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Keywords = natural bioactive compound

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37 pages, 1347 KB  
Review
Natural Bioactive Compounds in Polycystic Ovary Syndrome: Properties, Molecular Mechanisms, and Therapeutic Potential
by Rosa Linares, Gabriela Rosas, Elizabeth Vieyra, Andrea Chaparro, Julieta-Azucena Espinoza, Deyra de los Angeles Ramírez, Carlos-Camilo Silva, Patricia Rosas, Víctor-Manuel Macías and Leticia Morales-Ledesma
Int. J. Mol. Sci. 2026, 27(11), 4715; https://doi.org/10.3390/ijms27114715 (registering DOI) - 23 May 2026
Abstract
Polycystic ovary syndrome (PCOS) is one of the most common metabolic–endocrine disorders affecting women of reproductive age and represents a significant public health concern due to its clinical heterogeneity. It is characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphology, and is frequently [...] Read more.
Polycystic ovary syndrome (PCOS) is one of the most common metabolic–endocrine disorders affecting women of reproductive age and represents a significant public health concern due to its clinical heterogeneity. It is characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphology, and is frequently associated with hyperinsulinemia, obesity, dyslipidemia, chronic low-grade inflammation, and an increased risk of type 2 diabetes and cardiovascular disease. Conventional treatments, including combined oral contraceptives, metformin, and ovulation-inducing agents, primarily target symptoms and present limitations in efficacy, tolerability, and their ability to address underlying metabolic dysfunction. In this context, naturally derived bioactive compounds have emerged as promising complementary therapeutic strategies. Various phytochemicals exhibit antioxidant, anti-inflammatory, hypoglycemic, and reproductive axis-modulating effects by targeting key molecular pathways involved in insulin resistance, hyperandrogenism, and follicular dysfunction. Emerging preclinical and clinical evidence suggests that these compounds may improve metabolic, hormonal, and reproductive outcomes in women with PCOS. Full article
(This article belongs to the Special Issue The Role of Bioactive Natural Products in Human Health)
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28 pages, 1528 KB  
Review
Acerola and Its By-Products as Sources of Bioactive Compounds: Phytochemical Profile and Biological Effects in Experimental and Clinical Studies
by Jailane de Souza Aquino, Alana Natalícia Vasconcelos de Araújo, Januse Míllia Dantas de Araújo, Luana Clementino Santos, Jordania Candice Costa Silva, Kamila Sabino Batista and Lucas Rannier Ribeiro Antonino Carvalho
Molecules 2026, 31(11), 1792; https://doi.org/10.3390/molecules31111792 (registering DOI) - 23 May 2026
Abstract
Acerola (Malpighia emarginata DC.) is one of the richest natural sources of vitamin C and an important source of phenolic compounds, carotenoids, and bioactive polysaccharides. Although the fruit can be consumed fresh, it is more commonly processed into juices and frozen pulp, [...] Read more.
Acerola (Malpighia emarginata DC.) is one of the richest natural sources of vitamin C and an important source of phenolic compounds, carotenoids, and bioactive polysaccharides. Although the fruit can be consumed fresh, it is more commonly processed into juices and frozen pulp, generating substantial amounts of by-products (pomace, peels, and seeds), corresponding to approximately 20–60% of the fruit biomass, with high phytochemical content. These fractions represent underutilized sources of bioactive compounds. This narrative review, supported by a structured literature search, integrates evidence on the phytochemical composition of acerola pulp and its by-products and relates these profiles to biological effects in experimental and human studies, focusing on compound characterization, composition–function relationships, and underlying mechanisms. Key compounds, including ascorbic acid, hydroxycinnamic acids, flavonoids, and polysaccharides, are associated with the modulation of redox homeostasis, inflammatory signaling, and lipid metabolism, particularly under high-fat dietary conditions. Human evidence remains limited but suggests matrix-dependent effects on vitamin C bioavailability and selected cardiometabolic markers. Overall, the evidence is constrained by methodological heterogeneity, limited clinical data, and insufficient characterization of bioactive fractions. Future research should prioritize detailed phytochemical profiling, dose–response relationships, bioavailability assessment, and well-controlled clinical trials incorporating molecular biomarkers, supporting the development of acerola-derived matrices as functional and bioactive-rich ingredients. Full article
(This article belongs to the Special Issue Bioactive Compounds in Foods and Their By-Products)
27 pages, 12464 KB  
Article
Phytochemicals from Turnera subulata Exhibiting Antioxidant, Immunomodulatory, and Microbiological Activity
by Antonio Carlos Vital Júnior, Shênia Santos Monteiro, Genil Dantas de Oliveira, Yuri Mangueira do Nascimento, Fábio Miguel Santos Costa, Wêndeo Kennedy Costa, Alisson Macário de Oliveira, Maria Tereza dos Santos Correia, Daniele de Figueredo Silva, Rafael Wesley Bastos, Hugo Miguel Lisboa and Matheus Augusto de Bittencourt Pasquali
Foods 2026, 15(11), 1841; https://doi.org/10.3390/foods15111841 - 22 May 2026
Abstract
Turnera subulata is traditionally used to treat inflammatory and infectious conditions; however; its biological activities remain incompletely characterized. In this study, aqueous (AETS) and hydroethanolic (HETS) extracts obtained from the aerial parts (leaves, stems, and flowers), as used in traditional infusions, were compared [...] Read more.
Turnera subulata is traditionally used to treat inflammatory and infectious conditions; however; its biological activities remain incompletely characterized. In this study, aqueous (AETS) and hydroethanolic (HETS) extracts obtained from the aerial parts (leaves, stems, and flowers), as used in traditional infusions, were compared regarding physicochemical composition, redox behavior, cytotoxicity, immunomodulatory, and antimicrobial activities. HETS showed significantly higher phenolic content (2555.96 ± 43.55 mg GAE/100 mL) compared to AETS (1269.54 ± 20.60 mg GAE/100 mL) and exhibited stronger DPPH (83.05 ± 0.05%) and ABTS (85.1 ± 1.5%) radical scavenging activity. In contrast, AETS showed greater antioxidant capacity in the TRAP assay from 50 µg/mL (p < 0.0001). Both extracts displayed dose-dependent pro-oxidant behavior in the deoxyribose/Fenton system. In vitro assays demonstrated that both extracts exhibited dose-dependent cytotoxicity in SH-SY5Y cells, with no significant cytotoxic effects observed at concentrations ≤ 50 µg/mL. HETS significantly increased IL-10 levels (p < 0.05), indicating immunomodulatory activity. In antimicrobial assays, HETS showed selective activity against Staphylococcus aureus, with MIC values ranging from 0.625 to 1.25 mg/mL, while no relevant inhibition was observed against Escherichia coli. No synergistic interaction with vancomycin was detected. Overall, the results indicate that the extraction solvent strongly influences the phenolic enrichment and biological activity. The hydroethanol extract showed the most consistent bioactivity, highlighting its potential for applications as a natural antioxidant, immunomodulatory, and anti-staphylococcal agent. Future studies should focus on compound isolation, mechanistic validation, and evaluation in in vivo models to support potential commercial and therapeutic applications. Full article
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19 pages, 6762 KB  
Article
Kuwanon A from Morus alba L. Alleviates H2O2-Induced Oxidative Damage in HaCaT Keratinocytes by Inhibiting Ferroptosis and Enhancing Antioxidant Capacity
by Yan Liu, Hening Fu, Junjie Ma, Youqing Wang, Zhaohua Shi, Yupeng Liu, Xianju Huang, Bingchen Han and Jun Li
Antioxidants 2026, 15(6), 657; https://doi.org/10.3390/antiox15060657 - 22 May 2026
Abstract
The root bark of Morus alba L. is commonly used as a natural antioxidant; however, its active constituents and underlying molecular mechanisms remain unclear. In this study, a bioactivity-guided isolation approach was employed to identify antioxidant substances from the root bark of Morus [...] Read more.
The root bark of Morus alba L. is commonly used as a natural antioxidant; however, its active constituents and underlying molecular mechanisms remain unclear. In this study, a bioactivity-guided isolation approach was employed to identify antioxidant substances from the root bark of Morus alba L. and to investigate their protective effects against oxidative damage in HaCaT cells. Using techniques such as silica gel column chromatography and semi-preparative HPLC, combined with NMR and HR-ESI-MS analysis, 22 compounds were isolated and identified from the dichloromethane extract of Morus alba L. root bark, including Diels–Alder adducts, flavonoids, and benzofurans. Among them, compounds 1 and 2 are new compounds, while compounds 12 and 16 were isolated from this plant for the first time. Bioactivity screening revealed that Kuwanon A (compound 17) exhibited significant cytoprotective effects in an H2O2-induced HaCaT cell injury model, effectively scavenging intracellular reactive oxygen species (ROS), restoring mitochondrial function, and enhancing the activities of antioxidant enzymes such as SOD and GSH. Further studies indicated that H2O2 induced ferroptosis in HaCaT cells, characterized by abnormal Fe2+ levels, lipid peroxidation, and elevated levels of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α). Kuwanon A significantly ameliorated these pathological changes. Consistently, ELISA and Astral DIA quantitative proteomics analyses demonstrated that Kuwanon A specifically upregulates the expression of the sulfurtransferase NFS1, thereby promoting the expression of the core antioxidant enzyme GPX4 and the iron storage protein ferritin-H, collectively inhibiting ferroptosis. This study elucidates that Kuwanon A is a key active component responsible for the antioxidant and anti-inflammatory effects of Morus alba L. root bark, and its mechanism is closely associated with regulating the NFS1-mediated ferroptosis defense pathway. Full article
(This article belongs to the Topic Natural Compounds in Plants, 3rd Edition)
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21 pages, 3426 KB  
Article
Phytochemical Characterization and Evaluation of Antioxidant and Tyrosinase Inhibitory Activities of Verbascum wiedemannianum Essential Oil and Methanolic Extract
by Fatih Göger, Mehmet Tekin, Gülmira Özek, Süleyman Yur, Mevlüt Akdağ and Temel Özek
Molecules 2026, 31(11), 1783; https://doi.org/10.3390/molecules31111783 - 22 May 2026
Abstract
Verbascum species have long been recognized for their medicinal properties; however, detailed studies on the endemic species Verbascum wiedemannianum Fisch. & C.A. Mey. remain limited. The purpose of this study is to evaluate the antioxidant and anti-tyrosinase activities of essential oil (EO) and [...] Read more.
Verbascum species have long been recognized for their medicinal properties; however, detailed studies on the endemic species Verbascum wiedemannianum Fisch. & C.A. Mey. remain limited. The purpose of this study is to evaluate the antioxidant and anti-tyrosinase activities of essential oil (EO) and methanol extract (ME) derived from V. wiedemannianum, an endemic species from Türkiye. The EO was obtained by hydrodistillation, and its chemical composition was characterized using GC-FID and GC/MS. The principal constituents of the EO were palmitic acid (27.3%), myristic acid (11.9%), 1-octadecanol (13.0%), and pentacosane (6.6%). LC-MS/MS analysis of the ME identified luteolin and chrysoeriol derivatives as the predominant compounds. The antioxidant potential of both the EO and ME was evaluated using three assay systems based on electron transfer reactions: the Folin–Ciocalteu reagent, the Trolox equivalent antioxidant capacity assay, and the cupric ion (Cu2+) reducing antioxidant capacity assay. The potential skin care effects of the EO and ME were further evaluated using a tyrosinase inhibition assay. Across all the assays, the ME consistently showed notable activities, whereas the activity of the EO was less clearly defined. These findings indicate that the ME of V. wiedemannianum contains bioactive compounds with potential applications in natural antioxidant and skin care formulations. Further studies are warranted to clarify its therapeutic uses. Full article
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29 pages, 1891 KB  
Article
RSM- and ANN-Based Optimization of Bioactive Anthocyanin and Phenolic Compound Recovery from Rosa damascena Flowers Using Natural Deep Eutectic
by Georgia D. Ioannou, Atalanti Christou, Michaella Pieri, Panayiota Piri, George Botsaris and Vlasios Goulas
Antioxidants 2026, 15(6), 656; https://doi.org/10.3390/antiox15060656 - 22 May 2026
Abstract
The present study investigated the use of natural deep eutectic solvents (NaDESs) combined with ultrasound-assisted extraction (UAE) for the efficient recovery of anthocyanins and antioxidant phenolics from Damask rose (DR). A wide range of environmentally friendly solvents was screened, and choline chloride–propylene glycol [...] Read more.
The present study investigated the use of natural deep eutectic solvents (NaDESs) combined with ultrasound-assisted extraction (UAE) for the efficient recovery of anthocyanins and antioxidant phenolics from Damask rose (DR). A wide range of environmentally friendly solvents was screened, and choline chloride–propylene glycol (ChCl-PG) was identified as the most effective extraction medium. The extraction conditions were optimized using response surface methodology (RSM) and artificial neural network (ANN) models to maximize anthocyanin and phenolic contents, as well as antioxidant activity. Under the optimal parameters, the DR extracts exhibited relatively high levels of bioactive compounds, including total anthocyanin content of 5.2–5.3 mg cyanidin-3-glucoside equivalents g−1 sample, total phenolic content of 63.4–64.2 mg gallic acid equivalents g−1 sample, along with substantial antioxidant potential (DPPH: 68.2–68.8% inhibition, FRAP: 581.6–591.9 μmol Trolox equivalents g−1 sample). Chromatographic analysis of the optimum extract revealed cyanidin as the predominant anthocyanidin in DR, and its stability was further evaluated, revealing improved preservation under dark conditions at lower temperatures over a 15-day storage period. Moreover, the IC50 values confirmed antimicrobial effects against the tested foodborne pathogens. Furthermore, the inhibitory effect of the DR extract remained stable against S. aureus and S. cerevisiae throughout the storage period. Overall, the findings demonstrate that NaDES-UAE is a promising and sustainable approach for obtaining anthocyanin-rich DR extracts with antioxidant and antimicrobial potential. Full article
(This article belongs to the Special Issue Sustainable Strategies for Natural Antioxidant Utilization)
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29 pages, 6026 KB  
Article
Core Substances and Related Bio-Activities on Anti-Lung Cancer Cell A549 of Pleione Pseudobulb
by Chao Huang, Ge Li, Surong Li, Ruyu Yao, Angkhana Inta, Lu Gao and Lixin Yang
Pharmaceuticals 2026, 19(5), 800; https://doi.org/10.3390/ph19050800 (registering DOI) - 20 May 2026
Viewed by 151
Abstract
Background/Objectives: The Naxi people in Northwest Yunnan of China have used alcohol-soaked Pleione Pseudobulbus, which is the Pseudobulbus of Pleione bulbocodioides Rolfe (PBR), for lung diseases and tumors for a long period of time. This study aims to explore underlying mechanisms of [...] Read more.
Background/Objectives: The Naxi people in Northwest Yunnan of China have used alcohol-soaked Pleione Pseudobulbus, which is the Pseudobulbus of Pleione bulbocodioides Rolfe (PBR), for lung diseases and tumors for a long period of time. This study aims to explore underlying mechanisms of bioactive ingredients in PBR, as well as to underscore the synergy between traditional medicine and modern pharmacological research. Methods: We verified the anti-tumor effects of the PBR extract through in vitro cell experiments, and explored its underlying mechanisms by combining untargeted metabolomics with network pharmacology to predict the related targets. Results: The anti-tumor potential of PBR extracts was systematically evaluated by integrating chemical profiling with in vitro cell-based assays. Untargeted metabolomics tentatively annotated metabolites spanning 12 major chemical classes, several of which have been previously reported to possess anti-tumor activity. To validate these annotations, prioritized candidates were further examined by LC-MS/MS against authentic reference standards at the nanogram scale, which confirmed the presence of sclareol—a naturally occurring diterpene with documented anti-tumor properties—as a constituent of PBR. Consistent with this chemical evidence, the PBR extract exerted multi-faceted anti-tumor effects in A549 lung cancer cells: it significantly suppressed proliferation, migration, and invasion; induced G0/G1-phase cell-cycle arrest; disrupted mitochondrial membrane potential; and modulated the expression of apoptosis-related proteins. Conclusions: By highlighting the pharmacological properties of cultivated PBR, we identified 118 overlapping targets between PBR compounds and lung disease-related targets, and we further selected 25 core lung cancer targets with high topological importance. This study suggests that the primary active compounds of Pleione bulbocodioides (Franch.) Rolfe may exert anti-lung cancer activity, potentially through targeting the EGFR tyrosine kinase inhibitor resistance pathway and the PI3K-Akt signaling pathway. Furthermore, in silico molecular docking suggested that the two major active compounds exhibited favorable predicted binding affinities with four core targets, particularly EGFR and AKT1, providing a basis for further experimental validation. These results support the potential value of Naxi traditional medicine and the need to further research onthese medicinal plants, thereby promoting Chinese herb medicine conservation efforts in the Naxi region. Full article
(This article belongs to the Section Natural Products)
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27 pages, 7969 KB  
Article
Gastrodin Ameliorates Type II Diabetes Through the YY1–FXR–Bile Acid Axis
by Xiaolin Zhang, Yushan Du, Penghui Yang, Shiji Li, Fengya Cui, Xinran Li, Xinyue Du, Bingyao Sun, Yulu Ma, Wenjie Sui, Min Zhang and Jing Meng
Int. J. Mol. Sci. 2026, 27(10), 4593; https://doi.org/10.3390/ijms27104593 - 20 May 2026
Viewed by 65
Abstract
Type II diabetes mellitus (T2DM), a chronic metabolic disorder characterized by insulin resistance, is often accompanied by dysregulated bile acid metabolism. Although gastrodin, a bioactive compound derived from Gastrodia elata, has demonstrated potential in diabetes management, its therapeutic mechanisms remain incompletely understood. The [...] Read more.
Type II diabetes mellitus (T2DM), a chronic metabolic disorder characterized by insulin resistance, is often accompanied by dysregulated bile acid metabolism. Although gastrodin, a bioactive compound derived from Gastrodia elata, has demonstrated potential in diabetes management, its therapeutic mechanisms remain incompletely understood. The aim of this study is to investigate the therapeutic effects and potential mechanisms of gastrodin on T2DM mice from the perspective of bile acid metabolism. In this study, we found that gastrodin could not only reduce lipid accumulation, reduce inflammation, improve antioxidant capacity, alleviate oxidative stress, change the composition of intestinal flora, and improve the disorder of flora caused by the disease in T2DM mice, but also target Yin yang 1 (YY1) to reduce the expression level of YY1 in the liver under a high-fat diet condition. At the same time, YY1 negatively regulates the expression level of Farnesoid X Receptor (FXR), which increases the expression level of FXR, inhibits the enzyme activity of Cholesterol-7α-hydroxylase (CYP7A1) through Small Heterodimer Partner (SHP), reduces the production of chenodeoxycholic acid (CDCA) in the liver, and further affects the production of secondary bile acids through liver–intestinal circulation, promoting the secretion of Glucagon-Like Peptide-1 (GLP-1) and insulin, thereby reducing blood glucose. At the same time, combined with the results of HE staining, gastrodin can reduce the pathological damage of the liver and pancreas in type II diabetic mice, repairing their normal morphology and function. It provides a direct pathological basis for the improvement of diabetes and liver complications, provides theoretical support for the subsequent research and development of precision targeted drugs, provides experimental basis for the development of new natural hypoglycemic drugs, and promotes the transformation and application of the modernization of traditional Chinese medicine in the field of metabolic diseases. Full article
(This article belongs to the Special Issue Natural Products in Drug Discovery and Development: 2nd Edition)
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21 pages, 1032 KB  
Review
Beneficial Effects of Natural Bioactive Compounds on Eye Health: A Narrative Review
by Sandun De Silva and Baojun Xu
Int. J. Mol. Sci. 2026, 27(10), 4592; https://doi.org/10.3390/ijms27104592 - 20 May 2026
Viewed by 256
Abstract
Ocular diseases like age-related macular degeneration (AMD), diabetic retinopathy (DR), glaucoma and cataracts are major causes of visual impairment all over the world and are closely linked to oxidative stress, inflammation and mitochondrial dysfunction. This narrative review critically summarizes the available evidence on [...] Read more.
Ocular diseases like age-related macular degeneration (AMD), diabetic retinopathy (DR), glaucoma and cataracts are major causes of visual impairment all over the world and are closely linked to oxidative stress, inflammation and mitochondrial dysfunction. This narrative review critically summarizes the available evidence on how various natural bioactive compounds, such as carotenoids, polyphenols, flavonoids, omega-3 fatty acids and botanical extracts, can affect important molecular pathways associated with ocular degeneration. Their antioxidant, anti-inflammatory, anti-angiogenic and neuroprotective properties are given particular emphasis, especially regarding the Nrf2, NF-κB and VEGF signaling pathways. This review is different from past reviews that simply discuss the potential of bioactives in the general nutritional context; rather, it unfolds the disease-specific mechanisms and compound-specific molecular actions and gives special attention to recent advances in nano-delivery systems and precision nutrition strategies to increase the bioavailability and therapeutic targeting of these nutrients in the eyes. Moreover, it offers a framework for a comparison of evidence between preclinical and clinical studies, as well as identifying current translational gaps, including limited bioavailability and a lack of long-term clinical trials, and suggesting future directions such as genotype-guided nutrition and microbiome-informed interventions. In general, this review provides a mechanistic and translational overview of how dietary bioactive compounds relate to eye health and offers the perspective of their possible use in prevention and complementary treatment for vision-related diseases. Full article
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22 pages, 3134 KB  
Article
Comparative Phytochemical Profiling and In Vitro Investigation of the Antioxidant and Antimicrobial Potential of Arnica montana L., Melissa officinalis L. and Capsella bursa-pastoris Medik. Extracts and Their Synergistic Combinations
by Sorina-Georgiana Onea Mînz, Cristina Burlou-Nagy Fati, Neli Kinga Olah, Anett Balasko Karetka, Rodica Anamaria Negrean, Mariana Ganea, Olimpia Daniela Frent, Florin Banica and Annamaria Pallag
Molecules 2026, 31(10), 1735; https://doi.org/10.3390/molecules31101735 - 19 May 2026
Viewed by 200
Abstract
This study investigated the phytochemical composition, antioxidant potential, and antimicrobial activity of ethanolic extracts obtained from Arnica montana L., Melissa officinalis L., and Capsella bursa-pastoris Medik., as well as their ternary mixtures. Liquid chromatography coupled with mass spectrometry analysis revealed the presence of [...] Read more.
This study investigated the phytochemical composition, antioxidant potential, and antimicrobial activity of ethanolic extracts obtained from Arnica montana L., Melissa officinalis L., and Capsella bursa-pastoris Medik., as well as their ternary mixtures. Liquid chromatography coupled with mass spectrometry analysis revealed the presence of several phenolic compounds, including luteolin, apigenin, acacetin, and phenolic acids, while rutin and hyperoside were previously reported as dominant constituents in Capsella bursa-pastoris Medik. The extracts and their mixtures exhibited significant antioxidant activity in different radical scavenging and reducing power assays, with the highest activity observed for the ACM4 mixture. Antimicrobial activity was evaluated against Staphylococcus aureus and Streptococcus pneumoniae, showing inhibitory effects with minimum inhibitory concentration values ranging from below 100 mg/L for Melissa officinalis L. extracts to above 250 mg/L for Capsella bursa-pastoris Medik. extracts. These findings suggest that the phenolic compounds identified in the studied plants contribute to their antioxidant and antibacterial properties and support the potential use of these extracts and their combinations as natural sources of bioactive compounds. Full article
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22 pages, 10664 KB  
Article
Mature-Stage Eisenia fetida Proteins Suppress Macrophage Inflammation via NF-κB and MAPK Pathways
by Hind Althagafi, Hussam A. Althagafi, Fahad Alharthi, Abdullah A. A. Alghamdi, Abdullah M. Almotayri, Ibrahim Jafri, Leena S. Alqahtani, Atif Abdulwahab A. Oyouni, Abdulaziz Albogami and Deyala M. Naguib
Int. J. Mol. Sci. 2026, 27(10), 4568; https://doi.org/10.3390/ijms27104568 - 19 May 2026
Viewed by 156
Abstract
Earthworm-derived bioactive compounds are emerging as promising pharmaceutical agents; however, the immunomodulatory effects of Eisenia fetida proteins at different developmental stages remain unclear. This study evaluated, for the first time, the stage-dependent immunomodulatory activity of E. fetida protein extracts in RAW 264.7 macrophages. [...] Read more.
Earthworm-derived bioactive compounds are emerging as promising pharmaceutical agents; however, the immunomodulatory effects of Eisenia fetida proteins at different developmental stages remain unclear. This study evaluated, for the first time, the stage-dependent immunomodulatory activity of E. fetida protein extracts in RAW 264.7 macrophages. Soluble proteins isolated from juvenile, mature, and senescent worms were lyophilized and tested for their effects on cell viability, phagocytic activity, nitric oxide (NO), reactive oxygen species (ROS), and inflammatory gene expression. Amino acid profiling and Western blot analysis were additionally performed to investigate biochemical composition and signaling mechanisms. Mature-stage extracts exhibited the highest protein yield, minimal cytotoxicity, enhanced macrophage phagocytosis, and significant suppression of LPS-induced NO, ROS, and proinflammatory cytokines. In contrast, juvenile-stage extracts showed moderate immunomodulatory activity, whereas senescent-stage extracts induced oxidative stress and inflammatory responses. Western blot analysis demonstrated that mature-stage proteins strongly inhibited phosphorylation of NF-κB and MAPK signaling proteins, including p65, IκBα, p38, ERK1/2, and JNK, while senescent-stage extracts maintained elevated pathway activation. Amino acid analysis further revealed enriched immunologically relevant amino acids in mature-stage extracts. These findings demonstrate that developmental stage strongly influences the biological activity of E. fetida proteins and highlight mature-stage extracts as promising natural immunomodulatory agents. Full article
(This article belongs to the Special Issue Advances in Bioactivity and Molecular Mechanisms of Natural Products)
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20 pages, 2091 KB  
Article
Subcritical Water Extract from Grape Pomace Protects Human Bronchial Epithelium Cells by Mitigating Oxidative Stress Through Nrf2 Pathway
by Federica Affranchi, Giovanni Pratelli, Raffaele Raimondo, Pavel Kiselev, Michela Giuliano, Antonietta Notaro and Sonia Emanuele
Molecules 2026, 31(10), 1736; https://doi.org/10.3390/molecules31101736 - 19 May 2026
Viewed by 110
Abstract
In the context of the circular economy, the valorization of natural biomolecules from by-products has recently represented a major goal in health promotion. From this perspective, this study examined the antioxidant potential of Sicilian white grape pomace from the Pinot Gris variety, using [...] Read more.
In the context of the circular economy, the valorization of natural biomolecules from by-products has recently represented a major goal in health promotion. From this perspective, this study examined the antioxidant potential of Sicilian white grape pomace from the Pinot Gris variety, using subcritical water extraction as an eco-friendly and innovative method to recover bioactive compounds. Different extraction parameters allowed for comparing the potential of various fractions. Among these, the Subcritical Water Extract obtained after 5 min at 160 °C (SWE160.1) was rich in gallic acid and protocatechuic acid, as evidenced by characterization with UHPLC-Q Exactive Orbitrap-HRMS system. SWE160.1 showed efficacious antioxidant activity, as confirmed by DPPH assay and total polyphenol and flavonoid content. Interestingly, SWE160.1 displayed cytotoxic activity in tumor cell lines, while preserving the viability of non-tumor bronchial epithelial cells. Specifically, SWE160.1 protected these cells from exogenous oxidative stress, reducing the ROS levels and activating Nrf2-mediated antioxidant response. Surprisingly, upregulation of antioxidant enzymes (HO-1 and SOD-2) induced by SWE160.1 was maintained in the presence of lipopolysaccharide, indicating a specific involvement of SWE160.1 in the anti-inflammatory response. Finally, SWE160.1 was also able to limit the formation of stress granules following acute stress, thereby supporting its potential to maintain cellular homeostasis. Overall, this study highlights the potential of grape pomace as a source of active molecules to prevent oxidative stress and inflammation. Full article
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20 pages, 1396 KB  
Article
Phytochemical and Biological Activities of Euphorbia clavarioides Boiss., a Traditional Wound-Healing Plant
by Khulile Ngcukana, Siphamandla Qhubekani Njabuliso Lamula, Thando Bhanisa, Sandisiwe Maposa, Anathi Dambuza, Martha Wium, Juliano Domiraci Paccez, Luiz Fernando Zerbini and Lisa V. Buwa-Komoreng
Plants 2026, 15(10), 1550; https://doi.org/10.3390/plants15101550 - 19 May 2026
Viewed by 193
Abstract
Euphorbia clavarioides Boiss. is traditionally used in wound healing and other medicinal applications. Its bioactive compounds and pharmacological potential remain underexplored. This study investigated the phytochemical composition, antioxidant, anti-inflammatory, and anticancer activities of E. clavarioides Boiss. traditionally used in wound healing. Plant extracts [...] Read more.
Euphorbia clavarioides Boiss. is traditionally used in wound healing and other medicinal applications. Its bioactive compounds and pharmacological potential remain underexplored. This study investigated the phytochemical composition, antioxidant, anti-inflammatory, and anticancer activities of E. clavarioides Boiss. traditionally used in wound healing. Plant extracts were characterized using phytochemical screening, Fourier-transform infrared spectroscopy (FTIR), and liquid chromatography–mass spectrometry (LC-MS). Antioxidant activity was evaluated via DPPH and nitric oxide (NO) scavenging assays, anti-inflammatory effects through nitrite inhibition in LPS-stimulated RAW 264.7 macrophages, and anticancer potential using the MTT assay against DU-145, PC-3, SKU-T, and AGS cell lines. Phytochemical screening confirmed tannins, phlobatannins, saponins, flavonoids, alkaloids, steroids, terpenoids, and cardiac glycosides. FTIR spectra of aqueous extracts revealed peaks at 2990.66 cm−1 (O–H), 1738.68 cm−1 (C=O), 1217.22 cm−1 (C–N), and 527.37 cm−1 (C–Cl). LC-MS profiling identified diverse metabolites, including phenolics (pseudolaroside B, cinnamtannin A2, (−)-medicarpin, butyrolactol A) and terpenoids (zerumbone, sclareol isomer, diterpenoid-like compounds), underpinning the plant’s bioactivity. Methanol extracts exhibited the strongest DPPH scavenging activity (IC50 = 755.71 µg/mL), whereas aqueous and ethanol extracts demonstrated superior NO scavenging. Ethanol extracts showed maximal anti-inflammatory activity, while aqueous extracts induced pro-inflammatory effects. Cytotoxicity assays indicated negligible toxicity. In anticancer assays, ethanol and methanol extracts significantly inhibited the proliferation of all tested cell lines at 100 µg/mL, exceeding drug control, whereas aqueous extracts displayed lower activity. The bioactive compounds in E. clavarioides support its traditional wound-healing use and demonstrate mechanistic antioxidant, anti-inflammatory, and anticancer activities, highlighting its potential as a source of multi-target natural therapeutics. Full article
(This article belongs to the Section Phytochemistry)
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13 pages, 1488 KB  
Article
Pterostilbene-Incorporated Tissue Conditioners Exhibit Sustained Antifungal Activity Against Candida albicans In Vitro with Preserved Biocompatibility
by Teuta Komoni and Ivana Sutej
Materials 2026, 19(10), 2126; https://doi.org/10.3390/ma19102126 - 19 May 2026
Viewed by 145
Abstract
Candida albicans-associated denture stomatitis is a common inflammatory condition in denture wearers. Conventional tissue conditioners provide temporary relief but lack intrinsic antifungal activity, allowing persistent microbial colonization and biofilm formation. Functionalization with bioactive agents represents a promising preventive strategy. This study evaluated [...] Read more.
Candida albicans-associated denture stomatitis is a common inflammatory condition in denture wearers. Conventional tissue conditioners provide temporary relief but lack intrinsic antifungal activity, allowing persistent microbial colonization and biofilm formation. Functionalization with bioactive agents represents a promising preventive strategy. This study evaluated the antifungal efficacy and biocompatibility of pterostilbene (PTE), a natural stilbenoid compound, incorporated into a commercially available tissue conditioner. Antifungal activity of PTE against C. albicans ATCC 10231 was evaluated using broth microdilution and XTT biofilm assays. Tissue conditioner discs containing 1% and 2.5% (w/w) PTE were fabricated and tested after 24 h, 72 h, and 1 week using colony-forming unit (CFU) counts and metabolic activity assays. Biocompatibility was assessed by exposing mouse embryonic fibroblast (MEF) cells to conditioned eluates followed by an MTT viability assay. PTE inhibited biofilm formation in a concentration-dependent manner, with significant suppression observed at ≥8 µg/mL (p < 0.001). A time-dependent antifungal effect was observed over one week. PTE-functionalized tissue conditioners significantly reduced fungal adhesion compared with controls at all-time points (p < 0.001). Cell viability remained above 70%, meeting ISO 10993-5 criteria for non-cytotoxicity, indicating potential for localized prevention of denture stomatitis. Full article
(This article belongs to the Special Issue Advanced Materials for Oral Application (3rd Edition))
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Review
Inhibition of Diabetes-Related Enzymes by Plant Secondary Metabolites: A Promising Therapeutic Strategy
by Oana-Cristina Șeremet, Corina Andrei, Ciprian Pușcașu, Anca Zanfirescu, Georgiana Nițulescu, Cerasela-Elena Gîrd and Octavian-Tudorel Olaru
Life 2026, 16(5), 834; https://doi.org/10.3390/life16050834 (registering DOI) - 19 May 2026
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Abstract
Diabetes mellitus is a chronic and increasingly prevalent metabolic disorder characterized by persistent hyperglycemia, resulting from defects in insulin secretion, insulin action, or both. Despite the availability of pharmacological agents that effectively manage blood glucose levels, many are associated with adverse effects, limited [...] Read more.
Diabetes mellitus is a chronic and increasingly prevalent metabolic disorder characterized by persistent hyperglycemia, resulting from defects in insulin secretion, insulin action, or both. Despite the availability of pharmacological agents that effectively manage blood glucose levels, many are associated with adverse effects, limited efficacy over time, and high costs. Consequently, there is growing interest in alternative therapies, especially those derived from traditional medicinal plants, that have long been employed in various cultures for managing diabetes. Recent advances in phytochemistry have identified bioactive plant secondary metabolites with promising antidiabetic properties. This review aims to provide a comprehensive overview of plant-derived compounds that exhibit inhibitory activity against key diabetes-related enzymes, including α-glucosidase, α-amylase, protein tyrosine phosphatase 1B (PTP1B) and dipeptidyl peptidase-4 (DPP-4). These enzymes play critical roles in glucose metabolism and insulin signaling pathways. The review highlights the structural diversity of these natural inhibitors, their mechanisms of action, and their effectiveness in preclinical models. Understanding the molecular interactions and pharmacological profiles of these metabolites may facilitate the development of safer and more effective antidiabetic agents. Full article
(This article belongs to the Special Issue Bioactive Phytotherapeutics in Metabolic and Inflammatory Disorders)
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