Metabolites最新文献

In this study, we present a novel approach using amperometric microsensors to detect quercetin in cosmetic formulations and track its metabolic behavior after topical application. This method offers a sensitive, real-time alternative to conventional techniques, enabling the detection of quercetin's bioavailability, its transformation into active metabolites, and its potential therapeutic effects when applied to the skin. Quercetin (Q) is a bioactive flavonoid known for its potent antioxidant properties, naturally present in numerous plants, particularly those with applications in cosmetic formulations. In response to the growing interest in developing novel plant-based dermo-cosmetic solutions, this study investigates the electrochemical detection of quercetin, a ketone-type flavonoid, extracted from Gingko biloba essential oil. Three newly designed amperometric microsensors were developed to assess their efficacy in detecting quercetin in botanical samples. The sensor configurations utilized two forms of carbon material as a foundation: graphite (G) and carbon nanoparticles (CNs). These base materials were modified with paraffin oil, chitosan (CHIT), and cobalt(II) tetraphenylporphyrin (Co(II)TPP) to enhance sensitivity. Differential pulse voltammetry (DPV) served as the analytical method for this investigation. Among the sensors, the CHIT/G-CN microsensor exhibited the highest sensitivity, with a detection limit of 1.22 × 10^-7 mol L^-1, followed by the G-CN (5.64 × 10^-8 mol L^-1) and Co(II)TPP/G-CN (9.80 × 10^-8 mol L^-1) microsensors. The minimum detectable concentration was observed with the G-CN and CoP/G-CN microsensors, achieving a threshold as low as 0.0001 μmol L^-1. Recovery rates and relative standard deviation (RSD) values averaged 97.4% ± 0.43, underscoring the sensors' reliability for quercetin detection in botanical matrices.

Background: Owing to the progressive rise in saline waters globally, resulting in detrimental impacts on freshwater aquaculture, the underlying molecular distinctions governing the response to alkaline stress between diploid and triploid crucian carp remain unknown. Methods: This investigation explores the effects of 20 and 60 mmol NaHCO₃ stress over 30 days on the gills of diploid and triploid crucian carp, employing histological, biochemical, and multi-omic analyses. Results: Findings reveal structural damage to gill lamellas in the examined tissue. Diploid crucian carp exhibit heightened activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and alkaline phosphatase (AKP), alongside lower malondialdehyde (MDA) and urea nitrogen (BUN) levels compared to triploid counterparts. Metabolomic investigations suggest alterations in purine metabolism, lipid metabolism, sphingolipid metabolism, and aminoglycan and nucleotide sugar metabolism following NaHCO₃ exposure. Transcriptomic data indicate differential expression of genes associated with nitrogen metabolism, complement and coagulation cascades, IL-17 signaling pathways, and Toll-like receptor signaling pathways. Conclusions: Overall, NaHCO₃-induced stress leads to significant gill tissue damage, accompanied by reactive oxygen species (ROS) production causing oxidative stress and disruptions in lipid metabolism in crucian carp. Furthermore, an inflammatory response in gill cells triggers an immune response. Diploid crucian carp exhibit superior antioxidant and immune capacities compared to triploid counterparts, while also displaying reduced inflammatory responses in vivo. Notably, diploid carp efficiently excrete excess BUN through purine metabolism, mitigating protein metabolism and amino acid imbalances caused by BUN accumulation. This enables them to allocate less energy for coping with external environmental stress, redirecting surplus energy toward growth and development. The above results indicate that diploid organisms can better adapt to saline-alkaline environments. Overall, this study provides novel perspectives into species selection of crucian carp of different ploidy in saline-alkaline waters.

Background/Objectives: Mandarin orange peel (MOP) is recognized for its traditional medicinal properties due to its high flavonoid content. This study aimed to analyze MOP harvested in Japan for specific bioactive compounds and to explore its health applications in dogs, including effects on gut microbiota and cognitive symptoms. Methods: Flavonoid content (particularly hesperidin and nobiletin) of MOP was measured. High-flavonoid MOP was then incorporated into gelatin cubes. In the time-course blood concentration study, experimental beagle dogs received a single oral dose (4 g). For intestinal microbiota analysis and blood biochemical tests, beagle dogs were administered 1 g twice daily. For the Demonstration Test, older dogs (a 14-year-old female Shiba Inu, a 14-year-old female Miniature Dachshund, and a 19-year-old male Miniature Dachshund) were administered 1 g twice daily. Analysis included microbiota profiling via 16S rDNA sequencing and observational assessment of cognitive indicators in a pilot study involving senior dogs with Alzheimer's disease. Results: The MOP powder contained 9.3% hesperidin in early-ripening varieties (October harvest) and 6.9% in ripe varieties (December harvest). Nobiletin content was 41 mg/100 g (0.041%) and 35 mg/100 g (0.035%) for the early and late harvests, respectively. Administration of MOP-enriched gelatin cubes reduced Fusobacteriaceae and increased Eggerthellaceae. Cognitive symptoms like howling and counterclockwise turning showed improvement in senior dogs (n = 3). Conclusions: This study provides preliminary support for the potential health benefits of MOP in canine dietary applications, particularly for gut health and cognitive function. Improvement in cognitive symptoms may be due to the anxiolytic effects of mandarin peel.

Chlorophyll is the primary pigment responsible for capturing light energy during photosynthesis, while carotenoids assist in light absorption and provide photoprotection by dissipating excess energy. Both pigments are essential for plant growth and development, playing distinct and complementary roles in maintaining photosynthetic efficiency and protecting plants from oxidative stress. Because of their function in photosynthesis and photoprotection, chlorophyll and carotenoid accumulation are strongly associated with light conditions, especially blue and red lights, which play key roles in regulating their metabolisms. Despite advancements in understanding pigment metabolism, there remains a limited comprehensive overview of how various parts of the light spectrum influence these pathways throughout the entire process. The effects of other spectral ranges of light, such as green light, far-red light, and UV, are not yet fully understood. This review aims to synthesize recent findings about the regulatory network of chlorophyll and carotenoid pathways under different light spectral bands, emphasizing the interplay between light-regulated transcription factors and genes involved in their biosynthesis and degradation.

Background: Metabolomics measurements are noisy, often characterized by a small sample size and missing entries. While data-driven methods have shown promise in terms of analyzing metabolomics data, e.g., revealing biomarkers of various phenotypes, metabolomics data analysis can significantly benefit from incorporating prior information about metabolic mechanisms. This paper introduces a novel data analysis approach to incorporate mechanistic models in metabolomics data analysis. Methods: We arranged time-resolved metabolomics measurements of plasma samples collected during a meal challenge test from the COPSAC₂₀₀₀ cohort as a third-order tensor: subjects by metabolites by time samples. Simulated challenge test data generated using a human whole-body metabolic model were also arranged as a third-order tensor: virtual subjects by metabolites by time samples. Real and simulated data sets were coupled in the metabolites mode and jointly analyzed using coupled tensor factorizations to reveal the underlying patterns. Results: Our experiments demonstrated that the joint analysis of simulated and real data had better performance in terms of pattern discovery, achieving higher correlations with a BMI (body mass index)-related phenotype compared to the analysis of only real data in males, while in females, the performance was comparable. We also demonstrated the advantages of such a joint analysis approach in the presence of incomplete measurements and its limitations in the presence of wrong prior information. Conclusions: The joint analysis of real measurements and simulated data (generated using a mechanistic model) through coupled tensor factorizations guides real data analysis with prior information encapsulated in mechanistic models and reveals interpretable patterns.

Background/Objectives: Hyperlipidemia is a major contributor to metabolic complications and tissue damage, leading to conditions such as liver steatosis, atherosclerosis, and obesity. This study aimed to investigate the effects of aqueous artichoke bract extract (AE) on lipid metabolism, liver antioxidative defense, and liver steatosis in mice fed a high-fat, high-sucrose diet while elucidating the underlying mechanisms. Methods: An 8-week study used hyperlipidemic mice treated with AE at daily doses of 100 and 200 mg/kg bw, compared to fenofibrate. Plasma, liver, fecal, and biliary lipids, as well as blood glucose, were analyzed enzymatically. The liver antioxidative defense was assessed by measuring reduced glutathione, malondialdehyde (MDA), and antioxidant enzyme activities, while liver steatosis was evaluated through transaminase and alkaline phosphatase activities and histological monitoring of lipid droplets. Polyphenol profiling and quantification were performed using HPLC-DAD, and potential mechanisms were predicted by molecular docking and confirmed in HepG2 cells. Results: At 200 mg/kg, AE significantly improved plasma lipid profiles by reducing total cholesterol, triglycerides, and LDL-cholesterol while increasing HDL-cholesterol. It facilitated cholesterol reduction in the liver and its excretion, indicating activation of reverse cholesterol transport, which led to reduced body weight and liver steatosis. AE lowered MDA levels and enhanced antioxidant enzyme activities. AE was found to be safe (LD50 > 5000 mg/kg) and modulated gene expression in HepG2 cells. Conclusions: Based on our results, the artichoke bract extract could be considered a natural resource of bioactive compounds to treat hyperlipidemia and related cardiometabolic diseases.

Background/Objectives:Acinetobacter baumannii is a highly multidrug-resistant pathogen resistant to almost all classes of antibiotics; new therapeutic strategies against this infectious agent are urgently needed. Shikimate kinase is an enzyme belonging to the shikimate pathway and has become a potential target for drug development. This work describes the search for Food and Drug Administration (FDA)-approved drugs and natural compounds, including gallic acid, that could be repurposed as selective shikimate kinase inhibitors by integrated computational and experimental approaches. Methods: Approaches to drug design using structure-based and ligand-based methodology, in-silico screening, molecular docking, and molecular dynamics for the study of both binding affinity and stability. Experimental Validation Determination of minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) on Acinetobacter baumannii and Enterococcus faecalis. Results/Conclusions: Among them, gallic acid, obtained from plants, proved to be the most promising compound that showed sufficient binding with shikimate kinase through computational studies. Gallic acid showed very good activity against Acinetobacter baumannii and Enterococcus faecalis in the MIC and MBC assay, respectively. Gallic acid exhibited better activity against Acinetobacter baumannii due to the overexpression of shikimate kinase. Gallic acid has emerged as a potential therapeutic candidate drug against A. baumannii infection and, therefore, as a strategy against the appearance of multidrug-resistant microorganisms. This study not only identifies a novel repurposing opportunity for gallic acid but also provides a comprehensive computational and experimental framework for accelerating antimicrobial drug discovery against multidrug-resistant pathogens.

Background/objectives: Catha edulis, commonly known as khat, is used for its psychoactive effects and is considered a natural amphetamine. The current study investigated the metabolomic profile in the cerebellum of mice after repeated exposure to khat and evaluated the effects of clavulanic acid on the metabolomic profile in the cerebellum in khat-treated mice.

Methods: Male C67BL/6 mice that were 6-9 weeks old were recruited and divided into three groups: the control group was treated with 0.9% normal saline for 17 days; the khat group was given khat extract at a dose of 360 mg/kg via the intraperitoneal (i.p) route for 17 days; and another khat group was treated with khat for 17 days and clavulanic acid at a dose of 5 mg/kg for the last 7 days (days 11-17). At the end of the 17th day, the animals were sacrificed, and their brains were immediately collected and stored at -80 °C. The cerebellum region of the brain was isolated in each group by micropuncture using cryostat and underwent a metabolomics study via Gas Chromatography/Mass Spectroscopy (GC/MS). The total peak area ratios of the selected metabolites in the cerebellum after repeated exposure to the khat extract were significantly reduced (p < 0.05) and treatment of the khat group with clavulanic acid significantly increased (all p < 0.05) the total peak areas ratios of the selected metabolites when compared to their corresponding areas in the alternative khat group. These levels of selected metabolites were further confirmed by observing the metabolite peak area ratios and performing a heat map analysis and a principal compartment analysis of the samples in the cerebellum.

Results: A network analysis of altered metabolites in the cerebellum showed a strong correlation between the different metabolites, which showed that an increase in one metabolite can modulate the levels of others. An analysis using the MetaboAnalyst software revealed the involvement of selected altered metabolites like lactic acid in many signaling pathways, like gluconeogenesis, while enrichment analysis data showed altered pathways for pyruvate metabolism and disease pathogenesis. Finally, a network analysis showed that selected metabolites were linked with other metabolites, indicating drug-drug interactions.

Conclusions: The present study showed that repeated exposure of mice to khat altered the levels of various metabolites in the cerebellum which are involved in the pathogenesis of different diseases, signaling pathways, and interactions with the pharmacokinetic profile of other therapeutic drugs. The treatment of khat-treated mice with clavulanic acid positively modified the metabolomics profile in the cerebellum and increased the levels of the altered metabolites.

Background/objectives: Low fasting blood lysosomal acid lipase (LAL) activity is associated with the pathogenesis of metabolic hepatic steatosis. We measured LAL activity in blood and plasma before and after an oral fat tolerance test (OFTT) in patients with metabolic-dysfunction-associated steatotic liver disease (MASLD).

Methods: Twenty-six controls and seventeen patients with MASLD but without diabetes were genotyped for the patatin-like phospholipase 3 (PNPLA3) rs738409 variant by RT-PCR and subjected to an OFTT, measuring LAL activity in blood and plasma with a fluorimetric method.

Results: LAL activity in blood both under fasting and 4 h after OFTT (0.846 ± 0.309 nmol/spot/h vs. 1.180 ± 0.503 nmol/spot/h p < 0.01) was lower in patients with MASLD compared to controls. These differences were present only in carriers of the PNPLA3 variant. In controls not carrying the PNPLA3 variant, the postprandial increase in blood LAL activity was negatively correlated with that of serum triglycerides (p < 0.05). Extracellular LAL activity in plasma was lower in patients with MASLD (n = 9) compared to controls (n = 8) in the fasting state (p < 0.01) and 4 h post-meal (p < 0.05). The area under the curve up to 6 h of plasma LAL activity was lower in patients with MASLD than in controls (p < 0.05) and correlated negatively with that of triglycerides only in controls (r = -0.841; p < 0.01).

Conclusions: Patients with MASLD have reduced LAL activity in blood and plasma both before and 4 h after a meal. In patients with MASLD, the physiological negative correlation between circulating LAL levels and postprandial hypertriglyceridemia is lost.