Search Results (4,397)

Background/Objectives: Synthetic stimulants represent the most prevalent subclass on the new psychoactive substances (NPSs) market. However, the toxicokinetic properties of M-ALPHA, a regioisomer of MDMA and N-methyl-cyclazodone a pemoline derivative, are not yet characterized. Methods: Therefore, this study investigated the metabolism of both NPSs in pooled liver S9 fraction and rat urine, characterized cytochrome P450 (CYP) kinetics and plasma protein binding (PPB), and assessed the CYP inhibition potential of M-ALPHA, using high-performance liquid chromatography coupled to high resolution tandem mass spectrometry (HPLC-HRMS/MS). Results: Four metabolites of M-ALPHA were detected including one phase I and three phase II metabolites, resulting from demethylenation followed by subsequent methylation or glucuronidation. For N-methyl-cyclazodone, one phase I metabolite formed via N-demethylation was identified. The primary enzymes involved in M-ALPHA metabolism were CYP2B6 and CYP2D6. Notably, M-ALPHA inhibited these enzymes to a strong or moderate extent, respectively. In contrast, the metabolism of N-methyl-cyclazodone was primarily mediated by CYP2A6. PPB studies indicated low-to-moderate binding for both compounds, suggesting that significant protein-binding interactions are unlikely. Conclusions: As M-ALPHA only formed metabolites that overlapped with those of MDMA, differing only by minor retention time shifts, reliable HPLC-HRMS/MS-based identification may be challenging in clinical and forensic toxicology settings as well as doping analysis. Furthermore, drug–drug interactions following polydrug use cannot be excluded for either NPS, particularly when co-ingested with other CYP substrates metabolized by the same isoforms. Full article

The valorization of agro-industrial by-products is of increasing importance within circular economy strategies. Aronia melanocarpa pomace, a by-product of juice production, represents a valuable source of polyphenols with potential applications in food, nutraceutical, and cosmetic formulations. This study aimed to evaluate the effect of different preservation methods on the polyphenolic composition of Aronia pomace and to optimize accelerated solvent extraction (ASE). Pomace samples were subjected to drying, freeze-drying, freezing (−18 °C), and deep freezing (−80 °C). UAE was applied as a rapid screening method for polyphenol extraction, while ASE was used as an advanced technique for efficient recovery of target compounds. ASE parameters, including temperature (40–120 °C), methanol concentration (40–100%), and number of extraction cycles (1–3), were optimized using response surface methodology (RSM) based on a Box–Behnken design. Qualitative and quantitative analyses were performed using UHPLC–MS and HPLC–DAD. The developed models were statistically significant (p < 0.01) with high coefficients of determination (R² = 0.88–0.97). Temperature had a positive effect on phenolic acid extraction but negatively affected anthocyanins due to thermal degradation. Optimal extraction conditions differed between compound groups: phenolic acids were maximized at 120 °C and 75% methanol (two cycles), while anthocyanins required milder conditions (82 °C, 92% methanol, three cycles). Moreover, our study showed that drying significantly reduced the content of several compounds, particularly anthocyanins, whereas low-temperature methods had minimal impact. The results highlight the importance of tailored extraction strategies and support the sustainable utilization of Aronia pomace as a source of bioactive compounds. Full article

Background: Colorectal intraepithelial neoplasia (CR-EN) is a precursor lesion of colitis-associated colorectal cancer (CAC). This study investigated the interventional effects and molecular mechanisms of Rhapontici Radix extract on CR-EN. Methods: An azoxymethane/dextran sulfate sodium (AOM/DSS)-induced mouse model of colonic intraepithelial neoplasia, bioinformatics analysis, organoid models, and HCT116 cell experiments were employed, coupled with histopathological examination, inflammatory cytokine detection, Western blot, immunofluorescence, and HPLC-MS/MS. Results: The results showed that the YAP/AKT-PI3K signaling pathway is aberrantly activated in CRC. Rhapontici Radix extract ameliorated colonic pathology, suppressed inflammatory responses, and remodeled gut microbiota composition in model mice. The extract selectively inhibited the proliferation of CR-EN organoids by downregulating Ki67 and β-catenin while upregulating p53, and suppressed the proliferation, colony formation, and migration of HCT116 cells. Mechanistically, the extract modulated the YAP/PI3K/AKT pathway by upregulating phosphorylated YAP (p-YAP) and downregulating phosphorylated AKT (p-AKT), phosphorylated PI3K (p-PI3K), and their downstream targets p-SRC and c-MYC. Conclusions: This study suggests that Rhapontici Radix extract intervenes in inflammation-associated carcinogenesis through a multi-pathway, multi-target strategy, offering potential therapeutic targets for CAC prevention and treatment. Full article

Imidazolinone herbicides such as imazethapyr (IMT) pose potential ecological risks due to their high mobility and ecotoxicity. This study synthesized the bismuth-based photocatalyst BiOIO₃ via a facile hydrothermal method and systematically characterized its physicochemical properties. BiOIO₃ features a 2D lamellar structure, pure phase composition, and a built-in internal polarization electric field that efficiently separates photogenerated electron–hole pairs. Photocatalytic experiments exhibited that BiOIO₃ achieved 84.5% elimination of IMT, with a rate constant 66 times higher than that of TiO₂ (Rutile). Mechanistic studies revealed that photogenerated electrons (e⁻), holes (h⁺), and superoxide radicals (·O₂⁻) are the primary reactive species. HPLC-MS/MS identified key intermediates, and QSAR-based toxicity prediction showed reduced mutagenicity for most intermediates. Importantly, BiOIO₃ effectively eliminated five imidazolinone herbicides simultaneously. This work highlights BiOIO₃ as a promising photocatalyst for efficient and practical remediation of imidazolinone herbicide-contaminated water. Full article

In this study, new types of eutectic solvents (ESs) are tested for their ability to remove the eight most common bisphenols (BPA, BPB, BPC, BPE, BPF, BPG, BPS, BPAP), which are environmentally monitored substances, from aqueous matrices. A total of 18 ESs based on hydrophobic organic acids, such as capric, caprylic, lauric, and myristic acids, and terpenes, such as DL-menthol, terpineol, linalool, and geraniol, are prepared and mixed in various molar ratios. The highest extraction yield for all types of BPs is achieved with a binary mixture of geraniol:caprylic acid prepared in a molar ratio of 1:1. This ES can be used repeatedly for five consecutive cycles achieving almost 100% recovery for BPB, BPC, BPG, and BPAP, while for BPA, BPE, and BPF, the yield drops to 97% and for BPS to 90%. The efficiency of ES extraction is verified using HPLC-MS/MS to determine the BPs in the aqueous phase. This is performed at a pentafluorophenylpropyl stationary phase with LOQs ranging from 0.24 to 29.1 ng/mL. The applicability of this HPLC-MS/MS method was demonstrated by monitoring the occurrence of BPs in thermal paper and other industrial samples. Full article

Deoxynivalenol (DON), a Group III carcinogenic mycotoxin frequently detected in cereals and animal-derived food products, poses serious health risks to animals and humans. In this study, we developed a genetically engineered Saccharomyces cerevisiae strain as a proof-of-concept platform for DON detoxification. The yeast was engineered to co-express two detoxification genes, YTDepA and YTDepB (homologs of DepA and DepB from Devosia mutans 17-2-E-8) originally identified in Youhaiella tibetensis. Concurrently, the pyrroloquinoline quinone (PQQ) biosynthesis gene cluster from Klebsiella pneumoniae was integrated to supply the essential cofactor. Gene expression was verified by qRT-PCR and Western blot. The recombinant strain demonstrated a significant 13.98% detoxification of DON after 72 h of fermentation (p < 0.05), as confirmed by HPLC–MS, while the strain expressing only the PQQ cluster showed no detoxification activity. This study establishes an integrated yeast cell factory for DON detoxification and highlights key limitations to guide future optimization efforts. Full article

Background: The dorsal raphe nucleus (DRN) produces and distributes serotonin, while the hypothalamus (HYP) uses serotonergic signals to regulate physiological processes in chickens. Coconut oil (COCO), rich in medium-chain fatty acids, is rapidly absorbed without re-esterification. Methods: Day-old broilers (Ross 708 male, n = 160) were distributed into two dietary treatments with five replicates of 16 birds each. The birds were fed a corn–soybean meal (SBM) basal diet supplemented with 3% of poultry fat (CON) or coconut oil (COCO). The body-weight gain (BWG), feed intake (FI), and feed conversion ratio (FCR) were recorded over a 3-week period, and the data were subjected to a t-test. Untargeted metabolomic analysis by high-performance liquid chromatography (HPLC-MS) was used to evaluate the influence of the type of dietary fat on metabolite profiles in the DRN, HYP, and plasma of broiler chickens. Principal component analysis (PCA) was used to identify unique metabolites, and ANOVA was used to identify the metabolites that were significantly abundant (p < 0.05). The metabolites were then annotated using the KEGG and HMDB databases. Results: Birds in the COCO treatment gained more weight on average (0.8446 kg/bird) than birds in the CON group (0.8132 kg/bird; p = 0.0496). Five metabolites associated with multiple significant cellular processes, such as brain function, energy metabolism, and neurotransmission, showed similar differential expression patterns, while two metabolic pathways (butanoate metabolism and alanine, aspartate and glutamate metabolism) were identified. Conclusions: The dietary inclusion of COCO improves BWG in poultry and enhances their overall well-being by modulating metabolite profiles, supporting neurotransmission, and enriching the metabolic pathways essential for growth and brain function. Full article

Walnut septum (WS), a major by-product of walnut processing, represents a promising source of bioactive compounds with potential antioxidant and antimicrobial properties. This study aimed to characterise the phytochemical composition of WS extracts from different habitat origins and evaluate their antimicrobial activity. Total amino acids were profiled by gas chromatography–mass spectrometry, while phenolic compounds were analysed using high-performance liquid chromatography. Both methods were evaluated according to ICH Q2 (R2) guidelines for analytical procedure validation. The results showed a complex composition of amino acids and polyphenols, including ellagic acid and quercitrin. However, it was clear that habitat variations in WS samples had a significant impact on the quantities and composition of phenolic compounds and total amino acids in WS extracts. Antimicrobial activity was assessed against Gram-positive and Gram-negative bacterial strains. Variations in antimicrobial efficacy were associated with differences in phenolic composition and content due to habitat differences in WS sample origins. Collectively, this study highlights the WS as a valuable agro-industrial by-product with potential applications as a natural source of antimicrobial compounds in food and pharmaceutical systems. Full article

Cajanus cajan (L.) Huth (Fabaceae) is a food legume of considerable nutritional and functional significance. This study examined the comparative effects of salt stress on seed germination, hydroponic growth, and phytochemical accumulation across two developmental stages: 10-day-old germinated seeds and 45-day-old hydroponically grown plants, using NaCl solutions at concentrations of 0, 25, 50, 75, 100, and 150 mM. Both germination rate and growth were greatest at 0–25 mM NaCl, with performance declining at higher concentrations. LC–MS/MS analysis of free amino acids in 10-day-germinated seeds revealed a salt-induced metabolic shift. Proline, leucine, and phenylalanine were the dominant free amino acids and increased progressively with rising NaCl concentrations. Phytochemical profiling by HPLC identified gallic acid, catechin, and genistin as the major compounds, with increased levels under salinity stress. Germinated seeds at 150 mM NaCl, germinated seeds exhibited the highest phytochemical accumulation, with total phenolic content (TPC), total flavonoid content (TFC), and DPPH activity reaching 18.192 ± 0.020 mg GAE/g extract, 8.519 ± 0.026 mg QE/g extract, and 11.623 ± 0.284 mg AAE/g extract, respectively. Phytochemical responses in 45-day hydroponic plants varied by tissue type. Leaves exhibited declining TPC and TFC with increasing NaCl (from 29 to 16 mg GAE/g and 41 mg QE/g extract), while stems showed the opposite trend, reaching 18 mg GAE/g and 21 mg QE/g extract at 50 mM. Root tissues maintained comparatively low phytochemical levels throughout. Notably, DPPH scavenging capacity increased across all tissues under salt stress, with peak values of 12–13 µg AAE/g extract recorded at 50 mM NaCl. These results indicate that salt stress exerts stage- and organ-dependent effects on phytochemical accumulation in C. cajan. High salinity during germination stimulates bioactive compound production, whereas moderate salinity appears to be the threshold at which antioxidant capacity is maximized in hydroponic systems. These observations point to the practical utility of controlled salt elicitation as a strategy for enriching pigeon pea with health-promoting phytochemicals, reinforcing its potential as a functional food crop. Full article

The species Psychotria densicostata Müll.Arg. is a shrub belonging to the Rubiaceae family, endemic to Brazil. So far, there are reports neither of phytochemical work on nor of biological evaluation of it. This study investigated its alkaloid profile and evaluated the inhibitory effects of extracts, alkaloid-enriched fractions and one of its major constituents on human neutrophil elastase (HNE). The monoterpene indole alkaloids (MIAs) strictosidine (1), (3α,5α)-5-carboxystrictosidine (2), strictosidine lactam (3), lyaloside (4), lyalosidic acid (5), 5-carboxystrictosamide (6), 3,4-dehydrostrictosidinic acid (7), and N-glucopyranosyl vincosamide (8) were characterized in mixture, in its leaves, and/or stems by using an integrated approach combining nuclear magnetic resonance (NMR) techniques, high performance liquid chromatography coupled to a tandem mass spectrometer with an electrospray ionization source (HPLC-ESI-MS/MS), and molecular networks. The crude leaf extract and an alkaloid-enriched fraction derived from it showed inhibitory activity against HNE. These results contribute to the chemical knowledge of the species and suggest its potential biological property. Full article

Siponimod, a selective sphingosine 1-phosphate (S1P) receptor modulator, represents a next-generation therapeutic drug for active secondary progressive multiple sclerosis. This study conducted in-depth forced degradation studies of siponimod in solid state subjected to acidic, alkaline, oxidative, photolytic, and thermal conditions, in compliance with ICH guidelines Q1A (R2) and Q3A (R2). An HPLC method was developed to quantify siponimod and separate its degradation products (DPs). The DPs were characterized using LC-HRMS/MS and LC-MSⁿ techniques. Moreover, the toxicological profiles of siponimod and its DPs were evaluated through the in silico tools ProTox 3.0 and ADMETlab 3.0, with molecular docking and dynamics simulations assessing their binding to the S1P1 receptor. Siponimod was stable to light but degraded under acidic, alkaline, oxidative, and thermal stress, producing five products: DP-1 (acidic), DP-2/3 (oxidative), DP-4 (hydrolytic), and DP-5 (thermal). The toxicity prediction suggested that neither siponimod nor its DPs exhibited carcinogenic or mutagenic potential, and the molecular modeling analysis revealed that DP-2 and DP-3 demonstrated favorable binding affinities, with stable dynamic profiles and thermodynamic properties that closely resembled those of siponimod. As far as we know, this is the first study on the structural elucidation of the DPs of siponimod by LC-HRMS/MS and LC-MSⁿ. Full article

Tricholoma terreum, a mushroom rich in bioactive compounds, exhibits notable antioxidant and anticancer properties. Despite its traditional use, its effects on breast cancer metabolism remain underexplored. Here, we conducted comprehensive phytochemical and volatile organic compound profiling of T. terreum extracts and evaluated their cytotoxicity against MCF-7 breast cancer cells. Using SPME–GC–MS and HPLC, we identified a complex chemical matrix dominated by organic acids (acetic acid, 43.85%) and nitrogen-containing heterocyclics (2-acetylpyridine, 15.19%), alongside significant phenolic acids such as gallic acid and syringic acid. Biological assays indicated that the ethanol extract showed notable cytotoxic effects, reducing MCF-7 cell viability to 3.64% after 72 h, while higher viability was preserved in healthy CCD-1072sk fibroblast cells. Using cell viability assays, flow cytometry, and gene expression analysis, we found that ethanol extracts selectively reduced cancer cell viability, induced G0/G1 cell cycle arrest (71.92%), and promoted apoptosis. Mechanistically, treatment downregulated key nucleotide biosynthesis genes (DHFR, TK1) and the glycolytic enzyme gene (ENO1), while upregulating the oxidative stress response gene SLC7A11 (18.32-fold), suggesting disruption of cancer metabolic pathways. These findings reveal a metabolic reprogramming effect of T. terreum extracts, highlighting their potential as metabolism-targeted agents in breast cancer therapy. Further studies are warranted to validate these effects in vivo and isolate active constituents. Full article

Invasive plant species are increasingly recognized not only as ecological threats but also as potential sources of bioactive compounds with agricultural applications. However, the combined allelopathic and insecticidal potential of Ailanthus altissima’s different plant parts remains insufficiently explored. This study evaluated the bioactivity of different plant part (leaf, bark, and branch) extracts of A. altissima. Secondary metabolites were characterized by HPLC–DAD–MS, while ethanol extracts (0.5–5%) were tested on wheat (Triticum aestivum) seed germination, seedling growth, oxidative status, and on the survival and repellency of the rice weevil (Sitophilus oryzae). Biological responses were strongly plant part and concentration-dependent. Leaf extracts contained the highest phenolic levels, dominated by caffeoylquinic acids and quercetin derivatives, whereas bark and branch extracts showed lower but compositionally distinct profiles. Despite this, bark and branch extracts produced the strongest biological effects, inhibiting germination energy and root growth at higher concentrations, while leaf extracts stimulated seedling performance, including increased vigor index, while in insect bioassays, bark and branch extracts caused higher mortality and stronger suppression of rice weevil populations. This study provides new evidence that biomass extracts of the invasive species A. altissima represent a promising source of biologically active compounds with both allelopathic and insecticidal properties, highlighting its potential valorization as a plant-based biopesticide for sustainable pest management. Full article

Background/Objectives: Atopic dermatitis (AD)-related skin inflammation involves the release of cytokines and chemokines from keratinocytes; therefore, keratinocyte-based models are widely used to evaluate the anti-inflammatory potential of botanical extracts. This study examined the relationship between phytochemical profiles and anti-inflammatory potential of baobab fruit 30% and 70% ethanol extracts (BE-30 and BE-70, respectively) in a TNF-α/IFN-γ (TI)-stimulated HaCaT keratinocyte model. Methods: The anti-inflammatory effects of both extracts were evaluated by measuring cytokine and chemokine secretion in TI-stimulated HaCaT cells. Phytochemical characterization was performed using liquid chromatography–tandem mass spectrometry (LC–MS/MS) and targeted high-performance liquid chromatography (HPLC). Results: Both extracts were non-cytotoxic. TI-stimulation markedly increased interleukin (IL)-6, IL-8 and monocyte chemotactic protein (MCP)-1 secretion, while BE-30 and BE-70 significantly reduced all three mediators in a dose-dependent manner. At comparable doses, BE-70 exhibited greater inhibition than BE-30. BE-30 showed a non-monotonic IL-8 response at low concentrations, whereas BE-70 consistently reduced IL-8 in a dose-dependent manner. LC–MS/MS profiling revealed a polyphenol-rich composition, including flavonol glycosides and related phenolic compounds. HPLC confirmed the presence of four marker analytes (procyanidin B2, epicatechin, rutin and tiliroside), which were enriched in BE-70. The content of these four polyphenols was 1.94-fold higher in BE-70. Conclusions: Baobab fruit extracts exhibit anti-inflammatory activity associated with polyphenols. These findings suggest that they could be used as analytical standards and in dermatological applications. Full article

In this study, we compared the effects of microwave-assisted extraction (MAE) and ultrasound-assisted extraction (UAE) on the total phenolic content, antioxidant activity, morphological characteristics, and tentative identification of bioactive compounds by LC-ESI-MS/MS in pomegranate seeds. We conducted a phytochemical characterization of the extracts by determining the total phenolic content and total flavonoids. Antioxidant activity was evaluated using ferric-reducing antioxidant power (FRAP) and free radical inhibition methods (DPPH and ABTS). Morphological characteristics were analyzed via scanning electron microscopy, UV-Vis and FTIR of the extracts were recorded. Additionally, the main bioactive compounds were identified using HPLC-MS. Our results demonstrated that MAE was the most efficient technique, yielding a higher content of total phenols (35.47 mg GAE/g), total flavonoids (14.44 mg CAE/g) and antioxidant activity (0.19 and 0.41 mmol TEAC/g, as determined by FRAP and ABTS, respectively). In terms of morphological characteristics, UAE induced more changes in the structure of the plant material compared to MAE. According to HPLC-MS analysis, the extract obtained using MAE notably contained coumaric acid, cyanidin, and quercetin, whereas the UAE extract included coumaric acid, cyanidin, kaempferol, and epicatechin. In conclusion, this study demonstrated that MAE is a more efficient method than UAE for extracting bioactive compounds. Pomegranate seeds may represent a potential source of these compounds for application in various industrial areas. Full article