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Search Results (2,042)

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Journal = Nutrients
Section = Phytochemicals and Human Health

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32 pages, 1821 KiB  
Systematic Review
Skin Aging and Carotenoids: A Systematic Review of Their Multifaceted Protective Mechanisms
by Cristina Stanescu, Iulia Chiscop, Daniela Mihalache, Florina Popa, Camelia Tamas and Gabriela Stoleriu
Nutrients 2025, 17(16), 2596; https://doi.org/10.3390/nu17162596 - 9 Aug 2025
Viewed by 47
Abstract
Skin aging is a complex biological process influenced by intrinsic factorssuch as genetic predispositions and hormonal changes as well as extrinsic factors including ultraviolet radiation, environmental pollution, and lifestyle habits. This process culminates in a progressive decline in the structural and functional integrity [...] Read more.
Skin aging is a complex biological process influenced by intrinsic factorssuch as genetic predispositions and hormonal changes as well as extrinsic factors including ultraviolet radiation, environmental pollution, and lifestyle habits. This process culminates in a progressive decline in the structural and functional integrity of the skin. This review delves into the protective roles of carotenoids, highlighting their significant anti-oxidative, anti-inflammatory, and photoprotective properties. We included studies that investigated the effects of dietary or topical carotenoids on skin aging markers in human and animal models. Eligible studies were identified through searches of PubMed, Scopus, Web of Science, Embase, Google Scholar, and the Cochrane Library from January 2000 to March 2025. Risk of bias was assessed using the Cochrane RoB tool for randomized trials and animal studies. A total of 176 studies were included, and data were synthesized narratively due to heterogeneity in study designs and outcomes. The findings indicate that carotenoids mitigate oxidative stress-induced cellular damage by scavenging reactive oxygen species (ROS) and Reactive Nitrogen Species (RNS), attenuating chronic inflammation, and enhancing dermal matrix integrity via collagen biosynthesis and modulation of matrix metalloproteinases. Additionally, they support skin hydration and elasticity by indirectly regulating aquaporins and promoting hyaluronic acid synthesis. This review further explores emerging strategies that incorporate carotenoid supplementation in lifestyle medicine and preventive dermatology. By elucidating the cellular pathways through which carotenoids exert their effects and modulate mitochondrial function, this review highlights their translational potential in anti-aging skincare. Ongoing research is essential to comprehend the complex connections between carotenoids, skin physiology, and overall health. This understanding will ultimately facilitate the creation of personalized nutritional and dermocosmetic strategies. Full article
(This article belongs to the Special Issue The Importance of Carotenoids in Age-Related Disease—Current Data)
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22 pages, 2284 KiB  
Article
Balancing the Cellular Inflammatory-Homeostatic Axis Through Natural Ingredient Supplementation
by Valentina Bordano, Chiara Gerbino, Valentina Boscaro, Patrizia Rubiolo, Arianna Marengo, Stefania Pizzimenti, Marie Angèle Cucci, Stefania Cannito, Jessica Nurcis, Margherita Gallicchio, Simona Federica Spampinato, Luigi Cangemi, Claudia Bocca, Chiara Dianzani, Arianna Carolina Rosa and Elisa Benetti
Nutrients 2025, 17(16), 2587; https://doi.org/10.3390/nu17162587 - 8 Aug 2025
Viewed by 113
Abstract
Background/Objectives: Dietary supplements are sources of nutrients or other substances that added to a healthy lifestyle help to preserve human homeostasis. Since inflammation is one of the major contributors to the alteration of homeostasis, this work investigated the effects of a multi-ingredient dietary [...] Read more.
Background/Objectives: Dietary supplements are sources of nutrients or other substances that added to a healthy lifestyle help to preserve human homeostasis. Since inflammation is one of the major contributors to the alteration of homeostasis, this work investigated the effects of a multi-ingredient dietary supplement on human macrophages, cells involved in the inflammatory response. Methods: THP-1 cells were differentiated into macrophage-like cells and polarized in M1 or M2 phenotypes. Cell migration was evaluated by Boyden chamber assay; phenotypic markers by qRT-PCR; cytokine release by ELISA and LPS/ATP-induced pyroptosis by LDH assay. The antioxidant properties of the supplement were evaluated in human and mouse fibroblasts by DCF-DA assay. After supplement treatment, cell extracts were analyzed by HPLC-PDA-MS/MS and GC-MS to evaluate the presence of the ingredients. Results: Our results showed that the dietary supplement promoted M2 migration and polarization and significantly reduced migration of M1. In a model of LPS-induced inflammation in M0, it significantly reduced NF-κB activation, COX-2 expression, and cytokine release. The supplement was not a specific inhibitor of NLRP-3, but it was able to modulate LPS priming. In addition, the supplement decreased granulocyte adhesion to HUVEC and reduced the oxidative stress in fibroblasts. The analysis of cell extracts showed the presence of the following ingredients of the formulation inside the cells: CoQ10, spermidine, resveratrol, 5-hydroxytryptophan from Griffonia simplicifolia (Vahl ex DC.) Baill., bacosides from Bacopa monnieri (L.) Wettst, vit B2, B5, E acetate. Conclusions: Our results demonstrate how a combination of natural active ingredients may contribute to the maintenance of homeostasis in human cells. Full article
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15 pages, 5071 KiB  
Article
Bioactive Phenolics from Vinegar–Egg Accelerates Acute Wound Healing by Activation of Focal Adhesion and Mitogen-Activated Protein Kinase Signaling
by Taehoon Oh, Chan Hee Cho, Su Cheol Baek, Mun Seok Jo, Woo Bong Kang, Yun Seok Kang, Sung-Kyun Ko and Ki Hyun Kim
Nutrients 2025, 17(16), 2584; https://doi.org/10.3390/nu17162584 - 8 Aug 2025
Viewed by 94
Abstract
Background/Objectives: Vinegar–egg is a traditional health-promoting beverage prepared by soaking eggs in vinegar. While both eggs and vinegar are common dietary components with well-documented nutritional and pharmacological activities, eggs treated with vinegar have been rarely studied. This study aims to identify and characterize [...] Read more.
Background/Objectives: Vinegar–egg is a traditional health-promoting beverage prepared by soaking eggs in vinegar. While both eggs and vinegar are common dietary components with well-documented nutritional and pharmacological activities, eggs treated with vinegar have been rarely studied. This study aims to identify and characterize bioactive compounds in vinegar–egg and investigate their potential wound-healing activities. Methods: The vinegar–egg extract was analyzed using liquid chromatography–mass spectrometry (LC–MS) and column chromatography, including HPLC purification, which led to the isolation of four phenolic compounds. Results: These compounds were identified as 4-hydroxybenzoic acid (1), vanillic acid (2), methyl syringate (3), and leptosperin (4) using ESI-MS, UV, and NMR spectroscopic data. Among the isolates, 4-hydroxybenzoic acid (1) and vanillic acid (2) demonstrated wound-healing properties in mouse embryonic fibroblast (MEF) cells. None of the compounds, 4-hydroxybenzoic acid (1), vanillic acid (2), methyl syringate (3), or leptosperin (4), exhibited cytotoxicity in PC12, AGS, MEF, or MDA-MB-231 cells. Notably, 4-hydroxybenzoic acid (1) enhanced cell motility by 2.59-fold and cell invasion by 1.20-fold, while vanillic acid (2) increased cell motility by 2.69-fold and cell invasion by 1.23-fold. Western blot analysis revealed that treatment with 4-hydroxybenzoic acid (1) and vanillic acid (2) increased the phosphorylation of focal adhesion kinase (p-FAK) and matrix metalloproteinase 2 (MMP-2). Furthermore, both compounds elevated the phosphorylation of p38, a key regulator in wound-healing pathways. Conclusions: These findings demonstrate that 4-hydroxybenzoic acid (1) and vanillic acid (2) accelerate wound healing through the activation of focal adhesion and mitogen-activated protein kinase (MAPK) signaling pathways. These results highlight vinegar–egg as a promising therapeutic candidate for wound healing. Full article
(This article belongs to the Special Issue Effects of Plant Extracts on Human Health—2nd Edition)
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19 pages, 1996 KiB  
Review
Honey as a Neuroprotective Agent: Molecular Perspectives on Its Role in Alzheimer’s Disease
by María D. Navarro-Hortal, Jose M. Romero-Márquez, Johura Ansary, Daniel Hinojosa-Nogueira, Cristina Montalbán-Hernández, Alfonso Varela-López and José L. Quiles
Nutrients 2025, 17(16), 2577; https://doi.org/10.3390/nu17162577 - 8 Aug 2025
Viewed by 265
Abstract
Alzheimer’s disease (AD) is the most prevalent form of dementia and a major global health challenge, characterized by progressive cognitive decline and neurodegeneration. Despite decades of research, there is currently no cure, and available treatments provide only limited symptomatic relief without halting disease [...] Read more.
Alzheimer’s disease (AD) is the most prevalent form of dementia and a major global health challenge, characterized by progressive cognitive decline and neurodegeneration. Despite decades of research, there is currently no cure, and available treatments provide only limited symptomatic relief without halting disease progression. In this context, natural compounds with multi-targeted biological activities are being explored as potential complementary therapeutic strategies. Honey, a complex natural substance rich in bioactive phytochemicals, has emerged as a promising candidate due to its antioxidant, anti-inflammatory, anti-apoptotic, and enzyme-inhibitory properties. This review summarizes the molecular mechanisms underlying the neuroprotective effects of honey in the context of AD, with a particular focus on its ability to modulate oxidative stress, mitochondrial dysfunction, inflammation, apoptosis, β-amyloid accumulation, tau hyperphosphorylation, and neurotransmission-related enzymes. Notably, the botanical origin of honey significantly influences its composition and biological activity, as evidenced by studies on avocado, manuka, acacia, kelulut, chestnut, coffee, or tualang honeys. While preclinical findings are encouraging, especially in vitro and in invertebrate and rodent models, clinical validation is still lacking. Therefore, further research, including well-designed in vivo and human studies, is needed to clarify the therapeutic relevance of honey in AD. Overall, honey may represent a promising natural adjunct in the prevention or management of AD, but current evidence remains preliminary. Full article
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20 pages, 2559 KiB  
Article
Anticancer Activity of Vitex agnus-castus Seed Extract on Gastric Cancer Cells
by Özlem Türksoy-Terzioğlu, Feyza Tosya, Ayşe Büşranur Çelik, Sibel Bölek, Levent Gülüm, Gökhan Terzioğlu and Yusuf Tutar
Nutrients 2025, 17(15), 2564; https://doi.org/10.3390/nu17152564 - 6 Aug 2025
Viewed by 200
Abstract
Background/Objectives: Vitex agnus-castus has been traditionally used to treat hormonal disorders, and recent evidence suggests its potential anticancer properties. However, its effects on gastric cancer remain unclear. Methods: This study examined the cytotoxic, apoptotic, and anti-metastatic effects of hydroalcoholic Vitex agnus-castus [...] Read more.
Background/Objectives: Vitex agnus-castus has been traditionally used to treat hormonal disorders, and recent evidence suggests its potential anticancer properties. However, its effects on gastric cancer remain unclear. Methods: This study examined the cytotoxic, apoptotic, and anti-metastatic effects of hydroalcoholic Vitex agnus-castus seed extract in gastric cancer cells. Antioxidant capacity (DPPH, ABTS) and total phenolic and flavonoid contents were analyzed. Cytotoxicity was assessed using the MTT assay in HGC27, MKN45, and AGS gastric cancer cell lines and CCD-1072Sk fibroblasts. Apoptosis, mitochondrial membrane potential (MMP), and cell cycle changes were evaluated via Annexin V-FITC/PI, Rhodamine 123, and PI staining, respectively. RT-qPCR and gene enrichment analyses were conducted to investigate the molecular mechanisms. Apoptosis-related protein expression was analyzed through enzyme-linked immunosorbent assay (ELISA). Results: The extract exhibited high antioxidant activity and a significant phenolic content. It reduced cell viability in a dose-dependent manner in gastric cancer cells, while exerting low toxicity in fibroblasts. It significantly increased apoptosis, induced G0/G1-phase cell cycle arrest, upregulated pro-apoptotic genes (CASP3, CASP7, TP53, BCL2L11), and downregulated anti-apoptotic genes (XIAP, NOL3). Gene enrichment analysis highlighted pathways like apoptosis, necrosis, and cysteine endopeptidase activity. The extract also disrupted MMP, inhibited migration and spheroid formation, suppressed EMT markers (SNAIL, SLUG, TWIST1, N-CADHERIN), and upregulated E-CADHERIN. The expression of Caspase 3 and Bax proteins increased and Bcl2 protein decreased. Conclusions: These findings suggest that Vitex agnus-castus seed extract exerts strong anticancer effects in gastric cancer cells by promoting apoptosis, reducing proliferation, and inhibiting migration. Further studies are warranted to explore its clinical relevance. Full article
(This article belongs to the Section Phytochemicals and Human Health)
23 pages, 1970 KiB  
Review
Resveratrol as a Therapeutic Agent in Alzheimer’s Disease: Evidence from Clinical Studies
by Nidhi Puranik, Meenakshi Kumari, Shraddha Tiwari, Thakur Dhakal and Minseok Song
Nutrients 2025, 17(15), 2557; https://doi.org/10.3390/nu17152557 - 5 Aug 2025
Viewed by 461
Abstract
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, memory loss, and neuronal dysfunction. It is driven by the accumulation of amyloid-beta (Aβ) plaques, Tau protein hyperphosphorylation, oxidative stress, and neuroinflammation. Resveratrol (RSV) is a natural polyphenolic compound found in [...] Read more.
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, memory loss, and neuronal dysfunction. It is driven by the accumulation of amyloid-beta (Aβ) plaques, Tau protein hyperphosphorylation, oxidative stress, and neuroinflammation. Resveratrol (RSV) is a natural polyphenolic compound found in grapes, berries, and red wine that has garnered attention for its potential neuroprotective properties in combating AD. The neuroprotective effects of RSV are mediated through the activation of sirtuins (SIRT1), inhibition of Aβ aggregation, modulation of Tau protein phosphorylation, and the attenuation of oxidative stress and inflammatory responses. RSV also enhances mitochondrial function and promotes autophagy, which are important processes for maintaining neuronal health. Preclinical studies have demonstrated its efficacy in reducing Aβ burden, improving cognitive performance, and mitigating synaptic damage; however, challenges such as poor bioavailability, rapid metabolism, and limited blood–brain barrier penetration restrict its clinical applicability. Recent technological advances and selected modifications are being explored to overcome these limitations and enhance its therapeutic efficacy. This review summarizes the multifaceted neuroprotective mechanisms of RSV, the synergistic potential of natural compounds in enhancing neuroprotection, and the advancements in formulation strategies aimed at mitigating AD pathology. Leveraging the therapeutic potential of natural compounds represents a compelling paradigm shift for AD management, paving the way for future clinical applications. Full article
(This article belongs to the Special Issue The Neuroprotective Activity of Natural Dietary Compounds)
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15 pages, 953 KiB  
Review
Influence of Matcha and Tea Catechins on the Progression of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)—A Review of Patient Trials and Animal Studies
by Danuta I. Kosik-Bogacka and Katarzyna Piotrowska
Nutrients 2025, 17(15), 2532; https://doi.org/10.3390/nu17152532 - 31 Jul 2025
Viewed by 626
Abstract
Metabolic dysfunction-associated fatty liver disease (MASLD) is a chronic, non-communicable spectrum of diseases characterized by lipid accumulation. It is often asymptomatic, and its prevalence varies by region, age, gender, and economic status. It is estimated that 25% of the world’s population currently suffer [...] Read more.
Metabolic dysfunction-associated fatty liver disease (MASLD) is a chronic, non-communicable spectrum of diseases characterized by lipid accumulation. It is often asymptomatic, and its prevalence varies by region, age, gender, and economic status. It is estimated that 25% of the world’s population currently suffer from MAFLD, and 20 million patients will die from MAFLD-related diseases. In the last 20 years, tea and anti-obesity research have indicated that regularly consuming tea decreases the risk of cardiovascular disease, stroke, obesity, diabetes, and metabolic syndrome (MeS). In this review, we aimed to present studies concerning the influence of matcha extracts and epigallocatechin-3 gallate (EGCG) supplements on metabolic functions in the context of MAFLD in human and animal studies. The published data show promise. In both human and animal studies, the beneficial effects on body weight, cholesterol levels, and liver metabolism and function were noted, even in short-period experiments. The safety levels for EGCG and green tea extract consumption are marked. More experiments are needed to confirm the results observed in animal studies and to show the mechanisms by which green tea exerts its effects. The preliminary data from research concerning microbiota or epigenetic changes observed after polyphenols and green tea consumption need to be expanded. To improve the efficiency and availability of green tea or supplement consumption as a treatment for MAFLD patients, more research with larger groups and longer study durations is needed. Full article
(This article belongs to the Special Issue Phytonutrients in Diseases of Affluence)
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26 pages, 7326 KiB  
Article
Cocoa Polyphenols Alter the Fecal Microbiome Without Mitigating Colitis in Mice Fed Healthy or Western Basal Diets
by Eliza C. Stewart, Mohammed F. Almatani, Marcus Hayden, Giovanni Rompato, Jeremy Case, Samuel Rice, Korry J. Hintze and Abby D. Benninghoff
Nutrients 2025, 17(15), 2482; https://doi.org/10.3390/nu17152482 - 29 Jul 2025
Viewed by 393
Abstract
Background/Objectives: Chronic inflammation and Western-style diets elevate colorectal cancer (CRC) risk, particularly in individuals with colitis, a feature of inflammatory bowel disease (IBD). Diets rich in polyphenol-containing functional foods, such as cocoa, may reduce gut inflammation and modulate the gut microbiome. This [...] Read more.
Background/Objectives: Chronic inflammation and Western-style diets elevate colorectal cancer (CRC) risk, particularly in individuals with colitis, a feature of inflammatory bowel disease (IBD). Diets rich in polyphenol-containing functional foods, such as cocoa, may reduce gut inflammation and modulate the gut microbiome. This study investigated the impact of cocoa polyphenol (CP) supplementation on inflammation and microbiome composition in mice with colitis, fed either a healthy or Western diet, before, during, and after the onset of disease. We hypothesized that CPs would attenuate inflammation and promote distinct shifts in the microbiome, especially in the context of a Western diet. Methods: A 2 × 2 factorial design tested the effects of the basal diet (AIN93G vs. total Western diet [TWD]) and CP supplementation (2.6% w/w CocoaVia™ Cardio Health Powder). Inflammation was induced using the AOM/DSS model of colitis. Results: CP supplementation did not reduce the severity of colitis, as measured by disease activity index or histopathology. CPs did not alter gene expression in healthy tissue or suppress the colitis-associated pro-inflammatory transcriptional profile in either of the two diet groups. However, fecal microbiome composition shifted significantly with CPs before colitis induction, with persistent effects on several rare taxa during colitis and recovery. Conclusions: CP supplementation did not mitigate inflammation or mucosal injury at the tissue level, nor did it affect the expression of immune-related genes. While CPs altered microbiome composition, most notably in healthy mice before colitis, these shifts did not correspond to changes in inflammatory signaling. Basal diet remained the primary determinant of inflammation, mucosal damage, and colitis severity in this model. Full article
(This article belongs to the Section Phytochemicals and Human Health)
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15 pages, 574 KiB  
Article
Polyphenol Intake from Herbs and Spices
by Cynthia Blanton
Nutrients 2025, 17(15), 2445; https://doi.org/10.3390/nu17152445 - 27 Jul 2025
Viewed by 408
Abstract
Background: Culinary herbs and spices are potent sources of bioactive compounds such as (poly)phenols that confer health benefits to consumers. Observational studies have quantified (poly)phenol intake levels from foods and beverages but not herbs and spices. Hence, the contribution of herbs and [...] Read more.
Background: Culinary herbs and spices are potent sources of bioactive compounds such as (poly)phenols that confer health benefits to consumers. Observational studies have quantified (poly)phenol intake levels from foods and beverages but not herbs and spices. Hence, the contribution of herbs and spices to (poly)phenol intakes is unclear. Methods: The current study measured herb and spice total (poly)phenol consumption in a convenience sample of adults (n = 212) using a validated online herb and spice questionnaire. Respondents reported the frequency and amount of consumption of 27 herbs and spices during the past month. Total (poly)phenol concentration (mg) for each herb and spice was calculated using the online database Phenol-Explorer. Results: Responses showed monthly intakes of 679.92 (1134.06) (median, IQR) mg total (poly)phenols from 47.44 (60.71) g herbs and spices. Cinnamon, black pepper and cloves were the largest contributors to total (poly)phenol intakes from herbs and spices. Conclusions: These findings suggest that herbs and spices contribute potentially meaningful amounts of (poly)phenols to total dietary (poly)phenol intakes and that existing reports of (poly)phenol consumption for populations may underestimate actual levels by 3–12%. Full article
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30 pages, 3888 KiB  
Review
Advances in Nanotechnology Research in Food Production, Nutrition, and Health
by Kangran Han, Haixia Yang, Daidi Fan and Jianjun Deng
Nutrients 2025, 17(15), 2443; https://doi.org/10.3390/nu17152443 - 26 Jul 2025
Viewed by 817
Abstract
Nanotechnology, as a burgeoning interdisciplinary field, has a significant application potential in food nutrition and human health due to its distinctive structural characteristics and surface effects. This paper methodically examines the recent advancements in nanotechnology pertaining to food production, functional nutrition delivery, and [...] Read more.
Nanotechnology, as a burgeoning interdisciplinary field, has a significant application potential in food nutrition and human health due to its distinctive structural characteristics and surface effects. This paper methodically examines the recent advancements in nanotechnology pertaining to food production, functional nutrition delivery, and health intervention. In food manufacturing, nanoparticles have markedly enhanced food safety and quality stability via technologies such as antimicrobial packaging, intelligent sensing, and processing optimization. Nutritional science has used nanocarrier-based delivery systems, like liposomes, nanoemulsions, and biopolymer particles, to make active substances easier for the body to access and target. Nanotechnology offers innovative approaches for chronic illness prevention and individualized treatment in health interventions by enabling accurate nutritional delivery and functional regulation. Nonetheless, the use of nanotechnology encounters hurdles, including safety evaluations and regulatory concerns that require additional investigation. Future research should concentrate on refining the preparation process of nanomaterials, conducting comprehensive examinations of their metabolic mechanisms within the human body, and enhancing pertinent safety standards to facilitate the sustainable advancement of nanotechnology in food production, nutrition, and health. Full article
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16 pages, 701 KiB  
Article
Use of Botanical Supplements Among Romanian Individuals with Diabetes: Results from an Online Study on Prevalence, Practices, and Glycemic Control
by Cosmin Mihai Vesa, Delia Mirea Tit, Emilia Elena Babes, Gabriela Bungau, Andrei-Flavius Radu and Radu Dumitru Moleriu
Nutrients 2025, 17(15), 2440; https://doi.org/10.3390/nu17152440 - 25 Jul 2025
Viewed by 334
Abstract
Plant supplements are frequently used by diabetes mellitus (DM) patients in the management of their disease. Background/Objectives: The present study aimed to identify the prevalence of plant supplement use in DM patients from Romania and to evaluate patients’ practices, profiles, and beliefs regarding [...] Read more.
Plant supplements are frequently used by diabetes mellitus (DM) patients in the management of their disease. Background/Objectives: The present study aimed to identify the prevalence of plant supplement use in DM patients from Romania and to evaluate patients’ practices, profiles, and beliefs regarding plant supplements and the impact of their use on glycemic control. Methods: A cross-sectional online survey was conducted among Romanian diabetic patients. Results: Out of 329 validated responses, 44.07% reported supplement use. Momordica charantia L. (35.17%) was the most used. Female patients were statistically significantly more prevalent in the plant supplement user group. Plant supplement use was associated with statistically significantly lower HbA1c (7.11% vs. 7.66%, p < 0.01) and basal glycemia (127.75 mg/dL vs. 136.08 mg/dL, p < 0.01) over the previous three months. Diabetic polyneuropathy was statistically significantly less prevalent among patients who used plant supplements (31.03% vs. 42.39%, p = 0.035). The greatest proportion of responders reported that they started to use plant supplements for improving blood glycemia (88.97%), followed by the purpose of preventing DM complications (27.59%). A significant improvement in health status was reported by 53.79% of patients using herbal supplements. Conclusions: Plant supplement use was common and associated with improved glycemic parameters and lower complication prevalence. Full article
(This article belongs to the Special Issue Botanicals and Nutritional Approaches in Metabolic Disorders)
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25 pages, 8728 KiB  
Article
Trans-Sodium Crocetinate Ameliorates High-Altitude Acute Lung Injury via Modulating EGFR/PI3K/AKT/NF-κB Signaling Axis
by Keke Liang, Yanlin Ta, Liang Xu, Shuhe Ma, Renjie Wang, Chenrong Xiao, Yue Gao and Maoxing Li
Nutrients 2025, 17(15), 2406; https://doi.org/10.3390/nu17152406 - 23 Jul 2025
Viewed by 392
Abstract
Objectives: Saffron, a traditional Chinese medicine, is renowned for its pharmacological effects in promoting blood circulation, resolving blood stasis, regulating menstruation, detoxification, and alleviating mental disturbances. Trans-crocetin, its principal bioactive component, exhibits significant anti-hypoxic activity. The clinical development and therapeutic efficacy of [...] Read more.
Objectives: Saffron, a traditional Chinese medicine, is renowned for its pharmacological effects in promoting blood circulation, resolving blood stasis, regulating menstruation, detoxification, and alleviating mental disturbances. Trans-crocetin, its principal bioactive component, exhibits significant anti-hypoxic activity. The clinical development and therapeutic efficacy of trans-crocetin are limited by its instability, poor solubility, and low bioavailability. Conversion of trans-crocetin into trans-sodium crocetinate (TSC) enhances its solubility, stability, and bioavailability, thereby amplifying its anti-hypoxic potential. Methods: This study integrates network pharmacology with in vivo and in vitro validation to elucidate the molecular targets and mechanisms underlying TSC’s therapeutic effects against high-altitude acute lung injury (HALI), aiming to identify novel treatment strategies. Results: TSC effectively reversed hypoxia-induced biochemical abnormalities, ameliorated lung histopathological damage, and suppressed systemic inflammation and oxidative stress in HALI rats. In vitro, TSC mitigated CoCl2-induced hypoxia injury in human pulmonary microvascular endothelial cells (HPMECs) by reducing inflammatory cytokines, oxidative stress, and ROS accumulation while restoring mitochondrial membrane potential. Network pharmacology and pathway analysis revealed that TSC primarily targets the EGFR/PI3K/AKT/NF-κB signaling axis. Molecular docking and dynamics simulations demonstrated stable binding interactions between TSC and key components of this pathway. ELISA and RT-qPCR confirmed that TSC significantly downregulated the expression of EGFR, PI3K, AKT, NF-κB, and their associated mRNAs. Conclusions: TSC alleviates high-altitude hypoxia-induced lung injury by inhibiting the EGFR/PI3K/AKT/NF-κB signaling pathway, thereby attenuating inflammatory responses, oxidative stress, and restoring mitochondrial function. These findings highlight TSC as a promising therapeutic agent for HALI. Full article
(This article belongs to the Special Issue Natural Active Compounds in Inflammation and Metabolic Diseases)
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42 pages, 891 KiB  
Review
Targeting Oxidative Stress in Acute Pancreatitis: A Critical Review of Antioxidant Strategies
by Laura Ioana Coman, Daniel Vasile Balaban, Bogdan Florin Dumbravă, Horia Păunescu, Ruxandra-Cristina Marin, Mihnea Costescu, Lorena Dima, Mariana Jinga and Oana Andreia Coman
Nutrients 2025, 17(15), 2390; https://doi.org/10.3390/nu17152390 - 22 Jul 2025
Viewed by 503
Abstract
Acute pancreatitis (AP) is among the most frequent gastroenterology emergencies, with hospital admission rates on the rise in recent decades. However, a specific treatment for this condition is still lacking. Mitochondrial damage induced by oxidative stress is regarded as the key event in [...] Read more.
Acute pancreatitis (AP) is among the most frequent gastroenterology emergencies, with hospital admission rates on the rise in recent decades. However, a specific treatment for this condition is still lacking. Mitochondrial damage induced by oxidative stress is regarded as the key event in the pathophysiology and initiation of cellular damage in AP. In the early stages of AP, the oxidant–antioxidant balance changes rapidly, and there are significant data regarding the reduced serum levels of antioxidants, with this event being correlated with the clinical severity of pancreatitis. Therefore, addressing oxidative stress could represent a potential therapeutic target in AP. In this comprehensive review, we aimed to provide an update on current evidence regarding clinical and experimental data on antioxidant use in AP, focusing on human studies investigating the effects of single and combined antioxidant supplementation. Although a multitude of animal studies demonstrated that antioxidant therapy has beneficial effects in experimental AP by reducing oxidative injury, inflammatory markers, and ameliorating histological outcomes, human trials showed predominantly conflicting results, with some studies suggesting benefit while others showed no effect, or even potential harm, when antioxidants were administered in high doses or in combination. Moreover, some antioxidants with beneficial results in experimental settings did not show the same efficacy when translated to human studies, which may be a consequence of either inappropriate dosage, route of administration and duration of therapy, or altered pharmacodynamics in vivo. In conclusion, oxidative stress plays a key role in the pathophysiology of AP by enhancing acinar cell injury, inflammation, and systemic complications. Future studies should be centered on optimized dosing strategies, early administration protocols, targeted patient selection, and delivery methods of proper pharmaceutical forms. Full article
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22 pages, 3024 KiB  
Article
Effects of Ginger Supplementation on Markers of Inflammation and Functional Capacity in Individuals with Mild to Moderate Joint Pain
by Jacob Broeckel, Landry Estes, Megan Leonard, Broderick L. Dickerson, Drew E. Gonzalez, Martin Purpura, Ralf Jäger, Ryan J. Sowinski, Christopher J. Rasmussen and Richard B. Kreider
Nutrients 2025, 17(14), 2365; https://doi.org/10.3390/nu17142365 - 18 Jul 2025
Viewed by 2110
Abstract
Background: Ginger contains gingerols, shagaols, paradols, gingerdiones, and terpenes, which have been shown to display anti-inflammatory properties and inhibit pain receptors. For this reason, ginger has been marketed as a natural analgesic. This study examined whether a specialized ginger extract obtained through supercritical [...] Read more.
Background: Ginger contains gingerols, shagaols, paradols, gingerdiones, and terpenes, which have been shown to display anti-inflammatory properties and inhibit pain receptors. For this reason, ginger has been marketed as a natural analgesic. This study examined whether a specialized ginger extract obtained through supercritical CO2 extraction and subsequent fermentation affects pain perception, functional capacity, and markers of inflammation. Methods: Thirty men and women (56.0 ± 9.0 years, 164.4 ± 14 cm, 86.5 ± 20.9 kg, 31.0 ± 7.5 kg/m2) with a history of mild to severe joint and muscle pain as well as inflammation participated in a placebo-controlled, randomized, parallel-arm study. Participants donated fasting blood, completed questionnaires, rated pain in the thighs to standardized pressure, and then completed squats/deep knee bends, while holding 30% of body mass, for 3 sets of 10 repetitions on days 0, 30, and 56 of supplementation. Participants repeated tests after 2 days of recovery following each testing session. Participants were matched by demographics and randomized to ingest 125 mg/d of a placebo or ginger (standardized to contain 10% total gingerols and no more than 3% total shogaols) for 58 days. Data were analyzed by a general linear model (GLM) analysis of variance with repeated measures, mean changes from the baseline with 95% confidence intervals, and chi-squared analysis. Results: There was evidence that ginger supplementation attenuated perceptions of muscle pain in the vastus medialis; improved ratings of pain, stiffness, and functional capacity; and affected several inflammatory markers (e.g., IL-6, INF-ϒ, TNF-α, and C-Reactive Protein concentrations), particularly following two days of recovery from resistance exercise. There was also evidence that ginger supplementation increased eosinophils and was associated with less frequent but not significantly different use of over-the-counter analgesics. Conclusions: Ginger supplementation (125 mg/d, providing 12.5 mg/d of gingerols) appears to have some favorable effects on perceptions of pain, functional capacity, and inflammatory markers in men and women experiencing mild to moderate muscle and joint pain. Registered clinical trial #ISRCTN74292348. Full article
(This article belongs to the Section Phytochemicals and Human Health)
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41 pages, 1846 KiB  
Review
The Potential of Nutraceutical Supplementation in Counteracting Cancer Development and Progression: A Pathophysiological Perspective
by Carmen Altomare, Roberta Macrì, Maria Serra, Sara Ussia, Giovanna Ritorto, Jessica Maiuolo, Carolina Muscoli, Enzo Perri and Vincenzo Mollace
Nutrients 2025, 17(14), 2354; https://doi.org/10.3390/nu17142354 - 18 Jul 2025
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Abstract
Cancer is a major cause of morbidity and mortality across the globe, with a substantial increase in cases anticipated over the next few decades. Given the constraints and adverse effects associated with standard cancer therapies, the contribution of diet and nutraceuticals to cancer [...] Read more.
Cancer is a major cause of morbidity and mortality across the globe, with a substantial increase in cases anticipated over the next few decades. Given the constraints and adverse effects associated with standard cancer therapies, the contribution of diet and nutraceuticals to cancer prevention and treatment is receiving increased scrutiny. A diet rich in plant-based foods, extra virgin olive oil (EVOO), and bioactive compounds, including the Mediterranean Diet, has been associated with reduced cancer risk and improved treatment outcomes. This review aims to explore the complex mechanisms of the MedDiet and nutraceuticals (polyphenols, flavonoids, terpenoids) in cancer prevention, to determine their potential as cancer treatment adjuvants. Promising results show that key compounds such as bergamot polyphenolic fraction (BPF), cynaropicrin, oleuropein, quercetin, resveratrol, and serotonin can modulate oxidative stress, inflammation, the tumor microenvironment, the cell cycle, and drug resistance. A significant observation is that many of these substances demonstrate dual dose-dependent activity; they function as antioxidants in healthy cells but induce pro-oxidant and pro-apoptotic effects in cancerous cells. Their ability to boost chemotherapy’s effectiveness and safety while lessening side effects and offering combined advantages is also explored. To summarize, this review suggests that the Mediterranean Diet and nutraceutical supplements may help prevent and manage cancer, but more research is needed to confirm their benefits. Full article
(This article belongs to the Special Issue Effects of Plant Extracts on Human Health—2nd Edition)
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