Search Results (6,069)

Helichrysum species (Asteraceae) are renowned for their diverse phytochemical profiles and traditional medicinal applications. Among their specialized metabolites, phloroglucinol-α-pyrone derivatives represent a structurally unique and pharmacologically significant class of compounds. This review consolidates over five decades of phytochemical research, documenting 52 distinct compounds isolated from 11 Helichrysum species across the Mediterranean, African, and Iranian regions. The compounds are organized into structural subclasses, including monopyrones, dipyrones, and various phloroglucinol derivatives distinguished by their molecular scaffolds. Isolation yields reported in the literature range from trace amounts to relatively abundant constituents (0.48% w/w), with arzanol emerging as the most extensively studied compound. Bioactivity profiles reveal anti-inflammatory, antimicrobial, antioxidant, and antiparasitic properties, with arzanol demonstrating potent dual inhibition of mPGES-1 and 5-LOX. This review provides comprehensive reference data for future investigations into the chemistry and therapeutic potential of α-pyrone secondary metabolites from Helichrysum species. Full article

Black soldier flies (Hermetia illucens) are widely used in organic waste bioconversion, and their adaptive capacity to region-specific food waste is critical for efficient application. This study aimed to explore the molecular mechanisms underlying the adaptation of black soldier fly larvae to long-term domestication on regional food waste from Kunming and Qujing. Integrated transcriptomic and metabolomic analyses were performed to identify differences in gene expression and metabolite profiles between the two groups of larvae. The results showed significant divergence in gene expression networks, with key differences in cytochrome P450 detoxification pathways, TOR nutrient-sensing pathways, and zf-C2H2 zinc finger transcription factor families. Metabolomic analysis revealed region-specific metabolic reprogramming, including enhanced branched-chain amino acid degradation in one group and activated sphingolipid signaling pathways with accumulated indole derivatives in the other. Additionally, 13.86% of unannotated metabolites in the metabolome exhibited high connectivity in metabolic networks, suggesting potential roles as “bridge metabolites” in adaptation. These findings demonstrate that long-term domestication on regional food waste drives adaptive differentiation in black soldier fly larvae through regulatory network remodeling, metabolic reprogramming, and activation of hidden metabolic reserves. The study provides a theoretical basis for optimizing the application of black soldier flies in waste treatment and strain breeding and establishes a “substrate-gene-metabolism” multi-omics framework for understanding insect adaptive evolution. Full article

Background: High-throughput metabolomics studies have promoted the discovery of candidate biomarkers linked to atherosclerosis (AS). This narrative systematic review summarises metabolomics studies conducted in (1) individuals with subclinical AS (assessed by imaging techniques such as carotid intimal media thickness, IMT, and coronary artery calcium, CAC), (2) patients with established atherosclerotic plaques, and (3) individuals with AS risk factors. Methods: The systematic search was conducted in the PubMed database according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. The inclusion criteria were as follows: (i) publication date between 2009 and 2024; (ii) identification of potential biomarkers for AS in subjects with a diagnosis of AS or with one or more traits characteristic of the disease (i.e., CAC or IMT); (iii) identification of potential AS biomarkers in subjects with atherogenic clinical conditions (i.e., Down’s syndrome, DS, polycystic ovarian syndrome, PCOS, and systemic lupus erythematosus, SLE); (iv) metabolomic studies; and (iv) studies in human samples. Exclusion criteria comprised the following: (i) studies on lipid metabolic diseases unrelated to AS, (ii) “omics” results not derived from metabolomics, (iii) reviews and studies in animal models or cell cultures, and (iv) systematic reviews and meta-analyses. Of 90 eligible studies screened, 24 met the inclusion criteria. Results: Across subclinical and overt AS, consistent disturbances were observed in amino acid, lipid, and carbohydrate metabolism. Altered profiles included branched-chain amino acids (BCAAs), aromatic amino acids (AACs) and derivatives (e.g., kynurenine–tryptophan pathway), bile acids (BAs), androgenic steroids, short-chain fatty acids (FAs)/ketone intermediates (e.g., acetate, 3-hydroxybutyrate, 3-HB), and Krebs cycle intermediates (e.g., citrate). Several metabolites (e.g., glutamine, lactate, 3-HB, phosphatidylcholines, PCs/lysophosphatidylcholines, lyso-PCs) showed reproducible associations with vascular phenotypes (IMT/CAC) and/or clinical AS. Conclusions: The identification of low-weight metabolites altered in both subclinical and overt AS suggests their potential as candidate biomarkers for early AS diagnosis. Given the steady increase in deaths from cardiovascular disease, a manifestation of advanced AS, this finding could have significant clinical relevance. Full article

Somatic cell nuclear transfer (SCNT) or cloning technology is widely used in agriculture and biomedicine. However, the application of this technology is limited by the low developmental competence of cloned embryos or fetuses, which frequently exhibit abnormal development of trophoblast cells or placentas. The purpose of this study was to investigate the possible causes of the erroneous placental development of SCNT-derived pig fetuses. The placental transcriptomic and lipidomic profiles were compared between 30-day-old SCNT- and artificial insemination (AI)-produced pig fetuses. Differentially expressed lipid metabolites between two groups of placentas were selected to test their effects on porcine trophoblast cell activity. The results showed that SCNT placentas exhibit impaired lipid metabolism and function. The level of a metabolite, lysophosphatidylcholine (LPC), in the glycerophospholipid metabolism pathway was substantially increased in SCNT placentas, compared with AI placentas. The elevation in LPC content may lead to impaired placental development in cloned pig fetuses, as LPC inhibited the proliferation and migration of porcine trophoblast cells. This study discovers a main cause of erroneous development of cloned pig fetuses, which will be beneficial for understanding the regulation of SCNT embryo development, as well as developing new methods to improve the efficiency of pig cloning. Full article

In recent years, wine producers have increasingly experimented with ancient fermentation and ageing techniques, such as the use of ceramic containers or pitch-coated amphorae. Despite growing interest in these traditional practices, few studies have investigated the chemical composition of the resulting wines. This is the first study that characterises pine pitch, historically used as a coating material, and evaluates the impact of pitched pottery vessels on the winemaking process and wine composition using a foodomics approach. Vinification was carried out in both pitch-coated and uncoated (control) clay containers. Chemical differences between must and wine produced in pitched and unpitched vessels were assessed using targeted and untargeted ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS). Compared to the control, must and wine from the pitch-coated vessels had higher concentrations of many polyphenols such as anthocyanins, coumaric acid and tartaric acid, while procyanidins were present in significantly lower amounts. These findings reveal that pitch-coated ceramic vessels significantly influence wine composition, offering a first step toward deeper investigations into how fermentation environments shape metabolite profiles. This knowledge not only enhances our understanding of traditional practices but also opens new avenues for innovation in contemporary oenology. Full article

Background: Blue light-induced retinal photodamage represents a growing public health concern globally. Lactic acid bacteria and their bioactive metabolites represent a promising therapeutic strategy for mitigating such damage. Methods: This study evaluated the protective efficacy of Limosilactobacillus fermentum IOB802 and Lactobacillus plantarum subsp. plantarum IOB602 against blue light-induced retinal injury using both in vitro and in vivo models. Results: In ARPE-19 cells exposed to blue light, treatment with postbiotics from IOB802 and IOB602 significantly restored cell viability (p < 0.05), enhanced antioxidant enzyme activities (GSH-Px, SOD, and CAT, p < 0.05), and reduced inflammatory cytokine levels (IL-6, IL-1β, TNF-α, and VEGF, p < 0.05). Subsequent validation in a murine blue light-induced retinal damage model demonstrated that IOB802 notably preserved retinal architecture, upregulated antioxidant defenses, and promoted the expression of tight junction proteins. Mechanistically, IOB802 suppressed inflammation by inhibiting the phosphorylation of the IκBα/NF-κB pathway. Through 16S rDNA sequencing and short-chain fatty acid (SCFA) profiling, IOB802 was further shown to restore gut microbial diversity, increase beneficial bacteria, including Lachnospiraceae, Rikenellaceae, and Bacteroidaceae (p < 0.05), and elevate concentrations of key SCFAs (butyrate, acetate, and propionate; p < 0.05), underscoring the role of the gut–retina axis in mediating retinal protection. Conclusions: In summary, IOB802 and its postbiotics alleviate blue light-induced retinopathy through antioxidative, anti-inflammatory, and microbiota-modulating mechanisms, offering novel insights into microbiome-based interventions for retinal diseases. Full article

Muscari neglectum is a Mediterranean geophyte with a long tradition of ethnomedicinal use, yet the phytochemistry of its bulbs remains underexplored compared with aerial parts. This study aimed to characterise the metabolite profile of M. neglectum bulbs and to assess their antioxidant and radical scavenging potential, and anti-inflammatory potential. Bulb extracts were obtained by hydroethanolic extraction and analysed through HPLC-ESI-qTOF-MS, leading to the annotation of 72 compounds spanning diverse chemical families, including flavonoids, hydroxycinnamic acids, terpenoids, fatty acids, and triterpenoid saponins. Flavonoids constituted the most abundant group, with homoisoflavanones representing a characteristic class of metabolites in the Muscari genus and reflecting its distinctive secondary metabolism. Quantitative analyses revealed a high total phenolic content (65.5 mg GAE/g DE) and total flavonoid content (14.3 mg Epi/g DE). Antioxidant assays demonstrated measurable reducing power (FRAP: 0.26 mmol Fe²⁺/g DE; TEAC: 0.45 mmol TE/g DE), while radical scavenging assays indicated activity against superoxide anion (IC₅₀ = 848 mg/L) and hypochlorous acid (IC₅₀ = 9.2 mg/L). Additionally, the extract inhibited xanthine oxidase (IC₅₀ = 20.6 mg/L). Furthermore, the extract exhibited significant anti-inflammatory activity, effectively scavenging nitric oxide radicals (IC₅₀ = 78 ± 3 mg/L) and inhibiting lipoxygenase (IC₅₀ = 66 ± 2 mg/L), suggesting that phenolic compounds and triterpenoid saponins contribute to the modulation of oxidative and enzymatic inflammatory pathways. These findings highlight M. neglectum bulbs as a rich source of structurally diverse bioactive compounds with antioxidant and anti-inflammatory capacity. The results provide a chemical basis for their traditional use and reinforce the value of bulb-specific studies within the Asparagaceae family. Full article

Background/Objectives: Lavandula stoechas has reported bioactivities, but its selective anticancer potential in human models remains insufficiently defined. This study aimed to compare cytotoxicity and selectivity of ethanol and methanol extracts prepared from fresh and dried L. stoechas and to profile candidate bioactive metabolites. Methods: Aerial parts Lavandula stoechas L. subsp. stoechas (L. stoechas L.) were extracted with ethanol or methanol from fresh (LsFE, LsFM) and dried (LsDE, LsDM) material. Cytotoxicity was assessed in cancer (MDA-MB-231, T98G, RT4) and non-malignant (hGF, ARPE-19) cells using Hoechst 33342-stained nuclear counts and MTS viability at 24–48 h. Metabolite identification was performed using LC–QTOF–MS in both positive and negative ESI modes, supported by database search results. Results: All extracts reduced viability in a dose- and time-dependent manner. Among them, the ethanol extract from fresh material (LsFE) displayed the highest cytotoxic potency and the most favorable selectivity profile, markedly reducing viability in breast (MDA-MB-231) and glioblastoma (T98G) cells while exerting only mild effects on non-malignant fibroblast (hGF) and retinal epithelial (ARPE-19) cells. In contrast, extracts from dried material, particularly LsDE, showed broader cytotoxicity across both cancerous and non-cancerous lines. LC–MS highlighted sesquiterpenoids (Kikkanol A; 3(4→5)-Abeo-4,11:4,12-diepoxy-3-eudesmanol), phenolics (tyrosol; 3,4-dihydroxybenzoic acid), flavonoid/ionone derivatives (luteolin 5,3′-dimethyl ether; 3-hydroxy-β-ionone), oxidized fatty acids (9(S)-HpODE, α-EpODE, 5,12-dihydroxy-eicosatetraenoic acid), and jasmonates (12-hydroxyjasmonic acid; dihydrojasmonic acid methyl ester), especially enriched in LsFE. Conclusions: Ethanol extracts of L. stoechas L., especially LsFE, demonstrated selective cytotoxicity against cancer cells while exerting relatively mild effects on non-malignant cells. The metabolite profile of L. stoechas L. extracts revealed a diverse composition, including phenolics, terpenoids, flavonoids, and oxidized lipids, which are commonly associated with biological activity. These results suggest that LsFE is a promising candidate for further studies focusing on compound isolation and mechanistic analysis. Full article

This study presents a comprehensive analysis of the polyphenolic profiles of six red prickly pear varieties across eight ripening stages, employing liquid chromatography and machine learning. We identified 29 phenolic compounds, including flavonols, phenolic acids, flavan-3-ols, and dihydrochalcones. The ‘Grifa’ variety showed a robust biosynthesis pathway, indicating higher antioxidant potential. Notably, significant variety-specific variations were observed, particularly in hydroxycinnamic and hydroxybenzoic acids, suggesting genetic influences on phenolic biosynthesis. The Random Forest algorithm was effectively used for classifying fruit varieties and ripening stages, with key metabolites like chlorogenic acid playing a crucial role in differentiation. The study highlights the dynamic nature of phenolic metabolism in red prickly pear fruit and underscores the potential of machine learning in agricultural research. Our findings contribute significantly to understanding the phenolic composition of these fruits, offering valuable insights for agricultural practices and nutritional evaluations, as well as highlighting their potential as sources of antioxidants. Full article

Background/Objectives: Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by sustained inflammation, leading to diabetic kidney disease (DKD). This study investigated urinary tubular injury biomarkers and metabolomic profiles in relation to albuminuria and renal function across varying durations of T1D. Methods: A cross-sectional analysis was conducted in 247 youth-onset T1D patients categorized by disease duration: short ≤ 5 years (T1D-S, n = 62), medium 6–10 years (T1D-M, n = 67), and long > 10 years (T1D-L, n = 118). Urinary cytokines (MCP-1, KIM-1, NGAL) were measured by ELISA. Metabolomic profiling was performed using ¹H-NMR spectroscopy. Results: Urinary MCP-1/Cr, KIM-1/Cr, and NGAL/Cr levels were significantly elevated in T1D patients compared with non-diabetic controls, but did not correlate with disease duration. Metabolomic profiling identified distinct urinary signatures across T1D duration. Specifically, N-acetylcysteine (NAC) and N-delta-acetylornithine (NAO) increased progressively, while N-acetylaspartate (NAA) and pyruvic acid decreased with longer disease duration. These four metabolites remained statistically significant after both based on Mann–Whitney tests with false discovery rate (FDR) correction (q < 0.05) and application of a conservative alpha threshold (p < 0.01), suggesting potential disruptions in amino acid and carbohydrate metabolism. Conclusions: Urinary biomarkers (MCP-1/Cr, NGAL/Cr, and KIM-1/Cr) are sensitive indicators of subclinical kidney dysfunction in T1D patients, often preceding albuminuria. Alterations in amino acid-related metabolites (NAC, NAA, and NAO) and pyruvate highlight possible metabolic disturbances associated with T1D duration and oxidative stress. However, given the cross-sectional design, longitudinal studies are needed to confirm causality and clarify their predictive value in DKD progression. Full article

Background: To investigate the endogenous metabolites in Polygonatum odoratum (Mill.) Druce from different geographical origins within Guizhou Province, the metabolic profiles of samples from 12 regions were analyzed using ultra-high-performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS). Methods: Multivariate statistical methods including principal component analysis (PCA), hierarchical clustering analysis (HCA), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were employed to explore the influence of geographical origin on the metabolic composition of P. odoratum. Results: PCA revealed significant differences among samples from different regions which showed clear clustering patterns in our study, indicating that the growing environment considerably affects the metabolite profiles of P. odoratum. A total of 6055 potential metabolites were detected in both positive and negative ion modes. Significantly differential metabolites were then screened based on a fold change (FC) ≥ 2 or ≤0.5 and p < 0.05. Comparative analysis was conducted on representative samples from three clustered regions: As, ZYMT, and XY−1. The results indicated that alcohols, nucleotides and their derivatives were the major differential metabolites between AS and ZYMT, and alcohols were the key differential metabolites between AS and XY−1, while ketones and sphingolipids were the most significant differential metabolites between ZYMT and XY−1. KEGG enrichment analysis revealed that the pathways of nucleotide metabolism, amino acid biosynthesis, and aminoacyl-tRNA biosynthesis were notably disturbed, suggesting their crucial roles in the synthesis of differential metabolites in P. odoratum. Conclusions: These findings demonstrated the notable differences in the metabolite composition of P. odoratum from different regions of Guizhou province. Full article

Polygala tenuifolia Willd., a widely used traditional Chinese medicine, has the function of coordinating heart and kidney and eliminating swelling. However, its renal-protective efficacy and possible material basis remain unknown. The aim of the study was to investigate the renal-protective effect of Polygala tenuifolia Willd. and identify the potential active substance and molecular mechanism. A gentamicin-induced kidney injury model was established to investigate efficacy. Secondly, potential active substances and molecular mechanisms were studied through integrated gut microbiota–drug interaction analysis and network pharmacology at a cellular level. Finally, 16S rRNA sequencing and untargeted metabolomics were used to elucidate the gut microbiota composition and metabolic profile change. Polygala tenuifolia Willd. extracts (PWE), with tenuifoliside A (TFSA) as the key compound, significantly reversed gentamicin-induced acute kidney injury in mice. The gut microbiota-derived carboxylesterase metabolized TFSA into four characteristic metabolites (M1–M4). Notably, both TFSA and M4 were detected in kidney and exerted protective effects via inhibiting TLR4–NF-κB pathway. Furthermore, metabolic pathways and gut microbiota composition change were identified. PWE treatment significantly increased the abundance of beneficial bacteria such as Akkermansia and Blautia, while reducing the abundance of harmful bacteria such as Oscillospira. Subsequently, PWE can reverse amino acid metabolic abnormalities by regulating the biosynthesis of phenylalanine, tyrosine, and tryptophan and ameliorating tryptophan metabolism disorder. This study was the first to verify the renal-protective effect of PWE and identify the effective substance basis (TFSA) and the molecular mechanism, providing a scientific foundation for the development of kidney drug treatment strategies targeting the intestinal flora. Full article

Hepatocellular carcinoma (HCC), the most common primary liver malignancy, usually develops in patients with cirrhosis, yet the metabolic mechanisms that distinguish the two conditions remain poorly understood. This study aimed to explore metabolic dysregulations in HCC compared with cirrhosis and to identify potential biomarkers, especially lipids, with diagnostic and prognostic value. We prospectively studied 81 patients—41 with HCC and 40 with cirrhosis—using high-resolution UHPLC-QTOF-ESI⁺-MS to characterize their serum lipidome. Across both groups, 322 metabolites were identified, but their distribution was strikingly different. Patients with HCC showed higher levels of sphingolipids, glycerophospholipids, diglycerides, sterols, and certain fatty acids, reflecting tumor-related metabolic rewiring. In contrast, cirrhotic patients had increased D-glucose, 5-hydroxymethyluracil, lysophospholipids, acylcarnitines, and specific fatty acid derivatives. Several lipids, such as CerPE(d16:2/24:1(2OH)), SM(d18:0/14:0), PA(36:6), and GlcCer(d18:1/12:0), displayed excellent discriminative accuracy, highlighting their role as putative biomarkers. These findings underscore the importance of lipid metabolic reprogramming in HCC, characterized by membrane remodeling, energy adaptation, and oxidative stress resistance. Integrating lipidomic profiling into clinical practice could improve early detection and risk stratification in cirrhotic patients. Larger, multicenter studies are needed to validate these biomarkers and assess their therapeutic implications. Full article

Tomato is one of the most important vegetable crops worldwide, with about one quarter of the yearly production of fresh fruits dispatched to the processing industry. Paste, canned tomatoes, and sauces represent the three leading categories. Background/Objectives: The metabolic profile of processed tomatoes can be modified by several production steps, affecting the nutritional and sensory profile of the finished product. Despite this, a detailed metabolomic profiling of transformed tomatoes is currently missing. The goal of this investigation is to provide qualitative metabolomic profiling of tomato purees with two main advances: first, the use of a more sustainable analytical approach based on a single extraction protocol and one-shot analysis for multiple information retrieval on different compound classes; second, the achievement of a curated database consolidated over a wide collection of commercial samples representative of the Italian market. Methods: A non-selective ethanol extraction was applied to collect the main polar metabolites followed by untargeted high-resolution MS/MS analysis and software-based compound identification. Results: A list of more than five hundred features was collected and assigned to specific compounds or compound groups with different confidence levels. The results confirmed the persistence in processed tomatoes of the main primary and secondary metabolites already reported in fresh fruits, such as essential amino acids, sugar, organic acids, vitamins, fatty acyls, and phytohormones. Moreover, new insight on specific components never traced before in similar finished samples is provided. Bioactive compounds were detected in all samples, such as oligopeptides with ACE-inhibitor activity, ɣ-aminobutyric acid, alkaloids, and polyphenols (flavonoids, coumarins, and cinnamic acids). Many of these compounds have antioxidant activities, proving the relevance of transformed tomatoes as a source of health-promoting compounds for the human diet. Conclusions: A detailed metabolic profile of commercial tomato puree samples was obtained, and a curated database of metabolites was compiled, which can be useful for multiple purposes, for example, authentication, quality, or nutritional assessments. Full article

Exercise performance is a critical trait for evaluating the economic and breeding value of working and athletic horses, with cardiac structure and function serving as essential physiological determinants of athletic capacity. This study aimed to investigate the multi-omics response mechanisms associated with varying degrees of cardiac remodeling under identical exercise intensity. Twenty 2-year-old Yili horses were selected and categorized based on echocardiographic parameters into a high cardiac remodeling group (BH; EDV > 500 mL, SV > 350 mL, EF > 66%) and a low cardiac remodeling group (BL; EDV < 450 mL, SV < 330 mL, EF < 64%). Blood samples were collected before and after the 1000 m constant-speed test (pre-test high cardiac remodeling group (BH, n = 10), post-test high cardiac remodeling group (AH, n = 10), pre-test low cardiac remodeling group (BL, n = 10), post-test low cardiac remodeling group (AL, n = 10)), and integrated metabolomic, transcriptomic, and miRNA profiling were conducted to systematically characterize molecular responses to exercise-induced stress. Metabolomic analysis identified a total of 1936 lipid metabolites, with the BH group exhibiting stronger post-exercise lipid mobilization and significant enrichment of sphingolipid signaling pathways. Transcriptomic and miRNA analyses further revealed that key miRNAs in the BH group, including miR-186, miR-23a/b, and the let-7 family, along with their target genes (e.g., GNB4, RGS5, ALAS2), were involved in fine regulation of cardiac electrophysiology, oxidative stress, and energy metabolism. Integrated analysis indicated that the AH vs. BH comparison uniquely enriched pathways related to glycine-serine-threonine metabolism and glycosylphosphatidylinositol (GPI)-anchor biosynthesis, whereas the AL vs. BL comparison showed unique enrichment of α-linolenic acid and arachidonic acid metabolism pathways. Ultimately, multi-omics integration identified that in the BH group, eca-let-7d, eca-let-7e, eca-miR-196b, eca-miR-2483, and eca-miR-98 regulate ALAS2 and, together with GCSH, influence the enrichment of lipids such as PS(17:0_16:1), PS(18:0_18:1), and PS(20:0_18:1). These lipids participate in glycine, serine, and threonine metabolism through complex pathways, collectively modulating energy supply, inflammatory responses, and muscle function during exercise. This study reveals the molecular mechanisms by which horses with high cardiac remodeling maintain energy homeostasis and myocardial protection during exercise. Full article