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52 pages, 6978 KB  
Review
Medicine–Food Homology Plants and Bioactive Compounds in Polyendocrine Metabolic Ovarian Syndrome: Multi-Target Mechanisms and Functional Food Potential—A Review
by Qiuni Yang, Linzuo Zou, Yuxue Huang, Qingfeng Zhang, Chengyao He, Li Cheng and Chao Zhao
Nutrients 2026, 18(17), 2837; https://doi.org/10.3390/nu18172837 (registering DOI) - 28 Aug 2026
Abstract
Polyendocrine metabolic ovarian syndrome (PMOS), renamed from polycystic ovary syndrome (PCOS) by global consensus in May 2026, is one of the most common endocrine diseases in women of reproductive age, affecting physical and mental health. Growing evidence suggests that medicine–food homology (MFH) plants [...] Read more.
Polyendocrine metabolic ovarian syndrome (PMOS), renamed from polycystic ovary syndrome (PCOS) by global consensus in May 2026, is one of the most common endocrine diseases in women of reproductive age, affecting physical and mental health. Growing evidence suggests that medicine–food homology (MFH) plants and their bioactive compounds may help regulate PMOS-related metabolism and reproductive abnormalities through dietary intervention. This review summarizes their reported roles and potential mechanisms. Based on the existing literature, this review presents nine edible plant resources identified under the MFH/dietary-use framework and 21 bioactive constituents or constituent classes, all selected for detailed synthesis from a broader eligible evidence base and with reported PMOS-related bioactivity. Across preclinical studies, these constituents appear to act through convergent, multi-target mechanisms, including anti-inflammatory and antioxidant activities to reduce systemic inflammation, as well as restoring hormone balance, correcting abnormal lipid metabolism, relieving insulin resistance and protecting ovarian function. Importantly, the evidence base remains predominantly preclinical, with few human randomized trials. Key translational barriers include insufficient standardization of preparations and doses, limited oral bioavailability of several constituents, safety and herb–drug interaction concerns, and uncertain formulation feasibility for functional-food applications. By integrating evidence at the plant and compound levels, this review provides a mechanistic rationale—rather than clinical proof—for further investigation of dietary strategies relevant to PMOS and proposes a framework for the development and evaluation of MFH-based functional foods. Full article
(This article belongs to the Special Issue Endocrine Disturbances and Nutritional Therapies)
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24 pages, 6597 KB  
Article
Nitrogen Fertilizer Formulations Modulate the Yield–Cadmium Trade-Off in Rice Through Rhizosphere Processes and Translocation Nodes
by Yusheng Zhang, Hejun Ao, Xilin Fang, Xing Li, Hongyu Zhang, Ting Zhong, Xuefei Tian, Xianglan Zeng, Wupeng Ji and Min Luo
Plants 2026, 15(17), 2618; https://doi.org/10.3390/plants15172618 - 27 Aug 2026
Viewed by 151
Abstract
Cadmium (Cd) contamination in paddy soils represents a major risk to global food security and human health because Cd can readily enter the food chain through rice consumption. Therefore, clarification of the key processes and mechanisms by which agronomic practices regulate Cd accumulation [...] Read more.
Cadmium (Cd) contamination in paddy soils represents a major risk to global food security and human health because Cd can readily enter the food chain through rice consumption. Therefore, clarification of the key processes and mechanisms by which agronomic practices regulate Cd accumulation in rice is essential. Based on integrated two-year pot and field experiments, we showed that different nitrogen fertilizer formulations, including nitrate-N (N), ammonium-N (A), and urea (U), had distinct effects on Cd accumulation and grain yield in rice. The N treatment reduced Cd concentrations in brown rice by 25.29% to 70% in the pot experiment and by 4.25% to 89.97% in the field experiment but decreased grain yield by 5% to 25%. By contrast, the A treatment increased Cd concentrations in brown rice by 17.86% to 58.62%, while maintaining or slightly increasing grain yield (−3% to +5%), and the U treatment showed intermediate responses. These responses were mainly associated with nitrogen-induced shifts in rhizosphere chemistry, especially changes in soil Cd availability linked to pH and exchangeable H+, although unmeasured redox-related processes may have also contributed under flooded conditions. Further analyses of internal Cd distribution and translocation, together with exploratory random forest modeling, suggested that Cd transport efficiency at key stem internodes and Cd redistribution from the panicle to the grain were important regulatory nodes associated with Cd concentrations in brown rice. These regulatory nodes were markedly affected by fertilizer formulation. Overall, our results describe a continuous pathway from rhizosphere Cd availability to internal transport and partitioning, through which nitrogen fertilizer formulations regulate Cd accumulation in rice. This study aimed to clarify how different nitrogen fertilizer formulations regulate the trade-off between grain yield and Cd accumulation in rice, based on the hypothesis that these formulations differentially modify rhizosphere chemistry and Cd bioavailability, that specific stem nodes contribute to control of grain Cd accumulation, and that the main regulatory processes differ between pot and field systems. This study provides s a scientific basis for developing practical nitrogen-management strategies to support safe rice production in Cd-contaminated paddy fields. Full article
(This article belongs to the Special Issue Heavy Metal Contamination in Plants and Soil)
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24 pages, 2778 KB  
Review
Heavy Metal Pollution in River Sediments: Risk Assessment, Source Apportionment, and Remediation—A Review Focusing on Chinese River Basins
by Yuheng Tan, Jianqiao Qin, Binyi Tao, Huarong Zhao, Jinhuan Deng, Jiayin Ling, Min Dai and Xi Chen
Toxics 2026, 14(9), 765; https://doi.org/10.3390/toxics14090765 - 27 Aug 2026
Viewed by 175
Abstract
River sediments act not only as important sinks for heavy metal pollution in watersheds, but also as potential secondary sources under changing environmental conditions. Heavy metals can enter river systems through industrial wastewater discharge, agricultural non-point runoff, urban stormwater and sewage inputs, mining [...] Read more.
River sediments act not only as important sinks for heavy metal pollution in watersheds, but also as potential secondary sources under changing environmental conditions. Heavy metals can enter river systems through industrial wastewater discharge, agricultural non-point runoff, urban stormwater and sewage inputs, mining and smelting activities, and atmospheric deposition. During adsorption onto suspended particles, sedimentation, and resuspension, metals such as Cd, Pb, Cr, Cu, Zn, Ni, As, and Hg progressively accumulate in sediments. Because heavy metals are persistent, non-degradable, and bioaccumulative, contaminated sediments can record historical watershed pollution while also releasing metals back into overlying water under hydrodynamic disturbance, pH and redox fluctuations, organic matter mineralization, benthic bioturbation, and dredging activities, thereby threatening aquatic ecosystem stability and human health. Using a global methodological framework with particular emphasis on Chinese river basins, this review systematically summarizes key issues in the study of heavy metal pollution in river sediments, including spatial–temporal distribution and operationally defined fractionation, pollution levels and ecological risk assessment, source apportionment, and remediation and management technologies. Current evidence indicates that heavy metal contamination in river sediments exhibits pronounced spatial heterogeneity and watershed-specific characteristics. Its distribution is jointly controlled by geological background, land use patterns, source input intensity, hydrodynamic conditions, sediment particle size composition, and organic matter content. Methodologically, the field has evolved from single total concentration monitoring and exceedance-based evaluation toward integrated assessment systems that combine total concentrations, operationally defined fractionation, bioavailability, ecological risk, health risk, and source contribution. The joint use of BCR sequential extraction, the geoaccumulation index (Igeo), the pollution load index (PLI), the potential ecological risk index (RI), the risk assessment code (RAC), sediment quality guidelines (SQGs), receptor models, isotope tracing, and machine learning has substantially improved pollution identification, risk zoning, and source apportionment. Overall, research on heavy metal pollution in river sediments has shifted from descriptive judgments of whether contamination exists toward mechanistic and management-oriented questions concerning pollution sources, risk evolution, and remediation strategies. However, important gaps remain in compound pollution transformation mechanisms, regional background values and evaluation benchmarks, uncertainty in model parameters, long-term dynamic monitoring, and engineering-scale verification of remediation technologies. Future studies should strengthen multi-media, multi-scale, and long-term monitoring and further integrate fractionation analysis, toxicological effects, source apportionment models, and remediation technologies to provide a scientific basis for watershed ecological security and precision management of contaminated sediments. Full article
(This article belongs to the Special Issue Biomonitoring of Toxic Elements and Emerging Pollutants)
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18 pages, 2813 KB  
Review
Repurposing Disulfiram for Cancer Therapy: Mechanistic Insights and Translational Challenges
by Anna Bilska-Wilkosz, Magdalena Górny and Małgorzata Iciek
Int. J. Mol. Sci. 2026, 27(17), 7667; https://doi.org/10.3390/ijms27177667 - 27 Aug 2026
Viewed by 109
Abstract
Disulfiram (DSF), long used as an aversive agent in alcohol dependence therapy, has recently regained attention as a promising candidate for oncological drug repurposing. After administration, DSF is rapidly reduced to diethyldithiocarbamate (DDC), which, in the presence of Cu2+, forms the [...] Read more.
Disulfiram (DSF), long used as an aversive agent in alcohol dependence therapy, has recently regained attention as a promising candidate for oncological drug repurposing. After administration, DSF is rapidly reduced to diethyldithiocarbamate (DDC), which, in the presence of Cu2+, forms the complex Cu(DDC)2. This compound acts as a strong inducer of oxidative stress, an inhibitor of the ubiquitin–proteasome system, and a suppressor of endogenous hydrogen sulfide (H2S) synthesis. DSF also modifies protein and non-protein thiol groups, disrupting cancer cell metabolism and promoting apoptosis. Despite robust preclinical evidence, clinical translation remains limited. Key obstacles include DSF’s rapid metabolism, insufficient availability of free copper ions in humans, and the lack of predictive biomarkers capable of identifying responsive patients. Another challenge is DSF’s low oral bioavailability, which prevents the drug from reaching tumor tissue at therapeutically effective concentrations. Consequently, current research focuses on advanced nanocarrier systems designed to protect DSF from premature degradation and ensure its controlled release within the tumor microenvironment. This review summarizes the multifaceted anticancer mechanisms of DSF and discusses biological and pharmacological factors underlying the discrepancies between experimental findings and clinical outcomes. Full article
(This article belongs to the Section Molecular Pharmacology)
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36 pages, 10516 KB  
Review
Potential Therapeutic Roles of Icariin in Inflammatory Diseases: From Molecular Mechanisms to Clinical Translation Prospects
by Sirui Du, Weifeng Li and Meixiu Jiang
Antioxidants 2026, 15(9), 1068; https://doi.org/10.3390/antiox15091068 - 26 Aug 2026
Viewed by 254
Abstract
Inflammatory diseases are caused by overactivation of the immune system and lead to tissue damage; their high incidence and complications seriously threaten human health. Currently, non-steroidal anti-inflammatory drugs (NSAIDs) and immunosuppressants are the mainstay of clinical practice, but their long-term use can cause [...] Read more.
Inflammatory diseases are caused by overactivation of the immune system and lead to tissue damage; their high incidence and complications seriously threaten human health. Currently, non-steroidal anti-inflammatory drugs (NSAIDs) and immunosuppressants are the mainstay of clinical practice, but their long-term use can cause gastrointestinal damage, drug resistance, and other problems. In recent years, traditional Chinese medicine has become a research hotspot for the treatment of inflammatory diseases, among which Icariin (ICA), the main active ingredient of Epimedium, has demonstrated significant anti-inflammatory potential. In this review, a comprehensive literature search of PubMed and Web of Science was conducted, and original studies on the anti-inflammatory effects and mechanisms of ICA were included. The roles and mechanisms of ICA in inflammatory diseases in different systems are summarized. Specifically, ICA suppresses NF-κB and MAPK signaling, inhibits NLRP3 inflammasome activation, and activates the Nrf2/HO-1 antioxidant axis, thereby reducing the production of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1β. Overall, the current evidence indicates broad anti-inflammatory effects of ICA across multiple organ systems, particularly in atherosclerosis and myocardial infarction; however, clinical translation is limited by poor bioavailability and the lack of standardized dosage data. Future efforts should focus on pharmacokinetic optimization and well-designed clinical trials to facilitate its application in inflammatory diseases. Full article
(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)
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24 pages, 8661 KB  
Article
Contents, Pollution Indices, and Multivariate Associations of Potentially Toxic Elements in Soils of the Ortaklar Region, Türkiye
by Nevin Konakci, Emel Bacha Simoes, Bilge Sasmaz, Ali Abedini and Ahmet Sasmaz
Minerals 2026, 16(9), 871; https://doi.org/10.3390/min16090871 - 26 Aug 2026
Viewed by 218
Abstract
Elevated potentially toxic element (PTE) contents in soils can pose important environmental concerns, particularly in regions where natural metal enrichment associated with ultramafic and mineralized geological settings overlaps with potential anthropogenic inputs. This study evaluates the distribution, enrichment, and probable controls of As, [...] Read more.
Elevated potentially toxic element (PTE) contents in soils can pose important environmental concerns, particularly in regions where natural metal enrichment associated with ultramafic and mineralized geological settings overlaps with potential anthropogenic inputs. This study evaluates the distribution, enrichment, and probable controls of As, Ni, Co, Cu, Cr, Pb, and Zn in 35 geo-referenced soil samples from the Ortaklar region, Türkiye, with the aim of providing a geochemical basis for environmental monitoring and sustainable land management. PTE contents were determined by ICP-MS (inductively coupled plasma mass spectrometry), and their degree of enrichment was evaluated using the geo-accumulation index (Igeo), contamination factor (CF), and pollution load index (PLI), supported by correlation analysis and multivariate statistical approaches. Mean contents decreased in the order Ni (1972 mg kg−1) > Cr (924 mg kg−1) > Cu (290 mg kg−1) > Zn (188 mg kg−1) > Co (122 mg kg−1) > As (15.9 mg kg−1) > Pb (6.8 mg kg−1). Ni exhibited the highest degree of enrichment and was the dominant contributor to the overall PTE load, while Cr, Cu, and Co also showed substantial enrichment. Mean Igeo values indicated moderate to heavy enrichment for Ni (2.65) and As (2.36), and moderate enrichment for Cr (1.45) and Co (1.02). The mean PLI value of 6.99 indicates a substantial cumulative enrichment of PTEs relative to the adopted reference values. Strong associations among Ni, Cr, and Co are consistent with a dominant geogenic contribution from ultramafic/serpentinitic parent materials and their weathering products, whereas the distributions of As, Cu, and Zn suggest more complex controls involving lithology, mineralization, and potentially localized agricultural or other anthropogenic inputs. However, these statistical relationships indicate probable controls rather than definitively establishing elemental sources. The elevated total PTE contents and contamination indices identify the Ortaklar soils as requiring continued geochemical monitoring; nevertheless, they do not constitute direct evidence of human-health risk because metal speciation, mobility, bioavailability, and exposure pathways were not investigated. The findings provide a regional geochemical framework for distinguishing natural PTE enrichment from anthropogenic influences and for guiding future mineralogical, bioavailability, and spatial investigations in ultramafic and mineralized soil environments. Full article
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19 pages, 1758 KB  
Review
Processing, Bioaccessibility, Predicted Bioavailability, Gut Microbiome Interactions and Potential Food Applications of Vernonia amygdalina (Bitter Leaf): Bridging the Evidence-to-Practice Gap
by Khavhatondwi Rinah Mofokeng and Rhulani Caswell Chauke
Foods 2026, 15(17), 2962; https://doi.org/10.3390/foods15172962 - 23 Aug 2026
Viewed by 251
Abstract
Vernonia amygdalina Del. (bitter leaf) is a nutrient-rich indigenous leafy vegetable, but most research has examined raw material or laboratory extracts rather than the vegetable as consumed. This structured narrative review evaluates how household and food-processing methods affect nutrient retention, anti-nutritional factors, and [...] Read more.
Vernonia amygdalina Del. (bitter leaf) is a nutrient-rich indigenous leafy vegetable, but most research has examined raw material or laboratory extracts rather than the vegetable as consumed. This structured narrative review evaluates how household and food-processing methods affect nutrient retention, anti-nutritional factors, and bioaccessibility and distinguishes measured species-specific findings from extrapolated evidence. Boiling and aqueous debittering can reduce heat-sensitive nutrients, minerals, and anti-nutritional factors, but the heterogeneous primary studies do not permit a single quantitative estimate of these effects. Lactic acid fermentation is a potential research strategy: proposed reductions in anti-nutritional factors and bitterness are extrapolated from other fermented plant foods because no species-specific fermentation study was identified. Similarly, proposed gut-microbiome effects are inferred from general dietary-fibre and isolated-polyphenol literature, not from V. amygdalina feeding studies. No human study has directly measured nutrient absorption, systemic bioavailability, or clinical effects after consumption of processed bitter leaf. Hence, phytate-to-mineral ratios are interpreted only as indicators of predicted absorption, and proposed food formats and development pathways are identified as author-generated concepts rather than validated products. The review identifies priorities for species-specific processing studies, standardised in vitro digestion, product safety and acceptability testing, and ultimately human absorption and efficacy research. Full article
(This article belongs to the Section Nutraceuticals, Functional Foods, and Novel Foods)
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42 pages, 2593 KB  
Review
Microplastics and Nanoplastics in the Human Diet: Sources of Exposure, Bioavailability, Toxicokinetics, and Systemic Health Effects
by Łukasz Kogut, Czesław Puchalski, Julia Jastrzębska and Grzegorz Zaguła
Molecules 2026, 31(17), 2945; https://doi.org/10.3390/molecules31172945 - 22 Aug 2026
Viewed by 388
Abstract
Background/Objectives: Microplastics (MPs) and nanoplastics (NPs) have emerged as ubiquitous environmental contaminants resulting from the extensive production, use, and degradation of plastic materials. Human exposure occurs primarily through contaminated food and drinking water, with inhalation representing an additional important route. Growing concern [...] Read more.
Background/Objectives: Microplastics (MPs) and nanoplastics (NPs) have emerged as ubiquitous environmental contaminants resulting from the extensive production, use, and degradation of plastic materials. Human exposure occurs primarily through contaminated food and drinking water, with inhalation representing an additional important route. Growing concern has focused on the ability of these particles, particularly NPs, to cross biological barriers, enter the systemic circulation, and reach human tissues. The aim of this review was to summarize current evidence on dietary exposure to MPs and NPs, their gastrointestinal bioavailability and toxicokinetics, and their potential systemic health effects, with particular emphasis on organ-specific responses, underlying biological mechanisms, and the strength and limitations of the available evidence. Methods: A comprehensive narrative review of the scientific literature published between 2000 and 2026 was conducted using PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar. Original research articles and review papers addressing dietary exposure, occurrence in food and drinking water, migration from food-contact materials, gastrointestinal absorption, translocation, biodistribution, bioaccumulation, elimination, molecular mechanisms, and potential organ-specific or systemic health effects were included. Publications without full-text availability, conference proceedings, editorials, commentaries, duplicate publications, and studies without relevance to human exposure or health were excluded. Results: Food, drinking water, beverages, and food-contact materials represent important sources of human exposure to MPs and NPs. Following ingestion, most larger particles are eliminated through the gastrointestinal tract, whereas smaller MPs and particularly NPs may cross biological barriers and potentially reach the systemic circulation and distant tissues. Experimental studies consistently identify interconnected biological responses involving oxidative stress, inflammation, mitochondrial dysfunction, barrier impairment, immune dysregulation, genotoxicity, apoptosis, and endocrine disruption. These mechanisms have been associated with alterations in the gastrointestinal, respiratory, cardiovascular, nervous, urinary, reproductive, endocrine, and skeletal systems and with biological processes relevant to carcinogenesis. However, most mechanistic evidence derives from in vitro and animal models, whereas human evidence remains limited and predominantly observational. Consequently, the extent to which these experimental findings translate into clinically significant effects in humans remains uncertain. Conclusions: Current evidence supports the biological plausibility of systemic effects associated with MNP exposure but is insufficient to establish causal relationships between chronic dietary exposure and specific human diseases. The detection of MNPs in human tissues and reported associations with pathological conditions should therefore be interpreted cautiously. Standardized analytical methods, improved characterization of realistic human exposure, and well-designed longitudinal epidemiological studies integrating quantitative exposure assessment with validated clinical outcomes are required to clarify dose–response relationships, long-term health effects, and the clinical significance of MNP exposure. Full article
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24 pages, 2589 KB  
Review
Plant-Based Approaches for Inhibition of Advanced Glycation End Products Formation: Dietary Polyphenols
by Seray Akalin-Saygili and Aylin Ayaz
Molecules 2026, 31(16), 2928; https://doi.org/10.3390/molecules31162928 - 21 Aug 2026
Viewed by 378
Abstract
Advanced glycation end products arise during thermal processing and endogenous metabolism, contributing to oxidative stress, inflammation, and the progression of chronic diseases. Dietary polyphenols have emerged as promising advanced glycation end product (AGE) inhibitors through antioxidant activity, carbonyl trapping, metal chelation, and modulation [...] Read more.
Advanced glycation end products arise during thermal processing and endogenous metabolism, contributing to oxidative stress, inflammation, and the progression of chronic diseases. Dietary polyphenols have emerged as promising advanced glycation end product (AGE) inhibitors through antioxidant activity, carbonyl trapping, metal chelation, and modulation of inflammatory pathways. This review summarizes current evidence on the effects of polyphenols in food systems and highlights how different polyphenol subclasses vary in their antiglycation potential depending on chemical structure, food matrix, and cooking conditions. Although experimental studies consistently demonstrate inhibitory effects, the translation to humans remains limited by low bioavailability, metabolic transformation, and heterogeneous analytical methods. Standardized AGE measurements are needed to improve mechanistic insight, and evaluations of dose–response relationships are needed to clarify their relevance in real-world diets. Future research should prioritize long-term human studies and practical culinary strategies to determine whether polyphenol-rich foods can meaningfully reduce dietary AGE exposure and support chronic disease prevention. Full article
(This article belongs to the Special Issue Featured Review Papers in Food Chemistry—2nd Edition)
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22 pages, 1326 KB  
Review
Berberine-Drug Interactions: Mechanisms, Clinical Relevance and Risk Stratification—A Narrative Review
by Caterina Nela Dumitru, Teodora Marcu, Alina Oana Dumitru, Simona Steliana Tudor, Ionela Daniela Ferțu, Alina-Mihaela Elisei and Larisa Goroftei
Pharmaceuticals 2026, 19(8), 1313; https://doi.org/10.3390/ph19081313 - 20 Aug 2026
Viewed by 1174
Abstract
Background: Berberine, an isoquinoline alkaloid present in Berberis spp., Coptis chinensis and Hydrastis canadensis, is among the most widely consumed metabolic-health supplements, popularized as “nature’s Ozempic”. Concurrent, often undisclosed use with prescription drugs is common in older adults, yet berberine is far [...] Read more.
Background: Berberine, an isoquinoline alkaloid present in Berberis spp., Coptis chinensis and Hydrastis canadensis, is among the most widely consumed metabolic-health supplements, popularized as “nature’s Ozempic”. Concurrent, often undisclosed use with prescription drugs is common in older adults, yet berberine is far from inert. Objective: To synthesize the evidence on berberine as a perpetrator of supplement–drug interactions, propose a four-axis mechanistic taxonomy, with product quality treated separately as a modifier of exposure rather than as a mechanism, and derive a clinically actionable risk-stratification framework. Methods: Structured narrative review, prepared per the SANRA quality criteria; PubMed/MEDLINE, Scopus, Web of Science and Embase were searched up to May 2026. Results: Despite very low systemic exposure (oral bioavailability 0.68% in rats; low ng/mL plasma concentrations in humans), high luminal, enterocytic and hepatic concentrations generate interaction liability, documented in humans for a few pairs and mechanistic for most, along four mechanistic axes: inhibition, and transcriptional induction, of CYP3A4, with CYP2D6/CYP2C9 inhibition that is quasi-irreversible through a metabolite-intermediate complex; transporter modulation (P-glycoprotein, OCT1/OCT2, and MATE1); pharmacodynamic additivity (hypoglycemia, hypotension, and QT prolongation); and microbiome- and gut-barrier-mediated effects, the last of these being a candidate axis rather than a demonstrated one. Product-quality variability is treated separately, as a modifier of exposure. The clinical anchor is increased cyclosporine exposure in renal-transplant recipients (AUC +34.5%; trough 29.3% above control). These elements are integrated into a three-tier risk-stratification framework that combines perpetrator potency, victim-drug vulnerability, and patient vulnerability, with each tier being linked to a defined pharmacy action. Conclusions: In patients on multiple medications, and particularly when berberine is co-administered with drugs of narrow therapeutic index, it should be managed as an active pharmacological perpetrator rather than as an inert supplement. Unstandardized product quality and an unsettled European regulatory framework, under which national limits differ by more than an order of magnitude, further widen the uncertainty around the dose actually delivered. Berberine use should therefore be elicited routinely at medication reconciliation and stratified by mechanism, by victim-drug vulnerability, and by patient risk, with particular attention to metabolic self-medication in the GLP-1 era. Full article
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15 pages, 3603 KB  
Article
Moxifloxacin-Mediated Downregulation of Intestinal P-Glycoprotein Alters the Pharmacokinetics of Dabigatran Etexilate: Mechanistic Insights in Rats and PBPK Model-Informed Dose Optimization
by Yuchen Qu, Zhuan Yang, Wen Ma, Peng Xiao, Yani Gu, Jie Pan, Xinyun Zhang, Chen Zhao and Yunli Yu
Pharmaceutics 2026, 18(8), 1031; https://doi.org/10.3390/pharmaceutics18081031 - 20 Aug 2026
Viewed by 254
Abstract
Background: In patients with atrial fibrillation receiving long-term anticoagulation therapy with dabigatran etexilate (DABE), moxifloxacin (MFLX) is frequently coadministered to treat concurrent infections; however, the potential drug–drug interaction (DDI) between these agents remains unclear. Herein, we examined the underlying mechanism by which [...] Read more.
Background: In patients with atrial fibrillation receiving long-term anticoagulation therapy with dabigatran etexilate (DABE), moxifloxacin (MFLX) is frequently coadministered to treat concurrent infections; however, the potential drug–drug interaction (DDI) between these agents remains unclear. Herein, we examined the underlying mechanism by which MFLX attenuates DABE pharmacokinetics in rats; subsequently, we elucidated the DDI in humans by establishing a physiologically based pharmacokinetic (PBPK) model based on these animal data. Methods: The 3- and 14-day effects of 40 mg/kg MFLX once daily and secondary bile acid (SBA)-containing dietary intervention on the pharmacokinetic profile of DABE and its active form, dabigatran (DAB), were examined in a rat model. Ileum tissues were harvested to measure the expression of P-glycoprotein (P-gp), pregnane X receptor (PXR), and peroxisome proliferator-activated receptor alpha (PPARα). In addition, we examined the effects of secondary bile acids (SBAs) on P-gp expression and quantified P-gp-mediated DABE efflux transport activity in Caco-2 cells. A PBPK model was used to predict the risk of DAB exposure under this DDI scenario and under combined high-risk conditions, including renal impairment and advanced age. Results: Treatment with MFLX for 3 and 14 days inhibited SBA-producing gut microbiota, thereby suppressing the conversion of primary bile acids to SBAs. Concurrently, a marked reduction in intestinal P-gp expression was observed, along with a significant enhancement of the oral bioavailability of DABE. These effects were reversed by SBA-containing diets. In vitro experiments using Caco-2 cells revealed that physiologically relevant concentrations of SBA significantly upregulated P-gp expression and function, whereas MFLX incubation alone showed no direct modulatory effect on these transporters or regulators. PBPK simulation results showed that in vivo exposure of DAB would increase by 41.7%, 104%, 251%, and 115% when coadministered with MFLX alone, with coexisting mild renal impairment, moderate renal impairment, and aging, respectively. Conclusions: MFLX increases DAB exposure by reducing SBA-regulated intestinal P-gp function. PBPK simulations suggest a low risk of DDI from MFLX coadministration alone; however, caution is warranted in patients with aging or renal impairment. Full article
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33 pages, 1373 KB  
Review
Dietary Aluminium Exposure and Human Health: Sources, Bioavailability, Toxicokinetics, and Health Risk Assessment
by Łukasz Kogut, Czesław Puchalski, Julia Jastrzębska and Grzegorz Zaguła
Nutrients 2026, 18(16), 2719; https://doi.org/10.3390/nu18162719 - 20 Aug 2026
Viewed by 353
Abstract
Background/Objectives: Aluminium is a widespread environmental element and food contaminant to which the general population is continuously exposed, primarily through diet and drinking water. Although gastrointestinal absorption is generally low, bioavailability varies according to chemical form, food matrix, and interactions with dietary [...] Read more.
Background/Objectives: Aluminium is a widespread environmental element and food contaminant to which the general population is continuously exposed, primarily through diet and drinking water. Although gastrointestinal absorption is generally low, bioavailability varies according to chemical form, food matrix, and interactions with dietary components. Prolonged exposure can nevertheless result in gradual tissue accumulation. This review summarises current evidence on dietary aluminium exposure, factors influencing its bioavailability, toxicokinetics, biological effects, gut microbiota interactions, and population-level health risk. Methods: A comprehensive narrative literature review was conducted using publications retrieved from PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar. Original research articles, review papers, and reports issued by international organisations were critically evaluated with particular emphasis on dietary sources, drinking water, food additives, food contact materials, gastrointestinal absorption, toxicokinetics, biological mechanisms, gut microbiota, and health risk assessment. Results: Food represents the principal source of aluminium exposure in the general population, while drinking water usually contributes a smaller but continuous fraction of total oral intake. Dietary exposure varies substantially between populations and is influenced by food composition, processing practices, the use of aluminium-containing additives, and migration from food contact materials. Aluminium bioavailability is modified by chemical speciation and dietary constituents, including citrate, phosphates, silicates, phytates, polyphenols, and essential minerals. Despite limited absorption, prolonged exposure can lead to gradual aluminium accumulation, particularly in bone tissue and the central nervous system. Proposed biological mechanisms include oxidative stress, mitochondrial dysfunction, disruption of mineral homeostasis, and inflammatory signalling. Emerging evidence also indicates that aluminium may alter the gut microbiota, impair intestinal barrier integrity, and influence the gut–brain axis. Population exposure assessments show considerable regional variation, with some groups approaching or exceeding established tolerable weekly intake values. Conclusions: Dietary aluminium exposure represents a relevant issue in nutritional toxicology and food safety. Although current evidence does not establish that typical dietary exposure directly causes chronic disease, long-term exposure, differences in bioavailability, and the possibility of elevated intake in selected population groups justify continued monitoring and further prospective human studies. Future research should integrate dietary intake, aluminium speciation, nutritional status, biomarkers of internal exposure, and long-term health outcomes to improve risk assessment and support effective exposure-reduction strategies. Full article
(This article belongs to the Section Micronutrients and Human Health)
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52 pages, 2008 KB  
Review
Resveratrol and Curcumin in Stroke Therapy: From Experimental Evidence to Clinical Perspectives
by Mikołaj Grabarczyk, Aleksandra Szychowska, Weronika Szczepańska, Ewa Smolińska, Andrzej Glabinski and Piotr Szpakowski
Nutrients 2026, 18(16), 2713; https://doi.org/10.3390/nu18162713 - 19 Aug 2026
Viewed by 436
Abstract
Stroke remains one of the leading causes of death and long-term neurological disability worldwide, while currently available therapeutic strategies are limited by narrow treatment windows and incomplete neuroprotection. In this context, plant-derived polyphenols have attracted increasing attention as potential adjunctive agents because of [...] Read more.
Stroke remains one of the leading causes of death and long-term neurological disability worldwide, while currently available therapeutic strategies are limited by narrow treatment windows and incomplete neuroprotection. In this context, plant-derived polyphenols have attracted increasing attention as potential adjunctive agents because of their multimodal biological activity. This review focuses on resveratrol and curcumin, two of the most extensively investigated polyphenols, and evaluates their potential role in the prevention and treatment of ischaemic and haemorrhagic stroke. Evidence from in vitro studies, animal models, and early clinical trials indicates that both compounds may attenuate key mechanisms involved in stroke-related brain injury, including oxidative stress, neuroinflammation, mitochondrial dysfunction, apoptosis, autophagy dysregulation, blood–brain barrier disruption, and microglial activation. Emerging evidence further suggests that interactions with the gut microbiota and modulation of the gut–brain axis may contribute to their biological effects by influencing intestinal barrier integrity, microbial metabolite production, systemic inflammation, and vascular risk. Preclinical studies show that resveratrol and curcumin can reduce infarct volume, limit cerebral oedema, preserve neuronal viability, promote angiogenesis and neurogenesis, and improve neurological and cognitive outcomes. Their beneficial effects have been reported both when administered before stroke onset and after cerebral injury, suggesting potential relevance for both prevention and post-stroke therapy. However, interpretation of these findings requires consideration of the translational limitations of experimental stroke models, which do not fully reproduce the heterogeneity, comorbidities, age profile, and variable reperfusion patterns characteristic of human stroke. Although commonly used models such as middle cerebral artery occlusion provide important mechanistic and therapeutic insights, preclinical efficacy should therefore not be regarded as a direct predictor of clinical benefit. Resveratrol and curcumin may also complement established and emerging treatment strategies, including thrombolysis, endovascular interventions, antihypertensive therapy, and stem cell-based approaches. Nevertheless, their clinical translation remains limited by poor solubility, low bioavailability, rapid metabolism, and insufficient clinical evidence. Novel formulations, including nanoparticles, exosome-based delivery systems, and structurally modified analogues, may help overcome these barriers by improving brain targeting and therapeutic efficacy. Overall, resveratrol and curcumin represent promising but still investigational candidates for adjunctive stroke therapy, requiring further well-designed clinical trials to define their optimal dosing, timing, safety, and clinical value. Full article
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30 pages, 1699 KB  
Review
Bioactive Peptides from Andean Crops: Lactic Acid Bacteria Fermentation, Complementary Proteolysis, and Biological Activities
by Carlos Barba-Ostria, María José Barreno-Sánchez, Luis Fabián Salazar-Garcés, Jéssica Guamán-Bautista and Linda P. Guamán
Foods 2026, 15(16), 2895; https://doi.org/10.3390/foods15162895 - 19 Aug 2026
Viewed by 351
Abstract
Andean crops, including quinoa (Chenopodium quinoa), amaranth species including kiwicha (Amaranthus caudatus), chocho (Lupinus mutabilis), and cañihua (Chenopodium pallidicaule), constitute promising protein matrices for bioactive peptide generation by microbial fermentation and enzymatic proteolysis. These pseudocereals [...] Read more.
Andean crops, including quinoa (Chenopodium quinoa), amaranth species including kiwicha (Amaranthus caudatus), chocho (Lupinus mutabilis), and cañihua (Chenopodium pallidicaule), constitute promising protein matrices for bioactive peptide generation by microbial fermentation and enzymatic proteolysis. These pseudocereals and legumes contain storage proteins, mainly 11S globulins and 2S albumins, enriched in lysine and sulfur-containing amino acids, and therefore provide suitable precursors for multifunctional peptides. In addition, secondary metabolites, such as quinoa saponins and chocho alkaloids, may influence proteolysis, peptide release, and peptide stability during fermentation. This review critically examines LAB fermentation as a food-grade strategy for bioactive peptide production from Andean crops. Evidence from enzymatic hydrolysis and simulated gastrointestinal digestion is included as complementary information and is discussed separately from fermentation-derived evidence. Reported activities include antioxidant, ACE-inhibitory, DPP-IV- and α-glucosidase-inhibitory, antimicrobial and anti-inflammatory activities. Particular attention is given to peptide generation, molecular-weight fractionation, peptidomic characterization, structure–activity relationships, simulated gastrointestinal digestion, and bioaccessibility. Most reported activities were measured in hydrolysates or molecular-weight fractions rather than in defined sequences, and individually validated peptides remain a minority. The strength of evidence differs markedly among crops: fermentation-derived data are more developed for quinoa and amaranth, whereas evidence for chocho and cañihua relies largely on enzymatic hydrolysis. Current limitations, including substrate variability, sensory acceptability, process standardization, peptide identification, bioavailability, and the lack of human validation studies, are also discussed. Andean crop proteins are promising precursors of functional peptide ingredients; however, peptide-specific bioavailability and human efficacy remain largely untested. Full article
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33 pages, 479 KB  
Review
Comprehensive Insights into Plant-Derived Bioactive Peptides: Sources, Technological Strategies, and Health Implications
by Gabriela Kowalska, Gabriela Rzepkowska, Karolina Miśkiewicz, Mateusz Joachimowski and Justyna Rosicka-Kaczmarek
Molecules 2026, 31(16), 2866; https://doi.org/10.3390/molecules31162866 - 17 Aug 2026
Cited by 1 | Viewed by 343
Abstract
Interest in sustainable protein sources is increasing because of environmental concerns related to animal agriculture and the growing burden of chronic non-communicable diseases. Plant-derived bioactive peptides (PDBAPs), amino acid sequences released from dietary proteins, are gaining attention because experimental studies have reported activities [...] Read more.
Interest in sustainable protein sources is increasing because of environmental concerns related to animal agriculture and the growing burden of chronic non-communicable diseases. Plant-derived bioactive peptides (PDBAPs), amino acid sequences released from dietary proteins, are gaining attention because experimental studies have reported activities relevant to hypertension, type 2 diabetes, and cancer-associated processes. Although animal proteins have long been major sources of bioactive peptides, plant materials may offer advantages such as abundance, potentially lower production costs, and broad cultural acceptability; however, these benefits depend on the source, processing requirements, safety, and scale-up conditions. This review integrates plant sources, processing technologies, proposed mechanisms of action, and translational barriers. Current research covers traditional sources, including legumes and cereals, as well as agro-industrial by-products such as potato peels, spent coffee grounds, and broccoli stems. Modern processing strategies increasingly combine enzymatic hydrolysis or microbial fermentation with process-assisting technologies, including ultrasound treatment and subcritical water processing, to improve protein recovery or peptide release. Recent studies also examine proposed mechanisms of PDBAP activity, including Keap1/Nrf2-associated responses and inhibition of enzymes involved in metabolic disorders. Evidence is interpreted according to the stage of experimental validation, from computational prediction and cell-free assays to cellular, animal, and human studies. Key challenges remain, particularly digestive instability, uncertain systemic bioavailability, bitterness, safety standardization, and limited human clinical evidence. Future work should prioritize standardized extraction and analytical methods, optimized delivery systems, and robust clinical trials. Full article
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