Antioxidants最新文献

{"title":"Hydroxy-Selenomethionine Supplementation During Gestation and Lactation Improve Reproduction of Sows by Enhancing the Antioxidant Capacity and Immunity Under Heat Stress Conditions.","authors":"Juan Wang, Hua Sun, Zhe Peng, Shao-Qing Wang, Yi-Qin Yan, Wei-Cai Luo, Ren-Gui Yang, Wei-Cheng Bei, Lv-Hui Sun, Jia-Cheng Yang","doi":"10.3390/antiox14050525","DOIUrl":"10.3390/antiox14050525","url":null,"abstract":"<p><p>The objective of this study was to determine whether hydroxy-selenomethionine (OH-SeMet) exerts better protective effects on sows against heat stress than sodium selenite (SeNa) or seleno-yeast (SeY). A total of 60 sows (Landrace × Yorkshire) were randomly allocated into the three groups and fed a base diet supplemented with SeNa, SeY, or OH-SeMet at 0.3 mg Se/kg under a heat stress condition for a reproductive cycle. Compared to SeNa or SeY, OH-SeMet could more effectively sustain offspring growth performance, as evidenced by an increased number of live-born piglets, higher litter weight at day 21, and greater litter body weight gain from days 1 to 21. OH-SeMet was more effective in supporting endogenous redox systems, as shown by enhanced levels of TXNRD and GSH and reduced levels of GSSG in the serum of sows, improved T-AOC, TXNRD, and GSH alongside decreased MDA and GSSG in the serum of piglets, and heightened T-AOC in the jejunum of piglets. Furthermore, among the two tested organic Se sources, OH-SeMet was more effective than SeY in regulating immune responses compared to SeNa. OH-SeMet reduced inflammation-related markers CRP, HP, MAP, LPS, IL-1β, IL-6, and TNF-α, some or all of which were reduced in the serum of sows and their offspring. In addition, OH-SeMet also showed reduced glucose, TG, and NEFA levels, along with elevated insulin levels in the serum of sows. Correspondingly, among the two organic forms of Se, particularly those sows fed OH-SeMet showed better gut protection for the sows' offspring, as indicated by a reduced crypt depth and increased villus height/crypt depth ratio in the duodenum, jejunum, and ileum than those fed SeNa. Specifically, compared to SeNa or SeY, OH-SeMet upregulated the expression of selenoproteins (<i>GPX6</i>, <i>TXNRD3</i>, GPX4, and SELENON), the tight junction protein (ZO-1), and host defense peptide gene (<i>pBD1</i>, <i>pBD2</i>, <i>pBD3</i>, <i>NPG3</i>, <i>NPG4</i>), along with downregulating levels of inflammation factor (IL-1β, IL-6 and TNF-α) and pro-apoptotic factor (P53) in the jejunum of piglets. Taken together, OH-SeMet more effectively mitigated the adverse effects induced by heat stress in sows and their offspring.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 5","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12108442/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144155713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engeletin Targets Mitochondrial Dysfunction to Attenuate Oxidative Stress and Experimental Colitis in Intestinal Epithelial Cells Through AMPK/SIRT1/PGC-1α Signaling.","authors":"Jing Li, Zhijun Geng, Lixia Yin, Ju Huang, Minzhu Niu, Keni Zhang, Xue Song, Yueyue Wang, Lugen Zuo, Jianguo Hu","doi":"10.3390/antiox14050524","DOIUrl":"10.3390/antiox14050524","url":null,"abstract":"<p><p>Inflammatory bowel disease (IBD), encompassing Crohn's disease and ulcerative colitis, is characterized by chronic intestinal inflammation and epithelial barrier disruption. Emerging evidence highlights mitochondrial dysfunction as a pivotal contributor to IBD pathogenesis, where impaired mitochondrial homeostasis in intestinal epithelial cells (IECs) disrupts redox balance, exacerbates oxidative stress, and triggers apoptosis, further compromising barrier integrity. This study investigated the therapeutic effects of Engeletin (Eng), a dihydroflavonoid from <i>Smilax glabra</i> Roxb., in dextran sulfate sodium (DSS)-induced colitis mice and colonic organoid models. Eng administration (10, 20, 40 mg/kg) significantly alleviated colitis symptoms, including weight loss, disease activity index (DAI) scores, and colon shortening, while restoring intestinal barrier integrity through the upregulation of tight junction proteins (ZO-1, claudin-1) and goblet cell preservation. Eng suppressed NF-κB-mediated inflammation and activated the Nrf2 antioxidant pathway, as well as reduced oxidative stress markers (MDA, CAT, GSH, and SOD). It attenuated epithelial apoptosis by balancing pro- and anti-apoptotic proteins (Bax/Bcl2, c-caspase3) and ameliorated mitochondrial dysfunction via enhanced ATP production, mtDNA levels, and complex I/IV activity. Mechanistically, Eng activated the AMPK/SIRT1/PGC-1α axis, and pharmacological inhibition of PGC-1α abolished its mitochondrial protective and anti-apoptotic effects. These findings demonstrate that Eng alleviates colitis by targeting mitochondrial homeostasis and oxidative stress through AMPK/SIRT1/PGC-1α signaling, offering a multitargeted strategy for IBD therapy.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 5","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12108241/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144155803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Takotsubo Syndrome and Oxidative Stress: Physiopathological Linkage and Future Perspectives.","authors":"Alfredo Mauriello, Carmen Del Giudice, Gerardo Elia Del Vecchio, Adriana Correra, Anna Chiara Maratea, Martina Grieco, Arianna Amata, Vincenzo Quagliariello, Nicola Maurea, Riccardo Proietti, Antonio Giordano, Antonello D'Andrea, Vincenzo Russo","doi":"10.3390/antiox14050522","DOIUrl":"10.3390/antiox14050522","url":null,"abstract":"<p><p>Takotsubo syndrome (TTS) is an acute coronary syndrome of unknown prevalence with a physiopathological mechanism that is not yet fully understood. The course is generally benign. Current therapeutic management is based on limited evidence. Oxidative stress seems to play a role in the pathogenesis of cardiovascular diseases, especially regarding the endothelial dysfunction underlying TTS. The present review aims to describe the pathophysiological mechanisms linking oxidative stress and TTS, explore the impact of oxidative stress on TTS, and evaluate the efficacy of anti-oxidative stress therapies on TTS.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 5","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12108290/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144155864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, 8-Week Pilot Study of Tuna-Byproduct-Derived Novel Supplements for Managing Cellular Senescence and Cognitive Decline in Perimenopausal and Postmenopausal Women.","authors":"Jintanaporn Wattanathorn, Wipawee Thukham-Mee, Terdthai Tong-Un, Weerapon Sangartit, Woraluck Somboonporn, Pongsatorn Paholpak","doi":"10.3390/antiox14050520","DOIUrl":"10.3390/antiox14050520","url":null,"abstract":"<p><p>Due to the lack of clinical data, we aimed to assess the anti-cellular senescence and cognition-enhancing effects and the mechanisms of novel tuna-byproduct-derived supplements. An 8-week, three-arm, randomized, double-blind, placebo-controlled parallel study was performed. A total of 60 female perimenopausal and postmenopausal women (45-60 years old) were randomly assigned to placebo, low (2600 mg/day), and high (6000 mg/day) doses of the supplement. The N100 and P300 brain waves, working memory, serum levels of MDA, SOD, CAT, GPx TNF-α, IL-6, eNOS, AChE, MAO, GABA-T, and SIRT1, and density of <i>Lactobacillus</i> and <i>Bifidobacterium</i> spp. in feces were assessed before consumption and every 4 weeks throughout the study period. The telomere length and total phenolic compound and DHA levels were assessed before and at the end of the study. The low dose increased the N100 amplitude, working memory, telomere length, and SIRT1, whereas high doses improved the amplitudes of N00 and P300, P300 latency, and working memory; suppressed AChE, MAO, and GABA-T; and improved MDA, SOD, GPx, TNF-α, and IL-6 levels in the serum, further exhibiting an increase in DHA. Therefore, the novel supplement could be a potential remedy for managing cellular senescence and cognitive decline in perimenopausal and postmenopausal women; however, studies with larger sample sizes are required.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 5","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12108292/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144155610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced Extraction of Bioactive Compounds from Red Grape Pomace: Optimizing Ultrasound-Assisted Extraction with Ethanol and NaDES as Solvents.","authors":"Nicoleta Balan, Silviu Măntăilă, Gabriela Râpeanu, Nicoleta Stănciuc","doi":"10.3390/antiox14050526","DOIUrl":"10.3390/antiox14050526","url":null,"abstract":"<p><p>This study aims to investigate two types of solvents, ethanol and natural deep eutectic solvent (NaDES), using the ultrasound-assisted extraction techniques, in order to analyze their efficiency and ability to extract polyphenolic compounds from red grape pomace. The optimization and validation of the most feasible extraction conditions leading to maximization of the dependent variables (total anthocyanins, polyphenols, flavonoids and antioxidant activity), were carried out using response surface methodology with a central composite design. For ethanol extraction, the validated optimal conditions were at 35 °C for 22.5 min and a concentration of 70% ethanol. The values obtained under these conditions were 105.32 mg cyanindin-3-glucoside (C3G)/g DW, 465.81 mg gallic acid equivalents (GAE)/100 g DW, 15.3 mg catechin equivalents (CE)/100 g DW and 1414.15 mMol Trolox/g DW, respectively. Concerning the extraction using NaDES, consisting of a 1:2:1 molar mixture of choline chloride, lactic acid and water, the optimal conditions that led to a profile consisting in 57.58 mg C3G/g DW, 414.04 mg GAE/100 g DW, 15.8 mg CE/100 g DW and 7.28 mMol Trolox/g DW, respectively, were at 60 °C for 60 min and a solvent volume of 10 mL. Two different chromatographic profiles were obtained, with 12 polyphenolic compounds identified in ethanolic extracts and only 5 in NaDES, respectively. The in vitro digestion study revealed the high bioaccessibility of polyphenols in the gastric environment, with a drastic decrease in simulated intestinal fluid. The results are valuable in terms of identifying the best extraction conditions for polyphenols using alternative, non-toxic, ecofriendly solvents.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 5","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12108469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144155804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimized <i>Sambucus nigra</i> L., <i>Epilobium hirsutum</i> L., and <i>Lythrum salicaria</i> L. Extracts: Biological Effects Supporting Their Potential in Wound Care.","authors":"Diana Antonia Safta, Ana-Maria Vlase, Anca Pop, Julien Cherfan, Rahela Carpa, Sonia Iurian, Cătălina Bogdan, Laurian Vlase, Mirela-Liliana Moldovan","doi":"10.3390/antiox14050521","DOIUrl":"10.3390/antiox14050521","url":null,"abstract":"<p><p>This study aimed to optimize the extraction of phytocompounds intended for wound care applications from three plant species, <i>Sambucus nigra</i> L. flowers and <i>Epilobium hirsutum</i> L. and <i>Lythrum salicaria</i> L. aerial parts, by using a Quality by Design approach. The effects of different extraction methods (ultra-turrax and ultrasonic-assisted extraction), ethanol concentrations (30%, 50%, 70%), and extraction times (3, 5, 10 min) were studied, and during the optimization step, the polyphenol and flavonoid contents were maximized. The phytochemical profiles of the optimized HEs (herbal extracts) were assessed using LC-MS/MS methods. The antioxidant capacity of the optimized HEs was determined using DPPH (2,2-diphenyl-1-picrylhydrazyl radical scavenging capacity) TEAC (Trolox equivalent antioxidant capacity), and FRAP (ferric reducing antioxidant power) assays, while the antibacterial activity was evaluated against <i>Escherichia coli</i>, <i>Pseudomonas aeruginosa</i>, and MSSA-methicillin-sensitive <i>Staphylococcus aureus</i> and MRSA-methicillin-resistant <i>Staphylococcus aureus</i>). Cell viability and antioxidant and wound healing potential were assessed on keratinocytes and fibroblasts. The anti-inflammatory effect was assessed on fibroblasts by measuring levels of interleukins IL-6 and IL-8 and the production of nitric oxide from RAW 264.7 cells. The major compounds of the optimized HEs were rutin and chlorogenic acid. The <i>Lythrum salicaria</i> optimized HE showed the strongest antibacterial activity, while the <i>Sambucus nigra</i> optimized HE demonstrated high cell viability. <i>Lythrum salicaria</i> and <i>Epilobium hirsutum</i> optimized HEs showed increased antioxidant capacities. All extracts displayed anti-inflammatory effects, and the <i>Epilobium hirsutum</i> optimized HE exhibited the best in vitro wound-healing effect.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 5","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12108421/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144155838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimized Fermentation Conditions of Pulses Increase Scavenging Capacity and Markers of Anti-Diabetic Properties.","authors":"Andrea Jimena Valdés-Alvarado, Erick Damián Castañeda-Reyes, Elvira Gonzalez de Mejia","doi":"10.3390/antiox14050523","DOIUrl":"10.3390/antiox14050523","url":null,"abstract":"<p><p>Fermented pulses offer health benefits due to their antioxidant and antidiabetic properties. The objective was to optimize the fermentation conditions of black bean (BB), black eyed pea (BEP), green split pea (GSP), red lentil (RL), and pinto bean (PB), using <i>Lactiplantibacillus plantarum</i> 299v (Lp299v), based on the antioxidant-scavenging capacity and the ability to modulate type-2 diabetes markers. Pulses were grounded, dispersed in water, hydrolyzed with α-amylase, and pasteurized and inoculated with Lp299v. Optimization was performed by using the Box-Behnken response surface methodology, with the fermentation time, bacterial concentration, and flour concentration as variables. The values of antioxidant capacity measured as 2,2-diphenyl-1-picrylhydrazyl (DPPH)-radical scavenging of RL, BEP, PB, BB, and GSP were 57%, 68%, 71%, 72%, and 83%, respectively, under optimal conditions (8-9 h, 0.76-3.5 × 10⁹ a colony-forming unit (CFU)/mL, and 5.5-15 g flour/100 mL). These models demonstrated strong predictive power (<i>p</i> < 0.01) and a non-significant lack of fit (<i>p</i> ≥ 0.05). Additionally, fermentation increased the soluble protein content (3-10 mg/mL) and significantly inhibited dipeptidyl peptidase-IV and α-glucosidase activities by 40-70% and 30-60%, respectively. These results suggest that fermentation with Lp299v enhances the nutritional and functional quality of pulses, producing bioactive ingredients with antioxidant and antidiabetic potential. These functional ingredients may be used in the development of dietary interventions or as part of health-promoting foods, especially those targeted at the management of type-2 diabetes.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 5","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12108444/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144155839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antioxidant and Anti-Inflammatory Properties of Mushroom-Based Food Additives and Food Fortified with Them-Current Status and Future Perspectives.","authors":"Agata Michalska, Małgorzata Sierocka, Beata Drzewiecka, Michał Świeca","doi":"10.3390/antiox14050519","DOIUrl":"10.3390/antiox14050519","url":null,"abstract":"<p><p>Due to an aging population and the prevalence of illnesses associated with modern lifestyles, mushrooms, well known for their nutritional value and health-promoting properties, are becoming an increasingly important part of the diet. They are consumed in various forms, including food, nutraceuticals, and dietary supplements. A relatively new trend involves incorporating mushrooms or their components as additives and supplements to enhance the quality and functionality of traditional food products. The processing and preservation methods of fresh mushrooms can significantly impact the activity of resulting powders, extracts, or other functional forms used in food additives, supplements, and fortified foods. The functional benefits of mushrooms are frequently attributed to their antioxidant and anti-inflammatory properties. However, to date, the literature lacks comprehensive reviews that consolidate existing knowledge on mushroom-based food additives and products enriched with them. Therefore, this review aims to compile and methodically analyze the existing data in this field, identify existing knowledge gaps, and outline future perspectives for the development and application of such products. Special attention is given to food supplementation with microencapsulated additives, which represent a promising form of functional powders. All these aspects are evaluated in terms of their antioxidant and anti-inflammatory properties. Finally, future perspectives on improving the health benefits of food through mushroom-based additives are discussed.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 5","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12108364/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144155686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effect of Chokeberry Juice and Fiber Consumption on the Concentration of Antioxidant Minerals in Serum.","authors":"Ewa Olechno, Małgorzata Elżbieta Zujko, Katarzyna Socha, Anna Puścion-Jakubik","doi":"10.3390/antiox14050516","DOIUrl":"10.3390/antiox14050516","url":null,"abstract":"<p><p>Aronia is a fruit that has become increasingly popular in recent years. Numerous health-promoting effects resulting from consumption have been indicated, including the possibility of using aronia as a functional food in the prevention and support of therapy for various ailments. For the first time, we assessed the effects of the impact of a 90-day nutritional intervention on the level of selected minerals in the serum of women (<i>n</i> = 67) and men (<i>n</i> = 35). The consumption of 100 mL of juice for 60 days resulted in a significant increase in the levels of copper, manganese, and selenium. The addition of 10 g of aronia fiber resulted in a further increase in the concentration of these elements with antioxidant properties. An interesting observation is that the concentration of zinc decreased, which may indicate the operation of compensatory mechanisms. The above results indicate that regular consumption of aronia bio-products may have a beneficial effect on the concentration of microelements in the serum.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 5","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12108450/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144155872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trimethylamine N-Oxide (TMAO) Acts as Inhibitor of Endothelial Nitric Oxide Synthase (eNOS) and Hampers NO Production and Acetylcholine-Mediated Vasorelaxation in Rat Aortas.","authors":"Alma Martelli, Federico Abate, Michele Roggia, Giada Benedetti, Eugenio Caradonna, Vincenzo Calderone, Gian Carlo Tenore, Sandro Cosconati, Ettore Novellino, Mariano Stornaiuolo","doi":"10.3390/antiox14050517","DOIUrl":"10.3390/antiox14050517","url":null,"abstract":"<p><p>Trimethylamine N-oxide (TMAO) is an endogenous osmolyte produced by enzymatic reactions starting in the human gut, where microbiota release trimethylamine (TMA) from foods, and ending in the liver, where TMA is oxidized to TMAO by flavin-containing monooxygenase 3 (FMO3). While physiological concentrations of TMAO help proteins preserve their folding, high levels of this metabolite are harmful and promote oxidative stress, inflammation, and atherosclerosis. In humans, elevated levels of circulating TMAO predispose individuals to cardiovascular diseases and chronic kidney disease and increase mortality risk, especially in the elderly. How TMAO exerts its negative effects has been only partially elucidated. In hypertensive rats, the eNOS substrate L-arginine and Taurisolo^®, a nutraceutical endowed with TMAO-reducing activity, act synergistically to reduce arterial blood pressure. Here, we investigate the molecular mechanisms underpinning this synergism and prove that TMAO, the target of Taurisolo^®, acts as direct inhibitor of endothelial nitric oxide synthase (eNOS) and competes with L-arginine at its catalytic site, ultimately inhibiting NO production and acetylcholine (Ach)-induced relaxation in murine aortas.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 5","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12108457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144155813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}