MetabolitesPub Date : 2025-06-03DOI: 10.3390/metabo15060367
Ninna Leslie Trejo-Gonzalez, Martin Palomar-Morales, Luis Arturo Baiza-Gutman, Guadalupe Diaz-Rosas, Clara Ortega-Camarillo, Alejandra Contreras-Ramos
{"title":"Circulating MicroRNAs Associated with Changes in the Placenta and Their Possible Role in the Fetus During Gestational Diabetes Mellitus: A Review.","authors":"Ninna Leslie Trejo-Gonzalez, Martin Palomar-Morales, Luis Arturo Baiza-Gutman, Guadalupe Diaz-Rosas, Clara Ortega-Camarillo, Alejandra Contreras-Ramos","doi":"10.3390/metabo15060367","DOIUrl":"10.3390/metabo15060367","url":null,"abstract":"<p><p>MicroRNAs (miRs) are epigenetic regulators of several metabolic diseases, including gestational diabetes mellitus (GDM).</p><p><strong>Objectives: </strong>Following a systematic review, we propose a pattern of key circulating miRs associated with placental changes and their potential role in the fetus.</p><p><strong>Methods: </strong>A systematic investigation of studies published between January 2011 and July 2024 was conducted in the PubMed, ScienceDirect, Trip Database, and Wiley databases. A total of 90 articles were analyzed.</p><p><strong>Results: </strong>Two hundred twenty-six circulating microRNAs were identified in women with GDM, and fifty miRs were validated by PCR, with miRs-16-5p, -29a-5p, and -195-5p being the most frequently reported. Interestingly, miR-16-5p was also expressed in the placenta but not in umbilical cord blood or amniotic fluid. Conversely, miR-126-3p was expressed in circulation, the placenta, umbilical cord blood, and amniotic fluid. Several reports describe high expression levels of miR-518d in maternal circulation, umbilical cord blood, and placenta. Controversial results regarding the expression of miR-29a-3p, -137, and -148a-3p were identified when comparing umbilical cord blood and the placenta.</p><p><strong>Conclusions: </strong>In silico analyses suggest that the miR-29 family, as well as miRs-16-5p, -126-3p, -195-5p, and -518b, may be involved in alterations in the heart, brain, and kidneys in the embryo when exposed to a hyperglycemic environment.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 6","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12194830/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144485002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Optimization of Tunisian <i>Myrtus communis</i> L. Essential Oil Extraction by Complete Factorial Experimental Design.","authors":"Rania Zayani, Eya BenSalem, Mariem Khouja, Amani Bouhjar, Mohamed Boussaid, Chokri Messaoud","doi":"10.3390/metabo15060369","DOIUrl":"10.3390/metabo15060369","url":null,"abstract":"<p><p><b>Background:</b><i>Myrtus communis</i> L. is a typical aromatic species of the Mediterranean basin, whose leaves are rich in essential oil known for its biological properties. <b>Methods:</b> The essential oil of Tunisian <i>Myrtus communis</i> L. leaves was extracted via hydrodistillation using a Clevenger-type apparatus and optimized using a complete factorial design including three factors with two different modalities and one factor with three modalities, hence the total number of experiments N<sub>total</sub> = 2<sup>3</sup> × 3<sup>1</sup>. This optimization concerns the yield, the terpene composition by GC-MS and the antioxidant activity by the two radical scavenging assays, DPPH and ABTS. Four factors were retained, namely, the type of leaf used (dry or fresh sample), the leaf granulometry (whole or ground), the extraction time (1 h 30 min, 2 h 30 min and 3 h 30 min) and the water volume/plant material ratio (1/4 and 1/10). <b>Results:</b> The dry and whole leaves, duration 3 h 30 min, and V/M 1/10 modalities gave the best yield of essential oil (0.77%). The optimal contents of the majority of the terpene compounds, 1,8-cineole (37.23%), α-pinene (54.79%), myrtenyl acetate (23.43%) and limonene (17.77%), were recorded using the modalities dry and whole leaves, duration 2 h 30 min, V/M 1/10; dry and ground leaves, duration 1 h 30 min, V/M 1/4; fresh and whole leaves, duration 3 h 30 min, V/M 1/4; and fresh and whole leaves, duration 3 h 30 min, V/M 1/4, respectively. The antioxidant activity of the essential oil of myrtle leaves was optimized for the two DPPH (7.477 mg TE/g EO) with the GDL, duration 3 h 30 min, V/M 1/4 and ABTS assays (14.053 mg TE/g EO) with WDL terms, duration 3 h 30 min, V/M 1/10. <b>Conclusions:</b> Optimizing essential oil extraction is of significant interest to the cosmetic, perfumery, and pharmaceutical industries, which are constantly seeking optimal conditions to enhance essential oil yield and to ensure a high concentration of terpenic compounds, valued for their aromatic qualities and diverse biological activities.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 6","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12195216/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144485067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Soluble Siglec-9 Improves Intestinal Barrier Function in a Mouse Model of Metabolic Dysfunction-Associated Steatohepatitis.","authors":"Hisanori Muto, Fumitaka Mizuno, Takashi Honda, Shinya Yokoyama, Taku Tanaka, Kenta Yamamoto, Takanori Ito, Norihiro Imai, Yoji Ishizu, Kiyoshi Sakai, Hideharu Hibi, Masatoshi Ishigami, Hiroki Kawashima","doi":"10.3390/metabo15060366","DOIUrl":"10.3390/metabo15060366","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Metabolic dysfunction-associated steatohepatitis (MASH), characterized by liver inflammation, fibrosis, and fat accumulation, can develop into cirrhosis and liver cancer. Despite its increasing prevalence worldwide, there are few established therapies for advanced MASH. We previously demonstrated that stem cells from human exfoliated deciduous teeth-conditioned media (SHED-CM) exerted therapeutic effects in a MASH mouse model. The gut-liver axis is thought to be associated with liver disease progression, and soluble Siglec-9 (sSiglec-9), an immunoinhibitory receptor, is a key protein in SHED-CM that induces anti-inflammatory macrophages and has intestinal epithelial protective effects. Therefore, we evaluated sSiglec-9's role in intestinal barrier protection in MASH mice. <b>Methods</b>: We evaluated sSiglec-9 effects on intestinal barrier function using in vitro Caco-2 cell monolayers injured by TNF-α and IFN-γ. For the MASH mouse model, male C57BL/6J mice were given a Western diet and high-sugar solution orally; to induce liver injury, CCl4 was intraperitoneally administered for 12 weeks. Mice were treated weekly with 10 ng/g sSiglec-9 or vehicle. Intestinal permeability was assessed by blood 4 kDa FITC-dextran concentration, and intestinal transcriptomes and liver histology were analyzed. <b>Results</b>: sSiglec-9 decreased intestinal permeability and liver inflammation in MASH mice. sSiglec-9 and SHED-CM reduced 4 kDa FITC-dextran permeability in injured Caco-2 cells, and sSiglec-9 significantly reduced intestinal permeability and modulated expression of 34 intestinal genes. The NAFLD Activity Score indicated significantly reduced inflammation following sSiglec-9 treatment. <b>Conclusions</b>: sSiglec-9 may protect intestinal barrier function by mitigating mucosal inflammation. sSiglec-9 treatment may represent a novel therapeutic approach for MASH via gut-liver axis modulation.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 6","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12195191/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144485015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MetabolitesPub Date : 2025-05-30DOI: 10.3390/metabo15060364
Mohammed E Hefni, Cornelia M Witthöft, Patrik Hellström, Ingegerd Johansson, Anders Esberg
{"title":"Plasma TMAO Concentrations and Gut Microbiota Composition in Subjects with and Without Metabolic Syndrome: Results from Pilot Study.","authors":"Mohammed E Hefni, Cornelia M Witthöft, Patrik Hellström, Ingegerd Johansson, Anders Esberg","doi":"10.3390/metabo15060364","DOIUrl":"10.3390/metabo15060364","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Trimethylamine N-oxide (TMAO) is a gut microbiota-dependent metabolite considered as a risk metabolite for various non-communicable diseases. This study aims to identify differences in the gut microbiota composition and concentrations of TMAO and related metabolites in subjects with and without metabolic syndrome (MetS). <b>Methods</b>: Plasma samples were collected following an overnight fast on two occasions from subjects with (n = 12) and without (n = 21) MetS. Feces samples were collected on the day before the first blood sampling. The gut microbiota was profiled using 16S rRNA full-gene amplification sequencing. TMAO and related methylamines were quantified using UPLC-MSMS. The fasted plasma glucose, plasma lipid profile, and HbA1c were determined, and blood pressure, circumference, height, and weight were measured. <b>Results</b>: A divergent gut microbiota composition was observed in feces samples from both groups. In contrast to subjects without MetS, subjects with MetS had a reduced microbial diversity, with lower <i>Blautia glucerasea</i> and higher <i>Ruminococcus torques</i>-a pattern associated with (increased) inflammation. Trimethylamine (TMA)-producing bacteria were low in abundance across both groups. While plasma TMAO and related methylamines displayed no significant differences between both groups, L-carnitine was elevated (<i>p</i> = 0.0191) in subjects with MetS. A strong positive correlation was detected between TMAO and TMA (<i>r</i> = 0.439, <i>p</i> = 0.003), with a tendency to correlate with carnitine (<i>r</i> = 0.212, <i>p</i> = 0.087). <b>Conclusions</b>: Subjects with MetS were characterized by gut microbiota favoring inflammation-associated species but not TMA producers. This suggests that TMAO may not play a role in MetS subjects without overt comorbidities, e.g., CVD or T2D. The influence of the gut microbiota on early MetS is likely mediated through inflammatory mechanisms driven by specific bacterial shifts rather than TMAO production.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 6","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12195445/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144485074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MetabolitesPub Date : 2025-05-30DOI: 10.3390/metabo15060365
Hongli Liu, Cristian Coarfa, Arzoo N Charania, Jennifer L Larson-Casey, Ivan O Rosas, Chao He
{"title":"Secreted Phosphoprotein 1 in Lung Diseases.","authors":"Hongli Liu, Cristian Coarfa, Arzoo N Charania, Jennifer L Larson-Casey, Ivan O Rosas, Chao He","doi":"10.3390/metabo15060365","DOIUrl":"10.3390/metabo15060365","url":null,"abstract":"<p><p>Secreted phosphoprotein 1 (SPP1), also known as osteopontin (OPN) or early T lymphocyte activation protein 1 (ETA-1), is a multifunctional protein involved in numerous biological processes, including immune modulation, stress response, and tissue remodeling. The role of SPP1 in interstitial lung diseases (ILDs) has become an area of increasing interest, given its elevated expression in various ILDs such as idiopathic pulmonary fibrosis (IPF), connective tissue disease-associated ILD (CTD-ILD), and pneumoconiosis, especially with recent data derived from single-cell RNA sequencing. In addition to ILDs, SPP1 has been implicated in infectious granulomatous lung diseases, lung and pleural malignancies, airway diseases, and COVID-19. In most cases, higher SPP1 levels in serum, bronchoalveolar lavage fluid, or lung tissue carry a poor prognosis. SPP1 is expressed in multiple cells critical for fibrogenesis, including macrophages, epithelial cells, and fibroblasts, and SPP1 has emerged as a potential target for therapeutic interventions. Here, we review the proposed mechanisms by which SPP1 contributes to the development of lung disease, with an emphasis on ILD.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 6","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12195332/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144485080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MetabolitesPub Date : 2025-05-29DOI: 10.3390/metabo15060361
Vincenza Gragnaniello, Chiara Cazzorla, Daniela Gueraldi, Andrea Puma, Christian Loro, Alberto B Burlina
{"title":"The Hidden Burden: Gastrointestinal Involvement in Lysosomal Storage Disorders.","authors":"Vincenza Gragnaniello, Chiara Cazzorla, Daniela Gueraldi, Andrea Puma, Christian Loro, Alberto B Burlina","doi":"10.3390/metabo15060361","DOIUrl":"10.3390/metabo15060361","url":null,"abstract":"<p><strong>Background: </strong>Lysosomal storage disorders (LSDs) are rare inherited metabolic diseases characterized by defects in lysosomal enzyme function or membrane transport. These defects lead to substrate accumulation and multisystemic manifestations. This review focuses on gastrointestinal (GI) involvement in LSDs, which is a significant but often overlooked aspect of these disorders.</p><p><strong>Methods: </strong>A comprehensive literature review was conducted to examine the pathophysiology, clinical presentation, diagnosis and management of GI manifestations in several LSDs, including Fabry disease, Gaucher disease, Pompe disease, Niemann-Pick disease type C, mucopolysaccharidoses and Wolman disease.</p><p><strong>Results: </strong>The pathogenesis of GI involvement in LSDs varies and encompasses substrate accumulation in enterocytes, mesenteric lymphadenopathy, mass effects, smooth muscle dysfunction, vasculopathy, neuropathy, inflammation and alterations to the microbiota. Clinical presentations range from non-specific symptoms, such as abdominal pain, diarrhea and malabsorption, to more severe complications, such as protein-losing enteropathy and inflammatory bowel disease. Diagnosis often requires a high level of suspicion, as GI symptoms may precede the diagnosis of the underlying LSD or be misattributed to more common conditions. Management strategies include disease-specific treatments, such as enzyme replacement therapy or substrate reduction therapy, as well as supportive care and targeted interventions for specific GI complications.</p><p><strong>Conclusions: </strong>This review highlights the importance of recognizing and properly managing GI manifestations in LSDs to improve patient outcomes and quality of life. It also emphasizes the need for further research to develop more effective treatments for life-threatening GI complications associated with these rare genetic disorders.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 6","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12195498/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144485020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MetabolitesPub Date : 2025-05-29DOI: 10.3390/metabo15060363
Jie Zong, Haiyang Wu, Xuan Hu, Ami Yao, Wenhua Zhu, Guifang Dou, Shuchen Liu, Xiaoxia Zhu, Ruolan Gu, Yunbo Sun, Zhuona Wu, Shanshan Wang, Hui Gan
{"title":"Plasma and Fecal Metabolites Combined with Gut Microbiome Reveal Systemic Metabolic Shifts in <sup>60</sup>Co Gamma-Irradiated Rats.","authors":"Jie Zong, Haiyang Wu, Xuan Hu, Ami Yao, Wenhua Zhu, Guifang Dou, Shuchen Liu, Xiaoxia Zhu, Ruolan Gu, Yunbo Sun, Zhuona Wu, Shanshan Wang, Hui Gan","doi":"10.3390/metabo15060363","DOIUrl":"10.3390/metabo15060363","url":null,"abstract":"<p><p><b>Background</b>: High-dose γ-ray exposure (≥7 Gy) in nuclear emergencies induces life-threatening acute radiation syndrome, characterized by rapid hematopoietic collapse (leukocytes <0.5 × 10⁹/L) and gastrointestinal barrier failure. While clinical biomarkers like leukocyte depletion guide current therapies targeting myelosuppression, the concomitant metabolic disturbances and gut microbiota dysbiosis-critical determinants of delayed mortality-remain insufficiently profiled across the 28-day injury-recovery continuum. <b>Methods</b>: This study investigates the effects of <sup>60</sup>Co γ-ray irradiation on metabolic characteristics and gut microbiota in Sprague Dawley rats using untargeted metabolomics and 16S rRNA sequencing. Meanwhile, body weight and complete blood counts were measured. <b>Results</b>: Body weight exhibited significant fluctuations, with the most pronounced deviation observed at 14 days. Blood counts revealed a rapid decline in white blood cells, red blood cells, and platelets post-irradiation, reaching nadirs at 7-14 days, followed by gradual recovery to near-normal levels by 28 days. Untargeted metabolomics identified 32 upregulated and 33 downregulated plasma metabolites at 14 days post-irradiation, while fecal metabolites showed 47 upregulated and 18 downregulated species at 3 days. Key metabolic pathways impacted included Glycerophospholipid metabolism, alpha-linolenic acid metabolism, and biosynthesis of unsaturated fatty acids. Gut microbiota analysis demonstrated no significant change in α-diversity but significant <i>β</i>-diversity shifts (<i>p</i> < 0.05), indicating a marked alteration in the compositional structure of the intestinal microbial community following radiation exposure. Principal coordinate analysis confirmed distinct clustering between control and irradiated groups, with increased abundance of <i>Bacteroidota</i> and decreased <i>Firmicutes</i> in irradiated rats. These findings highlight dynamic metabolic and microbial disruptions post-irradiation, with recovery patterns suggesting a 28-day restoration cycle. Spearman's rank correlation analysis explored associations between the top 20 fecal metabolites and 50 abundant bacterial taxa. <i>Norank_f_Muribaculaceae</i>, <i>Prevotellaceae_UCG-001</i>, and <i>Bacteroides</i> showed significant correlations with various radiation-altered metabolites, highlighting metabolite-microbiota relationships post-radiation. <b>Conclusions</b>: This study provides insights into potential biomarkers for radiation-induced physiological damage and underscores the interplay between systemic metabolism and gut microbiota in radiation response.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 6","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12194991/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144485073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MetabolitesPub Date : 2025-05-29DOI: 10.3390/metabo15060360
Anna L Chien, Hua Liu, Saleh Rachidi, Jessica L Feig, Ruizhi Wang, Kristina L Wade, Katherine K Stephenson, Aysegul Sevim Kecici, Jed W Fahey, Sewon Kang
{"title":"Oral Glucoraphanin and Curcumin Supplements Modulate Key Cytoprotective Enzymes in the Skin of Healthy Human Subjects: A Randomized Trial.","authors":"Anna L Chien, Hua Liu, Saleh Rachidi, Jessica L Feig, Ruizhi Wang, Kristina L Wade, Katherine K Stephenson, Aysegul Sevim Kecici, Jed W Fahey, Sewon Kang","doi":"10.3390/metabo15060360","DOIUrl":"10.3390/metabo15060360","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Oxidative stress plays a pivotal role in skin aging and carcinogenesis. Phytochemicals such as sulforaphane (SF, from broccoli sprouts or seeds) or curcumin (CUR, from turmeric) can be highly protective against this stress. They each induce a suite of cytoprotective and antioxidant enzymes that are coordinately transcribed via the Keap1-Nrf2-ARE pathway in mammals, such as the prototypical cytoprotective enzyme NAD(P)H dehydrogenase 1 (NQO1). <b>Methods:</b> Eighteen healthy human volunteers (9 males, 9 females, aged 18-69. were randomized to receive daily glucoraphanin (GR), which is converted to SF upon ingestion (450 mg; 1 mmol), CUR (1000 mg; 2.7 mmol), or both (450 mg GR + 1000 mg CUR), as oral supplements. After 8 days of a diet low in both compounds, blood and urine were collected for compliance and biomarker measurements. Randomized spots on the buttock's skin were exposed to 2 x M.E.D. of UVB, and punch biopsies were obtained 1 and 3 days later for biomarker and histological measurement. Erythema was measured with a chromameter daily for 3 consecutive days following UVB. The process was repeated after receiving oral supplements, both with and without UVB exposure. <b>Results:</b> Compared to baseline, each treatment (<i>n</i> = 6 for each) induced NQO1 mRNA levels in skin biopsies: 3.1-fold with GR, 3.3-fold with CUR, and 3.6-fold with the combination of GR and CUR. Across all treatments (<i>n</i> = 18), expression of the pro-inflammatory cytokines IL-1β and TNF-α were reduced, as were IL-6, IL-17, STING, and CYR61, though less robustly. Modulation of these biomarkers persisted, but was less pronounced, in biopsies taken following UV exposure. The presence of SF and its metabolites in the skin post-treatment was confirmed by examining 6 of 12 subjects who ingested GR. Supplement effects on erythema following UV exposure were not significant, and no significant changes were measured in the same biomarkers in blood cells (PBMC), or by counting dyskeratotic keratinocytes. Supplements were well tolerated and compliance was excellent. <b>Conclusions:</b> Oral GR and CUR are well tolerated and have for the first time been shown to result in increased expression of cytoprotective genes and reduced expression of inflammatory cytokine genes in human skin in vivo. This mechanism-based clinical study suggests that an antioxidant, anti-inflammatory, and cytoprotective benefit from these oral supplements is delivered to the skin in humans.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 6","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12195189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144485068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MetabolitesPub Date : 2025-05-29DOI: 10.3390/metabo15060362
Kekeletso H Chele, Lizelle A Piater, Justin J J van der Hooft, Fidele Tugizimana
{"title":"Bridging Ethnobotanical Knowledge and Multi-Omics Approaches for Plant-Derived Natural Product Discovery.","authors":"Kekeletso H Chele, Lizelle A Piater, Justin J J van der Hooft, Fidele Tugizimana","doi":"10.3390/metabo15060362","DOIUrl":"10.3390/metabo15060362","url":null,"abstract":"<p><p>For centuries, plant-derived natural products (NPs) have been fundamental to traditional medicine, providing essential therapeutic compounds. Ethnobotanical knowledge has historically guided NP discovery, leading to the identification of key pharmaceuticals such as aspirin, morphine, and artemisinin. However, conventional bioactivity-guided fractionation methods for NP isolation are labour-intensive and can result in the loss of bioactive properties due to the focus on a single compound. Advances in omics sciences-genomics, transcriptomics, proteomics, metabolomics, and phenomics-coupled with computational tools have altogether revolutionised NP research by enabling high-throughput screening and more precise compound identification. This review explores how integrating traditional medicinal knowledge with multi-omics strategies enhances NP discovery. We highlight emerging bioinformatics tools, mass spectrometry techniques, and metabologenomics approaches that accelerate the identification, annotation, and functional characterisation of plant-derived metabolites. Additionally, we discuss challenges in omics data integration and propose strategies to harness ethnobotanical knowledge for targeted NP discovery and drug development. By combining traditional wisdom with modern scientific advancements, this integrated approach paves the way for novel therapeutic discoveries and the sustainable utilisation of medicinal plants.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 6","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12195599/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144484999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MetabolitesPub Date : 2025-05-28DOI: 10.3390/metabo15060357
Linda Monaci, Anna Luparelli, William Matteo Schirinzi, Laura Quintieri, Alexandre Verdu
{"title":"DART-Triple Quadrupole Mass Spectrometry Method for Multi-Target and Fast Detection of Adulterants in Saffron.","authors":"Linda Monaci, Anna Luparelli, William Matteo Schirinzi, Laura Quintieri, Alexandre Verdu","doi":"10.3390/metabo15060357","DOIUrl":"10.3390/metabo15060357","url":null,"abstract":"<p><p>Saffron is a high-cost spice due to the specific conditions for optimal growth and because of being harvested by hand. The massive income from commercializing saffron substituted with other plant parts or low-cost spices makes this spice the main target of fraudsters. <b>Background</b>: Different methods have been developed for detecting saffron adulteration. Most of them are time consuming and complex, and in some types of analysis, the whole untargeted dataset is combined with advanced chemometric tools to differentiate authentic from non-authentic saffron. The official method, combining UV-vis spectroscopy and LC to determine the colour strength and the crocin content, is unable to detect saffron adulterants (safflower, marigold, or turmeric) added at a level lower than 20% (<i>w</i>/<i>w</i>). As a result, innovative approaches based on rapid, high-throughput methods for the identification of adulterated saffron samples are urgently demanded to counteract food frauds. <b>Methods</b>: This paper describes, for the first time, the development of a method combining Direct Analysis in Real Time (DART) with the triple quadrupole MS EVOQ based on the detection of specific MS/MS transitions, promoting a rapid, robust and chromatography-free method capable of monitoring safflower and turmeric adulteration in saffron. <b>Results</b>: The method proved to reach low LODs, allowing the determination of tiny amounts of turmeric and safflower powder in saffron as low as 3% and 5%, respectively, speeding up the whole analytical workflow and enabling us to perform 20 analyses in 10 min. Finally, the greenness of the method was also assessed according to the 0.88 score achieved by submitting it to the greenness calculator AGREE. <b>Conclusions</b>: Given its speed, simplicity, and robustness, this method stands out as a strong candidate for routine implementation in testing laboratories as a rapid screening tool to detect saffron adulteration with safflower or turmeric.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"15 6","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12195507/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144485007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}