Journal of Nutritional Biochemistry最新文献

{"title":"Vitamin E and related tocols in cancer: Unraveling the paradox of antioxidant and pro-oxidant roles","authors":"Fen Xiao ,&nbsp;Zhi-Bin Wang ,&nbsp;Nayiyuan Wu ,&nbsp;Xiu Zhang ,&nbsp;Xing Yu ,&nbsp;Zu-Ping He ,&nbsp;Jing Wang","doi":"10.1016/j.jnutbio.2026.110265","DOIUrl":"10.1016/j.jnutbio.2026.110265","url":null,"abstract":"<div><div>Vitamin E, strictly defined as α-tocopherol, exhibits a complex dual role in cancer pathogenesis through its context-dependent pro-oxidant and antioxidant activities. Other members of the tocopherol and tocotrienol families (collectively referred to as tocols) have also been extensively studied for their bioactivities. At physiological levels, certain tocols such as γ-tocopherol and δ-tocotrienol act as potent antioxidants by neutralizing reactive oxygen species, inhibiting lipid peroxidation, and activating NRF2-mediated defenses, thereby suppressing tumor initiation, proliferation, and metastasis in models of colon, breast, and prostate cancers. On the contrary, under conditions such as high concentration of vitamin E in plasma, metabolic dysregulation, and the presence of transition metals (<em>e.g.</em>, Cu²⁺), or specific genetic backgrounds, vitamin E exerts pro-oxidant effects. However, such effects are relatively rare and more often documented <em>in vitro</em> than <em>in vivo</em>. These include promoting reactive oxygen species generation, reducing p53 expression, enhancing angiogenesis, and facilitating cancer cell survival—ultimately driving tumor progression and metastasis. Critically, vitamin E modulates ferroptosis, a regulated cell death pathway pivotal in cancer; it inhibits ferroptosis via GPX4 upregulation and NRF2 activation but may paradoxically promote it in certain settings. Clinical studies highlight isomer-specific outcomes, with tocotrienols showing promise in adjuvant therapy. The dichotomy hinges on dosage, cellular microenvironment, redox balance, and vitamin E isoform. Overall, the biological impact of vitamin E is highly context-dependent, influenced by dosage, cellular microenvironment, redox status, and the specific tocol studied. Future research must prioritize isoform-specific mechanisms, optimal dosing strategies, and interactions with conventional therapies to harness vitamin E and related tocols’s anticancer potential while mitigating risks.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"151 ","pages":"Article 110265"},"PeriodicalIF":4.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145984938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brown adipocyte-derived SAA3–CPT1A axis regulates diet-induced thermogenesis and protects against obesity","authors":"Pei-Chi Chan ,&nbsp;Chun-Han Jhuang ,&nbsp;Hsin-Yi Chang ,&nbsp;Po-Shiuan Hsieh","doi":"10.1016/j.jnutbio.2026.110263","DOIUrl":"10.1016/j.jnutbio.2026.110263","url":null,"abstract":"<div><div>Diet-induced thermogenesis (DIT), a critical component of energy expenditure driven by brown adipose tissue (BAT), is essential for maintaining metabolic health; however, its precise molecular regulation remains poorly understood. We investigated whether serum amyloid A3 (SAA3), a factor secreted by brown adipocytes, regulates DIT and protects against diet-induced obesity. Using two distinct mouse models: mice with brown adipocyte-specific Saa3 deletion and mice with lentiviral-mediated Saa3 overexpression in BAT, we examined energy expenditure, substrate utilization, and thermogenic responses under chow or short-term high-fat diet feeding. SAA3 expression in BAT was acutely induced by refeeding. Loss of SAA3 severely diminished postprandial DIT and total energy expenditure, leading to accelerated weight gain on a high-fat diet. Mechanistically, Saa3 deletion compromised uncoupling protein‑1 induction, chiefly by impairing adipose triglyceride lipase-driven lipolysis and, critically, by inhibiting carnitine palmitoyltransferase 1A (CPT1A)-dependent fatty acid oxidation (FAO). Conversely, SAA3 overexpression robustly enhanced DIT, stimulated lipolysis and FAO, and promoted mitochondrial oxidative phosphorylation. Studies in primary brown adipocytes confirmed that SAA3 deficiency reduced CPT1A expression, palmitate-stimulated lipolysis, and mitochondrial respiration. Together, these findings identify the SAA3–CPT1A axis as a novel, BAT-intrinsic mechanism that couples nutrient sensing to uncoupling protein‑11 function via enhanced FAO. By promoting lipid utilization and postprandial energy dissipation, SAA3 optimizes postprandial thermogenesis and defends against obesity, highlighting conserved SAA signaling as a potential nutritional and therapeutic target in metabolic disease.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"151 ","pages":"Article 110263"},"PeriodicalIF":4.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145984980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic theobromine administration attenuates short-term memory decline via neurotrophic, anti-inflammatory and antioxidant mechanisms in senescence-accelerated mouse prone 8 (SAMP8)","authors":"Eri Sumiyoshi ,&nbsp;Kentaro Matsuzaki ,&nbsp;Masanori Katakura ,&nbsp;Shadman Nazib ,&nbsp;Shahdat Hossain ,&nbsp;Sho Maejima ,&nbsp;Ying Zhang ,&nbsp;Hiroko Kishi ,&nbsp;Naotoshi Sugimoto ,&nbsp;Osamu Shido","doi":"10.1016/j.jnutbio.2025.110258","DOIUrl":"10.1016/j.jnutbio.2025.110258","url":null,"abstract":"<div><div>Aging-related cognitive decline is a major concern in aging societies. Theobromine (TB), a cacao-derived methylxanthine, exerts neuroprotective effects through anti-inflammatory, antioxidant, and neurotrophic mechanisms; however, its efficacy in aging models remains unclear. This study investigated the mechanisms underlying neuroprotective effects of chronic TB administration in senescence-accelerated mouse prone 8 (SAMP8), a model of age-related memory impairment. SAMP8 and SAMR1 mice were fed either a control diet or a diet supplemented with 0.05% TB for 50 d. Cognitive performance was evaluated by the novel object recognition (NOR) test. Neurotrophic factors (BDNF and NT-3), synaptic proteins (PSD95 and synaptophysin), and plasticity-related signaling molecules (phosphorylated CREB and TrkB) were analyzed in the prefrontal cortex and hippocampus. Inflammatory cytokines, lipid peroxides, and antioxidant enzymes were quantified. Molecular docking was used to assess TB’s interaction with phosphodiesterase (PDE) enzymes. TB improved short-term memory in SAMP8, increasing discrimination index in the NOR test. This was accompanied by increased BDNF, NT-3, PSD95, and synaptophysin levels and enhanced CREB and TrkB phosphorylation. Furthermore, TB lowered the levels of pro-inflammatory cytokines (IL-1β, TNF-α) and phosphorylated NF-κB, reduced lipid peroxidation, and increased the levels of antioxidant markers (HO-1, GSH). These effects were minimal in SAMR1. No adverse effects on body weight or blood parameters were observed. Molecular docking indicated that TB binds to PDE enzymes with weaker inhibitory activity than selective inhibitors. TB enhances short-term memory and synaptic function in aged mice via neurotrophic, antioxidant, and anti-inflammatory mechanisms, supporting its potential as a safe dietary intervention for age-related cognitive decline.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"151 ","pages":"Article 110258"},"PeriodicalIF":4.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145892525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prebiotic fructan chain length influences enteric microbiota-host GABAergic signaling and intestinal motility","authors":"Benjamin A. Levine ,&nbsp;Alexis J. Lynch ,&nbsp;Michael T. Bailey ,&nbsp;Brett R. Loman","doi":"10.1016/j.jnutbio.2025.110234","DOIUrl":"10.1016/j.jnutbio.2025.110234","url":null,"abstract":"<div><div>Dietary fiber ingestion serves as a critical regulator of intestinal motility and the structure and function of the enteric microbiome. Yet, the extent to which subtle structural differences among fibers modulate motility via microbiota-host interactions remains undefined. GABA is a microbial metabolite intimately related to microbial fructan fermentation and host intestinal motility. The purpose of this study was to investigate how fructan chain length influenced microbiota-host signaling underlying ileal and colonic contractions. Male and female mice were pair-fed diets containing no fiber (fiber-free diet, FFD) or the same diet containing cellulose (CELL, fiber control), short-chain fructooligosaccharides (scFOS), or inulin (INU) for 2 weeks. scFOS and INU similarly enhanced total microbial load (fluorescence in situ hybridization), relative abundances of GABA-synthesizing bacteria (16S rRNA sequencing), and luminal GABA concentrations (ELISA) in the ileum and colon versus FFD. Conversely, scFOS altered expression (Fluidigm qPCR) of more motility- and GABA-related genes than INU in the ileum, whereas INU altered expression of more motility and GABA-related genes than scFOS in the colon. Incubation of ileal segments with GABA potentiated contraction force in INU but not scFOS ex vivo. Conversely, incubation of colon segments with GABA repressed contraction force in scFOS, reducing them to levels observed in INU with or without GABA. Notably, GABA altered contraction forces only in female mice. Our study highlights dietary fructan chain length as a determinant of segment- and sex-specific GABA-mediated intestinal motility and creates a rationale and framework for investigation of how prebiotic fiber structures influence microbiota-host interactions and physiology.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"151 ","pages":"Article 110234"},"PeriodicalIF":4.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145805016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between dairy-derived bioactive peptides and the risk of type 2 diabetes mellitus and cardiovascular diseases: Tehran lipid and glucose study","authors":"Fatemeh Ghasemi ,&nbsp;Farshad Teymoori ,&nbsp;Sajjad Roosta ,&nbsp;Mitra Kazemi Jahromi ,&nbsp;Hossein Farhadnejad ,&nbsp;Parvin Mirmiran ,&nbsp;Ebrahim Falahi ,&nbsp;Fereidoun Azizi","doi":"10.1016/j.jnutbio.2026.110260","DOIUrl":"10.1016/j.jnutbio.2026.110260","url":null,"abstract":"<div><div>Cardiometabolic diseases, including type 2 diabetes mellitus (T2DM) and cardiovascular diseases (CVDs) are escalating globally, posing significant health challenges. While dairy products and their bioactive peptides (BPs) may influence chronic diseases risk, the evidence remains inconsistent. These peptides may act via modulation of gut microbiota, reducing inflammation, and regulating lipid metabolism. The current study aimed to investigate the possible association between dairy-derived BPs (DDBPs) and the risk of T2DM and CVDs in Iranian adult population within the framework of Tehran Lipid and Glucose Study (TLGS). In this population-based cohort study, 5,469 participants (T2DM analysis) and 4,980 participants (CVDs analysis) from the TLGS were followed for a mean follow-up period of 6 years. Dietary intake data were determined using a validated food-frequency-questionnaire. Various types of DDBPs were estimated via in-silico proteolysis simulations. The association of bioactive peptides with T2DM and CVDs risk were determined using Cox proportional hazards regression models. Higher intake of k-casein-derived peptides (HR:1.21;95% CI: 1.01–1.64), Hepta-peptides (HR:1.31;95% CI:1.02–1.67), peptides with glycosylated residues (HR:1.29;95%CI: 1.01–1.65), glycosylated residues (HR:1.39;95% CI: 1.07–1.80), and disulfide bond- containing peptides (HR:1.34;95% CI: 1.05–1.71) was associated with an elevated T2DM risk in the adjusted model. Dairy protein intake (highest vs. lowest tertile: HR:1.29;95% CI: 1.02–1.62) Also increased T2DM risk, while total dairy intake showed no association. No significant associations were found between DDBPs, dairy intake, or dairy protein intake and the risk of CVDs. Our results showed that specific DDBPs particularly k-casein-derived fragments and structurally modified peptides (including hepta-peptides, glycosylated peptides, and peptides with disulfide bonds), were associated with an increased risk of T2DM in Tehranian adults. Further studies are warranted to elucidate these associations.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"151 ","pages":"Article 110260"},"PeriodicalIF":4.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145906260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanism of tea polyphenols improving sleep by regulating neurotransmitters through the gut microbiota–brain axis","authors":"Bin Hu ,&nbsp;Yili Chen ,&nbsp;Xinrong Gong ,&nbsp;Youmeng Chen ,&nbsp;Songmei Luo ,&nbsp;Xin Zhang","doi":"10.1016/j.jnutbio.2026.110272","DOIUrl":"10.1016/j.jnutbio.2026.110272","url":null,"abstract":"<div><div>In today's fast-paced modern lifestyle, sleep disorders have become a pervasive challenge for many individuals. Conventional treatments often rely on pharmacological interventions, which carry risks of dependency and adverse effects. In recent years, the gut microbiota has gained increasing recognition as a \"second brain,\" engaging in bidirectional communication with the central nervous system via the microbiota–gut–brain axis (MGB axis). Tea polyphenols (TP), the primary bioactive compounds derived from tea, show considerable potential in improving sleep quality through this microbial–gut–brain circuitry. This review systematically elucidates how TP reshape the gut microbiota by selectively enriching beneficial bacteria such as <em>Lactobacillus</em> and <em>Bifidobacterium</em>, while suppressing pathogenic species. These structural changes are accompanied by functional benefits, including enhanced intestinal barrier integrity and attenuated systemic inflammation. Furthermore, gut microbiota metabolize TP into bioactive small molecules that enter systemic circulation, cross the blood-brain barrier (BBB), and modulate central neurotransmitters, notably serotonin (5-HT) and γ-aminobutyric acid (GABA). By delineating this gut-mediated neuromodulatory network, our study provides a novel theoretical foundation for the use of TP as a dietary strategy to ameliorate sleep disorders.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"151 ","pages":"Article 110272"},"PeriodicalIF":4.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145998332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"l-Theanine attenuates intestinal oxidative injury in mice through modulation of ferroptosis pathways","authors":"Chunting Shi,&nbsp;Ziyan Yuan,&nbsp;Xinyi Du,&nbsp;Zhiqing Huang,&nbsp;Gang Jia,&nbsp;Hua Zhao,&nbsp;Xiaoling Chen","doi":"10.1016/j.jnutbio.2026.110271","DOIUrl":"10.1016/j.jnutbio.2026.110271","url":null,"abstract":"<div><div>Oxidative stress impairs intestinal health in animals. As a potential antioxidant, <span>l</span>-theanine exerts anti-inflammatory and antioxidant effects. However, its biological functions and underlying mechanisms in intestinal oxidative damage remain unclear. This study aimed to investigate the protective effect of <span>l</span>-theanine against diquat-induced intestinal oxidative damage in mice and explore its potential molecular mechanisms. The results showed that dietary <span>l</span>-theanine supplementation significantly enhanced intestinal antioxidant capacity (reducing the levels of reactive oxygen species, malondialdehyde and hydrogen peroxide and elevating the activities of antioxidant enzymes), alleviated inflammation (downregulating pro-inflammatory cytokine levels and upregulating interleukin-10 mRNA expression), improved intestinal integrity (enhancing morphology, reducing permeability and upregulating tight junction-related genes), and boosted mitochondrial function (increasing mitochondrial membrane potential, adenosine triphosphate content and mitochondrial function-related gene expression) in oxidatively stressed mice. Concomitantly, <span>l</span>-theanine attenuated intestinal iron overload (inhibiting Fe²⁺ accumulation and upregulated ferritin heavy chain 1 expression) and suppressed the ferroptosis pathway (upregulating nuclear factor erythroid 2-related factor 2 (Nrf2), glutathione peroxidase 4 (GPX4), and solute carrier family 7 member 11 expression). In conclusion, <span>l</span>-theanine alleviates intestinal oxidative damage in oxidatively stressed mice by enhancing intestinal antioxidant capacity and inhibiting ferroptosis, a protective effect that may be mediated by the activation of the Nrf2/GPX4 signaling pathway.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"151 ","pages":"Article 110271"},"PeriodicalIF":4.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146003424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The interaction of ascorbic acid with hemoglobin: Relevance to hemin release and lipid peroxidation","authors":"Shi-Ya Peng,&nbsp;Naihao Lu,&nbsp;Rong Tian","doi":"10.1016/j.jnutbio.2025.110246","DOIUrl":"10.1016/j.jnutbio.2025.110246","url":null,"abstract":"<div><div>The interactions between L-ascorbic acid (<em>i.e.</em>, Vitamin C, VC) and bovine hemoglobin (Hb) were comprehensively analyzed using fluorescence, circular dichroism, UV−vis absorption spectra and molecular docking method, to elucidate the structural mechanisms through which VC altered Hb redox states and stabilities. VC interacted with the central cavities of Hb to form Hb-VC complex via static quenching mechanism involving nonradiative energy transfer, with van der Waals forces and hydrogen bonds playing predominant roles in the binding processes. VC was surrounded by residues such as α1-Thr137, α1-Ser138, α1-Tyr140 and α1-Arg141 residues. After that, the binding of VC would narrow the crevices near the heme domain of Hb, which converted ferric (met-) Hb to ferrous (oxy-) Hb and deoxy-Hb state and suppressed hemin liberation (level of free hemin was 4.35 µM (Hb alone) and 2.77 µM (Hb-VC complex)). Moreover, VC significantly inhibited Hb-catalyzed lipid peroxidation in liposome and washed muscle, which was probably due to the conversion to oxy-Hb state and reduced dissociation of hemin (not free iron). In accordance with its effects on Hb redox states and stability, VC effectively maintained the red color of hemeprotein during the storage. Altogether, the attenuation of free hemin release from Hb molecule represents a new mechanism towards the anti-oxidant capacity of VC in Hb-containing foods.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"151 ","pages":"Article 110246"},"PeriodicalIF":4.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145846686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dietary zinc deficiency regulates the ROS/TLR4/NF-κB pathway to induce pancreatic inflammation and cell death in mice","authors":"Ziyi Li,&nbsp;Yao Xue,&nbsp;Kan Li,&nbsp;Man Qian,&nbsp;Fuhan Wang,&nbsp;Ji-long Luo,&nbsp;Xue-jiao Gao","doi":"10.1016/j.jnutbio.2026.110262","DOIUrl":"10.1016/j.jnutbio.2026.110262","url":null,"abstract":"<div><div>Zinc (Zn) deficiency disrupts redox homeostasis in the body. The pancreas is a vital digestive and endocrine organ of the body, and its normal functional operation cannot proceed without the involvement of Zn. In this study, we established in vivo mouse models, including the normal Zn group (CG, 34 mg Zn/kg), Zn-deficient group (LZn, 2 mg Zn/kg), and Zn-supplemented group (HZn, 100 mg Zn/kg), as well as an in vitro Zn-deficient model of Mouse INsulinoma 6 (MIN6) cells. We systematically investigated the effects of Zn deficiency on pancreatic oxidative stress, inflammation, and cell death. The results showed that Zn deficiency significantly decreased the activities of α-amylase and lipase in the pancreas, and led to pancreatic histological damage. Through flow cytometry and detection of antioxidant enzyme activities, it was found that Zn deficiency induces excessive accumulation of reactive oxygen species (ROS) and malondialdehyde (MDA) in the pancreas, and inhibits antioxidant enzyme activities. Using reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot, it was observed that Zn deficiency activates the TLR4/NF-κB pathway and significantly increases the expression of the NLRP3 inflammasome and inflammatory factors. Furthermore, Zn deficiency significantly upregulates the expression of apoptosis-related factors (Bax, Caspase-3, Caspase-7, Caspase-9) and necroptosis-related factors (RIPK1, RIPK3, MLKL). Treatment with the antioxidant N-acetylcysteine (NAC) reduces the level of ROS and inhibits the activation of the TLR4/NF-κB pathway, thereby alleviating Zn deficiency-induced inflammation and cell death. Taken together, Zn deficiency induces pancreatic inflammation and cell death by regulating the ROS/TLR4/NF-κB pathway.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"151 ","pages":"Article 110262"},"PeriodicalIF":4.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145948793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Natural products as modulators of ferroptosis: Therapeutic implications and molecular mechanisms in disease treatment","authors":"Weifang Tong ,&nbsp;Xupeng Mu ,&nbsp;Haitao Xu ,&nbsp;Xunzhe Yin","doi":"10.1016/j.jnutbio.2026.110259","DOIUrl":"10.1016/j.jnutbio.2026.110259","url":null,"abstract":"<div><div>Ferroptosis is a regulated form of cell death characterized by iron-dependent lipid peroxide accumulation and is implicated in the pathogenesis of various diseases, including cancer, neurodegenerative disorders, diabetes, and cardiovascular diseases. Natural products, with their unique chemical scaffolds and multitarget pharmacological effects, have recently been recognized as potent modulators of ferroptosis, offering promising drug-like properties. This review comprehensively summarizes the molecular mechanisms underlying ferroptosis, encompassing iron metabolism, lipid peroxidation, and the SLC7A11-GSH-GPX4 antioxidant axis, and systematically categorizes natural products such as terpenoids, flavonoids, alkaloids, saponins, and polyphenols based on their structural classes and mechanisms of action. These compounds modulate ferroptosis through various pathways, including iron chelation, ROS regulation, and key protein interactions, demonstrating efficacy in both experimental and preliminary clinical settings across a spectrum of diseases. In oncology, natural compounds can sensitize tumors to chemotherapy and overcome drug resistance by activating ferroptotic cell death. Conversely, their antiferroptotic actions protect against tissue injury in nononcological diseases such as neurodegenerative conditions, metabolic disorders, and organ injury. Nevertheless, their application remains limited by restricted availability, compositional complexity, and unstable pharmacokinetic features. Advances in nano-delivery systems and synthetic biology are highlighted as promising strategies to overcome these barriers. Overall, natural products represent a valuable resource for developing novel ferroptosis-targeting therapies, with significant implications for future drug discovery and therapeutic innovation in a wide range of human diseases.</div></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"151 ","pages":"Article 110259"},"PeriodicalIF":4.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145906281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}