Search Results (2,331)

Neurodegenerative diseases, including Alzheimer’s disease (AD), represent one of the main global health challenges. Cannabis sativa synthesizes spermidine-type alkaloids, whose potential biological activities have been little studied. This study aimed to isolate bioactive alkaloids from an alkaloid-enriched extract (AEE) of C. sativa roots throughout a bioguided approach using conventional chromatographic techniques based on AChE and BuChE inhibitory activities. A qualitative and semiquantitative analysis by UPLC-ESI-MS/MS as well as molecular modeling simulations were performed. In addition, predictive in silico analyses were conducted to assess toxicity properties. The alkaloids cannabisativine (CS) and anhydrocannabisativine (ACS) were isolated, and showed highly selective BuChE inhibitory activity. The molecular modeling study revealed a conserved interaction profile across both alkaloids, indicating the amino acids TRP82, GLU197, TYR440, and HIS438 as the major contributors involved in the complex formation. Finally, CS and ACS exhibited low in silico predictive toxicity values. In conclusion, CS and ACS alkaloids emerge as new selective BuChE inhibitors with therapeutic potential that deserves the attention from the field of pharmacology in neurodegenerative disease research. Additionally, this approach promotes innovation and environmental sustainability through the use of C. sativa roots. Full article

Imperial chrysanthemum teas ‘Wuyuan Huangju’ (WYHJ) and ‘Jinsi Huangju’ (JSHJ), dried from the flowers of Chrysanthemum morifolium cv. Huangju, are traditional and popular herbal teas in China. However, their metabolite profiles and bioactivities remain unclear. In this study, we aimed to comprehensively elucidate the non-volatile and volatile metabolites of these two imperial chrysanthemum teas and assess their antioxidant activities and inhibitory effects on hyperglycemia and inflammation enzymes. Thus, we employed a widely targeted metabolomics approach based on UPLC-ESI-MS/MS and GC-MS/MS to characterize metabolite profiles of the two teas. In total, 1971 non-volatile and 1039 volatile metabolites were explored, and among these, 744 differential non-volatiles (classified into 11 categories) and 517 differential volatiles (classified into 12 categories) were identified. Further, 474 differential non-volatiles were upregulated in WYHJ, particularly flavonoids, terpenoids, and phenolic acids. In contrast, JSHJ exhibited a greater number of upregulated differential volatiles compared to WYHJ, contributing primarily to its sweet, fruity, and floral aroma. The results of scavenging activities towards DPPH·, ABTS·⁺, OH·⁻, and reducing power demonstrated that both imperial chrysanthemum teas, especially WYHJ, displayed high antioxidant capacity. We also noted that WYHJ exhibited stronger α-amylase, α-glucosidase, xanthine oxidase, and lipoxygenase inhibitory effects owing to its high active substance content. Therefore, this study provides insights into the metabolites of Chinese traditional medicinal herbal teas and highlights strategies for the comprehensive development and utilization of these traditional plant resources. Full article

Background: Obesity is a global health issue closely associated with dysregulated lipid metabolism and chronic inflammation. Effective strategies targeting both lipogenesis and inflammation are essential for managing obesity and its related metabolic disorders. Methods: This study evaluated the effects of Terminalia catappa Linn. leaf extract (TCE) on lipogenic and lipolytic pathways in high-fat diet (HFD)-induced obese mice. UPLC-QTOF-MS analysis was conducted to identify and quantify the major phenolic compounds in TCE. Mice were administered low and high doses of TCE, and various metabolic parameters, including lipid profiles, liver function markers, adipokine levels, and gene/protein expressions related to lipid metabolism and inflammation, were assessed. Results: UPLC-QTOF-MS analysis identified four major phenolic compounds in TCE—gallic acid, orientin, vitexin, and ellagic acid—with respective contents of 112.5, 163.3, 184.7, and 295.7 mg/g extract. TCE administration significantly reduced liver and adipose tissue weights, along with hepatic and adipose lipid accumulation. Both low and high doses of TCE markedly lowered serum lipid levels. Liver function was improved, as indicated by reduced levels of AST, ALT, and ALP, while BUN levels remained unchanged. On the molecular level, TCE downregulated adipogenic and lipogenic genes (PPARγ, PPARα, C/EBPα, aP2) and upregulated metabolic regulators, including leptin, adiponectin, p-HSL/HSL, and p-perilipin/perilipin, without affecting ATGL expression. TCE also suppressed pro-inflammatory cytokines such as IL-6, IL-1β, TNF-α, and TGFβ-1. Conclusions: These findings highlight the therapeutic potential of TCE in managing obesity by inhibiting lipogenesis, enhancing lipolysis, and reducing inflammation. Full article

Lipids and polar metabolites are emerging as promising indicators of the brain’s molecular phenotype in both clinical and fundamental research. However, the impact of postmortem delay on these compounds, unavoidable in human brain studies, remains insufficiently understood. In this study, we examined the postmortem stability of lipids and polar metabolites over a 48-h interval in the brains of three species: humans, rats, and mice. We show that the abundance levels of 23% of the 867 studied lipids and 75% of the 104 studied polar metabolites were affected significantly by postmortem delay in at least one species. The postmortem effects correlated positively and significantly among the species, while showing an approximately tenfold slower rate in humans compared to rodents. The only exception to the postmortem rates deceleration was a group of oxidized fatty acids, which accumulated at similar speed in both humans and rodents. These findings provide valuable insights for improving reproducibility and refining the interpretation of human and rodent brain lipidome and metabolome data in future studies. Full article

Verifying the geographical origin of honey is crucial for its market value and for preventing fraudulent practices. This study aimed to characterize the chemical profiles of organic honeys from three distinct regions in Southeastern Türkiye—Şırnak Faraşin, Siirt Merkez, and Siirt Pervari—to establish a robust method for geographical authentication. A total of 51 multifloral honey samples were analyzed. The concentrations of 20 free amino acids (FAAs) and 16 phenolic compounds were quantified using (UPLC-ESI-MS/MS). The resulting data were subjected to both an unsupervised (PCA, CA) and supervised (PLS-DA, RF, SVM) chemometric analysis to identify biochemical markers for each region. The results revealed a distinct chemical fingerprint for each region. Based on the FAA profiles, the PLS-DA method provided the best overall classification, achieving an excellent discrimination with a total accuracy of 94.1% in the Şırnak Faraşin honeys. For the phenolic compound profiles, the RF method achieved the highest correct classification rate for Şırnak Faraşin honeys at 88.2%. This study demonstrates that an integrated approach, combining FAA and phenolic profiles with supervised chemometric methods, provides a successful and reliable model for determining the geographical origin of these multifloral honeys. Full article

Pompe disease is an autosomal recessive metabolic disorder caused by acid alpha-glucosidase (GAA) deficiency. The use of umbilical cord blood (UCB) for newborn screening (NBS) of Pompe disease, compared to heel-prick sampling, has not been widely studied. This study compared GAA activity in UCB from term newborns with peripheral or heel-prick blood samples obtained on days 1, 2, and 3 after birth. Enzyme assays were performed using UPLC-MS/MS. Sanger sequencing was conducted in infants with low GAA activity to identify pathogenic variants. Among 4091 UCB samples analyzed over 18 months, the mean GAA activity was 10.04 ± 5.95 μM/h, higher in females than males [Median (IQR): 9.83 (5.45) vs. 9.08 (4.97) μM/h, respectively, p < 0.001], and similar across ethnicities. GAA levels in UCB and Day 3 heel-prick samples were comparable. A GAA cut-off value of 1.54 μM/h (0.1% of study population) identified one infant (0.024% prevalence) with a novel bi-allelic variant—c.2005_2010del (p.Pro669_Phe670del) and c.1123C>T (p.Arg375Cys), and 12 infants with non-pathogenic pseudodeficiency alleles. This study supports GAA measurement in UCB as a viable alternative for NBS, with enzyme activity remaining stable for up to 72 h post-collection. Larger-scale multicenter nationwide studies are warranted to confirm this prevalence in our population. Full article

The palo prieto (Lysiloma divaricata) is a tree with grayish bark and pinnate leaves that is native to Mexico. This tree can reach heights close to 15 m and is a source of phytochemical compounds, including polyphenols. The optimized extraction method is important for preserving phytochemical compounds, particularly gallic acid. In general, solid-liquid extraction methods are the most commonly used methods for obtaining phytochemical compounds from Lysiloma divaricata. Herein, we report the results of a complex experimental design in which different parts of the plant (leaf, stem, and fruit) were used to investigate their antioxidant activities and gallic acid contents. In this design, we included variations in the type of solvent, time, and temperature. This method yields an extract rich in phytochemical components that may exhibit significant antioxidant activity, making it suitable for isolating natural antioxidant compounds. For these compounds, bromatological analysis, quantification of phenolic content, and identification and quantification of phytochemical compounds via UPLC-MS/MS identified 27 compounds, with gallic epicatechin, catechin, kaemferol-3-glucoside, procyanidin B1, and gallic acid as the major compounds. For the quantification of gallic acid by HPLC, the highest concentration of gallic acid was detected in the water-leaf-40 °C-90 min fraction. In addition, antioxidant activity via 1,1-diphenyl-1,2-picrylhydrazyl (DPPH), 2,2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and ferric reducing antioxidant power (FRAP) was studied, and color measurements were performed. Additionally, the antioxidant activity of the fruit samples was evaluated via the DPPH method with an ethanol/water ratio of 30:70 % v/v at 60 °C for 60 min, which resulted in the highest percentage of inhibition. There was no significant difference in the antioxidant activity when ABTS was used between the samples. For the antioxidant activity determined via FRAP, the leaf sample exhibited the most significant activity when ethanol was used as the solvent at 50 °C for 90 min, with a value of 195,861 ± 44.20 µM eq Trolox/g DM. The phenol compounds of Lysiloma divaricata are promising sources of natural antimicrobials and antioxidants for potential applications in food packaging. Full article

Hamamelis virginiana (witch hazel) is traditionally used in dermatology for its antibacterial and anti-inflammatory effects. However, the number of studies on its chemical composition and potentials in skin protection remains limited. This study aimed to investigate the qualitative and quantitative composition of polyphenolic compounds in the leaves and bark of the plant, as well as to explore their antioxidant, anti-inflammatory, and extracellular matrix (ECM)-protective activities in skin-relevant cell models. Human dermal fibroblasts and keratinocytes were exposed to oxidative and inflammatory stimuli and pretreated with leaf and bark extracts. ROS levels, antioxidant enzyme activity (SOD, GPx, CAT), pro-inflammatory cytokines (IL-6, IL-1β, TNF-α), and inhibition of collagenase, hyaluronidase, and elastase were assessed. Both extracts strongly reduced ROS levels, enhanced SOD activity, and significantly decreased pro-inflammatory cytokines. Bark extract also exhibited potent inhibitory activity against collagenase and elastase. UPLC-DAD-MS analysis revealed that both plant parts contained high levels of tannins; however, the leaf extract showed a more diverse composition, including more complex tannin forms and a significant amount of flavonoids from the quercetin and kaempferol class. In conclusion, H. virginiana leaf and bark extracts demonstrate multifunctional antioxidant and anti-inflammatory properties, supporting their potential use in cosmeceuticals and dermatological formulations targeting skin aging and inflammation. Full article

The aim of this study was to investigate the metabolites in Aspergillus subramanianii 1901NT-1.40.2 extract using UPLC-MS, isolate and elucidate the structure of individual compounds, and study the antimicrobial and cytotoxic activities of the isolated compounds. The structures of two previously unreported ergostane triterpenoid aspersubrin A (1) and pyrazine alkaloid ochramide E (2) were established using NMR and HR ESI-MS. The absolute configuration of 1 was determined using quantum chemical calculations. Moreover, the known polyketides sclerolide (3) and sclerin (4); the indolediterpene alkaloid 10,23-dihydro-24,25-dehydroaflavinine (5); the bis-indolyl benzenoid alkaloids kumbicin D (6), asterriquinol D dimethyl ether (7), petromurin C (8); and the cyclopentenedione asterredione (9) were isolated. The effects of compounds 3-9 on the growth and biofilm formation of the yeast-like fungus Candida albicans and the bacteria Staphylococcus aureus and Escherichia coli were investigated. Compounds 5 and 6 inhibited C. albicans growth and biofilm formation at an IC₅₀ of 7–10 µM. Moreover, the effects of compounds 3-9 on non-cancerous H9c2 cardiomyocytes, HaCaT keratinocytes, MCF-10A breast epithelial cells, and breast cancer MCF-7 and MDA-MB-231 cells were also investigated. Compound 8 (10 µM) significantly decreased the viability of MCF-7 cells, inhibited colony formation, and arrested cell cycle progression and proliferation in monolayer culture. Moreover, 8 significantly decreased the area of MCF-7 3D spheroids by approximately 30%. A competitive test with 4-hydroxytamoxyfen and molecular docking showed that estrogen receptors (ERβ more than ERα) were involved in the anticancer effect of petromurin C (8). Full article

Polyphenols play a crucial role in promoting human health. This study aims to investigate the polyphenols of black hulless barley bran (HBP) and evaluate their anti-diabetic mechanisms in vivo. Using UPLC-QTOF-MS/MS, 27 compounds were identified in HBP, including four phenolic acids, 14 flavonoids, and nine anthocyanidins. High contents of Chrysoeriol 7-O-glucuronide (42.09 mg/g), Cyanidin 3-O-glucoside (21.02 mg/g), and Cyanidin 3-O-(6″-O-malonyl)-glucoside (24.45 mg/g) were quantified via UPLC in HBP. Administration of HBP significantly reduced fasting blood glucose (FBG), improved glucose intolerance and lipid profiles, and alleviated liver and pancreatic damage in type 2 diabetic (T2DM) mice. Furthermore, it enhanced serum antioxidant enzyme activities and modulated inflammatory cytokines. Transcriptomic analysis revealed that HBP influenced signal transduction and the immune system, particularly in key signaling pathways, including Hippo, TGF-beta, HIF-1, and p53, associated with T2DM. Although HBP had minimal impact on gut microbiota diversity and SCFA levels, it presents a promising candidate for T2DM intervention through its multifaceted mechanisms. Full article

Background/Objectives: As a non-medicinal part resource of Ziziphus jujuba, this study focuses on the total flavonoids from Ziziphus jujuba mesocarp (TFZJM), aiming to optimize the extraction process and explore its sedative and hypnotic effects. Methods: The extraction process of TFZJM was optimized by using single-factor experiments and the Box-Behnken response surface design method. The material basis of TFZJM was analyzed using Ultra-Performance Liquid Chromatography-Quadrupole-Time of Flight-Mass Spectrometry (UPLC-Q-TOF-MS). The mouse insomnia model was induced by intraperitoneal injection of PCPA, and the effects of TFZJM on this model and its potential mechanism were evaluated using multiple methods, such as sleep enhancement induced by pentobarbital sodium, HE staining of tissue sections, ELISA, RT-PCR, WB, and serum metabolomics. Results: The results showed that by optimizing the extraction conditions, a solid-liquid ratio (SLR) of 1:25 g·mL⁻¹, ethanol concentration of 60%, extraction time of 60 min, and extraction rate of 1.98% were achieved. The common chemical basis of the 10 flavonoid components was identified using UPLC-Q-TOF-MS analysis. Compared with the model group, the high-dose TFZJM (TFZJM-H) group had the most significant effect, followed by the medium-dose (TFZJM-M) and low-dose (TFZJM-L) groups. Conclusions: Metabolomic analysis revealed that TFZJM regulates pathways related to the metabolism of phenylalanine, tyrosine, cytochrome P450, and alanine. This lays the foundation for further exploration of the active substances and mechanisms of action of TFZJM in sedation and hypnosis. Full article

Background/Objectives: Forced degradation studies are critical for identifying potential degradation pathways of monoclonal antibodies (mAbs), particularly under thermal stress. Due to their structural complexity and sensitivity to elevated temperatures, mAbs are prone to fragmentation, aggregation, and post-translational modifications. This study aimed to evaluate and compare the degradation profiles of biosimilar anti-VEGF mAb and its originator counterparts sourced from both the United States (U.S.) and the European Union (EU) under thermal stress conditions. To our knowledge, this represents one of the few studies conducting a direct head-to-head comparability assessment across biosimilar and two geographically sourced originators, integrating orthogonal analytical approaches. Methods: Biosimilar candidate and originator products (U.S. and EU) were incubated at 37 °C and 50 °C for 3, 7, and 14 days. Fragmentation profiles were assessed using validated non-reduced and reduced capillary electrophoresis–sodium dodecyl sulfate (CE-SDS) methods. Additionally, size-exclusion ultra-performance liquid chromatography (SE-UPLC) and liquid chromatography–tandem mass spectrometry (LC-MS/MS) assays were performed on samples stressed for 14 days to provide deeper insights into degradation pathways. Results: Non-reduced CE-SDS analysis indicated a time- and temperature-dependent increase in low-molecular-weight fragments and a corresponding decrease in the intact form, with more pronounced effects observed at 50 °C. Reduced CE-SDS revealed a more rapid increase in total impurity levels at 50 °C, accompanied by a decrease in total light and heavy chain content. SE-UPLC showed enhanced aggregation under thermal stress, more pronounced at 50 °C. LC-MS/MS analysis identified increased asparagine deamidation in the PENNY peptide and pyroglutamic acid formation (pE) at the N-terminus of the heavy chain. Conclusions: The degradation profiles of the biosimilar and originator mAbs were highly comparable under thermal stress, with no significant qualitative differences detected. By applying a multi-tiered analytical characterization technique, this study provides a comprehensive comparability assessment that underscores the robustness of biosimilarity even under forced degradation conditions. Full article

Background: Nephrolepis exaltata (sword fern) possesses a considerable amount of phytochemicals and different biological activities. The current study investigates the anti-biofilm potential of greenly synthesized bimetallic nanoparticles of Nephrolepis exaltata leaf methanol extract (NEME-MnO₂-MgO BNPs). Methods: The NEME was subjected to UPLC/MS analysis, followed by characterization of its NPs by size, zeta potential, FTIR, entrapment efficiency, and release. Then, antioxidant, antimicrobial and antibiofilm assays were employed, followed by in silico studies. Results: The UPLC/MS analysis of NEME led to the tentative identification of 27 metabolites, mostly phenolics. The MnO₂-MgO BNPs presented a uniform size and distribution and exhibited IC₅₀ values of 350 and 215.6 μg/mL, in the DPPH and ABTS assays, respectively. Moreover, the NPs exhibited antimicrobial and anti-biofilm efficacies against Pseudomonas aeruginosa, Klebsiella pneumonia (ATCC-9633), Staphylococcus aureus (ATCC-6538), Escherichia coli, Bacillus cereus, and C. albicans, with MIC values of 250–500 μg/mL. The MnO₂-MgO BNPs inhibited Candida albicans biofilms with a % inhibition of 66.83 ± 2.45% at 1/2 MIC. The network pharmacology highlighted epigallocatechin and hyperoside to be the major compounds responsible for the anti-biofilm potential. The ASKCOS facilitated the prediction of the redox transformations that occurred in the green synthesis, while the docking analysis revealed enhanced binding affinities of the oxidized forms of both compounds towards the outer membrane porin OprD of P. aeruginosa, with binding scores of −4.6547 and −5.7701 kcal/mol., respectively. Conclusions: The greenly synthesized Nephrolepis exaltata bimetallic nanoparticles may provide a promising, eco-friendly, and sustainable source for antimicrobial agents of natural origin with potential biofilm inhibition. Full article

Background and purpose: Vulvovaginal candidiasis (VVC), caused by Candida albicans (C. albicans), is exacerbated by oxidative stress and uncontrolled inflammation. Pathogens like C. albicans generate reactive oxygen species (ROS) to enhance virulence, while host immune responses further amplify oxidative damage. This study investigates the antioxidant and antifungal properties of Hyssopus cuspidatus Boriss volatile extract (SXC), a traditional Uyghur medicinal herb, against fluconazole-resistant VVC. We hypothesize that SXC’s bioactive volatiles counteract pathogen-induced oxidative stress while inhibiting fungal growth and inflammation. Methods: GC-MS identified SXC’s major bioactive components, while broth microdilution assays determined minimum inhibitory concentrations (MICs) against bacterial/fungal pathogens, and synergistic interactions with amphotericin B (AmB) or fluconazole (FLC) were assessed via time–kill kinetics. Anti-biofilm activity was quantified using crystal violet/XTT assays, and in vitro studies evaluated SXC’s effects on C. albicans-induced cytotoxicity (LDH release in A431 cells) and inflammatory responses (cytokine production in LPS-stimulated RAW264.7 macrophages). A murine VVC model, employing estrogen-mediated pathogenesis and intravaginal C. albicans challenge, confirmed SXC’s in vivo effects. Immune modulation was assessed using ELISA and RT-qPCR targeting inflammatory and antioxidative stress mediators, while UPLC-MS was employed to profile metabolic perturbations in C. albicans. Results: Gas chromatography-mass spectrometry identified 10 key volatile components contributing to SXC’s activity. SXC exhibited broad-spectrum antimicrobial activity with MIC values ranging from 0.125–16 μL/mL against bacterial and fungal pathogens, including fluconazole-resistant Candida strains. Time–kill assays revealed that combinations of AmB-SXC and FLC-SXC achieved sustained synergistic bactericidal activity across all tested strains. Mechanistic studies revealed SXC’s dual antifungal actions: inhibition of C. albicans hyphal development and biofilm formation through downregulation of the Ras1-cAMP-Efg1 signaling pathway, and attenuation of riboflavin-mediated energy metabolism crucial for fungal proliferation. In the VVC model, SXC reduced vaginal fungal burden, alleviated clinical symptoms, and preserved vaginal epithelial integrity. Mechanistically, SXC modulated host immune responses by suppressing oxidative stress and pyroptosis through TLR4/NF-κB/NLRP3 pathway inhibition, evidenced by reduced caspase-1 activation and decreased pro-inflammatory cytokines (IL-1β, IL-6, TNF-α). Conclusions: SXC shows promise as a broad-spectrum natural antimicrobial against fungal pathogens. It inhibited C. albicans hyphal growth, adhesion, biofilm formation, and invasion in vitro, while reducing oxidative and preserving vaginal mucosal integrity in vivo. By disrupting fungal metabolic pathways and modulating host immune responses, SXC offers a novel approach to treating recurrent, drug-resistant VVC. Full article

Background: Lonicerae japonicae flos (LJF), a traditional food and medicine with a history spanning thousands of years, undergoes drying as a critical processing step in modern applications after regular processing. While the by-products of this process are typically discarded as waste, the potential value of LJF condensate water (JYHC) remains largely unexplored. To address this gap and investigate its potential utilization, this study conducted widely targeted metabolome and volatile metabolomics profiling analyses of ‘JYHC’. Methods: This study analyzed the differential metabolites of ‘JYHC’ and dried Lonicerae japonicae flos (JYHG) based on widely targeted metabolomics using UPLC-MS/MS. Additionally, the metabolic differences between fresh Lonicerae japonicae flos (JYHX) and ‘JYHC’ based on GC-MS volatile metabolomics were comprehensively analyzed. Results: A total of 1651 secondary metabolites and 909 volatile metabolites were identified in this study. Among these, flavonoids and terpenoids were the predominant secondary metabolites, while esters and terpenoids dominated the volatile fraction. Further comparison of the ‘JYHC’ and ‘JYHG’ groups revealed that 58 differential metabolites with potential biological activities were significantly up-regulated, with the types being terpenoids, phenolic acids, and alkaloids, which included nootkatone, mandelic acid, sochlorogenic acid B, allantoin, etc. Notably, a total of 186 novel compounds were detected in ‘JYHC’ that had not been previously reported in LJF such as isoborneol, hinokitiol, agarospirol, 5-hydroxymethylfurfural, α-cadinol, etc. Conclusions: This study’s findings highlight the metabolic diversity of ‘JYHC’, offering new theoretical insights into the study of LJF and its by-products. Moreover, this research provides valuable evidence supporting the potential utilization of drying by-products from LJF processing, paving the way for further exploration of their pharmaceutical and industrial applications. Full article