Search Results (9,271)

Background/Objectives: We aimed to evaluate the efficacy and safety of a short-term dietary intervention using trigonelline-rich Sakurajima radish on vascular endothelial function in patients with metabolic syndrome (MetS). Methods: In this multicenter, open-label, randomized, three-period crossover phase IIb trial, 21 patients with MetS were assigned to three 14-day sequences (Sakurajima radish powder, Aokubi radish powder, and a usual diet), separated by 14-day washouts. The primary outcome was flow-mediated dilation (FMD). Key Secondary outcomes included blood pressure (BP), urinary nitric oxide metabolites (NOx), and the oxidative stress marker 8-hydroxy-2′-deoxyguanosine (8-OHdG). Results: Sakurajima radish did not improve FMD versus the usual diet (p = 0.58) or Aokubi radish (p = 0.59), although a significant negative carryover effect following the Aokubi period likely confounded this estimation. Despite successfully stimulating NO production (elevated urinary NOx, p = 0.03), the intervention paradoxically increased oxidative stress (elevated 8-OHdG/creatinine, p = 0.02) and significantly elevated systolic BP compared with the usual diet (+9.67 mmHg, p = 0.03) and Aokubi radish (+8.86 mmHg, p = 0.04). Conclusions: Sakurajima radish does not appear to improve endothelial function in patients with MetS within the constraints of this short-term crossover design. Importantly, the unexpected negative carryover effect inherently limits the interpretability of this primary FMD outcome, as it may have masked potential physiological benefits. Despite boosting NO production, the intervention paradoxically exacerbated systemic oxidative stress and elevated systolic BP. These findings suggest that in the pro-oxidant environment of MetS, NO-boosting functional foods may induce unintended adverse hemodynamic responses, underscoring the need for careful risk–benefit evaluation and parallel-group trial designs in this specific population. Full article

Wine production is one of the most important agricultural activities worldwide, and generates significant amounts of organic by-products, particularly grape pomace. Traditionally, this was seen as waste, but currently, this residue has been reanalyzed from the perspective of the principles of the bioeconomy and circular economy, demonstrating its potential as a rich source of bioactive compounds with great potential for valorization. Its heterogeneous composition accumulates a variety of polyphenols, dietary fibers, flavonoids, phenolic acids, and other secondary metabolites that confer important biological properties, including antioxidant, anti-inflammatory, and antimicrobial activities. The chemical composition of grape pomace varies substantially according to variety, winemaking method, and extraction conditions, directly impacting its potential application. Extraction methods have progressed from traditional procedures to more advanced techniques such as ultrasound, supercritical fluids, and natural solvents, enabling the selective separation of high-value compounds. This review provides a comprehensive and critical overview of grape pomace valorization, emphasising its composition, green extraction and current industrial applications. In addition, regulatory frameworks and sustainability strategies supporting the integration of grape pomace into value-added production chains are discussed. Overall, grape pomace valorization supports waste reduction and the production of new functional products that balance economic efficiency and environmental responsibility. Full article

Objectives: Plant extracellular vesicles (EVs) mediate intercellular communication and carry tissue-specific metabolites, yet tissue-resolved EV metabolomics in non-model medicinal plants remains poorly explored. Hibiscus syriacus is a valuable medicinal and ornamental species rich in bioactive compounds, but the metabolic profiles of flower- and leaf-derived EVs are unknown. This study aimed to characterize tissue-specific EV metabolomes of H. syriacus and reveal their functional implications. Methods: EVs were isolated from flowers (MJH) and leaves (MJY) of H. syriacus and verified by TEM and DLS. Untargeted LC-MS/MS metabolomics was applied to profile EV metabolites. Multivariate statistics (PCA, OPLS-DA), differential metabolite screening (VIP > 1, p < 0.05), and KEGG pathway enrichment were performed. Results: MJH- and MJY-EVs exhibited typical EV morphology and high purity. In total, 3338 metabolites were identified, dominated by lipids (29.43%). Clear metabolic separation was observed between MJH- and MJY-EVs. Thirty-nine differential metabolites were identified: 31 upregulated in MJH-EVs (lipids, pentadecanoic acid) and eight in MJY-EVs (nucleotides, secondary metabolites). Glycerophospholipid metabolism was the most enriched pathway in MJH-EVs, while MJY-EVs were linked to energy and defensive metabolism. Conclusions: H. syriacus EVs display strong tissue-specific metabolic signatures. Leaf EVs prioritize lipid metabolism for photosynthetic function and stress tolerance, while flower EVs accumulate secondary and energy-related metabolites for reproduction and defense. These findings advance plant EV biology and support potential applications of H. syriacus EVs in cosmetics and agriculture. Full article

The genus Salvia L. represents one of the most pharmacologically significant groups within the Lamiaceae family. This study investigates the phytochemical profiles and biological activities of six Salvia species native to Türkiye (S. dorystaechas B.T.Drew, S. sclarea L., S. glutinosa L., S. tomentosa Mill., S. argentea L., and S. aethiopis L.) to scientifically validate their extensive use in Turkish traditional medicine. Phytochemical characterization was performed using Liquid Chromatography–High-Resolution Mass Spectrometry (LC-HRMS), while biological potential was evaluated through antioxidant (DPPH), antimicrobial (MIC), and cytotoxicity (MTT on NIH/3T3 cells) assays. Among the taxa, S. dorystaechas exhibited the most potent antioxidant activity, with IC₅₀ values of 0.090 mg/mL (infusion) and 0.072 mg/mL (ethanolic), which strongly correlated with high total phenolic contents (111.50 and 125.55 mg GAE/g, respectively). This species may also serve as a potential source of bioactive compounds. Antimicrobial screenings against pathogenic bacteria and Candida spp. demonstrated modest inhibitory effects, with MIC values ranging from 625 to >5000 µg/mL. Safety profiling indicated that the ethanolic extract of S. tomentosa showed the lowest cytotoxicity (IC₅₀ 562.37 ± 49.50 µg/mL) among the tested samples, which nonetheless indicates a relatively narrow therapeutic window. LC-HRMS profiling revealed the presence of flavonoids and phenolic diterpenes, such as carnosol and rosmanol, providing a chemical rationale for the observed moderate activities. Consequently, rather than direct systemic pharmacological agents, these findings suggest that the studied Salvia species could serve as preliminary botanical sources for the isolation of specific secondary metabolites or for restricted topical applications. Full article

The present study describes the phenolic profile of the leaves of 12 different willow species by UPLC^®-RP18-PDA in terms of variability between species, years, harvest month, and among sexes. The analyzed compound classes include salicylic alcohol derivatives (SADs), caffeic acid derivatives (CADs), coumaryl alcohol glucosides (CAGs), flavan-3-ols, flavanones, flavanonols, flavones, and flavonols. Furthermore, the Salix species were chemotaxonomically classified on this basis, and correlations between the constituent classes were analyzed. The investigations indicate that the phenolic spectrum is highly species-specific but reveals no sex-specific variation. The flavan-3-ol content varied substantially among species, ranging from 2.1–36 mg/g DW and S. bicolor was determined to be a species of particular phytochemical interest, as it contained high concentrations of flavanonols (13 mg/g DM) and flavones (24 mg/g DW). Furthermore, at the end of the growth period, the secondary metabolite content was significantly higher and the compound classes CADs and flavan-3-ols were found to be significantly influenced by the harvest year. Chemotaxonomical classification revealed the separation of S. bicolor, S. purpurea, and S. caprea from the other species when compared with the generally accepted classification of the genus. This study contributes to a more comprehensive phytochemical characterization of willow species, which may support the development of willow extracts. Full article

The gut microbiota produces chemically diverse metabolites whose levels fluctuate depending on the time of day, driven by bidirectional coupling between host intestinal circadian clocks and intrinsic microbial oscillators. Although short-chain fatty acids have received the most attention as microbial circadian effectors, a broad class of metabolites, including secondary bile acids, indole derivatives, and branched-chain fatty acids, engage distinct epithelial receptors and transcriptional programs through mechanisms that are, to varying degrees, subject to circadian regulation. However, the mechanisms by which these metabolite classes collectively regulate barrier integrity, mucosal immune tone, and stem cell-driven renewal, as well as the consequences of their rhythmicity loss under circadian misalignment, have not been systematically reviewed. This review constructs a mechanistic framework linking microbial metabolite rhythmicity to the circadian regulation of intestinal epithelial homeostasis and evaluates dietary and probiotic interventions that modulate this axis as chronobiotic strategies. Convergent mechanisms, unresolved questions, and translational opportunities are identified across in vitro, preclinical, and clinical evidence. Full article

Aspergillus nidulans, a model filamentous fungus endowed with well-established genetic tools and a repertoire of cryptic secondary metabolite biosynthetic gene clusters (BGCs), is extensively exploited as a microbial chassis for heterologous biosynthesis. Mining of its secondary metabolites facilitates the discovery of novel bioactive compounds and the development and application of chassis cells. In the course of heterologous expression of exogenous genes in A. nidulans, we unexpectedly observed the activation of cryptic host BGCs, which resulted in substantial alterations to its secondary metabolic profile. Four previously undescribed compounds (1–4), together with six known analogs (5–10), were isolated from three recombinant A. nidulans strains. Notably, compounds 1–3 are the first naturally occurring examples of diketopiperazine–isoindolinone hybrid alkaloids, while compound 4 is a previously unreported benzofuran carboxylic acid derivative. Their structures and absolute configurations were assigned by interpretation of a combination of spectroscopic data and electronic circular dichroism calculations. Compounds 4 and 5 exhibited potent DPPH radical scavenging activity (IC₅₀, 6.01 and 7.00 μg·mL⁻¹, respectively). This study uncovers a “metabolic perturbation” effect on the host metabolic network during heterologous expression and offers a new strategy for activating silent gene clusters and discovering novel natural products through genetic manipulation. Full article

Temporary immersion systems (TISs) are an advanced biotechnological platform for the large-scale cultivation of medicinal plants and the consistent production of high-value secondary metabolites. In this study, we evaluated three immersion regimes with stand-by periods of 4, 8, or 12 h, each paired with a 15-minute immersion period, to optimise shoot growth and colchicine accumulation in Colchicum autumnale L. and Colchicum bivonae Guss. The 4 h stand-by/15 min immersion regime yielded the highest growth index (C. autumnale: 0.75 ± 0.08; C. bivonae: 1.25 ± 0.03) and maximum colchicine content (C. autumnale: 0.19 ± 0.01 mg/g dry biomass; C. bivonae: 0.25 ± 0.02 mg/g dry biomass). Using gas chromatography-mass spectrometry (GC-MS), detailed metabolic profiling of cultures grown under this optimised regime was performed, resulting in the identification of 46 metabolites, including amino acids, organic acids, sugars, sugar alcohols, phenolic, and fatty acids. Volcano plot analysis revealed 11 upregulated and 5 downregulated metabolites in C. autumnale relative to C. bivonae. Significance analysis of metabolomics (SAM) identified 34 metabolites with statistically significant differences between two species. Hierarchical clustering and partial least squares discriminant analysis (PLS-DA) confirmed clear species separation, with Component 1 explaining 68.8% of the total metabolic variance. Glucose-6-phosphate (VIP = 2.01), citric acid (VIP = 1.85), asparagine (VIP = 1.67), and γ-aminobutyric acid (GABA; VIP = 1.52) were the primary biomarkers differentiating the species. These findings confirm that TISs provide an optimised environment for biomass accumulation and stable alkaloid biosynthesis in the Colchicum genus, with C. bivonae emerging as a promising candidate for biotechnological exploitation. Full article

Background: The genus Satureja L. (savory) includes approximately 200 aromatic herb and shrub species distributed worldwide. These plants are widely used in traditional and modern medicine, culinary practices, and agriculture. This review summarises knowledge on the traditional uses, phytochemistry, and pharmacological activities of Satureja species published between March 2014 and 2025. Methods: Peer-reviewed literature was searched on Web of Knowledge, PubMed, Scopus, and SciFinder using the keywords “Satureja” and “savory.” A total of 171 relevant articles were analyzed, focusing on ethnomedicinal use, chemical constituents, and pharmacological effects. Results: Recent ethnobotanical studies documented the use of local medicinal plants, including Satureja, in several European regions. Phytochemical research identified major groups of compounds such as essential oils, flavonoids, phenolic acids, jasmonates, di- and triterpenes, and steroids. Essential oils are the most studied and show high variability among species due to environmental and genetic factors. Pharmacological research largely highlights antimicrobial, antioxidant, and antitumor activities, as well as protective effects against chemotherapy-induced side effects. Additional studies report neurological benefits, including prevention of opioid analgesic tolerance, antiepileptic activity, and memory-enhancing effects. Satureja species have been the subject of various innovative developments aimed at preserving food quality, improving coating materials in the food industry, and developing new environmentally friendly biopesticides. Conclusions: Future research should prioritize the study of individual bioactive compounds, their mechanisms of action, and structure–activity relationships. Advances in nanoformulations and modern extraction technologies offer promising directions to support the medicinal and food-industry applications of Satureja-derived products. Full article

MicroRNAs (miRNAs) are key regulators of gene expression at the post-transcriptional level, playing multiple roles in plant growth and development, signal transduction, environmental stress response, and secondary metabolite formation. The biological functions of miRNAs are relatively conserved in plants, yet certain miRNAs display regulatory functions and mechanisms that are species-specific. Increasing evidence underscores the significance of miRNA-transcription factor (TF) molecular modules in plant organ development. Compared to other Poaceae plants such as Oryza sativa, bamboo (Poaceae: Bambusoideae) exhibits a greater diversity of developmental patterns in organ development throughout its life cycle. However, current research on miRNA-mediated bamboo organ development remains relatively scattered, and the mechanisms of action of key miRNA-TF modules are still poorly understood in bamboo plants. In the review, we outlined the unique biological characteristics of root, shoot, culm, leaf, and flower in bamboo plants and synthesized the research progress on miRNA-mediated regulation of bamboo organ development. Prominently, we focused on the potential regulatory functions of miRNA-TF modules in shaping developmental characteristics of bamboo organs. Last but not least, we summarized the current research limitations in this field and proposed future directions and strategic approaches to facilitate further in-depth exploration. This review not only deepens our understanding of the unique developmental characteristics of bamboo organs but also clarifies the research framework of miRNA-TF modules governing these processes, thereby providing theoretical references for innovative breeding and genetic improvement of bamboo plants. Full article

Liver injury is a complex pathological condition with increasing incidence due to diverse etiologies, including drug-induced liver injury, metabolic dysfunction-associated steatotic liver disease, alcoholic liver disease, viral hepatitis, and autoimmune disorders. Its progression is characterized by persistent hepatic damage and gradual loss of liver function, which may ultimately lead to fibrosis, cirrhosis, and liver failure. However, currently available hepatoprotective drugs still present several limitations, such as insufficient target specificity, limited therapeutic efficacy, and potential adverse effects, highlighting the need for safer and more effective alternatives. Based on a comprehensive search of databases including PubMed, Web of Science, China National Knowledge Infrastructure and Google Scholar, this review summarizes the pathogenic mechanisms of major liver injury types and the therapeutic potential of natural alkaloids. As key secondary metabolites of medicinal plants, alkaloids exhibit structural diversity, potent bioactivities, and favorable safety profiles. Increasing evidence suggests that natural alkaloids exert hepatoprotective effects through multi-target and multi-pathway mechanisms, including the regulation of oxidative stress, inflammation, lipid metabolism, and cell death. These findings highlight their promising potential for the prevention and treatment of liver injury and provide a theoretical basis for the development of novel hepatoprotective agents. Full article

Thirteen new decaline polyketides, namely, zosteropenillines T–W (1–4), 8-hydroxypallidopenilline A (5), 13-epi-zosteropenilline P (6), 11-epi-zosteropenilline N (7), 15-hydroxyzosteropenilline M (8), 8-hydroxyzosteropenilline M (9), 11-epi-zosteropenilline M (10), and zosteropenillines X–Z (11–13), along with 17 known related compounds (14–30) were isolated from the ethyl acetate extract of the marine-derived fungus Penicillium yezoense KMM 4679 cultivated on MgCl₂-containing nutrient medium. The structures of the isolated compounds were established based on spectroscopic methods. The absolute configurations of zosteropenillines T (1) and V (3) were determined using time-dependent density functional theory (TD-DFT) calculations of the ECD spectra. X-ray diffraction analysis data were obtained for the known zosteropenilline S (28). A biogenetic pathway for 1–13 was proposed. The effects of the compounds on Staphylococcus aureus and Candida albicans growth and biofilm formation were observed. Zosteropenillines U (2), Y (12) and Z (13) with higher activity against C. albicans biofilms were nontoxic for normal cardiomyocyte H9c2 cells, making them promising anti-candidal agents. Moreover, zosteropenillines U and Y demonstrated cardioprotective effects in acute ischemia/reperfusion and CoCl₂-mimicking hypoxia in vitro models. Full article

Cadmium (Cd) and polystyrene (PS) microplastic co-contamination in agricultural soils poses a potential threat to food security. Some functional microorganisms in soil can alleviate the dual stress of Cd and PS on crops. In this study, a biofilm-forming bacterium, Enterobacter sp. W5, was isolated from heavy metal-contaminated rhizosphere soil. Strain W5 exhibited Cd removal efficiency (46.3%) and strong biofilm-forming capacity (OD₅₇₀ = 5.05), and it effectively colonized PS microplastic surfaces. XPS analysis detected bacterial functional groups (C–O–C, C=O) and PS-associated signals (O–C=O), which may act synergistically in Cd²⁺ adsorption. Furthermore, XPS and XRD analyses revealed the presence of Cd-containing precipitates (including CdS, CdO, and Cd₃(PO₄)₂). In hydroponic wheat experiments, W5 inoculation alleviated Cd-PS combined stress, thus significantly promoting plant growth and reducing Cd accumulation by 22.6% in roots and by 34.2% in aboveground tissues. Subcellular distribution analysis revealed that W5 enhanced Cd retention in root cell walls, thereby limiting its translocation to active cellular compartments. Proteomic analysis identified a set of 11 consistently downregulated proteins, including A0A3B6HQ68 and A0A3B6KJV9, which were enriched in secondary metabolite biosynthesis pathways. Bioinformatic analysis suggests that these proteins may be associated with Cd stress responses, though their exact roles remain to be verified. Collectively, this study provides a valuable microbial resource and mechanistic insights into the application of biofilm-forming bacteria for mitigating combined heavy metal–microplastic pollution in agricultural systems. Full article

Objectives: This study aimed to isolate secondary metabolites from sea cucumber-associated fungus Trichoderma koningii KMM 4751, obtain their bromine derivatives, and investigate their antimicrobial and cytotoxic activities. Results: 3-Ethyl-4-hydroxy-6-methyl-2H-pyran-2-one (EHMP) was isolated from fungal extract. It was brominated, and a previously unreported 6-(bromomethyl)-3-ethyl-4-hydroxy-2H-pyran-2-one (Br-EHMP) was obtained. EHMP inhibited the formation of Candida albicans biofilms with an IC₅₀ of 49.3 µM, but Br-EHMP was less active. Simultaneously, bromination of EHMP significantly enhanced the inhibitory effect of Br-EHMP on Staphylococcus aureus growth and biofilm formation without increasing cytotoxicity to H9c2 cells. Br-EHMP at 10 μM can inhibit sortase A activity by near 30% in a cell-free assay. In silico molecular docking predicted the interaction of Br-EHMP with Cys184 in the sortase A active site. Conclusions: Br-EHMP emerges as a promising antibiofilm agent, and its mechanism involves sortase A inhibition. Full article

Although solid-state fermentation (SSF) has long been used in food production in various traditional contexts, it is now emerging as a particularly promising strategy for the development of functional food ingredients from plant materials and agro-industrial side streams. This review examines recent advances in the application of SSF to enhance the nutritional, functional, sensory, and technological properties of food matrices. Current evidence indicates that SSF can increase the bioactive potential of plant-based substrates by promoting the release and biotransformation of phenolic compounds, while also improving antioxidant capacity, protein digestibility, and techno-functional performance. In addition, the process may support the formation of food-relevant metabolites, including vitamins, peptides, organic acids, and other secondary compounds, while reducing selected antinutritional, allergenic, and undesirable constituents. These compositional changes are often accompanied by modifications in aroma, volatile profiles, visual attributes, and, more recently, gut microbiota-related effects. Attention is given to the use of fungal-based processes for the valorization of cereals, legumes, fruit by-products, and other underutilized substrates. The review also addresses the growing industrial interest in SSF, especially in relation to mycelium-based foods, alternative proteins, functional ingredients, and feed applications. Despite its clear potential, the broader implementation of SSF will require further research and development to support its effective translation into food applications. Full article