioxidant activity of sea grape kombucha. Our results showed that the pH of the kombucha was higher after 7 days of fermentation compared to later time points. The microbial community was composed of 97.08% bacteria and 2.92% eukaryotes, divided into 10 phyla and 69 genera. The dominant genus in all samples was Komagataeibacter. Functional profiling based on 16S rRNA data revealed that metabolic functions accounted for 77.04% of predicted microbial activities during fermentation. The most enriched functional categories were carbohydrate metabolism (15.70%), cofactor and vitamin metabolism (15.54%), and amino acid metabolism (14.24%). At KEGG Level 3, amino acid-associated pathways, particularly alanine, aspartate, and glutamate metabolism (4.24%), were predominant. The fermentation process in sea grape kombucha is primarily driven by carbohydrate and amino acid metabolism, supported by energy-generating and cofactor biosynthesis pathways. Our findings indicate that different metabolic pathways lead to variations in kombucha components, and distinct fermentation stages result in different metabolic reactions. For instance, early fermentation stages (Day 7) are dominated by amino acid metabolism, whereas the late stages (Day 21) show increased activity in carbohydrate and sulfur metabolism. Metabolomic analysis revealed that increasing the SCOBY starter concentration significantly influenced pH, soluble solid content, vitamin C, tannin, and flavonoid content. These variations suggest that fermentation duration and microbial composition significantly influence the spectrum of bioactive metabolites, which synergistically provide functional benefits such as antimicrobial, antioxidant, and metabolic health-promoting activities. For example, sample K1 produced more fatty acids and simple sugar alcohols, sample K2 enriched complex lipid compounds and phytosterols, while sample K3 dominated the production of polyols and terpenoid compounds. Full article

Neurodegenerative diseases (NDs) encompass a group of chronic conditions, characterized by neuronal losses in large areas of the brain, leading to cognitive and behavioral impairments. Alzheimer’s Disease (AD), the most common form of dementia, is a progressive ND, characterized by the accumulation of amyloid β and tau protein, entails cognitive decline, neuroinflammation, mitochondrial dysfunction, and blood–brain barrier impairment, with oxidative stress playing a critical role in its pathogenesis. To date, the available pharmacotherapy has shown limited efficacy, and multitarget activity of plant-derived neuroprotective bioactive compounds is currently in focus. This review synthesizes experimental evidence regarding Ocimum species with neuroprotective potential in AD, particularly Ocimum sanctum and Ocimum basilicum. These plants are rich in bioactive compounds including polyphenols, flavonoids, essential oils, and triterpenoids that synergistically scavenge reactive oxygen/nitrogen species, upregulate endogenous antioxidant enzymes (SOD, CAT, and GPx), and reduce lipid peroxidation. Furthermore, these extracts have demonstrated the ability to decrease β-amyloid accumulation and tau protein levels, key pathological features of AD. Even though additional research is required to fully assess their potential as therapeutic agents for NDs, by diving into the specific mechanisms through which they improve neurodegenerative processes, important steps can be made towards this endpoint. Full article

Obesity-induced insulin resistance and type 2 diabetes mellitus (T2DM) represent complex systemic disorders marked by chronic inflammation, oxidative stress, mitochondrial dysfunction, and endoplasmic reticulum (ER) stress. These pathophysiological processes disrupt insulin signaling and β-cell function, leading to impaired glucose homeostasis across multiple organs. Conventional therapies often target isolated pathways, overlooking the intricate molecular crosstalk and organelle-level disturbances driving disease progression. Citrus-derived polyphenols—including hesperidin, naringenin, nobiletin, and tangeretin—have emerged as promising agents capable of orchestrating a multi-targeted “metabolic reprogramming.” These compounds modulate key signaling pathways, including AMPK, PI3K/Akt, NF-κB, and Nrf2, thereby enhancing insulin sensitivity, reducing pro-inflammatory cytokine expression, and restoring redox balance. Furthermore, they improve mitochondrial biogenesis, stabilize membrane potential, and alleviate ER stress by modulating the unfolded protein response (UPR), thus supporting cellular energy homeostasis and protein folding capacity. Evidence from preclinical studies and select clinical trials suggests that citrus polyphenols can significantly improve glycemic control, reduce oxidative and inflammatory markers, and preserve β-cell function. Their pleiotropic actions across molecular and organ-level targets position them as integrative metabolic modulators. This review presents a systems-level synthesis of how citrus polyphenols rewire metabolic signaling networks and organelle resilience, offering a holistic therapeutic strategy to mitigate the root causes of obesity-induced insulin resistance. Full article

Gram-positive bacteria are responsible for initiating dental caries. In this process, lipoteichoic acid (LTA), which is expressed on Gram-positive bacteria cell walls, binds to the dental pulp cells, triggering an immune response, followed by inflammation and eventually pulp necrosis. Polydatin is a polyphenolic compound that has been shown to modulate inflammatory mediators in a manner favorable to healing. The purpose of this study was to assess levels of expression of the most prevalent cytokines in the inflamed pulp after polydatin treatment of LTA-stimulated human dental-pulp stem cells (hDPSCs). LTA-stimulated hDPSCs were treated with polydatin in three different concentrations (0.01 µM, 0.1 µM, and 1 µM). Interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α) levels were measured using reverse transcription–quantitative polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA) were quantified. Treatment with all concentrations of polydatin significantly decreased IL-6 and TNF-α levels as evaluated by ELISA and RT-qPCR, respectively. In addition, a significant reduction was observed in IL-8 levels of mRNA and in ELISA, with 0.01 µM and with 1 µM of polydatin in RT-qPCR. On the other hand, IL-10 levels increased with all of the concentrations. In conclusion, polydatin treatment of LTA-stimulated hDPSCs modulated inflammatory cytokine production by suppressing IL-6, IL-8, and TNF-α levels while elevating IL-10 levels. Full article

Honeybee populations are increasingly threatened by various environmental stressors, including pesticides, pathogens, and climate change. Emerging research highlights the vital role of pollen polyphenols in supporting honeybee health through a network of antioxidants, immune responses, and detoxification mechanisms. This review synthesizes current findings on the chemical diversity, bioactivity, and functional relevance of polyphenolic compounds in honeybee nutrition. Pollen polyphenols, which include flavonoids and phenolic acids, possess remarkably high antioxidant potential, up to 235 times greater than that of nectar. They also significantly increase the expression of antioxidant enzymes, immune system genes, and detoxification pathways such as cytochrome P450s and glutathione-S-transferases. These compounds also demonstrate antimicrobial effects against key pathogens and mitigate the toxic effects of pesticides. The content and composition of polyphenols vary seasonally and geographically, impacting the resilience of honeybee colonies. Field and laboratory studies confirm that polyphenol-rich diets improve survival, gland development, and stress resistance. Advanced analytical techniques, including metabolomics, have expanded our understanding of polyphenol profiles and their effects on honeybee physiology. However, knowledge gaps remain in pharmacokinetics and structure–function relationships. Integrating this evidence into conservation strategies and good beekeeping practices, such as habitat diversification and targeted feed supplementation, is crucial for maintaining honeybee health and ecosystem services in a rapidly changing environment. Full article

Yerba mate (Ilex paraguariensis) is widely consumed in South America and is valued for its bioactive compounds, such as polyphenols and methylxanthines. However, during traditional processing, mainly in the fire-based scorch and drying steps, polycyclic aromatic hydrocarbons (PAHs) and anthraquinone (AQ), substances with carcinogenic potential, may be formed. This study aimed to develop and validate an analytical method based on the balls-in-tube matrix solid-phase dispersion technique (BiT-MSPD) and analysis by gas chromatography with mass spectrometry (GC-MS) for the simultaneous determination of 16 priority PAHs and AQ in yerba mate. Parameters such as sorbent type, solvent, sample-to-sorbent ratio, and extraction time were optimized. The method showed good linearity (r² > 0.99), detection limits between 1.8 and 3.6 µg·kg⁻¹, recoveries ranging from 70 to 120%, and acceptable precision (RSD ≤ 20%). The method was applied to 31 yerba mate samples, including 20 commercial samples and 11 collected at different stages of processing. Most commercial samples showed detectable levels of PAHs, with some exceeding the limits established by the European Union. AQ was detected in 40% of the samples, with some values above the permitted limit of 20 µg·kg⁻¹. The results confirm that scorch (sapeco) and drying contribute to contaminant formation, highlighting the need to modernize industrial processing practices. The proposed method proved to be effective, rapid, and sustainable, representing a promising tool for the quality control and food safety monitoring of yerba mate. Full article

Thanks to its tolerance to drought, sorghum is a cereal crop that is extensively cultivated in the sub-Saharan region. Its good nutritional value makes it an interesting raw material for the food industry, although several anti-nutritional features pose a challenge to exploiting its full potential. In this study, we evaluated whether the process of germination may represent a way of improving the macro- and micro-molecular profile of sorghum, lowering the content of anti-nutritional factors, and promoting the synthesis of bioactive compounds. Germination for 48 and especially 72 h promoted the hydrolysis of starch and proteins, enhanced antioxidant activity, increased the content of polyphenols, mainly flavonols and flavanones, and promoted the conversion of γ- to α-isomers of tocopherols. At the same time, it significantly reduced the concentration of phytates and linoleic acid, enhancing pepsin activity and contributing to the inaugural examination of the impact of sprouted sorghum on digestive protease activity. These findings could help to promote the utilization of sprouted sorghum as a premium ingredient for food products, providing significant nutritional advantages. Full article

The aim of this study is to provide basic data on the yield and bioactive compound contents of the male asparagus cultivar ‘Avalim’ grown under two cultivation systems, i.e., an open field and a rain shelter house, in the Saemangeum reclaimed land. Spear sprouting, yield parameters, polyphenol and flavonoid contents, antioxidant enzyme activities (catalase, ascorbate peroxidase, peroxidase, and superoxide dismutase), and DPPH and ABTS radical scavenging activities of 22-month-old asparagus cultivated in each system were measured. Spear sprouting occurred approximately 10 days earlier in the rain shelter house than in the open field. The number of asparagus spears per 1000 m² was approximately 600 higher in the rain shelter house, and the total weight was 21% higher than that in the open field. Polyphenol and flavonoid contents, antioxidant enzyme activities, and DPPH and ABTS radical scavenging activities were higher in the open field than in the rain shelter house. The temperature in the rain shelter house during the cultivation period was 0.6 to 17.4 °C higher than that in the open field, while light intensity was 359.7 μmol·m⁻²·s⁻¹ higher in the open field. Consequently, cultivation in Saemangeum reclaimed land resulted in higher yields in the rain shelter house, whereas the bioactive compound levels were higher in the open field. Therefore, selecting an appropriate cultivation system based on the intended purpose, focusing on yield or functional quality, when cultivating asparagus on reclaimed land is important. Full article

Apple by-products are a valuable raw material due to their high content of dietary fiber, minerals, and bioactive compounds, making them a promising functional ingredient in food products. The aim of this study was to evaluate the effect of adding a residue obtained from the isolation of starch from unripe apples of the Pyros and Oliwka varieties on the nutritional composition, mineral content, polyphenol and fiber levels, and color of wheat muffins. Additionally, the oxidative stability was analyzed. The results showed that the addition of the residue significantly increased the total, soluble, and insoluble fiber content, as well as the protein content. The polysaccharide fraction residue from unripe Oliwka apples had a stronger impact on enhancing the fiber content of the muffins. In contrast, muffins enriched with the polysaccharide fraction residue from unripe Pyros apples exhibited higher levels of calcium, potassium, and magnesium, while the Oliwka residue increased the contents of sodium, strontium, and iron. The addition of the polysaccharide fraction residue significantly increased the levels of chlorogenic acid, phloridzin, quercetin, and procyanidin B1. Color analysis revealed a darkening effect in the muffins after the addition of the residue, and the oxidative stability decreased with increasing levels of the polysaccharide fraction residue. This study demonstrated that apple residues obtained after starch isolation can effectively enrich muffins with nutrients and health-promoting compounds; however, their impact on oxidative stability requires further investigation. Full article

The valorization of agro-industrial byproducts like Habanero pepper (Capsicum chinense Jacq.) leaves has gained attention due to their high polyphenol content and bioactivity. In this study, phenolic-rich extracts were obtained using ultrasound-assisted extraction with natural deep eutectic solvents (NADES). Extracts were microencapsulated with maltodextrin, guar gum, and modified starch and incorporated into an isotonic beverage. The bioaccessibility of total and individual polyphenols were assessed through in vitro digestion by simulating fasting and postprandial conditions. Under fasting conditions, the enriched isotonic beverage showed significantly higher total phenolic content (6.98 ± 0.03 mg GAE/100 mL) compared to the control isotonic beverage (5.02 ± 0.22 mg GAE/100 mL), representing a 39% increase. Rutin and quercetin remained detectable throughout digestion, with final concentrations of 1.24 ± 0.05 and 1.10 ± 0.10 mg/100 mL, respectively, in the enriched beverage under postprandial conditions. These findings confirm the protective effect of the encapsulation matrix and highlight NADES as promising solvents for sustainable extraction. This work supports the integration of polyphenol microencapsulated into functional beverages as a novel strategy for delivering bioactive compounds from Capsicum chinense by-products. Full article

The coffee cherry processing produces various waste products, such as coffee husks, which are a valuable source of pectin and phenolic acids that can be used as high-value biomolecules in human and animal food, cosmetics, and pharmaceutical production chains. This study aims to optimize the eco-friendly extraction of polysaccharides, as pectin, and phenolic compounds from coffee peel using response surface methodology (RSM). This model was used to evaluate the extraction variables (temperature, time, pH, ionic strength, ultrasonic frequency, particle size, and solid/liquid ratio in water) to identify the critical factors. All responses were fitted to the RSM model, which revealed high estimation capabilities. Ionic strength and temperature were found to be critical process variables for pectin extraction, while the main factors responsible for phenolic extraction were ultrasonic frequency, pH, and solid/liquid ratio. Therefore, the operating conditions to optimize the extraction of both pectin and phenolic compounds were 80 °C, ultrasonic frequency 60 kHz, solid/liquid ratio 1:20, using pH 2 or 12 in the case of pectin or polyphenols, respectively. Direct Analysis in Real Time Mass Spectrometry (DART-MS) and Fourier-Transform Infrared Spectroscopy–Attenuated Total Reflectance (FTIR-ATR) analyses were performed to evaluate the chemical profile of the extracts and pectin. The recycling of coffee husk waste into bioproducts in view of the circular economy contributes to minimizing the impact on the environment and to generating additional income for coffee growers. Full article

Eugenol is a compound with promising antimicrobial properties. The rising phenomenon of multidrug resistance of Candida albicans is driving researchers to search for new, alternative therapeutics that would synergize with conventional antifungal drugs. The aim of the present study is to investigate how eugenol and eugenol-based extracts impair C. albicans growth by generation of reactive oxygen species (ROS) and plasma membrane (PM) disruption. The methods that we applied involve structural analysis of eugenol extracts by HPLC, ATR-FTIR, and polyphenol detection. Additionally, determination of ROS level in C. albicans was performed using microscopic and flow cytometry studies and analysis of PM integrity (PI-staining, observation of PM transporter—Cdr1p—localization) and fluidity (fluorometric study). The results indicate that eugenol impacts fungal growth, and this corresponds with increased ROS levels and diminished PM fluidity in the C. albicans WT strain. C. albicans strains deprived of ergosterol (erg11Δ/Δ) exhibited lowered ROS level and no change in PM fluidity in response to the tested eugenol extracts, but they affected its growth and caused PM permeabilization and Cdr1p delocalization. These conclusions indicate that mode of action of eugenol can be related to disruption of PM structure by both ergosterol-dependent and -independent mechanisms. Ergosterol can play a crucial role in maintaining the PM integrity during treatment with lower concentrations of eugenol. Full article

Abeliophyllum distichum is rich in polyphenols and flavonoids with various bioactivities; however, studies on enzymatic modifications to enhance its functional properties remain limited. This study investigated the effect of Viscozyme^® L treatment on the secondary metabolite profile of A. distichum leaves. Phytochemical profiling using liquid chromatography–electrospray ionization tandem mass spectrometry revealed a decrease in the total number of detectable compounds, from 26 in the untreated extract to 16 in the enzyme-treated extract. Following Viscozyme^® L treatment, a notable shift in metabolite composition was observed, with significant enrichment of flavonoid glycosides, pyranone derivatives, and amino acid-related metabolites. Quantitative high-performance liquid chromatography analysis showed significant reductions in glycosylated compounds such as rutin (1), acteoside (2), and isoacteoside (3), while the aglycone quercetin (4) content increased more than four-fold compared to the control. These results indicate that Viscozyme^® L facilitates the deglycosylation of flavonoid glycosides into their aglycone forms. This enzymatic transformation suggests a potential strategy to enhance the bioavailability and functional value of A. distichum leaf extracts for nutraceutical and pharmaceutical applications. Full article