Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder with metabolic alterations not fully explained by obesity or androgen excess.
To define a plasma metabolomic signature of PCOS independent of BMI and to evaluate associations with measures of androgen excess.
Forty women with PCOS (mean age: 22.9 ± 2.7 years; mean BMI: 23.4 ± 4.6 kg/m2) and 40 age- and BMI-matched healthy controls underwent standardized clinical, biochemical, and hormonal assessment. Plasma metabolomic profiling was performed using integrated GC–MS and LC–MS platforms. Data were analyzed using principal component analysis (PCA), partial least squares–discriminant analysis (PLS-DA) with cross-validation and permutation testing, false discovery rate (FDR)-adjusted univariate analysis, receiver operating characteristic (ROC) analysis, pathway enrichment (MetaboAnalyst), and Spearman correlations with clinical parameters.
PCA and PLS-DA demonstrated clear separation of PCOS and control groups. PLS-DA achieved high discrimination (accuracy = 0.95, R2 = 0.92, Q2 = 0.78) and was validated by permutation testing (P = .002). Thirty-one metabolites were significantly altered after FDR correction.
Threitol, a four-carbon sugar alcohol, emerged as the top discriminatory metabolite (fold change = 5.86, FDR = 3.59×10⁻14), achieving near-perfect discrimination between PCOS and controls (multivariate ROC AUC = 0.993; 95% CI: 0.962-1.000), highlighting its potential as a novel metabolic marker.
Pathway analysis revealed significant perturbations in branched-chain amino acid (BCAA: valine, leucine, isoleucine)) biosynthesis (P = 5.49×10⁻5, FDR = 0.004), alanine–aspartate–glutamate metabolism (a central amino acid–energy pathway) (P = 1.56×10⁻4, FDR = 0.006), and the citrate cycle (P = .00103, FDR = 0.028), indicating disrupted core energy metabolism.
Threitol correlated inversely with total testosterone (r = −0.46), free androgen index (r = −0.56), and anti-Müllerian hormone (AMH) (all P < .001). Palmitoylcarnitine correlated positively with total testosterone (r = 0.35, P = .001). Other key metabolites, including BCAA and energy metabolites, showed no significant association with androgen or insulin resistance measures.
High-resolution metabolomics identifies a robust, BMI-independent metabolic signature in PCOS characterized by BCAA and energy metabolism alterations. Selected metabolites show targeted associations with androgen levels, supporting refined metabolic phenotyping in PCOS.
Utku Maraşlı, S. Aksun, Sevilay Erdoğan Kablan et al.· European Journal of Endocrin...· 0 citations
Background/Objectives: Berberis species are recognized for their ethnomedicinal importance and phytochemical richness associated with antidiabetic activity. Although B. crataegina is widely distributed in the Turkish flora and has a history of traditional use, its phytochemical properties and biological activities remain less extensively investigated than those of other Berberis species. This study aimed to comparatively evaluate the phytochemical profiles, in vitro antidiabetic potential, and cytoprotective effects of extracts prepared from different parts of B. crataegina in a high-glucose-induced SH-SY5Y cell-based model of diabetic neuropathy. Methods: Crude hydroethanolic extracts (70% ethanol) were prepared from the leaves, flowers, shoots, roots, and fresh fruits of B. crataegina collected from Kızılcahamam, Ankara, Türkiye. The total phenolic and flavonoid contents, antioxidant capacities and α-glucosidase inhibitory activities of leaf, flower, shoot, root, and fruit extracts were determined. The cytoprotective effects of the crude extracts were evaluated in a high-glucose-induced SH-SY5Y cell model. The metabolomic profiles of the extracts were comparatively analyzed using liquid chromatography–quadrupole time-of-flight mass spectrometry (LC-QTOF-MS). The most active fruit extract was fractionated by reversed-phase vacuum liquid chromatography (RP-VLC), and the phytochemical contents and α-glucosidase inhibitory activities of the fractions were evaluated. The major phenolic compounds in the most active fruit extract were quantitatively determined using high-performance liquid chromatography–diode array detection (HPLC-DAD). The relationships between metabolites and biological activities were investigated through correlation analysis. Results: The fruit extract was distinguished by its α-glucosidase inhibitory activity, total phenolic content, antioxidant capacity, and cytoprotective effect in the high-glucose-induced SH-SY5Y cell model. It showed no marked cytotoxicity at concentrations ranging from 25 to 400 µg/mL and, at 25 µg/mL, attenuated the high-glucose-induced reduction in cell viability, restoring viability to a level close to that of the normal control. Untargeted metabolomic analysis identified 191 metabolites detected in at least two crude extracts, while the metabolites detected exclusively in the fruit extract were predominantly flavonoids and flavonoid glycosides. Fractionation showed that α-glucosidase inhibitory activity was mainly concentrated in the medium-polarity fractions; however, none of the fractions reached the activity level of the crude extract. Chlorogenic acid, rutin, caffeic acid, protocatechuic acid, quercetin, and quercetin-3-O-glucoside were detected and quantified in the fruit extract by HPLC-DAD. Correlation analysis indicated that the observed biological activities may be associated with phenolic acids, flavonoids, and other polyphenolic metabolites. Conclusions: The fruit extract of B. crataegina showed promising α-glucosidase inhibitory activity and cytoprotective effects in the high-glucose-induced SH-SY5Y cell model. The findings suggest that these effects may arise from the combined contribution of multiple constituents within a polyphenolic matrix rather than from a single compound; however, synergistic interactions were not experimentally demonstrated. These results support further evaluation of the fruit extract through mechanistic, in vivo, and standardization studies.
Yiğit Erkmen, Zekiye Ceren Arıtuluk Aydın, E. Koçak et al.· Pharmaceuticals· 0 citations
Echinophora sibthorpiana Guss. (Apiaceae) is an aromatic plant of considerable ethnobotanical significance, traditionally employed as a flavouring and preservative agent in food and valued for its medicinal properties across the Eastern Mediterranean region, yet its non-volatile phytochemistry and biosafety profile remain insufficiently characterized. In the present study, the n-butanol fraction of the 80% methanolic extract of the aerial parts of E. sibthorpiana was fractionated using chromatographic methods and the structures of the isolated compounds were elucidated by 1D and 2D-NMR spectroscopy and HR-ESI-MS. The distribution of Echinophora metabolites isolated by our group across six species in Türkiye was assessed by LC-qTOF-MS. Antioxidant capacity was evaluated by CUPRAC, FRAP, and TEAC assays; DNA-protective activity by the pBR322 plasmid model; genotoxic and antigenotoxic potential in the Drosophila melanogaster wing SMART assay. Four secondary metabolites, known as vicenin-2 (1), rutin (2), isoquercitrin (3) and betulalbuside A (4), were isolated and reported from E. sibthorpiana for the first time. Notably, the C-glycoside flavone vicenin-2 and the acyclic monoterpene glucoside betulalbuside A also represent the first isolation of these compounds from the genus Echinophora. LC-qTOF-MS profiling identified widely distributed flavonoid constituents together with more restricted metabolites that may have chemotaxonomic relevance. The n-BuOH fraction and the flavonol glycosides rutin and isoquercitrin exhibited the highest antioxidant and DNA-protective activities. None of the tested samples displayed genotoxic activity, while all showed antigenotoxic effects against ethyl methanesulfonate-induced DNA damage, with total spot frequency inhibition ranging from 47% to 83%. Overall, these findings provide a first comprehensive characterization of the non-volatile phytochemistry and biosafety profile of E. sibthorpiana and support the further investigation of its constituents as safe antioxidant and chemopreventive agents with potential nutraceutical applications.
Seren Gündoğdu, Gulnur Ipek Erdemli, M. Baran et al.· Antioxidants· 0 citations
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