Search Results (57)

Plants are a rich source of active metabolites that have been used to treat inflammation troubles. The current study aimed to identify the analgesic and anti-inflammatory compounds in Farsetia aegyptia and Zilla spinosa extracts. The anti-inflammatory activity was evaluated using the xylene-induced ear edema model in mice and the carrageenan-induced paw edema model in Wistar rats. Additionally, both central and peripheral analgesic effects were assessed in mice. The anti-lipoxygenase activity was examined through an in vitro enzyme inhibition assay. The phytochemical composition of the bioactive extracts was characterized using High-Resolution Liquid Chromatography–Mass Spectrometry (HR-LCMS). The aqueous extracts of both species exhibited the strongest anti-inflammatory activity. The F. aegyptia extract showed inhibition percentages of 51.82% at 6.25 mg/kg and 51.14% at 0.78 mg/kg, while the Z. spinosa extract yielded 65.05% inhibition at 12.5 mg/kg and 56.14% at 1.56 mg/kg in the paw and ear edema models, respectively. These extracts also demonstrated significant analgesic activity and inhibited lipoxygenase, with IC₅₀ values of 0.063 mg/mL for F. aegyptia and 0.072 mg/mL for Z. spinosa. HR-LCMS analysis revealed that the main constituent in Fa was malic acid (18.83%), while retronecine (19.03%) was the primary compound in Z. spinosa. Quercetin 3-[rhamnosyl-(1->2)-rhamnosyl-(1->6)-glucoside] was detected in both extracts with important proportions 7.87% in F. aegyptia and 8.29% in Z. spinosa and displayed the best docking score of −9.2 kcal/mol against the 5-lipoxygenase receptor (PDB: 3V99) in molecular docking studies. Overall, these findings indicate that F. aegyptia and Z. spinosa have significant potential as sources of novel anti-inflammatory agents. Full article

Background/Objectives: Propolis is a complex bee product with a composition that varies according to local vegetation, environmental conditions, and bee foraging behaviours. Recently, gas chromatography–mass spectrometry (GC–MS) has been employed in Uganda to analyse its volatile components. This study examined Ugandan propolis non-volatile metabolites to determine chemotypes and identify antibacterial compounds. Methods: Ethanolic extracts were analysed using liquid chromatography–high-resolution quadrupole time-of-flight mass spectrometry (LC-HR-QTOF-MS) in an untargeted MS/MS mode. Data processing was carried out using MZmine, then annotated with Global Natural Products Social Molecular Networking (GNPS) and SIRIUS. Chemometric methods assisted in identifying regional chemical signatures. Metabolites highlighted by the heatmap were evaluated for antibacterial activity using molecular docking against bacterial targets, followed by ADMET (absorption, distribution, metabolism, excretion, and toxicity) assessments. Results: Out of 3252 features, 234 and 52 putative compounds were annotated in GNPS and SIRIUS, respectively, as indicated by molecular networking, suggesting high chemical complexity. The chemical space mainly comprises flavonoids (including glycosides, aglycones, methylated, and prenylated derivatives), phenolic acids, amides, hydroxycinnamate derivatives, lignans, megastigmanes, and various diterpenoid skeletons. Multivariate analyses clearly distinguish geographical chemotypes, separating flavonoid-rich regions from diterpenoid-rich regions. Docking studies revealed flavonoids, diterpenoids, and lignans with strong predicted antibacterial activities and favourable ADMET profiles. Conclusions: This study provides the first LC–MS characterisation of the non-volatile metabolome of Ugandan propolis, thereby expanding its chemical diversity. Metabolomics and computational approaches lay a foundation for future ecological, chemotaxonomic, and pharmacological research. Full article

(−)-Epicatechin (EC), taxifolin (Tax), and quercetin (Q) are flavonoids with different C-ring structures. We compared their physicochemical properties and biological activities. The comparison of their stability and redox properties was conducted at mildly acidic or neutral conditions mimicking the plant vacuole or gut, and their sympathetic hyperactivation ability was examined using catecholamine (CA) excretion and blood flow. At pH 5, flavonoids were stable, but at pH 7, their retention rates decreased in the order EC > Q > Tax. LC-MS analysis detected brown oxidized oligomers in EC, while Tax and Q primarily yielded degradation products. All flavonoids exhibited O₂^•− scavenging activity after incubation at pH 5. At pH 7 after 45-min, EC and Tax promoted O₂^•−, while Q only scavenged O₂^•− after 24-hr incubation, EC’s properties decreased but Tax’s properties enhanced. Computational chemistry analysis indicated EC has higher reactivity compared to Tax and Q. EC caused a significant increase in CA excretion and blood flow, which were not observed with Tax or Q or 24-h cultured EC. These results suggest that the C-ring structure of flavonoids plays a crucial role in their stability and redox properties. Furthermore, reactive oxygen species generated by flavonoids in the gut may exert beneficial effects through sympathetic activation. Full article

Background/Objectives: Long COVID (LC) has been linked to fatigue, exercise intolerance, and autonomic dysfunction, but sex-stratified data on cardiovascular responses to maximal exercise—an essential component of personalized medicine—are scarce. This study aimed to examine hemodynamic, autonomic, and functional responses during and up to 24 h after a cardiopulmonary exercise test (CPET) in young adults with and without Long COVID (LC). Methods: In this cross-sectional study, we assessed 38 physically active adults, who were allocated into four subgroups stratified by clinical condition (LC or control) and biological sex: control–female (CON-F; n = 10), LC–female (LC-F; n = 10), control–male (CON-M; n = 10), and LC–male (LC-M; n = 8). Outcomes included systolic (SBP) and diastolic blood pressure (DBP), heart rate (HR), cardiac output (CO), total (TPR) and peripheral vascular resistance (PVR), pulse wave velocity (PWV), augmentation index (AIx@75), and heart rate variability (HF, LF, LF/HF), assessed at rest, peak effort, recovery (1, 3, 5, 10, 30, and 60 min), and through 24 h ambulatory blood pressure monitoring (ABPM) after CPET. Results: SBP increase appropriately during exercise, with higher peaks in males (p < 0.01), and returned to baseline within 5 min across all groups. HR recovery was preserved; however, LC-F showed lower values than CON-F at 3, 5, and 10 min (126 vs. 144 bpm, p = 0.020; 119 vs. 136 bpm, p = 0.020; 94 vs. 109 bpm, p = 0.011), though all groups normalized by 60 min. PWV, AIx@75, TPR and PVR exhibited expected sex-related patterns without LC-related impairments. HRV indices showed transient post-exercise shifts (HF↓, LF↑, LF/HF↑). Ambulatory monitoring confirmed preserved circadian modulation, with normal systolic dipping (11–13%) and no abnormal nocturnal patterns. Conclusions: Young physically active adults with LC showed preserved hemodynamic, autonomic, and vascular responses during and after maximal exercise. These findings contribute to personalized medicine by showing that individualized, sex-stratified cardiovascular assessments reveal no clinically relevant impairments in this population, supporting tailored clinical decision making and exercise prescription. Full article

Agarwood from Aquilaria agallocha, known as chim-hyuang in Korea, is widely distributed throughout Southeast Asia and has traditionally been used to treat asthma, pain, and gastrointestinal disorders. As part of our ongoing efforts to identify bioactive metabolites from natural sources, a phytochemical investigation of the EtOAc fraction of A. agallocha extract led to the isolation and identification of four compounds, N-trans-feruloyltyramine (1), (3R,5R)-octahydrocurcumin (2), 1,7-bis(4-hydroxyphenyl)heptane (3), and trans-caffeoyltyramine (4), via HPLC purification and LC/MS-based analysis. Structural elucidation of the isolated compounds was achieved using NMR spectroscopy, LC/MS, and high-resolution electrospray ionization mass spectrometry (HR-ESIMS). The absolute configuration of compound 2 was further confirmed by optical rotation and electronic circular dichroism (ECD) analyses. All isolated compounds (1–4) were evaluated for their inhibitory activity against tau protein aggregation. Notably, compound 2 exhibited a 43.7% reduction in tau aggregation at 20 μM, without cytotoxicity at the same concentration. These findings indicate that phytochemicals from A. agallocha, particularly the diarylheptanoid compound 2, hold promise as natural lead candidates for the development of therapeutic agents targeting tau protein aggregation. Full article

Peach (Prunus persica) leaves, usually discarded in traditional Chinese medicine, were explored as a source of laxative agents. Using zebrafish larvae for bioactivity-guided fractionation, we isolated a single active flavanone that was identified by NMR and HR-MS as Sakuranetin. In vivo assays demonstrated that Sakuranetin (10–25 µM) accelerated intestinal transit in a dose-dependent fashion; at 25 µM, 64.8% of the fluorescent intestinal content was expelled. Untargeted LC-MS metabolomic analysis revealed significant perturbations in serine biosynthesis and N-glycan precursor biosynthesis, suggesting energetic rewiring of enterocytes. RNA-Seq analysis highlighted gnat1 as the most responsive gene, and molecular docking predicted a stable Sakuranetin–Gnat1 complex with a binding free energy of −8.7 kcal/mol. Concurrent down-regulation of rho transcripts indicated suppression of inflammatory signaling that often accompanies constipation. Our findings identified Sakuranetin as a potent promoter of gut motility and position the otherwise wasted peach leaves as an untapped botanical resource for developing anti-constipation therapeutics. Full article

During the course of genome mining initiatives, we identified a marine-derived Micromonospora, assigned here as strain WMMD956; the genome of WMMD956 appeared to contain a number of features associated with everninomicins, well-known antimicrobial orthosomycins. In addition, LCMS-based hierarchical clustering analysis and principal component analysis (hcapca) revealed that WMMD956 displayed an extreme degree of metabolomic and genomic novelty. Dereplication of high-resolution tandem mass spectrometry (HRMS/MS) and Global Natural Product Social molecular networking platform (GNPS) analysis of WMMD956 resulted in the identification of several analogs of the previously known everninomicin. Chemical structures were unambiguously confirmed by HR-ESI-MS, 1D and 2D NMR experiments, and the use of MS/MS data. The isolated metabolites, 1–3, were evaluated for their antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). Full article

Platycladus orientalis, an evergreen tree belonging to the Cupressaceae family, has been traditionally used to treat various ailments, including fever, cough, diarrhea, diuresis, cold symptoms, and gastrointestinal disorders in folk medicine. As part of our ongoing investigation aimed at discovering bioactive natural products and elucidating their mechanisms of action from various natural sources, we investigated a methanol (MeOH) extract of P. orientalis leaves. This investigation led to the isolation and identification of a labdane-type diterpene, lambertianic acid (LA), via column chromatography and HPLC purification. The structure of LA was elucidated using LC/MS and NMR spectroscopic analyses, including HR-ESIMS, while its absolute configuration was confirmed through electronic circular dichroism (ECD) calculations. Recent studies have reported that labdane-type diterpenes exhibit diverse pharmacological activities, such as anticancer, anti-inflammatory, anti-obesity, and hypolipidemic effects. Notably, LA has been shown to modulate adipocyte metabolism via AMPK signaling; however, its role in skeletal muscle atrophy remains unexplored. Therefore, in this study, we investigated the effects of LA on dexamethasone (Dex)-induced muscle atrophy in C2C12 myotubes. Treatment with LA at concentrations of 25 µM and 50 µM significantly rescued myotube diameter and reduced the expression of atrophy-related proteins, including MuRF-1 and atrogin-1/MAFbx, without compromising cell viability at these moderate concentrations. These findings suggest that LA derived from P. orientalis exerts protective effects against skeletal muscle atrophy, highlighting its potential as a promising natural therapeutic candidate for muscle-wasting disorders. Full article

Background/Objectives: Amyloid-β (Aβ) plaque accumulation, oxidative stress, and cholinergic dysfunction are hallmarks of Alzheimer’s disease (AD), a neurodegenerative disability that progresses over time, ultimately resulting in the loss of neurons. The side effects and limitations of current synthetic drugs have shifted attention toward natural alternatives. This study investigates the ethanolic extract of Aegle marmelos (L.) Corrêa fruits for their antioxidant, AChE-inhibitory, and anti-amyloidogenic properties, as well as their neuroprotective effects against amyloid beta-peptide (Aβ_1–42). Methods: Phytochemical constituents were identified through HR-LCMS analysis and their antioxidant (DPPH, FRAP) and neuroprotective activities (AChE inhibition, ThT binding, MTT assay, ROS reduction, MMP restoration, and AD-related gene expression via qRT-PCR) were assessed using SHSY-5Y neuroblastoma cells. Results: The extract revealed the existence of flavonoids, phenols, and other bioactive substances. In vitro assays demonstrated strong antioxidant and AChE-inhibitory activities, while the ThT binding assay showed protection against amyloid-β aggregation. The extract exhibited no cytotoxicity in SHSY-5Y cells, even at a concentration of 500 μg/mL, whereas Aβ_1–42 at 20 μM induced significant cytotoxicity. Co-treatment with Aβ_1–42 (10 μM and 20 μM) and the extract improved cell viability (˃50%) and reduced ROS levels. Additionally, the extract restored mitochondrial membrane potential in Aβ_1–42 treated cells, highlighting its role in preserving mitochondrial function. Conclusions: These findings suggest that A. marmelos fruits serve as a powerful source of natural antioxidants, AChE inhibitors, and anti-amyloidogenic agents, positioning them as a compelling option for AD treatment. Full article

Emerging contaminants (ECs), encompassing pharmaceuticals, personal care products, pesticides, and industrial chemicals, represent a growing threat to ecosystems and human health due to their persistence, bioaccumulation potential, and often-unknown toxicological profiles. Addressing these challenges necessitates advanced analytical tools capable of detecting and quantifying trace levels of ECs in complex environmental matrices. This review highlights the pivotal role of mass spectrometry (MS) in monitoring ECs, emphasizing its high sensitivity, specificity, and versatility across various techniques such as Gas Chromatography-Mass Spectrometry (GC-MS), Liquid Chromatography-Mass Spectrometry (LC-MS), and High-Resolution Mass Spectrometry (HR-MS). The application of MS has facilitated the real-time detection of volatile organic compounds, the comprehensive non-targeted screening of unknown contaminants, and accurate quantification in diverse matrices including water, soil, and air. Despite its effectiveness, challenges such as matrix interferences, a lack of standardized methodologies, and limited spectral libraries persist. However, recent advancements, including hybrid MS systems and the integration of artificial intelligence (AI), are paving the way for more efficient environmental monitoring and predictive modeling of contaminant behavior. Continued innovation in MS technologies and collaborative efforts are essential to overcome existing challenges and ensure sustainable solutions for mitigating the risks associated with emerging contaminants. Full article

Salix koreensis Anderss (Salicaceae), commonly referred to as Korean willow, is native to East Asia, particularly Korea and China, and it has been used in traditional Korean folk medicine for its potent anti-inflammatory, analgesic, and antioxidant properties. In our ongoing research efforts to discover biologically new natural products, phytochemical analysis on an ethanolic extract of S. koreensis twigs yielded the isolation and identification of ten phenolic compounds (1–10), including a newly discovered phenolic glycoside (1) named isograndidentatin D, isolated via HPLC purification. The structure of compound 1 was determined through extensive 1D and 2D NMR spectral data analysis and high-resolution electrospray ionization mass spectrometry (HR-ESIMS). Its absolute configuration was established using DP4+ probability analysis combined with gauge-including atomic orbital NMR chemical shift calculations and chemical reaction methods. The other known compounds were identified as isograndidentatin B (2), trichocarposide (3), glanduloidin C (4), tremuloidin (5), 3-O-acetylsalicin (6), 2-O-acetylsalicin (7), salicin (8), salireposide (9), and coumaric acid (10), confirmed by comparing their NMR spectra with previously reported data and further verified through liquid chromatography/mass spectrometry (LC/MS) analysis. The isolated compounds 1–10 were tested for their anti-Helicobacter pylori activities. Among these, compounds 4 and 5 demonstrated moderate anti-H. pylori activity at a concentration of 100 μM. Specifically, compound 5 showed an inhibitory activity of 35.9 ± 5.4%, making it slightly more potent than compound 4, with 34.0 ± 1.0% inhibition. These results were comparable to that of quercetin, a known anti-H. pylori agent used as a positive control in this study, which showed 38.4 ± 2.3% inhibition. The remaining compounds exhibited very weak inhibitory effects. This study highlights the potential of S. koreensis twigs as a valuable natural source of bioactive compounds for therapeutic applications against H. pylori. Full article

Mass spectrometry (MS) is the only instrumental analytical technology that utilizes unique properties of matter, that is, its mass (m) and electrical charge (z). In the magnetic and/or electric fields of mass spectrometers, electrically charged native or chemically modified (millions) endogenous and (thousands) exogenous substances, the analytes, are separated according to their characteristic mass-to-charge ratio (m/z) values. Mass spectrometers coupled to gas chromatographs (GC) or liquid chromatographs (LC), the so-called hyphenated techniques, i.e., GC-MS and LC-MS, respectively, enable reliable determination of the concentration of analytes in complex biological samples such as plasma, serum, and urine. A particular technology is represented by inductively coupled plasma-mass spectrometry (ICP-MS), which is mainly used for the analysis of metal ions. The highest analytical accuracy is reached by using mass spectrometers with high mass resolution (HR) or by tandem mass spectrometers, as it can be realized with quadrupole-type instruments, such as GC-MS/MS and LC-MS/MS, in combination with stable-isotope labeled analytes that serve as internal standards, like a standard weight in scales. GC-MS belongs to the oldest and most advanced instrumental analytical technology. From the very beginning, GC-MS found broad application in basic and applied research sciences. GC-MS has played important roles in discovering biochemical pathways, exploring underlying mechanisms of disease, and establishing new evidence-based pharmacological therapy. In this article, we make an inventory of the use of instrumental mass spectrometry in the life sciences and attempt to provide a perspective study on the future of analytical mass spectrometry in clinical science, mainly focusing on GC-MS and LC-MS. We used information freely available in the scientific database PubMed (retrieved in August–November 2024). Specific search terms such as GC-MS (103,000 articles), LC-MS (113,000 articles), and ICP-MS (14,000 articles) were used in the Title/Abstract in the “PubMed Advanced Search Builder” including filters such as search period (1970–2024). In total, around 103,000 articles on GC-MS, 113,000 articles on LC-MS (113,000), and 14,000 articles on ICP-MS were found. In the period 1995–2023, the yearly publication rate accounted for 3042 for GC-MS articles and 3908 for LC-MS articles (LC-MS/GC-MS ratio, 1.3:1). Our study reveals that GC-MS/MS, LC-MS/MS, and their high-resolution variants are indispensable instrumentations in clinical science including clinical pharmacology, internal and forensic medicine, and doping control. Long-tradition manufacturers of analytical instruments continue to provide increasingly customer-friendly GC-MS and LC-MS apparatus, enabling fulfillment of current requirements and needs in the life sciences. Quantitative GC-MS and GC-MS/MS methods are expected to be used worldwide hand in hand with LC-MS/MS, with ICP-MS closing the gap left for metal ions. The significance of analytical chemistry in clinical science in academia and industry is essential. Full article

Aeruginosins are common metabolites of cyanobacteria. In the course of re-isolation of the known aeruginosins KT608A and KT608B for bioassay studies, we isolated three new sulfated aeruginosins, named aeruginosins KT688 (1), KT718 (2), and KT575 (3), from the extract of a Microcystis cell mass collected during the 2016 spring bloom event in Lake Kinneret, Israel. The structures of the new compounds were established on the basis of analyses of the 1D and 2D NMR, as well as HRESIMS data. Marfey’s method, coupled with HR ESI LCMS and chiral HPLC, was used to establish the absolute configuration of the amino acid and hydroxyphenyl lactic acid residues, respectively. Compounds 1–3 were tested for inhibition of the serine protease trypsin, and compounds 1 and 2 were found to exhibit IC₅₀ values of 2.38 and 1.43 µM, respectively. Full article

Microorganisms are a valuable source of pharmaceutically active chemicals, serving as scaffolds for synthesis as well as lead structures. Investigating novel biomes frequently yields intriguing chemistry; the Atacama Desert in Chile is one such example. This study reports the isolation of a new reduced anthracycline-related compound from the Atacama Desert-derived bacterium Saccharothrix S26. Structural characterisation was achieved by one-dimensional and two-dimensional NMR, HR-LCMS, and X-ray crystallography. The compound was tested against the ESKAPE pathogens, bovine mastitis-related pathogens, and the fungal strain Cryptococcus neoformans, but no antimicrobial activity was observed. Full article

Two different collections of the gilled wild fungus Tricholoma terreum, collected in Italy, were subjected to phytochemical analysis. The fungal material was confidently identified by analysis of the ITS genomic sequences. Using both HR-LC-MS and NMR techniques, no evidence was found for the presence in the fruiting bodies of terreolides, terreumols or saponaceolides H-S, in striking contrast with the isolation of these terpenoids by Chinese authors from a mushroom collected in France and identified as T. terreum. The main cytotoxic terpenoid identified and isolated from the extracts of the specimens investigated in this work was the C₃₀ derivative saponaceolide B, which had been previously isolated from T. saponaceum and other T. terreum collections. Although saponaceolide B is a rather labile molecule, easily degradable by heat or in acidic conditions, our study indicated that none of the extraction protocols used produced saponaceolide H-S or terreolide/terreumol derivatives, thus excluding the possibility that the latter compounds could be extraction artifacts. Considered together, these findings point to the need for the unambiguous identification of mushroom species belonging to the complex genus Tricholoma, characterized by high variability in the composition of metabolites. Moreover, based on our data, T. terreum must be considered an edible mushroom. Full article