Metabolites

15 pages, 1583 KB

Open AccessArticle

Development and Application of an In-Capillary CE-DAD Method for the Inhibitory Screening of Natural Extracts Towards Acetylcholinesterase Enzyme

by Francesca Rinaldi, Sofia Salerno, Elena Frigoli, Giulia De Soricellis, Gloria Brusotti, Stefano Negri, Matteo Radice, Francesca Merlo, Andrea Speltini, Hellas Cena and Enrica Calleri

Metabolites 2025, 15(4), 283; https://doi.org/10.3390/metabo15040283 - 18 Apr 2025

Viewed by 626

Abstract

Background: The enzymatic activity of acetylcholinesterase (AChE) has been a focal point in neurodegenerative diseases research, particularly in relation to Alzheimer’s disease. This is attributed to the significantly reduced levels of cholinergic neurons observed in Alzheimer’s patients compared to healthy individuals. The strategy [...] Read more.

Background: The enzymatic activity of acetylcholinesterase (AChE) has been a focal point in neurodegenerative diseases research, particularly in relation to Alzheimer’s disease. This is attributed to the significantly reduced levels of cholinergic neurons observed in Alzheimer’s patients compared to healthy individuals. The strategy to mitigate the onset of these diseases in patients lies in the exploration of new potential AChE inhibitors with a focus also on natural extracts. A rapid and specific capillary electrophoresis method with direct ultraviolet detection (CZE-UV/Vis) was developed to screen natural extracts by assessing their potential to inhibit AChE. Materials and Methods: To enhance the specificity when analysing complex matrixes such as natural extracts, a sequential analysis approach based on the “sandwich model” was implemented using Ellman’s reagent [5,5′-dithiobis-(2-nitrobenzoic acid)] (DTNB) as a colorimetric indicator. Results: A reference inhibitor, neostigmine, was used for system validation through IC₅₀ and K_i values determination by subsequent injections of acetylthiocholine substrate in the presence of neostigmine at increasing concentrations, and the enzyme combined with DTNB in borate-phosphate buffer (30 mM, pH 8.0). The enzymatic product was selectively detected at 412 nm. The validated system was applied to the analysis of seven natural extracts. Conclusions: Results demonstrated promising outcomes for identifying phytotherapeutic agents with potential applications in the prevention of neurodegenerative diseases. This method provides high selectivity and automation, offering a streamlined and effective approach for screening natural matrices containing potential AChE inhibitors. Full article

(This article belongs to the Special Issue Secondary Metabolites and Their Activities: From the Identification to the Biological Investigation)

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27 pages, 788 KB

Open AccessEditor’s ChoiceReview

Lipid Metabolism and Statin Therapy in Neurodegenerative Diseases: An Endocrine View

by Antonella Di Sarno, Fiammetta Romano, Rossana Arianna, Domenico Serpico, Mariarosaria Lavorgna, Silvia Savastano, Annamaria Colao and Carolina Di Somma

Metabolites 2025, 15(4), 282; https://doi.org/10.3390/metabo15040282 - 18 Apr 2025

Cited by 1 | Viewed by 1807

Abstract

Background/aim: A growing body of evidence suggests a link between dyslipidemias and neurodegenerative diseases, highlighting the crucial role of lipid metabolism in the health of the central nervous system. The aim of our work was to provide an update on this topic, [...] Read more.

Background/aim: A growing body of evidence suggests a link between dyslipidemias and neurodegenerative diseases, highlighting the crucial role of lipid metabolism in the health of the central nervous system. The aim of our work was to provide an update on this topic, with a focus on clinical practice from an endocrinological point of view. Endocrinologists, being experts in the management of dyslipidemias, can play a key role in the prevention and treatment of neurodegenerative conditions, through precocious and effective lipid profile optimization. Methods: The literature was scanned to identify clinical trials and correlation studies on the association between dyslipidemia, statin therapy, and the following neurodegenerative diseases: Alzheimer’s disease (AD), Parkisons’s disease (PD), Multiple sclerosis (MS), and Amyotrophic lateral sclerosis (ALS). Results: Impaired lipid homeostasis, such as that frequently observed in patients affected by obesity and diabetes, is related to neurodegenerative diseases, such as AD, PD, and other cognitive deficits related to aging. AD and related dementias are now a real priority health problem. In the United States, there are approximately 7 million subjects aged 65 and older living with AD and related dementias, and this number is projected to grow to 12 million in the coming decades. Lipid-lowering therapy with statins is an effective strategy in reducing serum low-density lipoprotein cholesterol to normal range concentrations and, therefore, cardiovascular disease risk; moreover, statins have been reported to have a positive effect on neurodegenerative diseases. Conclusions: Several pieces of research have found inconsistent information following our review. There was no association between statin use and ALS incidence. More positive evidence has emerged regarding statin use and AD/PD. However, further large-scale prospective randomized control trials are required to properly understand this issue. Full article

(This article belongs to the Special Issue Lipid Metabolism in Age-Related Diseases)

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12 pages, 1097 KB

Open AccessArticle

Quality Evaluation of the Traditional Chinese Medicine Moutan Cortex Based on UPLC Fingerprinting and Chemometrics Analysis

by Wentao Fang, Qianqian Song, Han Luo, Rui Wang and Chengwu Fang

Metabolites 2025, 15(4), 281; https://doi.org/10.3390/metabo15040281 - 18 Apr 2025

Cited by 1 | Viewed by 879

Abstract

Background: This study aims to develop a fingerprint analysis method using ultra-high performance liquid chromatography (UPLC) for Moutan Cortex sourced from different regions. The objective is to establish quality control standards validated through the integration of chemometric methods and component structure theory. Methods: [...] Read more.

Background: This study aims to develop a fingerprint analysis method using ultra-high performance liquid chromatography (UPLC) for Moutan Cortex sourced from different regions. The objective is to establish quality control standards validated through the integration of chemometric methods and component structure theory. Methods: The mobile phase for UPLC consisted of acetonitrile (A) and a 0.1% aqueous formic acid solution (B), with gradient elution set as follows: 0–1 min, 8% A → 15% A; 1–8 min, 15% A → 18% A; 8–10 min, 18% A → 30% A; 10–15 min, 30% A → 35% A; 15–20 min, 35% A → 85% A; 20–21 min, 85% A → 8% A; and 21–26 min, 8% A → 8% A. Chemical markers significantly affecting Moutan Cortex from various regions were screened, and their identification was based on comparison with reference materials and content determination. Results: A total of 15 chemical markers were identified, including gallic acid, oxypaeoniflorin, catechin, methyl gallate, paeonolide, apiopaeonoside, albiflorin, paeoniflorin, benzoic acid, 1,2,3,6-tetra-O-galloyl-D-glucose, 1,2,3,4,6-pentagalloylglucose, mudanpioside C, benzoyloxypaeoniflorin, benzoylpaeoniflorin, and paeonol. These markers align with component structure theory, allowing for an analysis of the structural characteristics of Moutan Cortex from different regions. Conclusions: The findings provide a valuable reference for the future quality evaluation of traditional Chinese medicine preparations, enhancing the understanding of the material basis components in Moutan Cortex from diverse sources. Full article

(This article belongs to the Special Issue Advances in Secondary Metabolites: Phytochemical Analysis and Bioactivity Assays)

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13 pages, 715 KB

Open AccessArticle

Association Between Alpha-1-Acid Glycoprotein and Non-Alcoholic Fatty Liver Disease and Liver Fibrosis in Adult Women

by Yansong Fu, Siyi Zhang, Xin Zeng and Hong Qin

Metabolites 2025, 15(4), 280; https://doi.org/10.3390/metabo15040280 - 17 Apr 2025

Cited by 1 | Viewed by 1021

Abstract

Background: Alpha-1-acid glycoprotein (AGP) is a glycoprotein synthesized mainly by the liver. Nonalcoholic fatty liver disease (NAFLD) and liver fibrosis (LF) are associated with metabolic disorders. The aim of this study was to examine the potential correlation between AGP and both NAFLD and [...] Read more.

Background: Alpha-1-acid glycoprotein (AGP) is a glycoprotein synthesized mainly by the liver. Nonalcoholic fatty liver disease (NAFLD) and liver fibrosis (LF) are associated with metabolic disorders. The aim of this study was to examine the potential correlation between AGP and both NAFLD and LF. Methods: The data were derived from the 2017–2023 National Health and Nutrition Examination Survey (NHANES). The linear association between AGP and NAFLD and LF was examined by multivariate logistic regression models. Non-linear relationships were described by fitting smoothed curves and threshold effect analysis. Subgroup analysis was also performed to assess potential regulatory factors. Results: The study included 2270 females. AGP was found to be significantly and positively associated with NAFLD [OR = 12.00, 95% CI (6.73, 21.39), p < 0.001] and LF [OR = 2.20, 95% CI (1.07, 4.50), p = 0.042]. Furthermore, the association between AGP and NAFLD was significantly different in the diabetic subgroup (p < 0.05 for interaction). Additionally, we found an inverted U-shaped relationship between AGP and controlled attenuation parameter (CAP), with an inflection point at 1.20 g/L. Conclusions: We found a significant positive correlation between AGP and both NAFLD and LF, and there was an inverted U-shaped relationship between AGP and CAP. Full article

(This article belongs to the Special Issue Metabolic Syndrome and Non-Alcoholic Liver Disease)

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15 pages, 2601 KB

Open AccessArticle

A Scoring Model Using Multi-Metabolites Based on Untargeted Metabolomics for Assessing Dyslipidemia in Korean Individuals with Obesity

by Su-Geun Yang and Hye Jin Yoo

Metabolites 2025, 15(4), 279; https://doi.org/10.3390/metabo15040279 - 17 Apr 2025

Viewed by 745

Abstract

Background/Objectives: Metabolite risk score (MRS), which considers the collective effects of metabolites closely reflecting a phenotype, is a new approach for disease assessment, moving away from focusing solely on individual biomarkers. This study aimed to investigate a metabolite panel for dyslipidemia and verify [...] Read more.

Background/Objectives: Metabolite risk score (MRS), which considers the collective effects of metabolites closely reflecting a phenotype, is a new approach for disease assessment, moving away from focusing solely on individual biomarkers. This study aimed to investigate a metabolite panel for dyslipidemia and verify the diagnostic efficacy of MRS on dyslipidemia. Methods: Key metabolite identification and MRS establishment were conducted in the discovery set, and MRS validation was performed in the replication set, with 50 healthy individuals and 50 dyslipidemia patients in each set. The MRS was constructed using key metabolites, identified via UPLC-MS/MS analysis, employing a weighted approach based on linear regression analysis. Results: N-acetylisoputreanine-γ-lactam and eicosapentaenoic acid were identified as key metabolites for dyslipidemia and were utilized for establishing the MRS. In addition to the MRS model, a conventional dyslipidemia diagnostic model based on lipid profiles, as well as a combined model (MRS + lipid profiles), were also established. In the discovery set, the MRS model diagnosed dyslipidemia with 85.4% accuracy. When combined with lipid profiles, accuracy improved to 91.8%. In the replication set, the MRS demonstrated diagnostic power with 76.1% accuracy, while the combined model achieved 86.0% accuracy for dyslipidemia assessment. Conclusions: The MRS alone indicated sufficient assessment power in a real-world setting, despite a slight reduction in assessment ability when validated in the replication set. At this stage, therefore, the MRS serves as an auxiliary tool for disease diagnosis. This first attempt to apply MRS for dyslipidemia may offer a foundational concept for MRS in this disease. Full article

(This article belongs to the Section Endocrinology and Clinical Metabolic Research)

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19 pages, 2384 KB

Open AccessArticle

Effects of a 6-Week Concurrent Training Program Combining Resistance and Various Modalities of Aerobic Exercise in Obese Women with Prehypertension: A Randomized Controlled Trial

by Jinhyuk Yu, Eunjoo Lee, Jae-Ho Choi, Yerin Sun, Seungyeon Woo, Sohyang Cho, Deunsol Hwang, Sung-Woo Kim, Jisu Kim, Kiwon Lim and Hun-Young Park

Metabolites 2025, 15(4), 278; https://doi.org/10.3390/metabo15040278 - 17 Apr 2025

Cited by 2 | Viewed by 1804

Abstract

Background/Objectives: Our study aimed to verify the effects of 6 weeks of concurrent training composed of resistance training (RT) and different modalities of aerobic exercise (moderate-intensity continuous training (MICT) or high-intensity interval training (HIIT)) on body composition, blood pressure, vascular function, autonomic [...] Read more.

Background/Objectives: Our study aimed to verify the effects of 6 weeks of concurrent training composed of resistance training (RT) and different modalities of aerobic exercise (moderate-intensity continuous training (MICT) or high-intensity interval training (HIIT)) on body composition, blood pressure, vascular function, autonomic nervous system (ANS) function, blood lipid levels, cardiometabolic index (CMI), and health-related fitness in obese middle-aged women with prehypertension. Methods: We selected 26 middle-aged women with obesity and prehypertension and divided them equally into the RT + MICT (n = 13) and RT + HIIT (n = 13) groups. The concurrent training program consisted of warm-up, RT, aerobic exercise (MICT or HIIT), and cool-down, and was performed for 6 weeks, three times a week, 85–100 min per session. The measured dependent parameters were analyzed before and after training. Results: Concurrent training (RT + MICT and RT + HIIT) for 6 weeks showed significant improvements in body composition, blood pressure, vascular function, ANS function, CMI, and health-related fitness. However, the RT + HIIT group showed a relatively greater improvement in blood lipid levels compared to the RT + MICT group. Conclusions: Our study confirmed that both RT + MICT and RT + HIIT yielded similar positive effects on most health-related parameters in obese middle-aged women with prehypertension. Among them, RT + HIIT appeared to be relatively more effective in improving blood lipid profiles. Full article

(This article belongs to the Special Issue Effects of Various Exercise Methods on Metabolic Health)

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17 pages, 1407 KB

Open AccessEditor’s ChoiceArticle

Metabolic Effects of the Cancer Metastasis Modulator MEMO1

by Marziyeh Ghanbarian, Natalia Dolgova, Frederick S. Vizeacoumar, Franco J. Vizeacoumar, Deborah Michel, Anas El-Aneed and Oleg Y. Dmitriev

Metabolites 2025, 15(4), 277; https://doi.org/10.3390/metabo15040277 - 17 Apr 2025

Viewed by 983

Abstract

Background/Objectives: Cancer cells often display altered energy metabolism. In particular, expression levels and activity of the tricarboxylic acid cycle (TCA cycle) enzymes may change in cancer, and dysregulation of the TCA cycle is a frequent hallmark of cancer cell metabolism. MEMO1, a modulator [...] Read more.

Background/Objectives: Cancer cells often display altered energy metabolism. In particular, expression levels and activity of the tricarboxylic acid cycle (TCA cycle) enzymes may change in cancer, and dysregulation of the TCA cycle is a frequent hallmark of cancer cell metabolism. MEMO1, a modulator of cancer metastasis, has been shown to bind iron and regulate iron homeostasis in the cells. MEMO1 knockout changed mitochondrial morphology and iron content in breast cancer cells. Our previous genome-wide analysis of MEMO1 genetic interactions across multiple cancer cell lines revealed that gene sets involved in mitochondrial respiration and the TCA cycle are enriched among the gain-of-function interaction partners of MEMO1. Based on these findings, we measured the TCA cycle metabolite levels in breast cancer cells with varying levels of MEMO1 expression. Methods: ShRNA knockdown assay was performed to test essentiality of key TCA cycle enzymes. TCA metabolites were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS) in MDA-MB-231 (high MEMO1), M67-2 (MEMO1 knockdown), and M67-9 (MEMO1 knockout) cells under iron-depleted, basal iron, and iron-supplemented conditions. Results:ACO2 and OGDH knockdowns inhibit cell proliferation, indicating an essential role of the TCA cycle in MDA-MB-231 metabolism. α-Ketoglutarate and citrate levels exhibited an inverse relationship with MEMO1 expression, increasing significantly in MEMO1 knockout cells regardless of iron availability. In contrast, fumarate, malate, and glutamate levels were elevated in MEMO1 knockout cells specifically under low iron conditions, suggesting an iron-dependent effect. Conclusions: Overall, our results indicate that MEMO1 plays a role in regulating the TCA in cancer cells in an iron-dependent manner. Full article

(This article belongs to the Special Issue Reactive Oxygen Species and Energy Metabolic Alterations in Health and Disease)

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27 pages, 3031 KB

Open AccessReview

Plant Secondary Metabolites—Central Regulators Against Abiotic and Biotic Stresses

by Ameer Khan, Farah Kanwal, Sana Ullah, Muhammad Fahad, Leeza Tariq, Muhammad Tanveer Altaf, Asad Riaz and Guoping Zhang

Metabolites 2025, 15(4), 276; https://doi.org/10.3390/metabo15040276 - 16 Apr 2025

Cited by 15 | Viewed by 3879

Abstract

As global climates shift, plants are increasingly exposed to biotic and abiotic stresses that adversely affect their growth and development, ultimately reducing agricultural productivity. To counter these stresses, plants produce secondary metabolites (SMs), which are critical biochemical and essential compounds that serve as [...] Read more.

As global climates shift, plants are increasingly exposed to biotic and abiotic stresses that adversely affect their growth and development, ultimately reducing agricultural productivity. To counter these stresses, plants produce secondary metabolites (SMs), which are critical biochemical and essential compounds that serve as primary defense mechanisms. These diverse compounds, such as alkaloids, flavonoids, phenolic compounds, and nitrogen/sulfur-containing compounds, act as natural protectants against herbivores, pathogens, and oxidative stress. Despite the well-documented protective roles of SMs, the precise mechanisms by which environmental factors modulate their accumulation under different stress conditions are not fully understood. This review provides comprehensive insights into the recent advances in understanding the functions of SMs in plant defense against abiotic and biotic stresses, emphasizing their regulatory networks and biosynthetic pathways. Furthermore, we explored the unique contributions of individual SM classes to stress responses while integrating the findings across the entire spectrum of SM diversity, providing a comprehensive understanding of their roles in plant resilience under multiple stress conditions. Finally, we highlight the emerging strategies for harnessing SMs to improve crop resilience through genetic engineering and present novel solutions to enhance agricultural sustainability in a changing climate. Full article

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23 pages, 3688 KB

Open AccessEditor’s ChoiceArticle

Targeted and Non-Targeted Metabolomic Evaluation of Cerebrospinal Fluid in Early Phase Schizophrenia: A Pilot Study from the Hopkins First Episode Psychosis Project

by George E. Jaskiw, Mark E. Obrenovich, Curtis J. Donskey, Farren B. S. Briggs, Sun Sunnie Chung, Anastasiya I. Kalinina, Austin Bolomey, Lindsay N. Hayes, Kun Yang, Robert H. Yolken and Akira Sawa

Metabolites 2025, 15(4), 275; https://doi.org/10.3390/metabo15040275 - 15 Apr 2025

Viewed by 1573

Abstract

(1) Background: The lack of reliable biomarkers remains a significant barrier to improving outcomes for patients with schizophrenia. While metabolomic analyses of blood, urine, and feces have been explored, results have been inconsistent. Compared to peripheral compartments, cerebrospinal fluid (CSF) more closely reflects [...] Read more.

(1) Background: The lack of reliable biomarkers remains a significant barrier to improving outcomes for patients with schizophrenia. While metabolomic analyses of blood, urine, and feces have been explored, results have been inconsistent. Compared to peripheral compartments, cerebrospinal fluid (CSF) more closely reflects the chemical composition of brain extracellular fluid. Given that brain dysregulation may be more pronounced during the first episode of psychosis (FEP), we hypothesized that metabolomic analysis of CSF from FEP patients could reveal disease-associated biomarkers. (2) Methods: We recruited 15 patients within 24 months of psychosis onset (DSM-4 criteria) and 14 control participants through the Johns Hopkins Schizophrenia Center. CSF samples were analyzed using both non-targeted and targeted liquid chromatography–mass spectrometry. (3) Results: The non-targeted analysis identified lower levels of N-acetylneuraminic acid and N-acetyl-L-aspartic acid in the FEP group, while levels of uric acid were elevated. The targeted analysis focused on indolic and phenolic molecules previously linked to neuropsychiatric disorders. Notably, L-phenylalanine and 4-hydroxycinnamic acid levels were lower in the FEP group, and this difference remained significant after adjusting for age and sex. However, none of the significant differences in analyte levels between the groups survived an adjustment for multiple comparisons. (4) Conclusions: Our intriguing but preliminary associations align with results from other investigational approaches and highlight potential CSF analytes that warrant further study in larger samples. Full article

(This article belongs to the Special Issue Metabolomics in Human Diseases and Health)

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16 pages, 1293 KB

Open AccessEditor’s ChoiceArticle

Comprehensive Characterization of Serum Lipids of Dairy Cows: Effects of Negative Energy Balance on Lipid Remodelling

by Zhiqian Liu, Wenjiao Wang, Joanne E. Hemsworth, Coralie M. Reich, Carolyn R. Bath, Monique J. Berkhout, Muhammad S. Tahir, Vilnis Ezernieks, Leah C. Marett, Amanda J. Chamberlain, Mike E. Goddard and Simone J. Rochfort

Metabolites 2025, 15(4), 274; https://doi.org/10.3390/metabo15040274 - 15 Apr 2025

Cited by 1 | Viewed by 838

Abstract

Background: The presence and concentration of lipids in serum of dairy cows have significant implications for both animal health and productivity and are potential biomarkers for several common diseases. However, information on serum lipid composition is rather fragmented, and lipid remodelling during the [...] Read more.

Background: The presence and concentration of lipids in serum of dairy cows have significant implications for both animal health and productivity and are potential biomarkers for several common diseases. However, information on serum lipid composition is rather fragmented, and lipid remodelling during the transition period is only partially understood. Methods: Using a combination of reversed-phase liquid chromatography-mass spectrometry (RP-LC-MS), hydrophilic interaction-mass spectrometry (HILIC-MS), and lipid annotation software, we performed a comprehensive identification and quantification of serum of dairy cows in pasture-based Holstein-Friesian cows. The lipid remodelling induced by negative energy balance was investigated by comparing the levels of all identified lipids between the fresh lactation (5–14 days in milk, DIM) and full lactation (65–80 DIM) stages. Results: We identified 535 lipid molecular species belonging to 19 classes. The most abundant lipid class was cholesteryl ester (CE), followed by phosphatidylcholine (PC), sphingomyelin (SM), and free fatty acid (FFA), whereas the least abundant lipids included phosphatidylserine (PS), phosphatidic acid (PA), phosphatidylglycerol (PG), acylcarnitine (AcylCar), ceramide (Cer), glucosylceramide (GluCer), and lactosylceramide (LacCer). Conclusions: A remarkable increase in most lipids and a dramatic decrease in FFAs, AcylCar, and DHA-containing species were observed at the full lactation compared to fresh lactation stage. Several serum lipid biomarkers for detecting negative energy balance in cows were also identified. Full article

(This article belongs to the Special Issue Effects of Stress on Animal Metabolism)

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19 pages, 10209 KB

Open AccessArticle

Urine Metabolomic Patterns to Discriminate the Burnout Levels and Night-Shift-Related Stress in Healthcare Professionals

by Andreea Petra Ungur, Andreea-Iulia Socaciu, Maria Barsan, Armand Gabriel Rajnoveanu, Razvan Ionut, Carmen Socaciu and Lucia Maria Procopciuc

Metabolites 2025, 15(4), 273; https://doi.org/10.3390/metabo15040273 - 14 Apr 2025

Cited by 1 | Viewed by 1342

Abstract

Burnout syndrome, which significantly impacts both individual and societal quality of life, is primarily characterized by three key criteria: depersonalization, emotional exhaustion, and low personal accomplishment, all linked to work-related stress. Purpose: Comparative evaluation of urine metabolite patterns that may discriminate the [...] Read more.

Burnout syndrome, which significantly impacts both individual and societal quality of life, is primarily characterized by three key criteria: depersonalization, emotional exhaustion, and low personal accomplishment, all linked to work-related stress. Purpose: Comparative evaluation of urine metabolite patterns that may discriminate the burnout levels and the effects of night shifts on healthcare professionals. The Maslach Burnout Inventory survey was administered to 64 physicians and nurses working day and night shifts, with scores for each criterion recorded. Methods: Urine samples were collected, and metabolomic patterns were analyzed using UHPLC-QTOF-ESI+-MS technology. This analysis employed both untargeted and semi-targeted metabolomics, coupled with multivariate and ANOVA statistics, utilizing the online Metaboanalyst 6.0 platform. Partial Least Squares Discriminant Analysis (PLSDA) was performed, along with VIP values, Random Forest graphs, and heatmaps based on 79 identified metabolites. These were further complemented by biomarker analysis (AUC ranking) and pathway analysis of metabolic networks. Results: The findings highlighted the biochemical effects of night shifts and their correlation with burnout scores from each dimension. Conclusions: This study demonstrated the involvement of three major metabolic pathways in diagnosing burnout: lipid metabolism, particularly related to steroid hormones (cortisol, cortisone, and androsterone metabolites); energetic metabolism, involving long-chain acylated carnitines as transporters of free fatty acids, which play a role in burnout control; and a third pathway affecting catecholamine metabolism (neurotransmitters derived from tyrosine, such as dopamine, adrenaline, and noradrenaline), as well as tryptophan metabolism (serotonin and melatonin metabolites) and amino acid metabolism (including aspartate, arginine, and valine). Full article

(This article belongs to the Special Issue Integration of Emerging Technologies in Metabolite Analysis)

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18 pages, 1029 KB

Open AccessReview

Nephrological, Pulmonary, and Dermatological Complications in the Context of MAFLD/NAFLD: A Narrative Review

by Vlad Pădureanu, Dalia Dop, Lucrețiu Radu, Dumitru Rădulescu, Rodica Pădureanu, Denisa Floriana Vasilica Pîrșcoveanu and Daniel Cosmin Caragea

Metabolites 2025, 15(4), 272; https://doi.org/10.3390/metabo15040272 - 14 Apr 2025

Cited by 2 | Viewed by 1268

Abstract

Background: The most common cause of chronic liver disease is now known to be non-alcoholic fatty liver disease (NAFLD), recently redefined as metabolic-associated fatty liver disease (MAFLD). This review aims to synthesize current evidence on the pathophysiology and clinical implications of nephrological, [...] Read more.

Background: The most common cause of chronic liver disease is now known to be non-alcoholic fatty liver disease (NAFLD), recently redefined as metabolic-associated fatty liver disease (MAFLD). This review aims to synthesize current evidence on the pathophysiology and clinical implications of nephrological, pulmonary, and dermatological manifestations among NAFLD/MAFLD patients. In order to find safe and efficient treatments, NAFLD/MAFLD has emerged as a primary concern for hepatologists worldwide. Methods: We conducted a comprehensive review of the literature from major databases, focusing on studies that evaluated the extrahepatic manifestations of NAFLD/MAFLD. Emphasis was placed on identifying pathophysiological mechanisms and assessing their clinical impact on renal, pulmonary, and dermatological systems. Results: Recent developments in the management of chronic viral hepatitis have lowered the mortality rate associated with chronic liver disease. However, the prevalence of NAFLD/MAFLD continues to rise, making chronic liver disease a significant health concern for the future. An increasing percentage of patients on liver transplant waiting lists now have cirrhosis and hepatocellular carcinoma due to non-alcoholic liver disease. Furthermore, the incidence and prevalence of chronic kidney disease have surged, linking NAFLD/MAFLD to higher morbidity, mortality, and healthcare costs. Conclusions: NAFLD/MAFLD is underdiagnosed and underappreciated, yet its incidence is rapidly increasing, raising concerns about a potential global epidemic. Given its multisystemic impact—extending to renal, pulmonary, and dermatological complications—it is crucial to develop interdisciplinary strategies for early detection and effective management of the disease. Full article

(This article belongs to the Special Issue Metabolite Profiles in Inflammatory Diseases)

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13 pages, 253 KB

Open AccessArticle

The Effects of SGLT2 Inhibitors on Lipid Profile and Kidney Function in Patients with Chronic Kidney Disease Regardless of Diabetes and Hypertension Status

by Selena Gajić, Stefan Janković, Milorad Stojadinović, Kristina Filić, Ana Bontić, Jelena Pavlović, Ivana Mrđa, Kristina Petrović, Lara Hadži-Tanović, Jelena Žunić, Mihajlo Kostić, Aleksandra Kezić and Marko Baralić

Metabolites 2025, 15(4), 271; https://doi.org/10.3390/metabo15040271 - 13 Apr 2025

Cited by 1 | Viewed by 1085

Abstract

Background: Chronic kidney disease (CKD) is a progressive, irreversible impairment of kidney function due to various etiologies. Numerous studies have shown that sodium-glucose cotransporter-2 inhibitors (SGLT2i) slow the progression of CKD, due to their pleiotropic effects. Therefore, there has been an increase in [...] Read more.

Background: Chronic kidney disease (CKD) is a progressive, irreversible impairment of kidney function due to various etiologies. Numerous studies have shown that sodium-glucose cotransporter-2 inhibitors (SGLT2i) slow the progression of CKD, due to their pleiotropic effects. Therefore, there has been an increase in interest in their effects not only on kidney function but also on other parameters in patients with CKD. The aim of the study was to examine the effects of SGLT2i on serum lipid values and kidney function in patients with CKD undergoing SGLT2i treatment. Methods: This study was a retrospective data analysis of 75 patients with CKD on SGLT2i treatment. We compared the values of biochemical parameters, renal function outcomes, and blood pressure at two time points: baseline and 24 months after. Results: Total cholesterol (Chol) significantly decreased in all patients, while triglyceride (Tg) and low-density lipoprotein cholesterol (LDLc) levels also decreased in all patients. High-density lipoprotein cholesterol (HDLc) levels increased, but this increase was not significant. Creatinine clearance (Ccr) significantly decreased, and serum urea (Sur) significantly increased in all patients. The proteinuria (Prt) levels did not change significantly. The results showed that the diastolic blood pressure (DBP) significantly decreased in all patients. Conclusions: This study showed that the use of SGLT2i reduced total Chol in all patients with CKD during the 24-month follow-up, regardless of diabetes mellitus (DM) status. No significant differences were observed for the Tg, LDLc, and HDLc values. Full article

(This article belongs to the Special Issue Lipid Metabolism Dysregulation in Metabolic Disorders: Unraveling the Molecular Complexity)

19 pages, 2140 KB

Open AccessArticle

Combined Effects of Ketogenic Diet and Aerobic Exercise on Skeletal Muscle Fiber Remodeling and Metabolic Adaptation in Simulated Microgravity Mice

by Jun Chen, Wenjiong Li, Liang Yu, Bowei Zhang, Zhili Li, Peng Zou, Bai Ding, Xiaoqian Dai and Qirong Wang

Metabolites 2025, 15(4), 270; https://doi.org/10.3390/metabo15040270 - 13 Apr 2025

Viewed by 1469

Abstract

Objective: Prolonged microgravity environments impair skeletal muscle homeostasis by triggering fiber-type transitions and metabolic dysregulation. Although exercise and nutritional interventions may alleviate disuse atrophy, their synergistic effects under microgravity conditions remain poorly characterized. This study investigated the effects of an 8-week ketogenic diet [...] Read more.

Objective: Prolonged microgravity environments impair skeletal muscle homeostasis by triggering fiber-type transitions and metabolic dysregulation. Although exercise and nutritional interventions may alleviate disuse atrophy, their synergistic effects under microgravity conditions remain poorly characterized. This study investigated the effects of an 8-week ketogenic diet combined with aerobic exercise in hindlimb-unloaded mice on muscle fiber remodeling and metabolic adaptation. Methods: Seven-week-old male C57BL/6J mice were randomly divided into six groups: normal diet control (NC), normal diet with hindlimb unloading (NH), normal diet with hindlimb unloading and exercise (NHE), ketogenic diet control (KC), ketogenic diet with hindlimb unloading (KH), and ketogenic diet with hindlimb unloading and exercise (KHE). During the last two weeks of intervention, hindlimb unloading was applied to simulate microgravity. Aerobic exercise groups performed moderate-intensity treadmill running (12 m/min, 60 min/day, and 6 days/week) for 8 weeks. Body weight, blood ketone, and glucose levels were measured weekly. Post-intervention assessments included the respiratory exchange ratio (RER), exhaustive exercise performance tests, and biochemical analyses of blood metabolic parameters. The skeletal muscle fiber-type composition was evaluated via immunofluorescence staining, lipid deposition was assessed using Oil Red O staining, glycogen content was analyzed by Periodic Acid–Schiff (PAS) staining, and gene expression was quantified using quantitative real-time PCR (RT-qPCR). Results: Hindlimb unloading significantly decreased body weight, induced muscle atrophy, and reduced exercise endurance in mice. However, the combination of KD and aerobic exercise significantly attenuated these adverse effects, as evidenced by increased proportions of oxidative muscle fibers (MyHC-I) and decreased proportions of glycolytic fibers (MyHC-IIb). Additionally, this combined intervention upregulated the expression of lipid metabolism-associated genes, including CPT-1b, HADH, PGC-1α, and FGF21, enhancing lipid metabolism and ketone utilization. These metabolic adaptations corresponded with improved exercise performance, demonstrated by the increased time to exhaustion in the KHE group compared to other hindlimb unloading groups. Conclusions: The combination of a ketogenic diet and aerobic exercise effectively ameliorates simulated microgravity-induced skeletal muscle atrophy and endurance impairment, primarily by promoting a fiber-type transition from MyHC-IIb to MyHC-I and enhancing lipid metabolism gene expression (CPT-1b, HADH, and PGC-1α). These findings underscore the potential therapeutic value of combined dietary and exercise interventions for mitigating muscle atrophy under simulated microgravity conditions. Full article

(This article belongs to the Special Issue Muscle Metabolic Response and Adaptation to Exercise, Diet, and Environment)

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20 pages, 1291 KB

Open AccessReview

Metabolomics Insights into Gut Microbiota and Functional Constipation

by Fan Zheng, Yong Yang, Guanting Lu, Joo Shun Tan, Uma Mageswary, Yu Zhan, Mina Ehab Ayad, Yeong-Yeh Lee and Daoyuan Xie

Metabolites 2025, 15(4), 269; https://doi.org/10.3390/metabo15040269 - 12 Apr 2025

Cited by 4 | Viewed by 3358

Abstract

Background: The composition and metabolic activity of the gut microbiota play a crucial role in various health conditions, including the occurrence and development of chronic constipation. Recent metabolomic advances reveal that gut microbiota-derived metabolites—such as SCFAs, bile acids, neurotransmitters, and microbial gases—play critical [...] Read more.

Background: The composition and metabolic activity of the gut microbiota play a crucial role in various health conditions, including the occurrence and development of chronic constipation. Recent metabolomic advances reveal that gut microbiota-derived metabolites—such as SCFAs, bile acids, neurotransmitters, and microbial gases—play critical roles in regulating intestinal function. Methods: We systematically analyzed the current literature on microbial metabolomics in chronic constipation. This review consolidates findings from high-throughput metabolomic techniques (GC-MS, LC-MS, NMR) comparing metabolic profiles of constipated patients with healthy individuals. It also examines diagnostic improvements and personalized treatments, including fecal microbiota transplantation and neuromodulation, guided by these metabolomic insights. Results: This review shows that reduced SCFA levels impair intestinal motility and promote inflammation. An altered bile acid metabolism—with decreased secondary bile acids like deoxycholic acid—disrupts receptor-mediated signaling, further affecting motility. Additionally, imbalances in amino acid metabolism and neurotransmitter production contribute to neuromuscular dysfunction, while variations in microbial gas production (e.g., methane vs. hydrogen) further modulate gut transit. Conclusions: Integrating metabolomics with gut microbiota research clarifies how specific microbial metabolites regulate gut function. These insights offer promising directions for precision diagnostics and targeted therapies to restore microbial balance and improve intestinal motility. Full article

(This article belongs to the Special Issue Metabolomics in Human Diseases and Health)

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15 pages, 7513 KB

Open AccessArticle

Study on the Inhibitory Effects of Three Endophytic Bacillus Strains on Aspergillus flavus in Maize

by Siyu Ma, Min Li, Siqi Zhang, Yin Yang, Fengsha Zhu, Xingyu Li, Shahzad Munir, Pengfei He, Pengbo He, Yixin Wu, Yueqiu He and Ping Tang

Metabolites 2025, 15(4), 268; https://doi.org/10.3390/metabo15040268 - 11 Apr 2025

Viewed by 978

Abstract

Background: Maize is easily contaminated by Aspergillus flavus, and the aflatoxin produced by A. flavus has been classified as a Group 1 carcinogen, for which there are currently no effective control measures. Biological control is regarded as an environmentally friendly and safe [...] Read more.

Background: Maize is easily contaminated by Aspergillus flavus, and the aflatoxin produced by A. flavus has been classified as a Group 1 carcinogen, for which there are currently no effective control measures. Biological control is regarded as an environmentally friendly and safe approach. Strains ZH179, ZH409, and ZH99 are three bacteria isolated from our laboratory that exhibit antagonistic effects against A. flavus. We conducted experiments to investigate their biocontrol efficacy. Results: The experimental results demonstrated that these three strains effectively inhibited A. flavus on plates and stored maize seeds. Identification revealed that ZH179 is Bacillus velezensis, while ZH409 and ZH99 are B. amyloliquefaciens. We also identified lipopeptide synthetase-related genes, including srfAA, srfAD, fenA, fenB, ituA, ituB, ituD, bmyA, bmyB, and bmyC, in these three strains. Furthermore, LC-MS analysis confirmed that these strains could produce lipopeptide compounds such as surfactin, fengycin, iturin, and bacillomycin. Using the Oxford cup method, we found that the lipopeptide compounds produced by these strains can inhibit the growth of A. flavus. Conclusion: These findings suggest that strains ZH179, ZH409, and ZH99 have good control effects on A. flavus during the storage of maize, primarily due to the lipopeptide compounds. This study provides a theoretical basis for using these three strains in the biological control of A. flavus. Full article

(This article belongs to the Special Issue Advances in Plant and Microbial Metabolic Engineering)

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19 pages, 1595 KB

Open AccessEditor’s ChoiceReview

From Inflammation to Infertility: How Oxidative Stress and Infections Disrupt Male Reproductive Health

by Anastasios Potiris, Efthalia Moustakli, Eleni Trismpioti, Eirini Drakaki, Despoina Mavrogianni, Alkis Matsas, Athanasios Zikopoulos, Antonios Sfakianakis, Ioannis Tsakiridis, Themistoklis Dagklis, Athanasios Zachariou, Panagiotis Christopoulos, Ekaterini Domali, Peter Drakakis and Sofoklis Stavros

Metabolites 2025, 15(4), 267; https://doi.org/10.3390/metabo15040267 - 11 Apr 2025

Cited by 10 | Viewed by 3889

Abstract

Background/Objectives: Inflammation, infections, and oxidative stress (OS) all have an impact on male infertility, which is a complicated, multifaceted illness. OS affects motility and fertilization capability. It accomplishes this through damaging sperm DNA, oxidizing proteins, and triggering lipid peroxidation. These effects occur due [...] Read more.

Background/Objectives: Inflammation, infections, and oxidative stress (OS) all have an impact on male infertility, which is a complicated, multifaceted illness. OS affects motility and fertilization capability. It accomplishes this through damaging sperm DNA, oxidizing proteins, and triggering lipid peroxidation. These effects occur due to an imbalance between reactive oxygen species (ROS) and antioxidant defenses. Methods: This review aims to evaluate the impact of oxidative stress and inflammation on male infertility by assessing recent literature. Results: Pro-inflammatory cytokines, like TNF-α and IL-6, interfere with spermatogenesis and promote oxidative damage. Additionally, infections caused by pathogens like Escherichia coli and Chlamydia trachomatis alter the reproductive microenvironment, leading to sperm dysfunction and inflammation. Conclusions: Early detection and targeted treatment are essential due to the intricate interactions among these elements. Microbiota-modulating techniques, antimicrobial therapies, anti-inflammatory drugs, and antioxidants are therapeutic approaches that may help reduce oxidative damage and enhance male fertility. Full article

(This article belongs to the Special Issue Advancements in Reproductive Medicine: Unlocking the Secrets of the Ovary and Sperm for Fertility and Beyond)

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18 pages, 1901 KB

Open AccessEditor’s ChoiceArticle

Comparative Effects of Turmeric Secondary Metabolites Across Resorptive Bone Diseases

by Laura E. Wright, Jennifer B. Frye, Andrew G. Kunihiro, Barbara N. Timmermann and Janet L. Funk

Metabolites 2025, 15(4), 266; https://doi.org/10.3390/metabo15040266 - 11 Apr 2025

Viewed by 1230

Abstract

Background: Turmeric (Curcuma longa L.) rhizomes, whose secondary metabolites include polyphenols and terpenoids, have been used medicinally for millennia. However, modern scientific inquiry has primarily focused on medicinal effects of turmeric’s polyphenolic curcuminoids, including when evaluating turmeric use to maintain bone [...] Read more.

Background: Turmeric (Curcuma longa L.) rhizomes, whose secondary metabolites include polyphenols and terpenoids, have been used medicinally for millennia. However, modern scientific inquiry has primarily focused on medicinal effects of turmeric’s polyphenolic curcuminoids, including when evaluating turmeric use to maintain bone health. Methods: Disease-specific biological effects of turmeric’s major secondary metabolites (polyphenols and/or terpenoids), with or without associated turmeric rhizome-derived polysaccharides, were determined in vivo using pre-clinical models of clinically relevant resorptive bone diseases induced by different mechanisms. These included inflammatory arthritis, cancer-driven osteolytic bone metastases, and hormone deficiency-driven post-menopausal osteoporosis. Results: In the arthritis model, the safety profile of curcuminoids alone was superior. However, curcuminoids and terpenoids each had anti-inflammatory effects and prevented bone resorption, with polysaccharide-containing curcuminoid extracts having greater effect than curcuminoids alone. In the human osteolytic breast cancer bone metastases model, curcuminoid extracts containing polysaccharides tended to yield greater effects in reducing bone osteolysis and tumor progression than curcuminoids alone or more complex extracts. In contrast, only purified curcuminoids prevented bone loss in a post-menopausal osteoporosis model, while polysaccharide-containing curcuminoid extracts were without effect. In vitro metabolite effects on disease-specific mechanistic pathways in synoviocytes, osteoclasts, or breast cancer cells were consistent with documented in vivo outcomes and included differential metabolite-specific effects. Conclusions: In summary, these findings suggest that turmeric’s potential medicinal musculoskeletal effects are complex, pathway- and target-specific, and not limited to curcuminoids, with safety concerns potentially limiting certain uses. Full article

(This article belongs to the Special Issue Identification of Plant Metabolites: Characterization and Biological Activities, 2nd Edition)

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13 pages, 5638 KB

Open AccessArticle

Identification and Evaluation of Colour Change in Rosemary and Biluochun Tea Infusions

by Yuan Yuan, Caochuang Fang, Chaohan Li, Jiaqi You and Kun Ma

Metabolites 2025, 15(4), 265; https://doi.org/10.3390/metabo15040265 - 11 Apr 2025

Viewed by 851

Abstract

Background: The colour of tea beverages during processing and storage significantly influences their visual quality. However, natural pink tea products are rare. This study investigated the mechanism behind the pink colouration in the mixed infusion of Biluochun (a green tea) and rosemary. Methods: [...] Read more.

Background: The colour of tea beverages during processing and storage significantly influences their visual quality. However, natural pink tea products are rare. This study investigated the mechanism behind the pink colouration in the mixed infusion of Biluochun (a green tea) and rosemary. Methods: Infusions of Biluochun (B), rosemary (R), and their mixture (BR), brewed with boiling water for 10 min, were analysed using liquid chromatography-mass spectrometry (LC-MS). Additionally, the pH value and tea pigment content were measured. Results: A total of 134 differential metabolites (DEMs) were detected. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that phenylalanine metabolism and tyrosine metabolism pathways were enriched with abundant DEMs. Some amino acids in BR showed degradation. The content of pelargonin, a compound in the anthocyanin biosynthetic pathway, was significantly elevated in BR compared to that in B and R. DEMs related to fatty acid metabolism were at low levels in BR. Other compounds, such as quercetin, caffeate, rosmarinic acid, and isoferulic acid, were also more abundant in BR. No significant differences in pH value and tea pigment content were found among the three infusions. Conclusions: A model of pink colouration formation in BR was proposed based on the results of this study. Some substances in Biluochun and rosemary were released during the brewing process. Tyrosine was converted into p-coumaric acid, which further reacted to form pelargonin. Pelargonin, an orange-red (pH ≈ 5.0) anthocyanin, was the primary contributor to the pink colouration in BR. Additionally, p-coumaric acid formed co-pigments such as quercetin, caffeic acid, rosmarinic acid, and isovaleric acid. These co-pigments stabilised or enhanced the colour of pelargonin through co-pigmentation. The findings provide a theoretical basis for optimising tea processing techniques and improving quality control in beverage production. Full article

(This article belongs to the Section Food Metabolomics)

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11 pages, 614 KB

Open AccessOpinion

The Optimal Protective 25-Hydroxyvitamin D Level for Different Health Outcomes in Adults: A Brief Summary of Dose–Response Meta-Analyses

by Cem Ekmekcioglu and Michael Poteser

Metabolites 2025, 15(4), 264; https://doi.org/10.3390/metabo15040264 - 10 Apr 2025

Viewed by 3048

Abstract

Vitamin D is very important for bone metabolism as well as for the prevention of various diseases, such as type 2 diabetes, cardiovascular disease and different types of cancer. Although vitamin D deficiency is widespread and an important public health problem, there exists [...] Read more.

Vitamin D is very important for bone metabolism as well as for the prevention of various diseases, such as type 2 diabetes, cardiovascular disease and different types of cancer. Although vitamin D deficiency is widespread and an important public health problem, there exists controversy in the scientific community, with no established standard definition of adequate and deficient vitamin D status. To add new information on this topic, the aim of this brief opinion paper is to identify and discuss the optimal 25(OH)D concentration (range) for a reduction in the risk of various disease outcomes by summarizing dose–response reporting meta-analyses. Full article

(This article belongs to the Special Issue Vitamin D Metabolism and Human Health)

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20 pages, 3930 KB

Open AccessArticle

Cellular Metabolomics Reveals Differences in the Scope of Liver Protection Between Ammonium-Based Glycyrrhizinate and Magnesium Isoglycyrrhizinate

by Yihua Zhang, Han Hao, Hui Li, Qiong Duan, Xiaoming Zheng, Yan Feng, Kun Yang and Shigang Shen

Metabolites 2025, 15(4), 263; https://doi.org/10.3390/metabo15040263 - 10 Apr 2025

Viewed by 1000

Abstract

Background: Despite the well-established liver-protective efficacy of monoammonium glycyrrhizinate (MONO), diammonium glycyrrhizinate (DIAM), and magnesium isoglycyrrhizinate (MAGN), which has been translated into clinical practice, their clinical differentiation remains elusive owing to their structural similarities and overlapping therapeutic effects. Methods: The present study delves [...] Read more.

Background: Despite the well-established liver-protective efficacy of monoammonium glycyrrhizinate (MONO), diammonium glycyrrhizinate (DIAM), and magnesium isoglycyrrhizinate (MAGN), which has been translated into clinical practice, their clinical differentiation remains elusive owing to their structural similarities and overlapping therapeutic effects. Methods: The present study delves into the pharmacokinetics, cellular-level liver-protective potencies, and underlying mechanisms of action of these three compounds through a comprehensive analysis. Results: The findings reveal that both DIAM and MAGN exhibit superior bioavailability and hepatoprotective profiles compared to MONO. Notably, an investigation of the metabolic pathways mediating liver protection in normal human liver cells (LO2), utilizing an ultra-performance liquid chromatography–time of flight tandem mass spectrometry (UPLC-TOF-MS/MSe) platform, demonstrated that MAGN augments antioxidant components, thereby favoring its application in drug-induced liver injury (DILI). Conversely, DIAM appears to be a more suitable candidate for addressing non-alcoholic fatty liver disease (NAFLD) and viral hepatitis. Conclusion: This study contributes novel perspectives on the mechanisms of action and potential clinical utilities of DIAM and MAGN in liver disease prevention and management. Full article

(This article belongs to the Topic Natural Products in Prevention and Therapy of Metabolic Syndrome)

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23 pages, 6197 KB

Open AccessEditor’s ChoiceArticle

Combined Effects of Rhodiola Rosea and Caffeine Supplementation on Straight Punch Explosive Power in Untrained and Trained Boxing Volunteers: A Synergistic Approach

by Biaoxu Tao, Hao Sun, Huixin Li, Zhiqin Xu, Yuan Xu, Liqi Chen, Chengzhe Ma, Xiaoyu Zhang, Longqi Yu, Shanjun Bao and Chang Liu

Metabolites 2025, 15(4), 262; https://doi.org/10.3390/metabo15040262 - 10 Apr 2025

Cited by 1 | Viewed by 2902

Abstract

Objectives: This study aimed to investigate the effects of combined supplementation with Rhodiola rosea (RHO) and caffeine (CAF) on the explosive power and sustained output capacity of lead and rear straight punches in both untrained and trained volunteers, with a focus on potential [...] Read more.

Objectives: This study aimed to investigate the effects of combined supplementation with Rhodiola rosea (RHO) and caffeine (CAF) on the explosive power and sustained output capacity of lead and rear straight punches in both untrained and trained volunteers, with a focus on potential synergistic effects. Methods: randomized, double-blind, placebo-controlled design was employed, enrolling 96 participants (48 untrained, 48 trained). Participants were stratified and randomly assigned to the control (CTR), CAF, RHO, or CAF+RHO group. All subjects completed an 8-week standardized boxing training program (twice per week). Punch performance was assessed using professional boxing equipment and a biomechanical testing system, evaluating lead and rear straight punches, ground reaction force (GRF), and a 30 s continuous punching test. Results: the CAF+RHO group showed significant improvements in both untrained and trained volunteers. Com-pared to the RHO group, this group demonstrated higher lead punch velocity, shorter bi-lateral peak force time during rear punches, and more punches in the 30 s test (p < 0.05). Compared to the CAF group, the CAF+RHO group exhibited greater rear punch force, higher bilateral peak force during lead punches, increased forefoot peak force in rear punches, and improved 30 s power output (p < 0.05). The CAF+RHO group also outperformed the CTR group across all parameters (p < 0.05). Conclusions: Combined supple mentation with CAF and RHO significantly enhances both explosive power and sustained output in boxing performance. This may result from improved energy metabolism efficiency and neuromuscular coordination, providing a promising nutritional strategy for high-intensity intermittent exercise. Full article

(This article belongs to the Section Nutrition and Metabolism)

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18 pages, 5076 KB

Open AccessArticle

Enhancing Plant Resistance to Sri Lankan Cassava Mosaic Virus Using Salicylic Acid

by Chonnipa Pattanavongsawat, Srihunsa Malichan, Nattachai Vannatim, Somruthai Chaowongdee, Nuannapa Hemniam, Atchara Paemanee and Wanwisa Siriwan

Metabolites 2025, 15(4), 261; https://doi.org/10.3390/metabo15040261 - 10 Apr 2025

Cited by 1 | Viewed by 987

Abstract

Background: Cassava mosaic disease (CMD), caused by the Sri Lankan cassava mosaic virus (SLCMV), significantly increases cassava yield losses in Thailand, with losses ranging from 30% to 80%, and is exacerbated by limited access to healthy planting materials. Methods: This study explored salicylic [...] Read more.

Background: Cassava mosaic disease (CMD), caused by the Sri Lankan cassava mosaic virus (SLCMV), significantly increases cassava yield losses in Thailand, with losses ranging from 30% to 80%, and is exacerbated by limited access to healthy planting materials. Methods: This study explored salicylic acid (SA) as a potential treatment for enhancing disease resistance in CMD infected cassava plants. SA was applied at 100 and 200 mg/mL, and its effects were evaluated using quantitative real-time polymerase chain reaction (qPCR) and reverse transcription qPCR (RT-qPCR) to measure viral loads and the expression levels of resistance genes. Results: Although SA treatment did not considerably affect disease severity, foliar CMD symptoms visibly decreased, particularly with 200 mg/mL SA, which also reduced SLCMV particle counts at 1- and 2-weeks post-treatment. SA upregulated the expression of pathogenesis-related proteins (PRs), including HSP90.9, WRKY59, SRS1, and PR9e. Additionally, SA enhanced the regulation of secondary metabolite pathways involving L-serine within the glycine, serine, and threonine metabolism, as well as the phenylpropanoid biosynthesis pathways. Conclusions: These findings collectively indicate that SA enhances resistance through the systemic acquired resistance (SAR) pathway and can serve as a potential strategy for the management of CMD, particularly in regions where healthy cassava planting materials are scarce. The study highlights the efficacy of SA in reducing viral particles, inducing the immune response, and providing a promising approach for controlling CMD. Full article

(This article belongs to the Special Issue Unlocking Nature's Toolbox: Advances in Plant Metabolites Identification)

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14 pages, 684 KB

Open AccessReview

Impact on Metabolism Generated by Surgical and Pharmacological Interventions for Weight Loss in Women with Infertility

by Paulo César Gete Palacios, Alberto Moscona-Nissan, Renata Saucedo and Aldo Ferreira-Hermosillo

Metabolites 2025, 15(4), 260; https://doi.org/10.3390/metabo15040260 - 10 Apr 2025

Viewed by 2453

Abstract

Obesity increases the risk of anovulation, insulin resistance, hyperandrogenism, and endometrial dysfunction, resulting in women with infertility and increasing preconceptional and pregnancy complications. Bariatric surgery has been described as the most effective intervention for obesity, with improved fertility outcomes. However, its invasive nature [...] Read more.

Obesity increases the risk of anovulation, insulin resistance, hyperandrogenism, and endometrial dysfunction, resulting in women with infertility and increasing preconceptional and pregnancy complications. Bariatric surgery has been described as the most effective intervention for obesity, with improved fertility outcomes. However, its invasive nature increases the potential of nutritional deficiencies and the need for a delayed conception post-surgery. On the other hand, pharmacological treatments such as glucagon-like-peptide 1 receptor agonists offer non-invasive alternatives with promising results in body weight, improving insulin sensitivity and restoring ovarian function. However, their use must be discontinued before conception due to potential fetal risks. Other available pharmacological treatment options encompass topiramate, phentermine, and Orlistat. The choice of treatment must be individualized considering cost-effectiveness, accessibility, obesity severity, reproductive goals, and associated risks within each patient. A multidisciplinary approach is essential to optimize metabolic and reproductive health in obesity and infertility. This review will examine the impact on metabolism when comparing surgical and pharmacological interventions for weight loss in women with infertility. Full article

(This article belongs to the Section Endocrinology and Clinical Metabolic Research)

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16 pages, 1641 KB

Open AccessReview

Vitamin D and Its Role in Rheumatic Diseases

by Maritza Vidal and Nancy E. Lane

Metabolites 2025, 15(4), 259; https://doi.org/10.3390/metabo15040259 - 9 Apr 2025

Cited by 1 | Viewed by 1367

Abstract

Vitamin D is a fat-soluble molecule with pleiotropic effects, acting as a steroid hormone on three main organs: the intestine, bone, and kidney. Among its best-known functions at the skeletal level are regulating bone metabolism and mineralization. In 1983, the presence of vitamin [...] Read more.

Vitamin D is a fat-soluble molecule with pleiotropic effects, acting as a steroid hormone on three main organs: the intestine, bone, and kidney. Among its best-known functions at the skeletal level are regulating bone metabolism and mineralization. In 1983, the presence of vitamin D receptors on the surface of immune cells was described, which led to the discovery of new functions on immunological and inflammatory processes. Currently, we know that vitamin D modulates the adaptative immune system by suppressing cells that produce inflammatory cytokines by downregulation, acting as an important regulator of immunity and the inflammatory response. In this article, we will review the synthesis, metabolic pathways, and the role of vitamin D in rheumatic autoimmune diseases. Full article

(This article belongs to the Section Nutrition and Metabolism)

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17 pages, 1220 KB

Open AccessEditor’s ChoiceArticle

Serum Amino Acid Profiles in Dogs with a Congenital Portosystemic Shunt

by Robert Kyle Phillips, Amanda B. Blake, Michael S. Tivers, Alex Chan, Patricia E. Ishii, Jan S. Suchodolski, Jörg M. Steiner and Jonathan A. Lidbury

Metabolites 2025, 15(4), 258; https://doi.org/10.3390/metabo15040258 - 9 Apr 2025

Viewed by 1050

Abstract

Background/Objectives: A functional liver is vital for normal protein metabolism. Alterations of circulating amino acid (AA) concentrations have previously been reported in dogs with hepatocellular carcinoma, chronic hepatitis, and hepatocutaneous syndrome. The purpose of this study was to compare serum AA profiles [...] Read more.

Background/Objectives: A functional liver is vital for normal protein metabolism. Alterations of circulating amino acid (AA) concentrations have previously been reported in dogs with hepatocellular carcinoma, chronic hepatitis, and hepatocutaneous syndrome. The purpose of this study was to compare serum AA profiles between dogs with a congenital portosystemic shunt (CPSS) and healthy control dogs. Methods: Serum samples were collected from 50 dogs with an extrahepatic congenital portosystemic shunt (eCPSS) and 10 dogs with an intrahepatic congenital portosystemic shunt (iCPSS) at time of surgical intervention and from 21 healthy control dogs. Serum AA and other nitrogenous compounds were measured with a dedicated amino acid analyzer. The concentration of each AA was compared between groups using a Kruskal–Wallis test followed by Dunn’s multiple comparisons tests, as appropriate. The Benjamini–Hochberg procedure was used to control for false discovery. Significance was set at q < 0.05. Results: Compared to healthy controls, dogs with a CPSS had significantly increased serum concentrations of ammonia, asparagine, glutamic acid, histidine, phenylalanine, serine, and tyrosine and had significantly decreased concentrations of isoleucine, leucine, threonine, urea, and valine. There were no significant differences in serum AA concentrations between dogs with an eCPSS and dogs with an iCPSS. Conclusions: Dogs with a CPSS had altered serum AA concentrations compared to healthy control dogs, including decreased branched-chain amino acids (BCAAs) and increased aromatic amino acids (AAAs). In summary, serum AA profiles can differentiate dogs with a CPSS from healthy dogs but not dogs with an eCPSS from dogs with an iCPSS. Full article

(This article belongs to the Special Issue Proteomics and Metabolomics in Veterinary and Animal Health)

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14 pages, 3635 KB

Open AccessArticle

Aromatic Volatile Substances in Different Types of Guangnan Dixu Tea Based on HS-SPME-GC-MS Odor Activity Value

by Ying Feng, Di Tian, Chaoliang Wang, Yong Huang, Yang Luo, Xiuqiong Zhang and Lei Li

Metabolites 2025, 15(4), 257; https://doi.org/10.3390/metabo15040257 - 9 Apr 2025

Cited by 1 | Viewed by 825

Abstract

Dixu tea is one of the characteristic tea germplasm resources of southeastern Yunnan, and is also a precious wild tea germplasm resource. Background: In order to further develop Dixu tea products and improve their flavor, this article studies the effects of different [...] Read more.

Dixu tea is one of the characteristic tea germplasm resources of southeastern Yunnan, and is also a precious wild tea germplasm resource. Background: In order to further develop Dixu tea products and improve their flavor, this article studies the effects of different processing methods on the aroma quality of Dixu tea. Methods: A comprehensive analysis of the aroma quality of Diwei tea was conducted using HS-SPME combined with GC-MS and multivariate statistical analysis. A principal component analysis (PCA) was applied to process the detected volatile substances and an orthogonal partial least squares-discriminant analysis (OPLS-DA) model was established. We evaluated the contribution of major compounds in the tea aroma by calculating the odor activity value (OAV). Results: The results showed that a total of 67 compounds were identified. A total of 27 major aromatic volatile compounds (OAV > 1) were screened, and 17 key differential volatile compounds were identified in different tea samples, including octanoic acid, d-citrol, laurene, hexanal, citral, β-cyclic citral, trans-2-hexenal, γ-nonanolide, β-ionone, geranylacetone, 1,1,6-trimethyl-1,2-dihydronaphthalene, geraniol, methyl salicylate, linalool, nerolidol, and 7,11-dimethyl-3-methylene-1,6,10-dodecatriene. Combined with the OAV analysis, it is shown that a floral fragrance is a common feature of Guangnan Dixu tea varieties. In addition, white tea also has a fragrant aroma, while black tea, green tea, and bamboo tube tea are all accompanied by a fruity aroma. Conclusions: In summary, processing techniques regulate the aroma characteristics of various types of tea by changing the types and contents of volatile aroma compounds. This provides a theoretical basis for exploring and utilizing tea production resources in the future. Full article

(This article belongs to the Special Issue New Analytical Techniques and Applications of Metabolomics and Lipidomics)

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21 pages, 3432 KB

Open AccessArticle

Assessment of Biochemical Composition of Fruits of Hippophae rhamnoides (Elaeagnaceae juss.), Viburnum opulus (Viburnaceae raf.) and Lonicera caerulea subsp. altaica (Caprifoliaceae juss.)

by Tatiana Vdovina, Olga Lagus, Andrei Vinokurov, Zhanar Aimenova and Aidar Sumbembayev

Metabolites 2025, 15(4), 256; https://doi.org/10.3390/metabo15040256 - 9 Apr 2025

Cited by 1 | Viewed by 777

Abstract

Background/Objectives: This study explores the biochemical diversity of Hippophae rhamnoides, Viburnum opulus, and Lonicera caerulea subsp. altaica to identify genotypes rich in bioactive compounds for breeding nutritionally valuable cultivars. Methods: Selected forms and cultivars of each species were evaluated for key [...] Read more.

Background/Objectives: This study explores the biochemical diversity of Hippophae rhamnoides, Viburnum opulus, and Lonicera caerulea subsp. altaica to identify genotypes rich in bioactive compounds for breeding nutritionally valuable cultivars. Methods: Selected forms and cultivars of each species were evaluated for key biochemical traits. Analyses included quantification of vitamins (C, B9, B12), sugars, organic acids, carotenoids, and flavonoids using HPLC and TLC. Results: In H. rhamnoides, vitamin C content ranged widely, with ‘Pamyati Baytulina Sh-9-81’ reaching 156.0 mg/%, while ‘Shetlastinka No. 7’ showed the most favorable sugar-to-vitamin C ratio. ‘Krasnoplodnaya K-14-81’ had the highest carotenoids (55.3 mg/100 g), and ‘Dolgozhdannaya No. 5’ was notable for flavonoid richness. In V. opulus, considerable variation was observed in vitamin content, sugars, and dry matter; ‘Zhemchuzhnoe Ozhele’ and ‘Shtambovaya’ were rich in rutin and robinin. In L. caerulea subsp. altaica, forms No. 5, 7, and 9 stood out for vitamin C, sugar, and flavonoid content. Hyperoside, isorhamnetin, and myricetin were common, while kaempferol and hypolaetin were form-specific. Conclusions: H. rhamnoides demonstrated the highest variability in biochemical composition, while L. caerulea subsp. altaica showed a particularly rich flavonoid profile. These species offer valuable genetic resources for developing biofortified cultivars suited to both nutritional and adaptive breeding goals. Full article

(This article belongs to the Special Issue Metabolism of Bioactives and Natural Products)

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14 pages, 3359 KB

Open AccessArticle

Drug Repurposing for Non-Alcoholic Fatty Liver Disease by Analyzing Networks Among Drugs, Diseases, and Genes

by Md. Altaf-Ul-Amin, Ahmad Kamal Nasution, Rumman Mahfujul Islam, Pei Gao, Naoaki Ono and Shigehiko Kanaya

Metabolites 2025, 15(4), 255; https://doi.org/10.3390/metabo15040255 - 9 Apr 2025

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Abstract

Background/Objectives: Drug development for complex diseases such as NAFLD is often lengthy and expensive. Drug repurposing, the process of finding new therapeutic uses for existing drugs, presents a promising alternative to traditional approaches. This study aims to identify potential repurposed drugs for NAFLD [...] Read more.

Background/Objectives: Drug development for complex diseases such as NAFLD is often lengthy and expensive. Drug repurposing, the process of finding new therapeutic uses for existing drugs, presents a promising alternative to traditional approaches. This study aims to identify potential repurposed drugs for NAFLD by leveraging disease–disease relationships and drug–target data from the BioSNAP database. Methods: A bipartite network was constructed between drugs and their target genes, followed by the application of the BiClusO bi-clustering algorithm to identify high-density clusters. Clusters with significant associations with NAFLD risk genes were considered to predict potential drug candidates. Another set of candidates was determined based on disease similarity. Results: A novel ranking methodology was developed to evaluate and prioritize these candidates, supported by a comprehensive literature review of their effectiveness in NAFLD treatment. Conclusions: This research demonstrates the potential of drug repurposing to accelerate the development of therapies for NAFLD, offering valuable insights into novel treatment strategies for complex diseases. Full article

(This article belongs to the Special Issue Metabolomics and Computational Research on Drugs and Diseases)

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Open AccessEditor’s ChoiceArticle

Kinetics of Manganese Peroxidase Using Simple Phenolic Compounds as Substrates

by Madeline G. Gruenberg, Jonathan J. Halvorson and Michael A. Schmidt

Metabolites 2025, 15(4), 254; https://doi.org/10.3390/metabo15040254 - 9 Apr 2025

Cited by 1 | Viewed by 825

Abstract

Background/Objectives: Secondary metabolites encompass diverse groups of compounds; one such group is phenolics, which include small phenols up to larger polyphenols such as lignin and tannins. Smaller compounds such as phenolic acids can serve as substrates for soil microbes and enzymes. The specific [...] Read more.

Background/Objectives: Secondary metabolites encompass diverse groups of compounds; one such group is phenolics, which include small phenols up to larger polyphenols such as lignin and tannins. Smaller compounds such as phenolic acids can serve as substrates for soil microbes and enzymes. The specific interaction between plant secondary metabolites (PSMs) and soil enzymes determines whether the products of these reactions contribute to the formation of soil organic matter (SOM) or are degraded into small organic molecules. Methods: Here, we monitored the activity of a redox active soil enzyme, manganese peroxidase (MnP), with three small phenolic compounds. The compounds used in this study were pyrogallol, gallic acid, and benzoic acid. Results: Based on the kinetic parameters determined, pyrogallol and gallic acid are both substrates for MnP with different products and kinetics. Conclusion: Pyrogallol reacts faster and produces a more stable quinone than gallic acid. Benzoic acid is not a substrate for MnP. Full article

(This article belongs to the Special Issue Advances in Secondary Metabolites: Phytochemical Analysis and Bioactivity Assays)

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Metabolites, Volume 15, Issue 4 (April 2025) – 71 articles

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