Search Results (1,795)

Chestnut (Castanea sativa Mill.) is an edible nut recognized for its nutritional attributes, particularly its elevated levels of carbohydrates (starch) and proteins. Chestnuts are popular for their health-promoting properties and hold significant environmental and economic importance in Europe. During this study, after the characterization of the fruit, attention was directed toward the valorization of chestnut shells, a predominant by-product of industrial chestnut processing that is typically discarded. Valuable bioactive compounds were extracted from the shells using Pressurized Liquid Extraction (PLE), a green, efficient, scalable method. Response surface methodology (RSM) was utilized to determine optimal extraction conditions, identified as 40% v/v ethanol as the solvent at a temperature of 160 °C for 25 min under a constant pressure of 1700 psi. High total polyphenol content (113.68 ± 7.84 mg GAE/g dry weight) and notable antioxidant activity—determined by FRAP (1320.28 ± 34.33 μmol AAE/g dw) and DPPH (708.65 ± 24.8 μmol AAE/g dw) assays—were recorded in the optimized extracts. Ultrahigh-performance liquid chromatography coupled with a hybrid trap ion mobility-quadrupole time-of-flight mass spectrometer (UHPLC-TIMS-QTOF-MS) was applied to further characterize the compound profile, enabling the identification of phenolic and antioxidant compounds. These findings highlight the possibility of using chestnut shell residues as a long-term resource to make valuable products for the food, medicine, cosmetics, and animal feed industries. This study contributes to the advancement of waste valorization strategies and circular bioeconomy approaches. Full article

The widespread discharge of industrial and urban waste has led to significant increases in the environmental concentrations of numerous chemical substances. This work presents the development of a simple and environmentally friendly dispersive liquid–liquid microextraction (DLLME) method based on a hydrophobic natural deep eutectic solvent (NADES) for the determination of selected compounds from benzotriazole, benzothiazole, paraben, and UV filter families in wastewater samples. Of the twelve NADES formulations evaluated, those composed of a 4:1 molar ratio of thymol and menthol presented the highest extraction efficiencies. The influence of key experimental variables such as the pH of the aqueous sample, the ratio of NADES phase to sample volume, and the extraction time on the extraction efficiency was investigated using a multivariate optimization. Under optimal conditions, relative standard deviations below 15% and recoveries for spiked wastewater samples ranged between 82 and 108%, demonstrating the suitability of the method for routine water-quality monitoring. The sustainability and practicality of the developed method was evaluated using the assessment tools ChlorTox, AGREEprep, AGRRE, and BAGI, obtaining scores of 0.005 g in the NADES-DLLME method, 0.70, 0.52, and 72.5, respectively, demonstrating that the method is green and reliable. Full article

Burnout syndrome is characterized mainly by three criteria (emotional exhaustion, depersonalization, and low personal accomplishment), and further exacerbated by night shift work, with profound implications for individual and societal well-being. The Maslach Burnout Inventory survey applied to 97 medical care professionals (with day and night work) revealed different scores for these criteria. Blood metabolic profiles were obtained by UHPLC-QTOF-ESI⁺-MS untargeted metabolomics and multivariate statistics using the Metaboanalyst 6.0 platform. The Partial Least Squares Discrimination scores and VIP values, Random Forest graphs, and Heatmaps, based on 99 identified metabolites, were complemented with Biomarker Analysis (AUC ranking) and Pathway Analysis of metabolic networks. The data obtained reflected the biochemical implications of night shift work and correlated with each criterion’s burnout scores. Four main metabolic pathways with important consequences in burnout were affected, namely lipid metabolism, especially steroid hormone synthesis and cortisol, the energetic mitochondrial metabolism involving acylated carnitines, fatty acids, and phospholipids as well polar metabolites’ metabolism, e.g., catecholamines (noradrenaline, acetyl serotonin), and some amino acids (tryptophan, tyrosine, aspartate, arginine, valine, lysine). These metabolic profiles suggest potential strategies for managing burnout levels in healthcare professionals, based on validated criteria, including night shift work management. Full article

Malaria continues to pose a significant global health burden, driving the search for novel antimalarial agents to address emerging drug resistance. This study evaluated the antiplasmodial potential of Ziziphus mauritiana Lam. (Rhamnaceae) roots through an integrated phytochemical and pharmacological approach. The ethanol extract, along with its derived fractions, demonstrated potent in vitro activity against the chloroquine-sensitive Plasmodium falciparum strain 3D7 (Pf3D7), with the ethyl acetate-soluble (IC₅₀ = 11.35 µg/mL) and alkaloid-rich (IC₅₀ = 4.75 µg/mL) fractions showing particularly strong inhibition. UHPLC-DAD-ESI-QTOF-MS/MS-based molecular networking enabled the identification of thirty-two secondary metabolites (1–32), comprising twenty-five cyclopeptide alkaloids (CPAs), five of which had not yet been described (11, 20, 22, 23, 25), and seven known triterpenoids. Bioactivity-guided isolation yielded thirteen purified compounds (5, 6, 14, 26–30, 32–36), with betulinic acid (30; IC₅₀ = 19.0 µM) and zizyberenalic acid (32; IC₅₀ = 20.45 µM) exhibiting the most potent antiplasmodial effects. Computational ADMET analysis identified mauritine F (4), hemisine A (10), and nummularine R (21) as particularly promising lead compounds, demonstrating favourable pharmacokinetic properties, low toxicity profiles, and predicted activity against both family A G protein-coupled receptors and evolutionarily distinct Plasmodium protein kinases. Quantitative analysis revealed exceptionally high concentrations of key bioactive constituents, notably zizyberenalic acid (24.3 mg/g) in the root extracts. These findings provide robust scientific validation for the traditional use of Z. mauritiana in malaria treatment while identifying specific cyclopeptide alkaloids and triterpenoids as valuable scaffolds for antimalarial drug development. The study highlights the effectiveness of combining advanced metabolomics, bioassay-guided fractionation, and computational pharmacology in natural product-based drug discovery against resistant malaria strains. Full article

Background: Hydroxyl and amino compounds play a significant role in defining the flavor and quality of sauce-flavor Baijiu, yet their comprehensive analysis remains challenging due to limitations in detection sensitivity. In this study, we developed a novel bromine isotope labeling approach combined with ultra-high performance liquid chromatography–high-resolution mass spectrometry (UHPLC-HRMS) to achieve high-coverage profiling of these compounds in sauce-flavor Baijiu. Methods: The method employs 5-bromonicotinoyl chloride (BrNC) for rapid (30 s) and mild (room temperature) labeling of hydroxyl and amino functional groups, utilizing bromine’s natural isotopic pattern (Δm/z = 1.998 Da) for efficient screening. Annotation was performed hierarchically at five confidence levels by integrating retention time, accurate mass, and MS/MS spectra. Results: A total of 309 hydroxyl and amino compounds, including flavor substances (e.g., tyrosol and phenethyl alcohol) and bioactive compounds (e.g., 3-phenyllactic acid), were identified in sauce-flavor Baijiu. The method exhibited excellent analytical performance, with wide linearity (1–4 orders of magnitude), precision (RSD < 18.3%), and stability (RSD < 15% over 48 h). When applied to sauce-flavor Baijiu samples of different grades, distinct compositional patterns were observed: premium-grade products showed greater metabolite diversity and higher contents of bioactive compounds, whereas lower-grade samples exhibited elevated concentrations of acidic flavor compounds. Conclusions: These results demonstrate that the established method is efficient for the comprehensive analysis of hydroxyl and amino compounds in complex food matrices. The findings provide valuable insights for quality control and flavor modulation in sauce-flavor Baijiu production. Full article

Global warming represents one of the most pressing environmental challenges to cold-water fish farming. Heat stress markedly alters the mucosal symbiotic microbiota and intestinal microbial metabolites in fish, posing substantial barriers to the healthy artificial breeding of rainbow trout (Oncorhynchus mykiss). However, the relationship between mucosal commensal microbiota, intestinal metabolites, and host environmental adaptability under heat stress remains poorly understood. In this study, rainbow trout reared at optimal temperature (16 °C) served as controls, while those exposed to maximum tolerated temperature (24 °C, 21 d) comprised the heat stress group. Using 16S rRNA amplicon sequencing and ultra-high-performance liquid chromatography–mass spectrometry (UHPLC-MS), we analysed the mucosal commensal microbiota—including gastrointestinal digesta, gastrointestinal mucosa, skin mucus, and gill mucosa—and intestinal metabolites of rainbow trout under heat stress conditions to explore adaptive and regulatory mechanisms. Analysis of microbial composition and diversity revealed that heat stress exerted the greatest impact on the diversity of gill and skin mucus microbiota, followed by gastrointestinal digesta, with relatively minor effects on the gastrointestinal mucosa. At the phylum level, Proteobacteria, Firmicutes, and Bacteroidetes were predominant in the stomach, intestine, and surface mucosa. At the genus level, Acinetobacter showed the greatest increase in abundance in skin and gill mucosa under heat stress, while Enterobacteriaceae exhibited the most pronounced increase in intestinal digesta, gastric digesta, and gastric mucosa. Differential metabolites in the intestinal digesta under heat stress were predominantly enriched in pathways associated with amino acid metabolism, particularly tryptophan metabolism. This study provides a comprehensive characterisation of microbiota and metabolic profile alterations in rainbow trout under heat stress condition, offering a theoretical foundation for understanding the response mechanisms of fish commensal microbiota to thermal stress. Full article

Lippia multiflora Moldenke is widely used in Angola, on the African continent, and beyond for the treatment of many health conditions such as hypertension, enteritis, colds, gastrointestinal disturbances, stomachaches, jaundice, coughs, fevers, nausea, bronchial inflammation, conjunctivitis, malaria, and venereal diseases. However, there is limited literature about the active compounds linked with the reported biological activities. This study aims to assess the chemical profiles, antioxidant properties, and the cytotoxicity effects of the roots, stem bark, and leaves of L. multiflora. Chemical characterization of the crude extracts was assessed through quantification of total phenolic and flavonoid contents followed by Q exactive plus orbitrap™ ultra-high-performance liquid chromatography-mass spectrometer (UHPLC-MS) screening. The correlation between the extracts and the correlation between the compounds were studied using the multivariate analysis. Principal component analysis (PCA) loading scores and principal component analysis (PCA) biplots and correlation plots were used to connect specific compounds with observed biological activities. The antioxidant activities of the crude extracts were carried out in vitro using DPPH (2,2-diphenyl-1-picrylhydrazyl) free radical scavenging and reducing power assays, while the in vitro toxicology of the crude extracts was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. A total of twenty constituents were characterized and identified using the UHPLC–Q/Orbitrap/MS. The methanol leaf extract showed the highest antioxidant activity in the DPPH free radical scavenging activity (IC₅₀ = 0.559 ± 0.269 μg/mL); however, the stem bark extract had the highest reducing power (IC_0.5 = 0.029 ± 0.026 μg/mL). High phenolic and flavonoid content was found in the dichloromethane leaf extract (32.100 ± 1.780 mg GAE/g) and stem bark extract (624.153 ± 29.442 mg QE/g), respectively. The results show the stem bark, methanol leaf, and dichloromethane leaf extracts were well-tolerated by the Vero cell line at concentrations up to 50 µg/mL. However, at 100 µg/mL onward, some toxicity was observed in the root, methanol leaf, and dichloromethane leaf extracts. The UHPLC–Q/Orbitrap/MS profiles showed the presence of terpenoids (n = 5), flavonoids (n = 5), phenols (n = 4), alkaloids (n = 3), coumarins (n = 1), fatty acids (n = 1), and organic acids (n = 1). According to several studies, these secondary metabolites have been reported and proven to be the most abundant for antioxidant potential. The identified flavonoids (catechin, quercitrin, and (−)-epigallocatechin) and phenolic compound (6-gingerol) can significantly contribute to the antioxidant properties of different plant parts of L. multiflora. The research findings obtained in this study provide a complete phytochemical profile of various parts of L. multiflora that are responsible for the antioxidant activity using UHPLC–Q/Orbitrap/MS analysis. Furthermore, the results obtained in this study contribute to the scientific information or data on the therapeutic properties of Lippia multiflora and provide a basis for further assessment of its potential as a natural remedy. Full article

Helicobacter pylori is a gastric pathogen implicated in peptic ulcer disease and gastric cancer. The increasing prevalence of antibiotic-resistant strains underscores the urgent need for alternative therapeutic strategies. In this study, we investigated the chemical composition and antibacterial activity of an aqueous extract from Caulerpa lentillifera (sea grape), a farm-cultivated edible green seaweed collected from Krabi Province, Thailand. Ultra-high-performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS) revealed that the extract was enriched in bioactive nucleosides and phenolic compounds. In vitro assays demonstrated dose-dependent inhibition of H. pylori growth following exposure to sea grape extract. Furthermore, untargeted intracellular metabolomic profiling of H. pylori cells treated with the extract uncovered significant perturbations in central carbon and nitrogen metabolism, including pathways associated with the tricarboxylic acid (TCA) cycle, one-carbon metabolism, and alanine, aspartate, and glutamate metabolism. Pyrimidine biosynthesis was selectively upregulated, indicating a potential stress-induced shift toward nucleotide salvage and DNA repair. Of particular note, succinate levels were markedly reduced despite accumulation of other TCA intermediates, suggesting disruption of electron transport-linked respiration. These findings suggest that bioactive metabolites from C. lentillifera impair essential metabolic processes in H. pylori, highlighting its potential as a natural source of antimicrobial agents targeting bacterial physiology. Full article

Schefflera oleifera honey (SH) is produced from the nectar of S. Oleifera by worker bees. Due to its unique properties and potential biological activities, this winter honey has attracted much attention. In this study, the physicochemical characteristics, antioxidant and antibacterial activities, antitumor effect against HepG2 cells, and its potential mechanisms of SH were systematically evaluated. The results showed that different SH samples differed significantly in their physicochemical characteristics. The 910 chemical components, including 52 kinds of phenols, phenolic acids, and flavonoids, were detected in the methanol extract of SH using UHPLC-MS/MS by non-targeted metabolomics. Based on our limited knowledge, solanine and soyasaponin I are the first determined components in honey, and they may be used as characteristic substances of SH for identification and adulteration. SH had a weaker inhibitory effect against Salmonella typhimurium and Staphylococcus aureus than MH (UMF 10+), analyzed by MBC and MIC assays. Network pharmacology analysis showed that 95 overlapping targets were found between the active ingredients of SH and liver cancer cells (HepG2), which were enriched in KEGG of the PI3K-Akt pathway, Lipid and atherosclerosis, Proteoglycans in cancer, etc. The IC₅₀ of SH against HepG2 cells was 5.07% (dw/v), which is lower than the glucose, fructose, and sucrose contents in SH on HepG2 cells, of 16.24%, 9.60% dw/v, and 9.94% dw/v, respectively. SH significantly down-regulated the expression of EGFR, AKT1, and SRC in HepG2 cells (p < 0.05), determined by an enzyme-linked immunosorbent assay kit, and induced cell cycle arrest and apoptosis by multiple pathways. These results provide a theoretical basis for its potential application in developing functional foods and additives. Full article

The current study investigates the chemical profiling, antioxidant activities, and enzyme inhibitory and cytotoxic potential of the water and methanolic extracts of different parts (flower, leaf, and bulb) of Muscari armeniacum. Chemical profiling was performed using UHPLC-MS/MS. At the same time, different in vitro assays were employed to support the results for antioxidant potential, such as DPPH, ABTS, FRAP, CUPRAC, metal chelation, and PBD, along with the measurement of total phenolic and flavonoid contents. Enzyme inhibition was investigated for cholinesterase (AChE and BChE), α-amylase, α-glucosidase, and tyrosinase enzymes. Additionally, the relative expression of NRF2, HMOX1, and YGS was evaluated by qPCR. LC-MS/MS analysis indicated the presence of some significant compounds, including apigenin, muscaroside, hyacinthacine A, B, and C, and luteolin. According to the results, the highest TPC and TFC were obtained with both extracts of the leaves, followed by the water extract (flower) and methanolic extract of the bulb. In contrast, the methanolic extract from the bulb exhibited the highest antioxidant potential using DPPH, ABTS, CUPRAC, and FRAP, followed by the extracts of leaves. In contrast, the leaf extracts had the highest values for the PBD assay and maximum chelation ability compared to other tested extracts. According to the enzyme inhibition studies, the methanolic extract from the bulb appeared to be the most potent inhibitor for all the tested enzymes, with the highest values obtained for AChE (1.96 ± 0.05), BChE (2.19 ± 0.33), α-amylase (0.56 ± 0.02), α-glucosidase (2.32 ± 0.01), and tyrosinase (57.19 ± 0.87). Interestingly, the water extract from the bulb did not inhibit most of the tested enzymes. The relative expression of NRF2 based on qPCR analysis was considerably greater in the flower methanol extract compared to the other extracts (p < 0.05). The relative expression of HMOX1 was stable in all the extracts, whereas YGS expression remained stable in all the treatments and had no statistical differences. The current results indicate that the components of M. armeniacum (leaves, flowers, and bulb) may be a useful source of natural bioactive compounds that are effective against oxidative stress-related conditions, including hyperglycemia, skin disorders, and neurodegenerative diseases. Complementary in silico approaches, including molecular docking, dynamics simulations, and transcription factor (TF) network analysis for NFE2L2, supported the experimental findings and suggested possible multi-target interactions for the selected compounds. Full article

The current study evaluated the anticonvulsant properties of ethanolic extracts from Morus alba, Angelica archangelica, Passiflora incarnata, and Valeriana officinalis using integrated phytochemical, in vivo, biochemical, and computational approaches. Phytochemical analysis by UHPLC-HRMS/MS revealed the presence of various bioactive compounds, notably flavonoids such as isorhamnetin, quercetin, and kaempferol. In an electroshock-induced seizure model, Morus alba extract (MAE, 100 mg/kg) demonstrated significant anticonvulsant effects, reducing both seizure duration and incidence, likely mediated by flavonoid interactions with GABA-A and 5-HT3A receptors, as suggested by target prediction and molecular docking analyses. The extracts of Angelica archangelica (AAE, 100 mg/kg) and Passiflora incarnata (PIE, 50 mg/kg) exhibited moderate, non-significant anticonvulsant activities. At the same time, Valeriana officinalis (VOE, 50 mg/kg) displayed considerable antioxidant and anti-inflammatory properties but limited seizure protection. All extracts significantly reduced brain inflammation markers (TNF-α) and enhanced antioxidant defenses, as indicated by total thiols. Molecular docking further supported the interaction of key phytochemicals, including naringenin and chlorogenic acid, with human and mouse 5-HT3A receptors. Overall, Morus alba extract exhibited promising therapeutic potential for epilepsy management, warranting further investigation into chronic seizure models and optimized dosing strategies. Full article

Cichorium intybus L. (common chicory) is a medicinal plant valued for health-promoting effects. Although analgesic properties are known for chicory sesquiterpenes, the effects of extracts need yet to be explored. This study aimed to evaluate for the first time the analgesic effect (against nociceptive pain) of the root extract from C. intybus var. foliosum. The target evaluation was preceded by toxicity tests in vivo and phytochemical standardization of root extracts prepared with different extraction methods—pectinase-assisted, pressure-assisted, and a combination of both—to choose the most effective one. The phytochemical profiling involved UHPLC-PDA-ESI-MS/MS and UHPLC-PDA analyses. The toxicity and the analgesic effects were tested in mice following the OECD 423 guideline and the hot-plate test, respectively. The highest recovery of bioactive compounds was achieved for the pressure-assisted extract: 642.5 mg sesquiterpene lactones, 187.1 mg phenolic acids, and 47.3 g inulin/100 g of dry matter. The extract showed no toxic effects at the oral dose of 2000 mg/kg body weight, including no histopathologic changes, in mice within two weeks (GHS Category 5/Uncategorized). The maximum analgesic effect (MAE) of the extract at 600 mg/kg was 6.75% for rearing and 13.7% for jumping, with the impact on the nocifensive reactions not differing significantly from those of paracetamol at 60 mg/kg. Despite the relatively low effects at 600 mg/kg, the verified safety and abundance of active compounds encourage further studies on the extract and its active fractions as potential approaches to complementary pain therapy, with special concern for their mechanisms of action. Full article

Allium chinense G. Don is valued for its edible and medicinal qualities. It has been reported that Allium chinense has the potential to inhibit platelet activation, but its mechanism of action is unknown, which needs to be further explored. This study investigates the anti-myocardial ischemia–reperfusion (I/R) injury potential of Allium chinense from the perspective of platelet activation, focusing on its chemical composition and underlying mechanisms of action. A combination of transcriptome sequencing, molecular docking, and experimental validation was employed in our study. The antiplatelet active fraction MT-95ET of Allium chinense was screened by the ADP-induced platelet aggregation model in vitro. In vivo experiments demonstrated that MT-95ET can reduce the myocardial injury of I/R rats and inhibit I/R-induced platelet activation, adhesion, and aggregation. UHPLC-Q-Orbitrap-MS/MS was used to identify 13 compounds from MT-95ET. Transcriptome sequencing and molecular docking identified aerobic glycolysis key checkpoints PDK1 and PKM2 as key targets, with Sarsasapogenin and Hecogenin exhibiting strong binding affinities to these proteins. Western blot analysis further validated that MT-95ET downregulated PKM2 and PDK1, indicating a possible mechanism for its antiplatelet effects and anti-myocardial I/R injury. Full article

Background/Objectives: Vitamin D (VD) is metabolized in the body and plays a crucial role in regulating the antioxidant system. While exposure to heavy metals (HMs) inhibits VD activity, HMs can also be absorbed following VD stimulation. Despite differing views on the interaction between HM and VD activity, the effects of HM exposure on VD-related pathways have not been examined using metabolomics. This study aimed to investigate the impact of HM exposure on VD-related antioxidant activity under VD deficiency conditions using untargeted metabolic profiling. Methods: In this retrospective cohort study, 46 plasma samples were analyzed using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF/MS). Metabolic profiling was performed on two groups: individuals with severe VD deficiency and low HM exposure (SVDD–LHM) and those with VD deficiency and high HM exposure (VDD–HHM). Results: As a compensatory response to oxidative stress induced by HMs, VD-related antioxidant pathways may be associated with elevated levels of antioxidants, including bilirubin, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). In-creases in EPA and DHA were also linked to alterations in lipid metabolism, including diacylglycerol and phosphatidylcholine levels. DHA showed an area under the curve (AUC) of 0.850 (95% CI: 0.651–0.990), suggesting that DHA could serve as a potential biomarker for VD activity in response to HM exposure. Conclusions: The identified metabolites and metabolic pathways suggest that HM exposure may stimulate VD-related antioxidant activity, even under VD-deficient conditions. Full article

Beneficial interactions between nitrogen-fixing soil bacteria and legumes offer a solution to increase crop yield on Earth and potentially in future Martian colonies. Paraburkholderia phymatum is a nitrogen-fixing beta-rhizobium, which enters symbiosis with more than 50 legumes and can survive in acidic or aluminium-rich soils. In a previous RNA-sequencing study, we showed that the beta-rhizobium P. phymatum grows well in simulated microgravity and identified phymabactin as the only siderophore produced by this strain. Here, the growth of the beta-rhizobium P. phymatum was assessed in Martian simulant soil using Enhanced Mojave Mars Simulant 2 (MMS-2), which contains a high amount of iron (18.4 percent by weight) and aluminium (13.1 percent by weight). While P. phymatum wild-type’s growth was not affected by exposure to MMS-2, a mutant strain impaired in siderophore biosynthesis (ΔphmJK) grew less than P. phymatum wild-type on gradient plates in the presence of a high concentration of MMS-2 or aluminium. This result suggests that the P. phymatum siderophore phymabactin alleviates aluminium-induced heavy metal stress. Ultra-high performance liquid chromatography–mass spectrometry (UHPLC-MS) showed that phymabactin can bind to aluminium more efficiently than iron. These results not only deepen our understanding of the behaviour of rhizobia in simulated extraterrestrial environments but also provide new insights into the potential use of P. phymatum for bioremediation of aluminium-rich soils and the multiple roles of the siderophore phymabactin. Full article