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21 pages, 2041 KB  
Article
Short Peptide with Sequence of LAGAAHF, Identified from Edible Bird’s Nest, Reduces Dermatitis Symptoms in Mice
by Queenie Wing Sze Lai, Yaxin Wang, Shengying Lin, Gary Ka Wing Yuen, Dusadee Ospondpant, Alex Xiong Gao, Tina Ting Xia Dong, Xuncai Liu, Qunyan Fan and Karl Wah Keung Tsim
Pharmaceuticals 2026, 19(4), 649; https://doi.org/10.3390/ph19040649 (registering DOI) - 21 Apr 2026
Abstract
Background/Objectives: Native to the Indo-Pacific region, edible bird’s nests (EBN; Yan Wo in Chinese) are the solidified saliva of swiftlets (Aerodramus fuciphagus and A. maximus) and have been consumed as a traditional functional food for centuries. However, the bioactive components [...] Read more.
Background/Objectives: Native to the Indo-Pacific region, edible bird’s nests (EBN; Yan Wo in Chinese) are the solidified saliva of swiftlets (Aerodramus fuciphagus and A. maximus) and have been consumed as a traditional functional food for centuries. However, the bioactive components and underlying mechanisms of EBN remain poorly understood. EBN consists of over 60% protein, much of which is heavily glycosylated, forming complex glycoconjugates that are resistant to enzymatic digestion. This study examines the properties of EBN-derived bioactive peptides and assesses their potential for skin moisturization and anti-inflammation when applied topically. Methods: EBN was double-boiled for an extended period, then digested with gastric enzymes to extract active peptides. Digestion was over 90% efficient, and peptide molecular weights were measured. The enzymatic digest was then fractionated using an activity-guided approach based on assays for skin moisturization and anti-inflammatory properties. Results: A novel bioactive heptapeptide, with the sequence LAGAAHF and designated EBNP3, was identified and characterized. It attenuated TNF-α-induced inflammatory responses in HaCaT keratinocytes and alleviated dermatitis symptoms in a DNCB-induced C57BL/6 mouse model. Conclusions: EBN-derived peptides with skin moisturizing and anti-inflammatory activities hold significant promise for development into functional ingredients for skincare products. Full article
(This article belongs to the Section Biopharmaceuticals)
18 pages, 801 KB  
Article
Biodegradable Polymer-Coated Surgical Sutures for Controlled and Sustained Release of Sirolimus, Tacrolimus, and Paclitaxel
by Joanna Chałupka, Karolina Piecyk, Karol Kurpiejewski and Adam Sikora
Int. J. Mol. Sci. 2026, 27(8), 3695; https://doi.org/10.3390/ijms27083695 (registering DOI) - 21 Apr 2026
Abstract
Biodegradable polymer-coated surgical sutures represent a promising strategy for localized drug delivery to prevent post-surgical complications, such as restenosis, inflammation, and excessive tissue proliferation. In this study, bioactive coatings based on poly(L-lactic acid) (PLA), polycaprolactone (PCL), chitosan, and their binary blends were developed [...] Read more.
Biodegradable polymer-coated surgical sutures represent a promising strategy for localized drug delivery to prevent post-surgical complications, such as restenosis, inflammation, and excessive tissue proliferation. In this study, bioactive coatings based on poly(L-lactic acid) (PLA), polycaprolactone (PCL), chitosan, and their binary blends were developed and applied to PLA-based surgical sutures for controlled release of sirolimus, tacrolimus, and paclitaxel. A total of 36 coated suture formulations were prepared using solvent-based deposition techniques and systematically evaluated. In vitro drug release studies conducted under physiological conditions (PBS, 37 °C) over a 12-week period demonstrated sustained and formulation-dependent release profiles. Cumulative drug release varied significantly depending on polymer composition, ranging from 17.53% to 90.93% for sirolimus, 70.93% to 98.50% for tacrolimus, and 34.62% to 67.65% for paclitaxel. PLA-based coatings generally exhibited faster release kinetics, whereas PCL-containing formulations showed slower, more sustained release. Binary polymer blends enabled fine-tuning of release profiles, demonstrating tunable drug delivery performance. All coatings maintained structural integrity during handling and simulated suturing conditions. These findings confirm that polymer composition plays a critical role in controlling drug release kinetics and demonstrate the feasibility of biodegradable polymer-coated sutures as a versatile platform for sustained, localized drug delivery in surgical and vascular applications. Full article
28 pages, 2100 KB  
Article
Structural Characterization and Immunomodulatory Activity of an Acidic Polysaccharide from Rhodomyrtus tomentosa (Aiton) Hassk. Fruits
by Huihui Yin, Guoqing Yan, Yunfu Huang, Xueyan Zeng, Shenhong He, Tianyan Lan and Wei Liu
Molecules 2026, 31(8), 1365; https://doi.org/10.3390/molecules31081365 (registering DOI) - 21 Apr 2026
Abstract
A polysaccharide from Rhodomyrtus tomentosa (Aiton) Hassk. fruit (RTFP-2b) was isolated and purified. RTFP-2b has a molecular weight of 22.995 kDa and consists of nine monosaccharides, with arabinose (38.68%), galactose (21.86%), and galacturonic acid (14.83%) as its major components. Methylation and NMR analyses [...] Read more.
A polysaccharide from Rhodomyrtus tomentosa (Aiton) Hassk. fruit (RTFP-2b) was isolated and purified. RTFP-2b has a molecular weight of 22.995 kDa and consists of nine monosaccharides, with arabinose (38.68%), galactose (21.86%), and galacturonic acid (14.83%) as its major components. Methylation and NMR analyses revealed dominant glycosidic linkages, including α-L-Araf-(1→, →4)-α-D-GalpA-(1→, →4)-α-D-Galp-(1→, →5)-α-L-Araf-(1→, →3)-α-L-Araf-(1→ , →2)-α-L-Rhap-(1→, and →3,4,6)-β-D-Galp-(1→. Bioactivity assays using lipopolysaccharide (LPS)-stimulated RAW264.7 cells showed that RTFP-2b exhibits dose-dependent immunomodulatory properties. When administered at lower concentrations (100–200 μg/mL), RTFP-2b enhanced phagocytosis and IL-1β production. At higher concentrations (300–400 μg/mL), it significantly suppressed nitric oxide and showed biphasic regulation of IL-1β, but unexpectedly increased IL-6 levels in LPS-stimulated RAW264.7 cells. These immunomodulatory effects of RTFP-2b at higher doses were accompanied by inhibition of NF-κB signaling. These findings indicate that RTFP-2b is a structurally distinct acidic polysaccharide with dose-dependent immunomodulatory properties, suggesting its potential application in functional foods or pharmaceuticals. Full article
24 pages, 6350 KB  
Article
Bioactive Gum Arabic Enriched with Carvacrol or Caffeine Coatings Improve Antioxidant Capacity and Marketability of ‘Murcott’ Mandarins During Cold Storage
by Ahmed F. Abd El-Khalek, Ashraf M. S. Tubeileh, Gehan A. Mahmoud, Basma S. Salama, Nahed M. Rashed, Saleh M. Alturki, Alaa S. Alharbi, Amal A. Matar, Mostafa Y. Nassar and Mohamed S. Gawish
Agronomy 2026, 16(8), 843; https://doi.org/10.3390/agronomy16080843 (registering DOI) - 21 Apr 2026
Abstract
Gum arabic (GA)-based edible coatings enriched with natural bioactive compounds offer a promising strategy for reducing postharvest losses and maintaining fruit quality. This study evaluated the effectiveness of GA coatings supplemented with carvacrol or caffeine in preserving the physicochemical quality, antioxidant status, and [...] Read more.
Gum arabic (GA)-based edible coatings enriched with natural bioactive compounds offer a promising strategy for reducing postharvest losses and maintaining fruit quality. This study evaluated the effectiveness of GA coatings supplemented with carvacrol or caffeine in preserving the physicochemical quality, antioxidant status, and marketability of ‘Murcott’ mandarins during cold storage (5 ± 1 °C, 90–95% RH) for 60 days followed by 4 days of shelf life. Fruits were treated with distilled water (control), GA (10%), GA + imazalil (2000 ppm), GA + carvacrol (200 ppm), and GA + caffeine (200 ppm). Key quality parameters, including weight loss, decay incidence, firmness, electrolyte leakage, malondialdehyde (MDA), total soluble solids, titratable acidity, ascorbic acid, total phenolics, total flavonoids, and antioxidant enzyme activities of catalase (CAT) and peroxidase (POX), were evaluated. The results demonstrated that GA-based coatings, particularly GA + carvacrol, significantly reduced weight loss and decay while maintaining firmness and visual quality compared to the control. Coated fruits exhibited lower electrolyte leakage and MDA levels, indicating improved membrane integrity and reduced lipid peroxidation. In addition, the treatments enhanced antioxidant capacity, as reflected by increased phenolic and flavonoid contents and higher CAT and POX activities. Multivariate analysis further confirmed the strong association between coating treatments and improved quality attributes. In conclusion, GA coatings enriched with carvacrol or caffeine effectively improved postharvest quality and extended the shelf life of ‘Murcott’ mandarins, highlighting their potential as safe and eco-friendly alternatives to conventional postharvest treatments. Full article
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20 pages, 1048 KB  
Article
Application of Natural Deep Eutectic Solvents (NADES) for the Extraction of Floral Phenolics and Anthocyanin Degradation Kinetics
by Bartłomiej Zieniuk
Appl. Sci. 2026, 16(8), 4036; https://doi.org/10.3390/app16084036 (registering DOI) - 21 Apr 2026
Abstract
Natural deep eutectic solvents (NADES) are promising eco-friendly alternatives to traditional solvents for extracting phenolic compounds from plant materials. However, their effectiveness depends on both solvent composition and the botanical matrix. This study examined water, ethanol, and choline chloride–urea (CCU) and choline chloride–glycerol [...] Read more.
Natural deep eutectic solvents (NADES) are promising eco-friendly alternatives to traditional solvents for extracting phenolic compounds from plant materials. However, their effectiveness depends on both solvent composition and the botanical matrix. This study examined water, ethanol, and choline chloride–urea (CCU) and choline chloride–glycerol (CCG) systems containing 30% or 60% NADES for the extraction of anthocyanins, total phenolic content, total flavonoid content, and antioxidant capacity (DPPH and ABTS) from cornflower, safflower, and pomegranate flowers. Pomegranate flowers exhibited the highest levels of anthocyanins, total phenolics, and antioxidants, while safflower showed the highest total flavonoid content. Overall, the 60% NADES formulations delivered the best extraction results, whereas ethanol had the lowest overall efficiency. A combined heatmap analyzing all responses identified 60% CCU and 60% CCG as the most effective solvents across all tested materials. Anthocyanin stability in pomegranate flower extracts was further evaluated over 8 weeks at 4 and 20 °C. First-order kinetic analysis revealed that ethanol and 60% CCG maintained the highest anthocyanin stability, whereas 60% CCU exhibited the lowest stability, especially at 20 °C. These findings support the use of NADES as efficient solvents for floral bioactives, while indicating that the highest extraction yield does not necessarily correlate with the best storage stability. Full article
(This article belongs to the Section Chemical and Molecular Sciences)
23 pages, 2143 KB  
Review
Application of Suitable Bioactive Probiotic Strains Sustaining Gut Microflora for Healthcare and Disease Prevention
by Divakar Dahiya and Poonam Singh Nigam
Appl. Sci. 2026, 16(8), 4023; https://doi.org/10.3390/app16084023 (registering DOI) - 21 Apr 2026
Abstract
Background/Objectives: The human gastrointestinal tract is a dynamic and interactive micro-ecosystem, with its distinct microbial population residing in the gut. The healthy condition of the gut is integrated into the normal functioning of all physiological activities. The gut microbiome is critical for [...] Read more.
Background/Objectives: The human gastrointestinal tract is a dynamic and interactive micro-ecosystem, with its distinct microbial population residing in the gut. The healthy condition of the gut is integrated into the normal functioning of all physiological activities. The gut microbiome is critical for the functioning of metabolism via several gut-axis connections with different systems in the human body; thus, it affects the status of health and general well-being. The fundamental physiology and homeostatic shifts are associated with specific diseases caused by a disrupted balance in the diversity of the gut microbiome, which could be due to a condition of dysbiosis in a host, instigated by several reasons. Some studies have been conducted on the selective isolation of probiotic species from dairy and other food sources to obtain effective probiotic strains, which have been studied and used by dietary intake strategies to restore gut microbial diversity, which is disturbed by some disease/s. Methods: Our search strategy included specific keywords—gut, microbiota, microbiome, disease, dysbiosis, probiotic bacteria and yeast—and was based on a timeframe of 15 years in the web-based electronic databases of PubMed, Scopus, and Web of Science. Among the few hundred results, a secondary screening was conducted to select references on probiotics studied for disease management with preclinical evidence and some reports on clinically validated outcomes; we excluded the search results for screening fermented foods for taxonomy studies of isolated probiotics. Results: The summarised information using two figures and two tables has been presented in this article from the review of 137 selected references: >75% have been published in the last 10 years. Conclusions: Further advances in modelling and analysis of the gut microbiota are required to understand their influence on the occurrence of certain diseases; this approach will allow us to establish research strategies for filling knowledge gaps, inconsistencies in clinical evidence, or limitations in translating probiotic effects from experimental models to humans. Full article
(This article belongs to the Special Issue Advancements in Food Nutrition and Bioactive Compounds)
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24 pages, 6774 KB  
Article
Integrated Bioinformatics Analysis and In Vitro Evidence Support HSP90AA1 as a Candidate Target of Camellia petelotii (Merr.) Sealy in Pulmonary Arterial Hypertension
by Xinying Chen, Lipeng Zhou, Chenghao Zhu and Zhirong Sun
Int. J. Mol. Sci. 2026, 27(8), 3687; https://doi.org/10.3390/ijms27083687 (registering DOI) - 21 Apr 2026
Abstract
Pulmonary arterial hypertension (PAH) is a severe and progressive cardiopulmonary disorder with limited treatment options. Camellia petelotii (Merr.) Sealy (CP) contains multiple flavonoids and other phytochemicals, but its active compounds and molecular mechanisms in PAH remain unclear. Active compounds of CP were screened [...] Read more.
Pulmonary arterial hypertension (PAH) is a severe and progressive cardiopulmonary disorder with limited treatment options. Camellia petelotii (Merr.) Sealy (CP) contains multiple flavonoids and other phytochemicals, but its active compounds and molecular mechanisms in PAH remain unclear. Active compounds of CP were screened by comprehensive literature mining and absorption, distribution, metabolism, and excretion (ADME) evaluation. PAH-related hub targets were identified from transcriptomic data using weighted gene co-expression network analysis (WGCNA), machine learning, and external validation. Functional enrichment, immune infiltration, and single-cell RNA-sequencing analyses were performed to characterize their biological roles and cellular localization. Molecular docking and molecular dynamics simulations assessed compound–target interactions. The effects of CP were further evaluated in hypoxia-induced rat pulmonary artery smooth muscle cells (RPASMCs). Five core bioactive compounds were identified, among which luteolin and quercetin were prioritized for further analysis. HSP90AA1 and ROCK2 were screened as hub targets. Bioinformatic analyses suggested that these targets were mainly associated with the “Lipid and atherosclerosis” pathway, metabolic reprogramming, and modulation of the immune microenvironment. Single-cell analysis showed broad expression of HSP90AA1 and enrichment of ROCK2 in fibroblasts and endothelial cells. Molecular docking and molecular dynamics simulations supported stable binding of luteolin to HSP90AA1. In vitro, CP extract inhibited hypoxia-induced hyperproliferation of RPASMCs and reduced HSP90AA1 protein expression. HSP90AA1 may represent a candidate molecular mediator of CP in PAH, and CP inhibited hypoxia-induced RPASMC proliferation in association with downregulation of HSP90AA1. Full article
(This article belongs to the Section Molecular Informatics)
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46 pages, 1483 KB  
Review
Recent Advances in NADES-Assisted Process Intensification Technologies for Sustainable Recovery of Microalgal Bioactives: Challenges and Future Prospectives
by Muhammad Shafiq, Sardar Ali and Liaqat Zeb
Mar. Drugs 2026, 24(4), 146; https://doi.org/10.3390/md24040146 (registering DOI) - 21 Apr 2026
Abstract
Microalgae are increasingly recognized as renewable biofactories for producing high-value bioactive molecules. However, their industrial exploitation is limited by their rigid cell walls, metabolite heterogeneity, and the energy-intensive nature of the extraction processes. Recent advances in process-intensification technologies, including microwave-assisted, ultrasound-assisted, enzymatic, pressurized [...] Read more.
Microalgae are increasingly recognized as renewable biofactories for producing high-value bioactive molecules. However, their industrial exploitation is limited by their rigid cell walls, metabolite heterogeneity, and the energy-intensive nature of the extraction processes. Recent advances in process-intensification technologies, including microwave-assisted, ultrasound-assisted, enzymatic, pressurized liquid, and supercritical CO2-based methods, have significantly improved extraction efficiency and selectivity, with reported lipid recoveries exceeding 40–50% in some microalgal systems and carotenoid recoveries approaching 90% under optimized conditions. NADES-assisted systems further enhance mass transfer and solubilization through tailored hydrogen-bonding interactions, enabling selective extraction of polar and semi-polar metabolites under mild conditions. However, limitations remain, including high viscosity, variability in extraction performance, and challenges in solvent recovery and scale-up. This review critically evaluates the extraction efficiency, mechanistic basis, and sustainability of NADES-assisted processes, highlighting key limitations and identifying research priorities for their integration into scalable microalgal biorefinery systems. Full article
(This article belongs to the Section Marine Biotechnology Related to Drug Discovery or Production)
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30 pages, 16343 KB  
Review
Modulatory Effects of Bioactive Phytoconstituents on the Amplitude and Gating Properties of Membrane Ion Channels
by Sheng-Nan Wu, Guglielmina Froldi, Ya-Jean Wang and Rasa Liutkevičienė
Molecules 2026, 31(8), 1360; https://doi.org/10.3390/molecules31081360 (registering DOI) - 21 Apr 2026
Abstract
This review provides a comprehensive overview of the modulatory actions of plant-derived constituents on membrane ion channels in various cell types. Among their diverse bioactivities, ion channel regulation—governing membrane excitability, signal transduction, and cellular homeostasis—has emerged as a critical mechanistic basis for their [...] Read more.
This review provides a comprehensive overview of the modulatory actions of plant-derived constituents on membrane ion channels in various cell types. Among their diverse bioactivities, ion channel regulation—governing membrane excitability, signal transduction, and cellular homeostasis—has emerged as a critical mechanistic basis for their pharmacological effects. Twenty-four representative phytoconstituents are discussed and classified into five major categories based on their structural features: alkaloids, terpenoids, lignans and acetogenins, polyphenols, and other aromatic and conjugated compounds. Across these categories, the reviewed compounds exhibit distinct and often highly specific effects on the amplitude and gating kinetics of multiple ionic currents, including voltage-gated Na+ currents (INa), delayed-rectifier K+ currents (IK(DR)), M-type K+ currents (IK(M)), hyperpolarization-activated cation currents (Ih), erg-mediated K+ currents (IK(erg)), inwardly rectifying K+ currents, and Ca2+-activated K+ currents (IK(Ca)). Alkaloids predominantly suppress voltage-gated K+ currents, with notable exceptions such as aconitine, which alters the properties of both INa and IK(DR), thereby contributing to its proarrhythmic toxicity. Terpenoids, including cannabidiol, croton diterpenoids, lutein, thymol, and triptolide, exert multifaceted effects on IK(M), Ih, inwardly rectifying K+ currents, and Ca2+-activated K+ channels. Lignans and acetogenins, such as gomisin A, honokiol, sesamin, and squamocin, primarily modulate INa, Ih, and IK(Ca), with several compounds demonstrating strong links between ion-channel modulation and anti-neoplastic or neuroprotective actions. Polyphenolic compounds, including curcumin, eugenol, resveratrol, gastrodigenin, gastrodin, and pterostilbene, display diverse ion-channel targeting profiles, influencing multiple Na+ and K+ channel subtypes. Other aromatic or conjugated compounds, such as isoplumbagin, plumbagin, and verteporfin, regulate IK(erg) and IK(Ca), potentially contributing to both therapeutic efficacy and adverse effects. Collectively, the compound-specific modulation of current amplitude and gating kinetics offers valuable mechanistic insight into the pharmacological and toxicological significance of plant-derived natural products, highlighting the functional role of ion channel evaluation in guiding their therapeutic development and ensuring safety assessment. Full article
(This article belongs to the Special Issue Bioactivity of Natural Compounds: From Plants to Humans, 2nd Edition)
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18 pages, 1055 KB  
Article
Sphingolipid Expression During Corneal Wound Healing in a Sphingosine Kinase 1 Knockout Model
by Sandip K. Basu, Steve Mabry, Peter Nsiah, Sarah E. Nicholas, Nataliya Lenchik, Mark Altawil, Chi-Yang Chiu, Daniel J. Stephenson, Charles E. Chalfant, Dimitrios Karamichos and Nawajes Mandal
Cells 2026, 15(8), 733; https://doi.org/10.3390/cells15080733 (registering DOI) - 21 Apr 2026
Abstract
Corneal scarring is a result of unregulated fibrotic processes in wound healing, which causes visual impairment. Bioactive sphingolipids (SPLs) are known to modulate physiological processes that are central to wound healing. Of these bioactive SPLs, sphingosine-1-phosphate (S1P) is perhaps the most studied. Previous [...] Read more.
Corneal scarring is a result of unregulated fibrotic processes in wound healing, which causes visual impairment. Bioactive sphingolipids (SPLs) are known to modulate physiological processes that are central to wound healing. Of these bioactive SPLs, sphingosine-1-phosphate (S1P) is perhaps the most studied. Previous research has shown that knocking out sphingosine kinase 1 (Sphk1), which produces S1P, alters SPL species metabolism and improves wound healing in mice corneas. However, it is unknown how SphK1 knockout (SphK1-/-) affects SPL metabolism during stages of corneal wound healing. Following an alkali burn procedure on wild-type (WT) and SphK1-/- mice, corneal lipidomic profiles in unburned corneas at 1, 7, 14, and 28 days post-injury (DPI) were measured. Significant differences in SPL species between genotypes, both in uninjured mouse corneas and during distinct stages of corneal burn healing, were observed. WT mice expressed burn healing stage-dependent modulation of SPL species, with decreased expression of most SPL species observed at 1 and 14 DPI. Interestingly, this wild-type SPL modulation was absent in most measured SPL species in the SphK1-/- corneas. These findings provide evidence for a previously unknown modulatory role of SphK1 and S1P on the expression of SPLs during corneal wound healing. Full article
(This article belongs to the Section Tissues and Organs)
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25 pages, 3352 KB  
Article
Bioactive Compounds in Medicinal Plants as Affected by the Level of Potentially Toxic Element Contamination in Soil
by Jiřina Száková, Petr Maršík, Michael O. Asare, Zolboo Nguyen, Klára Nejdlová, Pavel Klouček and Pavel Tlustoš
Environments 2026, 13(4), 227; https://doi.org/10.3390/environments13040227 (registering DOI) - 21 Apr 2026
Abstract
Medicinal plants represent important sources of bioactive compounds with beneficial effects on human health. However, many medicinal species are ruderal plants capable of growing in soils with elevated contents of potentially toxic elements (PTEs) such as Cd, Pb, and Zn. In addition to [...] Read more.
Medicinal plants represent important sources of bioactive compounds with beneficial effects on human health. However, many medicinal species are ruderal plants capable of growing in soils with elevated contents of potentially toxic elements (PTEs) such as Cd, Pb, and Zn. In addition to the potential accumulation of PTEs in plant biomass, the response of the plant metabolome—including bioactive substances with beneficial health effects—to elevated PTE levels in plants should also be considered. The potential impact of soil PTEs on the plant metabolome was investigated in three widely used medicinal plants, Taraxacum sp., Achillea millefolium, and Hypericum maculatum, sampled in an area polluted with PTEs. The total soil contents of the PTEs ranged between 7.7 and 65 mg/kg for Cd, 1541 and 3897 mg/kg for Pb, and 245 and 6553 mg/kg for Zn. A qualitative analysis of the whole plant metabolomes of the three plant species indicated close interrelationships between the selected metals and bioactive substances. Subsequently, a model pot experiment was conducted in which Taraxacum sp. plants were cultivated in three soils with stepwise increasing Cd, Pb, and Zn contents, and selected bioactive compounds were quantified. The results showed a decrease in the concentrations of some phenolic compounds in the aboveground parts of Taraxacum sp. grown in extremely polluted soil, supporting the hypothesis that stress induced by PTEs may affect the metabolic pathways of these compounds. In contrast, higher levels of phenolic compounds were observed in Taraxacum sp. roots grown in moderately contaminated soil, suggesting that milder soil contamination may activate defence mechanisms and stimulate phenolic metabolism. However, although the contents of bioactive compounds in plants indicate an improvement of the quality of these medicinal plants, the elevated element contents in the plant biomass can represent a potential risk for consumers. Full article
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28 pages, 2835 KB  
Review
Unlocking Microbial Dark Matter: A Comprehensive Review of Isolation Technologies from Traditional Culturing to Single-Cell Technologies
by Xi Sun, Xiaoxuan Zhang and Jia Zhang
Microorganisms 2026, 14(4), 933; https://doi.org/10.3390/microorganisms14040933 (registering DOI) - 21 Apr 2026
Abstract
Microorganisms represent the Earth’s most abundant biomass and a vast reservoir of genetic diversity. However, traditional agar plate methods fail to recover the vast majority of these species, leaving a “microbial dark matter” that holds immense potential for the discovery of novel antibiotics [...] Read more.
Microorganisms represent the Earth’s most abundant biomass and a vast reservoir of genetic diversity. However, traditional agar plate methods fail to recover the vast majority of these species, leaving a “microbial dark matter” that holds immense potential for the discovery of novel antibiotics and bioactive compounds. While conventional techniques such as selective media and enrichment culture remain foundational, they are inherently limited by community biases and the inability to support low-abundance, oligotrophic species. To address these bottlenecks, a diverse array of innovative isolation strategies has emerged. This review systematically categorizes and evaluates these methodologies, ranging from in situ cultivation to high-resolution single-cell manipulation. We first examine membrane diffusion-based cultivation (e.g., iChip), which mimics natural microenvironments to resuscitate recalcitrant microbes. Subsequently, we explore high-throughput single-cell technologies, including microfluidics for physicochemical separation, optical tweezers for precise manipulation, and fluorescence-activated cell sorting (FACS). Special attention is given to Raman-activated cell sorting (RACS) as a label-free functional screening tool and reverse genomics for targeted capture. By synthesizing the strengths and limitations of these approaches, we propose integrated workflows designed to accelerate the mining of untapped microbial resources. Full article
(This article belongs to the Section Microbial Biotechnology)
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26 pages, 945 KB  
Review
Phytochemical Diversity of Punica granatum L. and Its Multi-Target Biological Functions
by Zofia Kobylińska, Aleksandra Bochno, Ewelina Och, Martyna Kotula, Patrycja Kielar, Sabina Galiniak and Mateusz Mołoń
Nutrients 2026, 18(8), 1306; https://doi.org/10.3390/nu18081306 (registering DOI) - 21 Apr 2026
Abstract
Punica granatum L. is a nutritionally relevant fruit with a complex phytochemical profile that varies across its anatomical fractions, including peel, arils, juice, seeds, and seed oil. Although pomegranate is widely recognized for its health-promoting potential, the nutritional significance of its matrix-dependent composition, [...] Read more.
Punica granatum L. is a nutritionally relevant fruit with a complex phytochemical profile that varies across its anatomical fractions, including peel, arils, juice, seeds, and seed oil. Although pomegranate is widely recognized for its health-promoting potential, the nutritional significance of its matrix-dependent composition, bioavailability, and gut microbiota-mediated metabolism remains insufficiently integrated. This review aimed to critically evaluate the phytochemical diversity of pomegranate and its nutrition-related multi-target biological functions, with particular emphasis on food matrices, bioaccessibility, and translational relevance. A structured review of peer-reviewed studies indexed in major scientific databases from 2000 to January 2026 was conducted. Eligible reports included analytical, preclinical, and clinical studies addressing the composition of pomegranate-derived materials and their biological effects, with attention to extraction matrix, processing, bioavailability, microbial biotransformation, and mechanisms of action. Pomegranate exhibits marked matrix-specific phytochemical diversity. Peel is particularly rich in ellagitannins, especially punicalagin and punicalin; arils and juices are enriched in anthocyanins and flavonols; and seed oil contains high levels of punicic acid. Reported biological activities include antioxidant, anti-inflammatory, antimicrobial, metabolic, anti-aging, and anticancer effects. These actions appear to result from synergistic interactions among multiple bioactive compounds rather than from a single dominant constituent. Importantly, gut microbiota-driven conversion of ellagitannins and ellagic acid into urolithins is a major determinant of systemic bioactivity and may contribute to interindividual variability in response. The health effects of pomegranate should be interpreted within a nutrition-focused, matrix-dependent framework integrating composition, processing, bioavailability, and microbiota-derived metabolism. Full article
(This article belongs to the Section Nutrition and Public Health)
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24 pages, 3753 KB  
Article
Red Macroalgae as Sources of Antioxidant and Multifunctional Ingredients for Functional Foods: A Biorefinery Approach
by Nuno Nunes, Emmanuel Nunes, Kilian Odenthal and Miguel Â. A. Pinheiro de Carvalho
Mar. Drugs 2026, 24(4), 145; https://doi.org/10.3390/md24040145 (registering DOI) - 21 Apr 2026
Abstract
Given the established interplay between oxidative stress, cholinergic dysfunction, and metabolic imbalance in cognitive decline, this study investigated the multifunctional potential of three red macroalgae from the Madeira Archipelago (Asparagopsis taxiformis, Grateloupia lanceola, and Nemalion elminthoides) using a sequential [...] Read more.
Given the established interplay between oxidative stress, cholinergic dysfunction, and metabolic imbalance in cognitive decline, this study investigated the multifunctional potential of three red macroalgae from the Madeira Archipelago (Asparagopsis taxiformis, Grateloupia lanceola, and Nemalion elminthoides) using a sequential biorefinery approach. Marine algae represent a sustainable source of functional food ingredients due to their rich content in bioactive compounds and their compatibility with low-impact production systems. Protein, ethanolic (phenolic-rich), and polysaccharide fractions were obtained through direct extraction and scalable biorefinery processing. Antioxidant activity was evaluated using ORAC, DPPH, FRAP, and FIC assays, while functionality relevant to human health was assessed through acetylcholinesterase, butyrylcholinesterase, and α-glucosidase inhibition. Protein extracts, particularly from N. elminthoides, exhibited strong hydrogen atom transfer-based antioxidant capacity, whereas ethanolic extracts demonstrated multifunctional activity, combining radical scavenging, metal chelation, and enzyme inhibition associated with neuroprotective and glycemic-regulation potential. Polysaccharide fractions contributed mainly to iron chelation and reducing capacity. Correlation analyses highlighted the complementary nature of antioxidant and bioactivity assays. Overall, these findings support the potential of Madeira red macroalgae as functional food ingredients and emphasize the importance of optimized biorefinery strategies to maximize nutritional and health-related benefits. Full article
(This article belongs to the Special Issue Marine Algae as Functional Foods)
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Article
A Standardized Onion Peel-Derived Bioactive Ingredient Attenuates Palmitate-Induced Steatosis and Oxidative Stress by Modulating Mitochondrial Dynamics and Autophagy in HepG2 Cells
by Ilaria Di Gregorio, Vincenzo Migliaccio, Maria D’Elia, Rita Celano, Valentina Santoro, Anna Lisa Piccinelli, Mariateresa Russo, Luca Rastrelli and Lillà Lionetti
Antioxidants 2026, 15(4), 513; https://doi.org/10.3390/antiox15040513 (registering DOI) - 21 Apr 2026
Abstract
Onion peel represents a valuable food by-product rich in bioactive phenolic compounds. Building on previous phytochemical investigations, an onion peel extract from the Rossadi Tropea variety was developed as a standardized bioactive ingredient (OPI-T), defined by flavonol (quercetin and its glycosylated and [...] Read more.
Onion peel represents a valuable food by-product rich in bioactive phenolic compounds. Building on previous phytochemical investigations, an onion peel extract from the Rossadi Tropea variety was developed as a standardized bioactive ingredient (OPI-T), defined by flavonol (quercetin and its glycosylated and oxidized derivatives) and anthocyanin (cyanidin derivatives) markers, ensuring batch-to-batch consistency, and evaluated for its potential against hepatic steatosis. The present study aimed to assess the protective effects of OPI-T against palmitate-induced steatosis and oxidative stress in HepG2 cells, a widely used in vitro model of hepatic lipid accumulation. An onion peel extract derived from the Ramata di Montoro variety was included as a natural negative reference to account for varietal variability. HepG2 cells were co-treated with palmitate (500 µM) and OPI-T (25 or 50 µg/mL). Lipid accumulation was evaluated by Oil Red O and BODIPY staining, while oxidative stress was assessed by the DCF assay. Mitochondrial dynamics and autophagy were investigated through the analysis of key protein markers, including MFN2, DRP1, SQSTM1/p62 and LC3 II/I. OPI-T significantly attenuated palmitate-induced lipid accumulation (−18%) and reduced intracellular ROS production (−75%), while modulating mitochondrial dynamics toward a reduced fission phenotype with a marked increase in the MFN2/DRP1 ratio (1.66) and improving autophagy flux. In contrast, the Ramata di Montoro variety showed weaker or inconsistent effects under the same experimental conditions. Overall, these findings support the functional validation of a standardized onion peel-derived ingredient, highlighting its potential application as a bioactive component for functional food or nutraceutical development targeting hepatic steatosis and oxidative stress. Full article
(This article belongs to the Special Issue Role of Mitochondria and ROS in Health and Disease—2nd Edition)
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