Search Results (4,401)

Background: Shikonins are natural naphthoquinones that exhibit a range of biological activities. They are typically extracted using nonpolar solvents; however, green extraction approaches remain underexplored. Methods: Phytochemical profiling of E. vulgare root extracts was performed using HPLC-ESI-QTOF-MS/MS and quantitative analysis using HPLC-PDA. Shikonin extraction was performed using VNADESs based on thymol, camphor, menthol and benzyl alcohol. The feasibility of removing the VNADES from the extracts via freeze-drying was assessed. The cytotoxic, antioxidant, anti-inflammatory and antimicrobial activities of the hexane extract and the selected VNADES-based extract (TBa 2:8) were compared. Results: Eight shikonin derivatives were identified in the extracts. VNADES extracts contained comparable amounts of shikonin to hexane extracts; however, freeze-drying resulted in significant shikonin content loss. TBa 2:8 extract exhibited noticeably lower cytotoxicity than the hexane extract while its antioxidant potential depended on the assay applied. In contrast to the hexane extract, TBa 2:8 demonstrated the ability to reduce intracellular ROS and NO levels. However, the hexane extract exhibited stronger antimicrobial activity. Conclusions: VNADES systems enable efficient extraction of shikonin derivatives with performance comparable to hexane. Although the resulting extracts exhibit multidirectional biological activity, it remains challenging to remove the VNADESs effectively without losing the shikonins. Full article

Combining plant-derived bioactives could produce effective anti-inflammatory interventions for myofascial inflammation. This study evaluated in vitro synergy and computational mechanisms of curcumin–evodiamine activity against TNF-α, IL-1β, iNOS and COX-2, with frontier molecular orbital analysis to inform putative mechanisms. Evodiamine and curcumin were identified/quantified by HPLC–PDA and LC–MS (λmax 226 nm and 426 nm; RT 8.61 and 9.53 min; [M−H]⁻m/z 302.2 and 367.2). Purities were 98.08 ± 1.92% and 98.04 ± 1.86%. Noncytotoxic concentrations in RAW264.7 cells were determined, then LPS-stimulated cells were treated with evodiamine (0.01 µM), curcumin (0.01 µM) and a 1:1 mixture (0.001 µM). Molecular docking against TNF-α, IL-1β, iNOS and COX-2 and HOMO–LUMO calculations were performed. Curcumin and the combination significantly reduced TNF-α and NO; curcumin and the combination reduced IL-1β, whereas evodiamine alone showed limited effects. Docking predicted stronger binding for curcumin and evodiamine than ibuprofen across targets (e.g., curcumin ΔG −10.18 kcal·mol⁻¹ for TNF-α; evodiamine ΔG −10.02 kcal·mol⁻¹ for COX-2). Frontier orbital energies indicated differing electronic profiles (ibuprofen ΔE 8.62 eV; evodiamine 9.65 eV; curcumin 9.89 eV), suggesting complementary reactivity. The curcumin–evodiamine combination exhibits in vitro anti-inflammatory activity with supportive docking and orbital data, providing mechanistic rationale for further development. Full article

Plants must constantly adapt to biotic and abiotic stressors, which the global climate change crisis has intensified. To monitor plant health and predict their ability to face these challenges, various target molecules, such as hormones, glucose, and reactive oxygen species, are used as proxies for their physiological status. This review provides a systematic assessment of the current state of biosensor technology, an innovative analytical approach designed for in situ, minimally invasive, and real-time monitoring. Using the PICO (Problem, Intervention, Comparison, and Outcome) strategy, relevant research papers were identified. The review highlights how biosensors can detect physiological responses to stress before visual symptoms manifest, offering a significant advantage over traditional, often destructive, laboratory techniques, like gas chromatography–mass spectrometer (GC-MS) or high-performance liquid chromatography (HPLC). These advancements aim to improve precision agriculture and forestry management by providing sustainable methods to assess resilience in changing environments. Finally, the challenges of translating research from model organisms to complex woody species and choosing the correct target are discussed, and future perspectives, including the integration of biosensors with Artificial Intelligence-driven predictive models for large-scale environmental monitoring, are outlined. Full article

Background: Long-acting drug delivery strategies could augment pediatric human immunodeficiency virus (HIV) treatment effectiveness by bypassing population-specific challenges such as adherence. We harnessed pharmacokinetic (PK) modeling to develop a biodegradable, subcutaneous (SQ), reservoir-style implant for HIV treatment in 2–5-year-old children. Methods: Plasma was collected from New Zealand White rabbits over 30 h after a single intravenous (IV) bolus of bictegravir (BIC, 0.75 mg/kg), islatravir (ISL, 5 mg/kg) and/or emtricitabine (FTC, 30 mg/kg) then over a year after subcutaneous insertion of two to three implants eluting these antiretrovirals. Plasma antiretrovirals were quantified by HPLC-MS/MS and population PK models were fit to the IV PK profile to derive a mean unit impulse response (UIR). UIR was used to numerically deconvolve SQ absorption rate from the implant PK profile. SQ dosing rates were translated to pediatric plasma concentrations using published clinical PK parameters. Results: BIC, FTC, and ISL PK profiles were best described by two-compartment models. Each implant achieved quantifiable plasma concentrations for >360 days. Median SQ absorption rates (μg/day) at 3, 6 and 12 months of implantation were 116, 98 and 71 for BIC; 116, 37 and 5 for ISL; and 236, 116 and 24 for FTC. These 6-month dosing rates translated to pediatric plasma concentrations of 24 ng/mL BIC, 0.14 ng/mL ISL, and 0.7 ng/mL FTC. Conclusion: Our novel long-acting delivery platform exhibited antiretroviral SQ dosing rates for ≥6 months that are anticipated to achieve plasma concentrations in children within an efficacious range warranting further development for pediatric HIV treatment. Full article

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