Metabolites

23 pages, 5648 KB

Open AccessArticle

Application of Plasma Metabolomic Biomarker Panels in Early Diagnosis and Disease Staging of Alzheimer’s Disease

by Jiao Chen, Xuhui Chen, Ting Chen and Jun Hu

Metabolites 2026, 16(6), 377; https://doi.org/10.3390/metabo16060377 (registering DOI) - 30 May 2026

Background: Previous metabolomics studies on Alzheimer’s disease (AD) have predominantly focused on Western populations, leaving Chinese cohorts and disease stage-specific data largely unexplored. Objectives: To characterize metabolic alterations across different clinical stages of AD in a Chinese population and identify early [...] Read more.

Background: Previous metabolomics studies on Alzheimer’s disease (AD) have predominantly focused on Western populations, leaving Chinese cohorts and disease stage-specific data largely unexplored. Objectives: To characterize metabolic alterations across different clinical stages of AD in a Chinese population and identify early diagnostic biomarkers. Methods: We enrolled 172 participants, including patients with AD, mild cognitive impairment (MCI), subjective cognitive decline (SCD), vascular cognitive impairment (VCI), and healthy controls (HC). Untargeted metabolomics (LC-MS and GC-MS) was performed on plasma samples, integrated with Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) assessments. Data were analyzed using multivariate statistics, pathway enrichment, and ROC modeling. Results: Distinct metabolic profiles emerged across disease stages, with phospholipids, ceramides, and glucose metabolites prominently enriched in glycerophospholipid, sphingolipid, and glucose pathways. A 16-metabolite panel achieved robust discrimination between AD+MCI and HC+VCI+SCD (AUC = 0.804). Specific metabolites, including ceramides, dihydroceramides, phosphatidylinositol, phosphatidylcholine, and glycodeoxycholic acid, correlated significantly with cognitive function and disease progression. Conclusions: This study reveals stage-specific metabolic dysregulation in Chinese AD patients and identifies potential plasma biomarkers for early detection, offering insights into AD pathogenesis. Trial registration number ChiCTR2400092653. Full article

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

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18 pages, 13163 KB

Open AccessArticle

Dendrobium huoshanense Ameliorates Sleep Deprivation-Induced Ileal Mucus Barrier Dysfunction by Regulating Steroid Hormone Biosynthesis and the HPA Axis in Rats

by Xue Luo, Shuxiang Jin, Yue Fang, Qun Zhao, Huiqun Xie and Lan Han

Metabolites 2026, 16(6), 376; https://doi.org/10.3390/metabo16060376 (registering DOI) - 30 May 2026

Abstract

Background/Objectives: Sleep deprivation (SD) induces the accumulation of reactive oxygen species (ROS) in the intestine, causing inflammation in the intestine, thereby damaging the intestinal epithelial barrier function. As a traditional Chinese medicine, Dendrobium huoshanense (DHS) modulates intestinal flora, maintains the intestinal mucosal [...] Read more.

Background/Objectives: Sleep deprivation (SD) induces the accumulation of reactive oxygen species (ROS) in the intestine, causing inflammation in the intestine, thereby damaging the intestinal epithelial barrier function. As a traditional Chinese medicine, Dendrobium huoshanense (DHS) modulates intestinal flora, maintains the intestinal mucosal barrier, and promotes gastrointestinal motility and digestive secretion. However, the role and mechanism of DHS in improving SD-induced intestinal injury have not been fully studied. Methods: The SD model was established by subjecting rats to complete SD using a specialised SD instrument. Hematoxylin and eosin (HE) staining was performed to evaluate pathological injury in ileal tissues. Enzyme-linked immunosorbent assay (ELISA) and biochemical methods were used to quantify the main inflammatory cytokines, oxidative stress markers, and hypothalamic–pituitary–adrenal (HPA) axis activity. The expression levels of E-cadherin and Occludin proteins in the ileum tissue were analyzed by Western blotting. Additionally, the pH value of ileal mucus, unit secretion, water content, and dry matter weight were measured. Differential metabolites in rat ileum mucus were profiled using ultra-high-performance liquid chromatography–quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS). Results: DHS alleviated the pathological injury of the ileum induced by SD. DHS reduced the levels of serotonin (5-HT), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), while increasing interleukin-10 (IL-10) levels, thereby attenuating systemic inflammatory responses. Furthermore, DHS decreased malondialdehyde (MDA) content and elevated glutathione (GSH) and superoxide dismutase (SOD) levels in ileal tissues. DHS also upregulated the protein expression of E-cadherin and Occludin in intestinal tissues. In addition, DHS decreased the pH of ileal mucus, promoted intestinal mucus secretion, and increased dry matter content, facilitating the restoration of the mucus barrier. DHS may alleviate SD-induced ileal injury by modulating steroid hormone biosynthesis. DHS decreased the levels of adrenocorticotropic hormone (ACTH), cortisol (CORT), and corticotropin-releasing hormone (CRH), indicating that DHS suppresses the abnormal activation of the hypothalamic–pituitary–adrenal (HPA) axis. Conclusions: In this study, a comprehensive multi-index evaluation showed that DHS could significantly improve the ileal injury caused by SD in rats. The mechanism involved regulating the balance of serum neurotransmitters and inflammatory factors, reducing oxidative stress in tissues, and improving the physicochemical properties of intestinal mucus. Metabolomic analysis further revealed that these protective effects may be mediated via the regulation of steroid hormone biosynthesis pathways and are associated with the inhibition of abnormal HPA axis activation. Full article

(This article belongs to the Section Pharmacology and Drug Metabolism)

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20 pages, 3625 KB

Open AccessArticle

Transcriptome and Metabolome Analyses Reveal the Molecular Relationship Between Dietary Crude Protein Level and Liver Metabolism in Fattening Hu Sheep

by Patiguli Abudukeyimu, Fengmei Xie, Yifan Hu, Haiying He, Cheng Hou, Yiming Sulaiman, Huiguo Yang and Gao Gong

Metabolites 2026, 16(6), 375; https://doi.org/10.3390/metabo16060375 - 29 May 2026

Abstract

Background: Dietary crude protein (CP) acts as a key nutritional factor that affects the growth performance and liver metabolism of fattening Hu sheep, with metabolizable energy (ME) representing a major confounding factor in CP-related responses. To isolate the specific effects of CP on [...] Read more.

Background: Dietary crude protein (CP) acts as a key nutritional factor that affects the growth performance and liver metabolism of fattening Hu sheep, with metabolizable energy (ME) representing a major confounding factor in CP-related responses. To isolate the specific effects of CP on liver metabolism and minimize energy–protein interactions, we standardized dietary ME at 9.4 MJ/kg dry matter. Methods: We then established three isoenergetic CP concentrations: 11.07%, 13.07%, and 15.11%. A total of ninety 4-month-old male Hu sheep (with an initial body weight of 27.09 ± 1.83 kg) were allocated at random to three dietary treatment groups, each containing 30 animals distributed across three replicate pens, and fed pelleted total mixed rations (PTMRs) for 75 days under pen conditions in southern Xinjiang. Exploratory combined transcriptomic and metabolomic profiling of liver tissue was conducted to characterize how graded CP levels modulate growth traits and hepatic metabolic pathways, thereby identifying the appropriate dietary CP level for efficient and sustainable fattening of Hu sheep in this region. Result: Results indicated that animals fed the 15.11% CP diet showed a significantly higher average daily gain (ADG) and cumulative weight gain compared with those fed 11.07% or 13.07% CP (p < 0.05). Exploratory multi-omics enrichment analysis demonstrated significant overrepresentation (p < 0.05) of differentially expressed genes and metabolites in key biological pathways—including bile secretion, AMP-activated protein kinase (AMPK) signaling, steroid biosynthesis, peroxisome proliferator-activated receptor (PPAR) signaling, and oxidative stress-related and oxidative phosphorylation. Correlation analyses characterized two hub genes—ATP6AP1 and LOC101119853—that were significantly and negatively correlated with ADG (p < 0.05), whereas two metabolites—calcidiol and ADP—displayed significant positive relationships with ADG (p < 0.05). Pathway-level comparisons further demonstrated that both the 13.07% vs. 15.11% CP and the 11.07% vs. 15.11% CP contrasts yielded significant enrichment in AMPK signaling and steroid biosynthesis. Notably, calcidiol and ADP both declined numerically in the 13.07% vs. 15.11% CP comparison, whereas only ADP reached statistical significance in the 11.07% vs. 15.11% CP contrast. Conclusions: Collectively, under an ME level of 9.4 MJ/kg, a dietary CP concentration of 15.11% contributes to favorable growth of 4-month-old fattening Hu sheep housed in pens in southern Xinjiang. This level is associated with improved growth performance and coordinated regulation of central hepatic regulatory networks—particularly those involved in energy homeostasis and steroidogenesis—thereby supporting metabolic stability without compromising animal health or production efficiency. These findings provide a preliminary molecular basis for precision protein nutrition in Hu sheep feeding systems and offer translational insights for optimizing ruminant nutrition under arid and semi-arid environmental constraints. All correlations indicate potential associations, not causal relationships. Full article

(This article belongs to the Special Issue Metabolic Responses to Feed and Nutrition in Livestock)

17 pages, 4034 KB

Open AccessArticle

Transcriptomic and Metabolomic Insights into the Enhanced Quality of Anoectochilus roxburghii Seedlings in Sugar-Free Versus Conventional Tissue Culture Systems

by Xiangtao Chen, Fangfang Chen, Chuanzhi Kang, Tongwei Lin, Hongyang Wang, Yiheng Wang, Dehua Wu, Wanying Duan, Zekun Zhang and Chengcai Zhang

Metabolites 2026, 16(6), 374; https://doi.org/10.3390/metabo16060374 - 29 May 2026

Abstract

Background/Objective: Anoectochilus roxburghii, a high-value medicinal orchid, faces significant challenges in quality standardization during large-scale tissue culture due to a lack of understanding of the underlying molecular mechanisms. This study aimed to compare “Jianlan No.2” plantlets cultured under a conventional tissue [...] Read more.

Background/Objective: Anoectochilus roxburghii, a high-value medicinal orchid, faces significant challenges in quality standardization during large-scale tissue culture due to a lack of understanding of the underlying molecular mechanisms. This study aimed to compare “Jianlan No.2” plantlets cultured under a conventional tissue culture system (CK) and a sugar-free tissue culture system (TD), to elucidate the phenotypic and molecular basis for quality improvement. Methods: A systematic comparison was conducted. Phenotypic traits of plantlets from both systems were measured. Integrated transcriptomic (RNA sequencing) and untargeted metabolomic analyses were employed to identify the molecular differences at the gene expression and metabolite accumulation levels. Results: TD-grown seedlings exhibited significantly superior growth characteristics, including greater plant height, higher rooting rate, and improved transplant survival. Transcriptomic analysis identified 416 differentially expressed genes (DEGs) (44 upregulated, 372 downregulated in TD), which were significantly enriched in pathways related to cell wall organization, apoplast, and photosynthesis. Sixteen key genes were pinpointed as closely associated with seedling growth and metabolic regulation. Metabolomic profiling revealed 502 differentially accumulated metabolites (DAMs), with significant perturbations primarily in phenylpropanoid biosynthesis and terpenoid metabolism. Conclusions: The sugar-free tissue culture system enhances A. roxburghii seedling quality by coordinately modulating photosynthetic capacity, carbon metabolism, and the biosynthesis of key secondary metabolites. These findings provide a crucial molecular foundation for optimizing tissue culture protocols and advancing the standardized, high-quality cultivation of this valuable medicinal plant. Full article

(This article belongs to the Section Plant Metabolism)

11 pages, 1034 KB

Open AccessArticle

Humanin Restores Metabolic Hormone Homeostasis of Leptin, Ghrelin, Irisin and Asprosin in Streptozotocin-Induced Diabetic Mice

by Ferah Bulut, Muhammed Adam, Aslısah Ozgen and Mete Ozcan

Metabolites 2026, 16(6), 373; https://doi.org/10.3390/metabo16060373 - 29 May 2026

Abstract

Objective: Diabetes mellitus is closely associated with mitochondrial dysfunction, which disrupts cellular energy metabolism and perturbs hormonal homeostasis. Humanin (HN), a 24-amino acid peptide encoded within the mitochondrial genome, has attracted considerable attention due to its cytoprotective and metabolic regulatory properties. Despite [...] Read more.

Objective: Diabetes mellitus is closely associated with mitochondrial dysfunction, which disrupts cellular energy metabolism and perturbs hormonal homeostasis. Humanin (HN), a 24-amino acid peptide encoded within the mitochondrial genome, has attracted considerable attention due to its cytoprotective and metabolic regulatory properties. Despite its recognized biological potential, the role of HN in coordinating key metabolic hormone networks under diabetic conditions remains poorly understood. This study aimed to investigate the integrative effects of repeated humanin administration on key metabolic hormones leptin, ghrelin, irisin, and asprosin and its potential role in restoring hormonal homeostasis in a streptozotocin (STZ)-induced diabetic mouse model. Materials and Methods: Forty male mice were randomly assigned to four groups (n = 10 for each group): control, HN (4 mg/kg/day), STZ (150 mg/kg), and STZ + HN. Humanin was administered intraperitoneally for 15 consecutive days. Serum levels of leptin, asprosin, irisin, and ghrelin were measured using enzyme-linked immunosorbent assay (ELISA), and data were analyzed using one-way ANOVA followed by Tukey’s post hoc test. Results: STZ-induced diabetes markedly disrupted metabolic hormone balance, as indicated by decreased leptin and irisin levels and increased asprosin concentrations. Repeated HN treatment effectively restored leptin levels and suppressed asprosin concentrations, while irisin levels showed a relative increase compared to the STZ animals. In addition, ghrelin levels were significantly elevated in HN-treated diabetic mice compared to untreated STZ animals. Conclusions: These findings indicate that humanin exerts an integrative, multi-hormonal regulatory effect, supporting the restoration of metabolic and endocrine homeostasis under diabetic conditions. Full article

(This article belongs to the Section Pharmacology and Drug Metabolism)

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13 pages, 1189 KB

Open AccessArticle

Screening and Stratification Utility of GDF-15 and FGF-21 in Individuals Evaluated for Suspected Mitochondrial Disease: A Malaysian Cohort Study

by Affandi Omar, Dyg Pertiwi Abg Kamaludin, Wan Ahmad Syazani Mohamed, Fatimah Diana Amin Nordin, Rosnani Mohamed, Badrul Hisyam Razali, Imilia Ismail, Ngu Lock Hock and Julaina Abdul Jalil

Metabolites 2026, 16(6), 372; https://doi.org/10.3390/metabo16060372 - 29 May 2026

Abstract

Background/Objectives: Early detection of mitochondrial disorders remains challenging due to phenotypic heterogeneity and limited access to definitive molecular diagnostics. Circulating biomarkers such as growth differentiation factor-15 (GDF-15) and fibroblast growth factor-21 (FGF-21) have emerged as potential adjunct indicators. This study evaluated the [...] Read more.

Background/Objectives: Early detection of mitochondrial disorders remains challenging due to phenotypic heterogeneity and limited access to definitive molecular diagnostics. Circulating biomarkers such as growth differentiation factor-15 (GDF-15) and fibroblast growth factor-21 (FGF-21) have emerged as potential adjunct indicators. This study evaluated the screening and stratification utility of GDF-15 and FGF-21 in individuals assessed for suspected mitochondrial disease. Methods: Archived biological specimens collected between 2016 and 2017 were analysed from 221 individuals stratified into clinically high-risk, screen-positive non-high-risk, post-mortem unexplained death and healthy controls groups. Plasma and fibroblast lysate concentrations of GDF-15 and FGF-21 were quantified using enzyme-linked immunosorbent assays. Biomarker performance was assessed using receiver operating characteristic (ROC) analysis, comparative group analysis and correlation testing across clinically defined referral groups. Results: Both biomarkers were significantly elevated in clinically high-risk and screen-positive individuals compared with controls. GDF-15 demonstrated better discriminatory performance than FGF-21, with an area under the curve (AUC) of 0.7187 ± 0.0556 versus 0.6301 ± 0.0603. At a threshold of 300 pg/mL, GDF-15 demonstrated high sensitivity with moderate specificity for differentiation between clinically defined high-risk individuals and controls. Correlation analysis showed weak associations between GDF-15 and lactate and ammonia, while FGF-21 correlated modestly with glucose and alkaline phosphatase. A moderate positive correlation was observed between GDF-15 and FGF-21 across the overall cohort. Conclusions: GDF-15 and, to a lesser extent, FGF-21 may support early screening and stratification of individuals evaluated for suspected mitochondrial disease and assist in prioritising cases for further diagnostic evaluation. Full article

(This article belongs to the Special Issue The Future Perspective on Screening and Diagnosis of Inborn Errors of Metabolism)

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12 pages, 2940 KB

Open AccessSystematic Review

Probiotics After Metabolic and Bariatric Surgery: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

by Mohammed Y. Ezzi

Metabolites 2026, 16(6), 371; https://doi.org/10.3390/metabo16060371 - 29 May 2026

Abstract

Background/Objectives: Patients undergoing metabolic and bariatric surgery (MBS) are at risk of micronutrient deficiencies and gut dysbiosis. Probiotics (such as Lactobacillus, Bifidobacterium) have been proposed as adjunct therapy to optimize postoperative outcomes. This review aimed to evaluate the effect of postoperative probiotic supplementation [...] Read more.

Background/Objectives: Patients undergoing metabolic and bariatric surgery (MBS) are at risk of micronutrient deficiencies and gut dysbiosis. Probiotics (such as Lactobacillus, Bifidobacterium) have been proposed as adjunct therapy to optimize postoperative outcomes. This review aimed to evaluate the effect of postoperative probiotic supplementation on anthropometric, metabolic, inflammatory, and micronutrient outcomes in MBS patients. Methods: Nine electronic databases were systematically searched, including PubMed, Web of Science, Cochrane Library, Google Scholar, Popline, Global Health Library, Virtual Health Library, New York Academy of Medicine, and OpenGrey, from inception through October 2024. Only randomized controlled trials (RCTs) were included. The Cochrane Collaboration risk-off-bias tool was used for quality assessment. Meta-analyses were performed using Comprehensive Meta-Analysis software version 2. Fixed-effects or random-effects models based on heterogeneity (I² threshold: 50%) were applied. Mean differences (MD) and 95% confidence intervals (CI) were calculated for all continuous variables. Results: Thirteen RCTs encompassing 666 patients (probiotics group: n = 344; control group: n = 322) were included. Incomplete outcome data represented the most prevalent high-risk domain (23%). Probiotic supplementation was associated with significantly improved serum vitamin D (MD: 25.32 nmol/L, 95% CI: 6.96–43.67, p = 0.007) and vitamin B12 levels (MD: 39.36 pg/mL, 95% CI: 1.88–76.84, p = 0.04). No statistically significant differences were observed in anthropometric outcomes (%EWL, BMI, weight, or waist circumference), lipid profile, glycemic indices, or inflammatory markers (TNF-α, IL-6, CRP). Conclusions: Postoperative probiotic supplementation may significantly improve vitamin D and B12 levels in patients undergoing MBS, suggesting a supportive role in mitigating micronutrient deficiencies. However, these findings should be interpreted with caution due to substantial heterogeneity across studies. Probiotics did not significantly affect weight loss, metabolic parameters, or inflammatory markers. Clinicians may consider probiotics as an adjunct strategy to support micronutrient status in at-risk postoperative patients. Large-scale, strain-specific trials incorporating standardized dietary control and microbiome profiling are warranted. Full article

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

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27 pages, 2091 KB

Open AccessArticle

Acute Capillary Plasma Biomarker, Neuromuscular, and Perceptual Responses to Standardised Soccer Match Play in Elite Players: A Descriptive Study of Asynchronous Multi-Domain Recovery

by Lun Du, Jie Xiao, Chunpeng Li, Shuning Liu, Yaji Jiang, Yue Dou, Haotian Zhao, Wen Zhong, Kai Zhao and Chang Liu

Metabolites 2026, 16(6), 370; https://doi.org/10.3390/metabo16060370 - 29 May 2026

Abstract

Background: Soccer match play induces substantial mechanical, metabolic, inflammatory, and neuromuscular stress, yet post-match monitoring in applied settings often relies on isolated markers, venous sampling, or limited time points. This observational repeated-measures study aimed to describe whether capillary-derived biomarkers, neuromuscular performance, and perceptual [...] Read more.

Background: Soccer match play induces substantial mechanical, metabolic, inflammatory, and neuromuscular stress, yet post-match monitoring in applied settings often relies on isolated markers, venous sampling, or limited time points. This observational repeated-measures study aimed to describe whether capillary-derived biomarkers, neuromuscular performance, and perceptual measures showed asynchronous recovery during the first 48 h after a standardised soccer match in elite players. Methods: Twenty-two elite male outfield soccer players completed a standardised 90 min match. Capillary blood biomarkers, countermovement jump (CMJ), 20 m sprint performance, maximal voluntary contraction (MVC), and delayed onset muscle soreness (DOMS) were assessed before the match, immediately post-match, and at 24 and 48 h post-match. Time effects were analysed using repeated-measures mixed-effects models, and associations between biochemical and functional responses were examined descriptively. Results: Match play induced clear but domain-specific disturbances. IL-6 and cortisol rose rapidly immediately post-match, whereas hsCRP, CK, LDH, myoglobin, and DOMS showed delayed peaks during early recovery. CK, LDH, myoglobin, and soreness remained above baseline at 48 h. CMJ and sprint performance were impaired after the match but largely recovered by 48 h, whereas MVC showed its greatest decrement at 24 h. Exploratory associations indicated that larger muscle damage responses tended to co-occur with greater strength and jump decrements and higher soreness, but these analyses were not causal. Conclusions: Recovery after a standardised elite soccer match was multidimensional and non-synchronous across physiological, neuromuscular, and perceptual domains. A capillary-based, multi-domain assessment strategy may provide a feasible descriptive perspective for field-based observation of post-match fatigue. Full article

(This article belongs to the Special Issue Metabolic Adaptations to Exercise: Mechanisms, Modulators, and Health Impacts)

14 pages, 1192 KB

Open AccessArticle

Metabolomics Analysis of Aged Garlic Extract for the Identification of Novel Compounds

by Masato Nakamoto, Tsubasa Nishimura, Masahiro Ohtani and Toshiaki Matsutomo

Metabolites 2026, 16(6), 369; https://doi.org/10.3390/metabo16060369 - 29 May 2026

Abstract

Background/Objectives: Aged garlic extract (AGE), produced by aging raw garlic in an aqueous ethanol solution for over 10 months, exhibits multiple pharmacological activities, including antioxidant and anti-inflammatory effects. However, because AGE has a complex composition and many constituents remain insufficiently characterized, the chemical [...] Read more.

Background/Objectives: Aged garlic extract (AGE), produced by aging raw garlic in an aqueous ethanol solution for over 10 months, exhibits multiple pharmacological activities, including antioxidant and anti-inflammatory effects. However, because AGE has a complex composition and many constituents remain insufficiently characterized, the chemical basis underlying its broad activities is not fully understood. This study aimed to investigate these previously overlooked compounds in AGE to better understand its chemical complexity. Methods: AGE was fractionated using bioactivity assays to select target fractions for detailed chemical analysis. Metabolomics profiling was performed using liquid chromatography-mass spectrometry (LC-MS). Compounds were tentatively identified through database matching, fragmentation pattern analysis, and comparison with authentic standards. Results: Thirteen compounds not previously reported in AGE were tentatively identified. Citric acid was present at high levels. Citrulline and galacturonic acid were detected in AGE but not in raw garlic, suggesting that they are formed during the aging process. Trigonelline was detected and tentatively identified in the AGE sample used in this study. The remaining compounds included choline, 5-oxoproline, malic acid, gluconic acid, adenine, succinic acid, mucic acid, pipecolinic acid, and caffeic acid. These compounds may contribute to the diverse biological activities of AGE. Conclusions: These findings expand the chemical characterization of AGE and provide a foundation for understanding its broad pharmacological activities. They may also support future studies on functional food development and the health benefits of AGE. Full article

(This article belongs to the Section Food Metabolomics)

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19 pages, 1048 KB

Open AccessArticle

Integrating Sensory Evaluation and Metabolomics to Reveal the Metabolic Basis of Taste and Flesh Color in Melon (Cucumis melo L.)

by Yu Zhou, Binbin Li, Weizhong He, Fengjuan Liu, Yingying Fan, Jiangtao Du, Xing Cui, Weijia Lian, Qi Shen, Yan Wang, Zhongkai Zhao and Cheng Wang

Metabolites 2026, 16(6), 368; https://doi.org/10.3390/metabo16060368 - 28 May 2026

Abstract

Background: The sensory quality of melon (Cucumis melo L.) is determined by the complex interplay of metabolites within the fruit. However, the underlying metabolic mechanisms based on consumer sensory experience remain underexplored. Methods: Sensory evaluation was conducted on twelve melon [...] Read more.

Background: The sensory quality of melon (Cucumis melo L.) is determined by the complex interplay of metabolites within the fruit. However, the underlying metabolic mechanisms based on consumer sensory experience remain underexplored. Methods: Sensory evaluation was conducted on twelve melon cultivars, recording flesh color and quantitatively scoring acidity, sweetness, firmness, and aroma intensity. Based on the sensory results, eight cultivars were selected to establish two contrasting groups: sweet-type vs. acidic-type and orange-fleshed vs. green-fleshed. Untargeted metabolomics (UPLC-QTOF-MS) was then performed to analyze the samples, and differential metabolites were screened using OPLS-DA combined with univariate analysis. Results: Pathway enrichment analysis revealed that the key distinction between sweet and acidic taste profiles was associated with the specific accumulation of citric acid within the tricarboxylic acid (TCA) cycle in the acidic-type group. Regarding flesh color, the orange-fleshed group was enriched with carotenoid derivatives like β-citraurinene and the oxidized tocopherol product α-tocopherolquinone, whereas the green-fleshed group mainly accumulated phytol, a chlorophyll degradation product, along with more abundant terpenoids. Conclusions: By integrating sensory phenotyping with metabolomic analysis, this study identified key differential metabolites and candidate pathways associated with taste and color in melon, providing metabolic insights and data resources for quality evaluation and regulation. Full article

(This article belongs to the Section Food Metabolomics)

15 pages, 2386 KB

Open AccessArticle

Enhanced Synthesis of Polyphenols and Terpenes by UV-A Irradiation in Artemisia argyi Leaves

by Shaozheng Li, Zikun Zhang, Lanqi Yang, Heyang Wang, Haike Gu and Junfeng Liu

Metabolites 2026, 16(6), 367; https://doi.org/10.3390/metabo16060367 - 28 May 2026

Abstract

Background: Secondary metabolites not only constitute the material basis for plant responses to multiple environmental stresses but are also extensively utilized in the pharmaceutical industry. Methods: In the present work, we investigated the metabolic response of Artemisia argyi to UV-A irradiation through transcriptomic [...] Read more.

Background: Secondary metabolites not only constitute the material basis for plant responses to multiple environmental stresses but are also extensively utilized in the pharmaceutical industry. Methods: In the present work, we investigated the metabolic response of Artemisia argyi to UV-A irradiation through transcriptomic and metabolomic analyses. Results: After 16 h of UV-A treatment with an intensity of 2.5 μmol m⁻² s⁻¹ and 8 h of dark cultivation, a total of 4343 differentially expressed genes were identified, most of which were associated with fatty acid metabolism, biosynthesis of secondary metabolites, and ribosome. Of the 1959 metabolites detected in samples exposed to a 16/8 h UV-A/dark cycle for 6 days, a total of 223 differentially accumulated metabolites were identified and classified into 12 subgroups, with phenolic acids and flavonoids representing the largest subgroups. Comprehensive analyses indicated that polyphenols and terpenes play critical roles in the adaptation of A. argyi to UV-A irradiation. The phytohormone methyl jasmonate was identified as a key regulator of the enhanced synthesis of these secondary metabolites, through activation of transcription factors from the MYB and bHLH families. Conclusions: This study deepens our understanding of secondary metabolic regulation in response to UV-A stress and provides a simple and reliable method to promote the accumulation of specific secondary metabolites in Artemisia species. Full article

(This article belongs to the Section Plant Metabolism)

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41 pages, 3535 KB

Open AccessReview

Bile Acids and the Gut–X Axis: TCM-Mediated Systemic Protection and Therapeutic Opportunities for Multi-Organ Diseases

by Jialu He, Linjie Qin and Xian Sun

Metabolites 2026, 16(6), 366; https://doi.org/10.3390/metabo16060366 - 28 May 2026

Abstract

The gut microbiota regulates host physiology and drives extraintestinal diseases through the gut–X axis. Bile acids (BAs) function as key mediators of this interorgan crosstalk by activating nuclear and membrane receptors (FXR, TGR5, PXR, VDR). Traditional Chinese Medicine (TCM) demonstrates efficacy across multiple [...] Read more.

The gut microbiota regulates host physiology and drives extraintestinal diseases through the gut–X axis. Bile acids (BAs) function as key mediators of this interorgan crosstalk by activating nuclear and membrane receptors (FXR, TGR5, PXR, VDR). Traditional Chinese Medicine (TCM) demonstrates efficacy across multiple organ systems through multi-component formulations. This narrative review synthesizes evidence from preclinical and clinical studies supporting that TCM exerts systemic protection via strategic modulation of the microbiota–BA–host receptor axis, which functions as a core regulatory circuit within a larger network of microbial metabolites. Mechanistically, representative TCM formulas remodel gut microbial ecology and reinforce intestinal barrier integrity, leading to optimized BA profiles. These favorable BA signatures engage tissue-specific receptor signaling to resolve inflammation, mitigate fibrosis, and restore metabolic homeostasis across the gut–heart, gut–kidney, gut–liver, gut–bone, and gut–endocrine axes. Support for this causal relationship is provided by microbiota depletion, fecal transplantation, and multi-omics studies, collectively suggesting that TCM’s benefits are microbiota-dependent and at least partially BA-mediated. Moreover, context-dependent modulation of BA receptors, such as differential regulation of FXR, enables TCM to achieve pathology-specific outcomes. Current evidence is derived predominantly from preclinical models, and clinical data remain lacking. Nonetheless, the microbiota–BA–organ axis thus provides a potential framework for understanding TCM’s systemic actions and establishes a molecular basis for developing microbiome-informed precision therapeutics. Future directions include patient stratification and precision intervention design inspired by TCM’s ecological modulation strategies. Full article

(This article belongs to the Section Pharmacology and Drug Metabolism)

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19 pages, 4723 KB

Open AccessArticle

Untargeted Metabolomics and Metabolite–Gene Network Analysis Predict NF-κB Inhibition in Artemisian B-Treated Triple-Negative Breast Cancer Cells

by Shujun Shan, Ziyun Hu, Guimin Xue, Ping Yao, Peipei Du, Ruixi Gan and Junsong Wang

Metabolites 2026, 16(6), 365; https://doi.org/10.3390/metabo16060365 - 28 May 2026

Abstract

Background: Triple-negative breast cancer (TNBC) remains a formidable clinical challenge due to the scarcity of targeted therapies and profound metabolic heterogeneity. Although Artemisian B, a dimeric sesquiterpene lactone derived from Artemisia argyi, exhibits potent antiproliferative activity, its comprehensive metabolic footprint and the translation [...] Read more.

Background: Triple-negative breast cancer (TNBC) remains a formidable clinical challenge due to the scarcity of targeted therapies and profound metabolic heterogeneity. Although Artemisian B, a dimeric sesquiterpene lactone derived from Artemisia argyi, exhibits potent antiproliferative activity, its comprehensive metabolic footprint and the translation of these perturbations into downstream signaling regulation remain poorly characterized. Methods: To address this gap, we employed an integrative analytical framework combining untargeted metabolomics, topology-guided metabolite–gene network mapping, and parallel experimental validation in MDA-MB-231 cells. This workflow systematically profiled cellular phenotypes, global metabolic reprogramming, and key signaling nodes, enabling the prioritization of high-confidence mechanistic links between metabolic alterations and signal transduction. Results: Artemisian B dose-dependently suppressed TNBC cell viability (IC₅₀ = 12.12 μM) and triggered mitochondrial apoptosis, characterized by Bax upregulation, Bcl-2 downregulation, and caspase-9/3 activation. Untargeted metabolomics identified 129 significantly altered metabolites, reflecting extensive dysregulation across lipid peroxidation, bioenergetics, and nucleotide metabolism. Topological analysis of the metabolite–gene network identified the NF-κB pathway as a highly interconnected hub within this perturbed landscape. Parallel experimental validation corroborated this prediction, demonstrating that Artemisian B consistently suppressed the phosphorylation of IKKα/β, IκBα, and p65, while markedly attenuating p65 nuclear translocation. Conclusions: Artemisian B induces TNBC apoptosis through extensive metabolic reprogramming coupled with concurrent inhibition of NF-κB signaling. By seamlessly integrating untargeted metabolomics with network topology, our framework not only successfully bridges metabolic perturbations with signaling outcomes but also establishes a versatile, dual-perspective strategy applicable to both biochemical reaction networks and signal transduction pathways. This approach provides a robust predictive paradigm for decoding the multi-target pharmacological mechanisms of natural products. Full article

(This article belongs to the Section Plant Metabolism)

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32 pages, 759 KB

Open AccessReview

Lean Mass and Musculoskeletal Preservation in GLP-1-Based Obesity Treatment: Nutrition, Exercise, Supplementation, and Monitoring Strategies

by Roko Šantić, Lovre Martinović, Nikola Pavlović, Doris Rušić, Marko Kumrić, Dinko Martinović, Tina Tičinović Kurir and Joško Božić

Metabolites 2026, 16(6), 364; https://doi.org/10.3390/metabo16060364 - 27 May 2026

Abstract

Background/Objectives: GLP-1-based obesity pharmacotherapy has shifted clinical attention from the magnitude of weight loss to the quality of weight loss. This review evaluates whether body composition changes during treatment with GLP-1-based agents represent clinically meaningful muscle loss and identifies nutrition, supplementation, exercise, and [...] Read more.

Background/Objectives: GLP-1-based obesity pharmacotherapy has shifted clinical attention from the magnitude of weight loss to the quality of weight loss. This review evaluates whether body composition changes during treatment with GLP-1-based agents represent clinically meaningful muscle loss and identifies nutrition, supplementation, exercise, and monitoring strategies that may help preserve lean mass, function, bone health, and nutritional adequacy. Methods: A comprehensive narrative review was performed using focused searches of PubMed, publisher-hosted journal platforms, and reference lists of key primary studies and recent evidence syntheses through March and May 2026. Evidence was organized around body composition, muscle quality and function, dietary protein and micronutrient adequacy, exercise, supplementation, bioelectrical impedance analysis, imaging, and emerging biomarkers. Results: Semaglutide and tirzepatide preferentially reduce fat mass, including visceral and ectopic adiposity, while producing smaller but consistent reductions in lean mass or lean soft tissue. However, DXA-derived lean mass and BIA-derived fat-free mass are not equivalent to skeletal muscle, and lean tissue loss does not necessarily indicate impaired strength or physical performance. The most defensible supportive care model combines food-first nutritional counseling, adequate protein intake, structured resistance exercise, management of gastrointestinal adverse effects, and risk-based monitoring of micronutrient inadequacy. Protein supplementation and nutritionally complete meal replacements may be useful when intake is insufficient, whereas creatine, essential amino acids or leucine, beta-hydroxy-beta-methylbutyrate, fiber, probiotics, omega-3 fatty acids, and multi-ingredient products remain adjunctive options supported mainly by indirect or phenotype-specific evidence. Conclusions: Future GLP-1 trials and clinical care should move beyond body weight and total lean mass toward integrated assessment of muscle quantity, muscle quality, function, bone, and nutritional adequacy, and standardized BIA-based clinical monitoring where advanced imaging is not feasible. Full article

(This article belongs to the Special Issue Nutrition and Dietary Supplementation in the Context of Health, Disease, and Physical Performance)

14 pages, 1796 KB

Open AccessArticle

Plasma Lipidomic Remodeling in Behçet’s Disease Reveals Alterations Associated with Vascular Involvement

by Engin Koçak, Çiğdem Yücel, Sevilay Erdoğan Kablan, Erdim Sertoğlu, Taner Özgürtaş, Emirhan Nemutlu and Ahmet Omma

Metabolites 2026, 16(6), 363; https://doi.org/10.3390/metabo16060363 - 27 May 2026

Abstract

Background/Objectives: Behçet’s disease (BD) is a chronic multisystem inflammatory disorder in which vascular involvement represents a major cause of morbidity and mortality. However, the molecular mechanisms underlying vascular involvement remain poorly understood. Lipidomics offers a powerful approach to investigate disease-associated metabolic alterations [...] Read more.

Background/Objectives: Behçet’s disease (BD) is a chronic multisystem inflammatory disorder in which vascular involvement represents a major cause of morbidity and mortality. However, the molecular mechanisms underlying vascular involvement remain poorly understood. Lipidomics offers a powerful approach to investigate disease-associated metabolic alterations at the lipid level. Methods: Plasma lipidomic profiles were analyzed in 48 patients with BD, including 18 with vascular involvement, and 40 age- and sex-matched healthy controls. Lipids were extracted using a chloroform–methanol-based protocol and analyzed by LC-qTOF-MS. Data processing and lipid annotation were performed using MS-DIAL. Multivariate and univariate statistical analyses, together with class-based KEGG pathway mapping, were applied to evaluate lipidomic alterations. Results: Principal component analysis demonstrated a clear separation between BD patients and healthy controls, indicating extensive lipidomic remodeling. BD was associated with significant alterations in phosphatidylcholines, sphingomyelins, diacylglycerols, and triacylglycerols, reflecting coordinated changes in membrane structure, lipid-mediated signaling, and energy metabolism. Pathway analysis further supported the involvement of glycerophospholipid, glycerolipid, and phosphatidylinositol-related metabolic pathways. Comparison between BD patients with and without vascular involvement revealed no major global lipidomic shift; however, specific lipid species showed consistent alterations. Two phosphatidylcholine species (PC 33:2 and ether-linked PC 31:4e) were decreased, whereas one triacylglycerol species (TAG 58:2) was increased in patients with vascular involvement. Conclusions: These findings suggest that BD is characterized by coordinated lipidomic reprogramming involving membrane remodeling, inflammatory signaling, and metabolic adaptation. Vascular involvement appears to be associated with subtle, lipid-specific alterations rather than a global lipidomic shift, highlighting potential molecular features of disease progression. Full article

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

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25 pages, 11834 KB

Open AccessArticle

Multiple Reaction Monitoring (MRM)-Based Targeted Kidney Metabolite Profiling of a Mouse Model of Hyperuricemia

by Hailong Li, Tingting Tang, Qingli Zhang, Tingting Song, Zichu Zhao, Lei Zhu, Qu Chen, Haili Zhang, Yan Zhang and Jingjing Kong

Metabolites 2026, 16(6), 362; https://doi.org/10.3390/metabo16060362 - 27 May 2026

Abstract

Background/Objectives: Chronic urate nephropathy (CUN), also referred to as gouty nephropathy, represents a severe renal disease primarily precipitated by long-term hyperuricemia (HUA) and gout. However, the precise molecular mechanisms underlying its pathogenesis remain poorly understood. The present study was designed to explore these [...] Read more.

Background/Objectives: Chronic urate nephropathy (CUN), also referred to as gouty nephropathy, represents a severe renal disease primarily precipitated by long-term hyperuricemia (HUA) and gout. However, the precise molecular mechanisms underlying its pathogenesis remain poorly understood. The present study was designed to explore these mechanisms from the perspective of targeted metabolomics. Methods: The HUA mice constructed by urate oxidase (Uox) gene knockout (KO) and their corresponding wild-type controls were employed for the present study. Serum clinical biochemical parameters were determined, and renal histopathological changes were evaluated using hematoxylin-eosin (HE) staining and Masson’s trichrome staining. A targeted metabolomic strategy based on multiple reaction monitoring (MRM) was utilized to profile the renal metabolic landscape of Uox-KO mice, and potential metabolic biomarkers for CUN were identified via multivariate data analysis. Results: Clinical biochemical analysis revealed a significant elevation in serum uric acid, creatinine, and urea nitrogen levels in Uox-KO mice compared with control mice. Histopathological observations confirmed a typical CUN phenotype in Uox-KO mice, characterized by renal tubular vacuolar degeneration and dilatation, desquamation of tubular epithelial cells into the lumen, neutrophil infiltration, glomerular crowding, and renal interstitial fibrosis. Metabolomic analysis identified a total of 291 differentially regulated metabolites in Uox-KO mice relative to control animals. These perturbed metabolites were involved in multiple key biochemical pathways, including amino acid biosynthesis, ABC transporter signaling pathway, purine metabolism, aminoacyl-tRNA biosynthesis, protein digestion and absorption, glycerophospholipid metabolism, and serotonergic synaptic transmission. Notably, pathological parameters, including biochemical measurements and histological observations, were significantly correlated with key differential metabolites associated with CUN progression. Furthermore, eleven differential metabolites (pyroglutamic acid, fructose, riboflavin, dimethyl-L-arginine, glucaric acid, indoxyl sulfate, palmitoylethanolamide, trimethylamine N-oxide, 3-hydroxyanthranilic acid, spermidine, and hippuric acid) were identified as potential metabolic biomarkers for the diagnosis and prognosis of CUN. Conclusions: These findings illustrate that targeted tissue metabolomic analysis constitutes a powerful tool for deciphering the molecular mechanisms of diseases, thus offering novel insights into the pathogenesis of CUN. Full article

(This article belongs to the Topic Animal Models of Human Disease 3.0)

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13 pages, 3390 KB

Open AccessArticle

Impact of Oil Spill Stress on Amino Acid Abundance in Heterosigma akashiwo

by Dan Xue, Haohan Su, Jie Yu, Xiaowen Yang, Na Li and Shimeng Chen

Metabolites 2026, 16(6), 361; https://doi.org/10.3390/metabo16060361 - 27 May 2026

Abstract

Background: Oil spills have dramatically increased, causing significant damage and pollution to marine ecosystems. The entry of petroleum hydrocarbons into the ocean may lead to the occurrence of harmful algal blooms (HABs). The amino acid changes in harmful algae after oil spills [...] Read more.

Background: Oil spills have dramatically increased, causing significant damage and pollution to marine ecosystems. The entry of petroleum hydrocarbons into the ocean may lead to the occurrence of harmful algal blooms (HABs). The amino acid changes in harmful algae after oil spills remain unclear. Methods: In order to study the effect of oil spills on the amino acid mechanism of typical causative species, the composition and relative abundance of amino acids in Heterosigma akashiwo were investigated under different water accommodated fractions (WAFs) of 180# fuel oil. Results: Random forest prediction of polycyclic aromatic hydrocarbon toxicity to microalgae identified pyrene, benzo[k]fluoranthene, and fluoranthene as significant contributors. A total of 16 species of amino acids were detected in Heterosigma akashiwo, among which alanine, proline, aspartic acid, cysteine, lysine, and histidine were the predominant ones. As the concentration of the WAF increased, alanine abundance decreased significantly, indicating that the WAF disrupted the metabolic balance of alanine, with the degree of interference being positively correlated with exposure concentration. With the increase in culture time, the abundance of cysteine increased at 1%, 3%, and 5% WAFs, whereas the cysteine increased and then decreased at 7% and 10% WAFs. The abundance of aspartic acid and lysine showed no obvious pattern with culture time under WAF stress. Significant increases in the abundance of proline and histidine were observed in the WAF treatments. Conclusions: This study investigated the impact of oil spill pressure on the amino acid content of harmful algae, providing a scientific basis for understanding the potential impact of oil spills on the occurrence of HABs. Full article

(This article belongs to the Section Microbiology and Ecological Metabolomics)

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19 pages, 30849 KB

Open AccessArticle

Integrating Metabolomics and Gut Microbiota to Reveal the Therapeutic Effect of Lonicerae japonicae Flos Against Respiratory Syncytial Virus

by Yanghai Wang, Yan Gao, Yuting Liang, Bonian Zhao and Lu Liu

Metabolites 2026, 16(6), 360; https://doi.org/10.3390/metabo16060360 - 27 May 2026

Abstract

Objectives: This study aimed to investigate the therapeutic effects and potential mechanisms of Lonicerae japonicae Flos (Jinyinhua, JYH) against respiratory syncytial virus (RSV)-induced pneumonia by integrating lung tissue metabolomics with gut microbiota analysis. Methods: An RSV-infected mouse model was established through [...] Read more.

Objectives: This study aimed to investigate the therapeutic effects and potential mechanisms of Lonicerae japonicae Flos (Jinyinhua, JYH) against respiratory syncytial virus (RSV)-induced pneumonia by integrating lung tissue metabolomics with gut microbiota analysis. Methods: An RSV-infected mouse model was established through intranasal inoculation. Lung pathological changes, viral RNA levels, lung index, and inflammatory cytokine levels were evaluated. Untargeted metabolomics and 16S rRNA gene amplicon sequencing were performed to characterize JYH-mediated alterations in pulmonary metabolites and the gut microbiota. Spearman correlation analysis was conducted to assess associations between differentially abundant bacterial genera and significantly altered metabolites. Results: JYH alleviated RSV-induced pulmonary histopathological injury, reduced viral RNA levels, decreased lung index and interleukin-6 (IL-6) levels, and increased interferon-γ (IFN-γ) levels. Metabolomic profiling identified 46 differential metabolites, among which 26 showed a reversal trend following JYH administration. These metabolites were mainly enriched in pathways associated with the synaptic vesicle cycle, lysosomal function, and Forkhead box O (FoxO) signaling. Gut microbiota analysis showed that JYH increased microbial richness and diversity, whereas KEGG-based functional prediction indicated that the differentially abundant taxa were primarily involved in amino acid, carbohydrate, and nucleotide metabolism. Moreover, correlation analysis revealed significant associations between key bacterial genera, including Gemella, Sutterella, and CC_115, and differential metabolites such as pyridoxamine, uridine monophosphate (UMP), and argininosuccinic acid. Conclusions: JYH may protect against RSV-induced pneumonia by restoring pulmonary metabolic homeostasis and modulating gut microbiota composition. These findings provide new insights into metabolite–microbiota interactions underlying the anti-RSV activity of JYH. Full article

(This article belongs to the Special Issue Novel Approaches for Metabolomics in Drugs and Biomarkers Discovery: 2nd Edition)

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19 pages, 4815 KB

Open AccessArticle

Metabolic Responses of Grapevine Leaves to Grapevine Leafroll-Associated Virus 3 Infection

by Ivana Tomaz, Darko Preiner, Nina Buljević and Darko Vončina

Metabolites 2026, 16(6), 359; https://doi.org/10.3390/metabo16060359 - 27 May 2026

Abstract

Background: Grapevine leafroll-associated virus 3 (GLRaV-3) is a severe phloem-limited grapevine virus, meaning it is restricted to sugar-transporting vascular tissue, which helps explain its strong effects on leaf physiology and carbon transport. However, its impact on leaf oxidative status, phenolic composition, and [...] Read more.

Background: Grapevine leafroll-associated virus 3 (GLRaV-3) is a severe phloem-limited grapevine virus, meaning it is restricted to sugar-transporting vascular tissue, which helps explain its strong effects on leaf physiology and carbon transport. However, its impact on leaf oxidative status, phenolic composition, and volatile organic compounds (VOCs) remains insufficiently characterized. Methods: Virus-free and GLRaV-3-infected grapevine leaves were analyzed for photosynthetic pigments, oxidative stress markers, phenolic compounds, and VOCs using spectrophotometric assays, HPLC-DAD/FLD, and SPME-Arrow-GC/MS. Data were evaluated using one-way ANOVA, multiple testing correction, principal component analysis (PCA), and exploratory partial least squares-discriminant analysis (PLS-DA). Results: GLRaV-3-infected leaves showed lower chlorophyll a (576.75 vs. 657.85 mg 100 g⁻¹ DW), chlorophyll b (282.96 vs. 314.05 mg 100 g⁻¹ DW), and total carotenoids (125.89 vs. 154.65 mg 100 g⁻¹ DW), but higher malondialdehyde (11.91 vs. 8.73 nmol g⁻¹ DW), H₂O₂ (0.36 vs. 0.25 μmol g⁻¹ DW), and proline (8.83 vs. 7.98 μmol g⁻¹ DW). Phenolic profiling showed increased levels of several flavonols and hydroxycinnamic acids, including kaempferol-3-O-glucuronide (2.81-fold), myricetin-3-O-glucoside (1.75-fold), quercetin-3-O-glucuronide (1.48-fold), and caffeic acid (1.30-fold). VOC profiling revealed higher relative abundances of several green leaf volatile-related compounds and methyl salicylate, including 1-methoxy-2-propanol (1.85-fold), 1-penten-3-ol (1.58-fold), hexanal (1.42-fold), and methyl salicylate (1.37-fold). PCA summarized treatment-related differences, with the first two components explaining 63.73% of phenolic and 74.09% of VOC variability, while exploratory PLS-DA/VIP analysis further supported the identification of treatment-associated discriminant metabolic features. Conclusions: GLRaV-3 infection is associated with reduced pigment content, increased oxidative stress markers, and coordinated changes in phenolic and VOC profiles. These metabolite changes provide insight into grapevine responses to viral infection and highlight GLRaV-3-associated metabolic features for future targeted studies of grapevine leafroll disease. Full article

(This article belongs to the Special Issue Plant Biotic and Abiotic Stress Responses and Tolerance: Phytohormonal and Metabolic Insights)

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