Antioxidants最新文献_第3页

Targeting Lysosomal Dysfunction and Oxidative Stress in Age-Related Macular Degeneration. 针对年龄相关性黄斑变性的溶酶体功能障碍和氧化应激。

IF 6 2区医学

Antioxidants Pub Date : 2025-05-16 DOI: 10.3390/antiox14050596

Ana S Falcão, Margarida L Pedro, Sandra Tenreiro, Miguel C Seabra

引用次数: 0

Obtainment of Flavonoid-Enriched Fractions from Maqui (Aristotelia chilensis) and Murta (Ugni molinae) Extracts via Preparative HPLC and Evaluation of Their Anti-Inflammatory Effects in Cell-Based Assays. 利用制备高效液相色谱法从黄芪（亚里斯多德）和木犀草（亚里斯多德）提取物中提取富含黄酮类化合物，并在细胞基础上评价其抗炎作用。

IF 6 2区医学

Antioxidants Pub Date : 2025-05-16 DOI: 10.3390/antiox14050600

Amador Alburquenque, Carolina Busch, Gabriela Gómez-Lillo, Alexander Gamboa, Camilo Perez, Nelson Caro Fuentes, Martin Gotteland, Lilian Abugoch, Cristian Tapia

{"title":"Obtainment of Flavonoid-Enriched Fractions from Maqui (Aristotelia chilensis) and Murta (Ugni molinae) Extracts via Preparative HPLC and Evaluation of Their Anti-Inflammatory Effects in Cell-Based Assays.","authors":"Amador Alburquenque, Carolina Busch, Gabriela Gómez-Lillo, Alexander Gamboa, Camilo Perez, Nelson Caro Fuentes, Martin Gotteland, Lilian Abugoch, Cristian Tapia","doi":"10.3390/antiox14050600","DOIUrl":"10.3390/antiox14050600","url":null,"abstract":"Polyphenols exert anti-inflammatory and antioxidant effects by modulating cell signalling pathways and transcription factors involved in inflammatory bowel disease (IBD). However, their stability during digestion can be compromised. Polymer coatings like chitosan (-C) help preserve their stability. Maqui (Aristotelia chilensis) and murta (Ugni molinae) are rich in antioxidant and anti-inflammatory compounds. This work aims to obtain extracts (E) and blends (B) enriched in delphinidin and quercetin glucosides from maqui (Ma) and murta (Mu) crude extracts using preparative chromatography methodology (Prep-HPLC) and to evaluate their effectiveness through in vitro and cellular assays. HPLC-DAD analysis revealed a marked increase in phenolic compound concentration in the BEMaMu and BCMaMu extract blends. Total quercetin glycosides (TQG) increased by 11-fold, and total anthocyanins increased by approximately 8-fold compared to the fruit blend (BMaMu). BCMaMu exhibited a significantly higher ORAC value compared to the estimated additive mixture, suggesting a synergistic effect. No cytotoxicity was observed for BEMaMu, BCMaMu, and their chitosan-coated versions (BEMaMu-C and BCMaMu-C) in Caco-2 and HT29-MTX-E12 cells at concentrations of 0.1-50 mg/mL. Notably, only chitosan-coated BCMaMu inhibited NF-κB expression and activated Nrf2 in TNF-α-challenged Caco-2 cells at 0.1 and 0.5 mg/mL.","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 5","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12108407/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144155750","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}

引用次数: 0

Correction: Gambelunghe et al. Redox-Sensitive Glyoxalase 1 Up-Regulation Is Crucial for Protecting Human Lung Cells from Gold Nanoparticles Toxicity. Antioxidants 2020, 9, 697. 更正：Gambelunghe等人。氧化还原敏感的乙二醛酶1上调对保护人类肺细胞免受金纳米颗粒毒性至关重要。抗氧化剂，2020,9,697。

IF 6 2区医学

Antioxidants Pub Date : 2025-05-16 DOI: 10.3390/antiox14050597

Angela Gambelunghe, Stefano Giovagnoli, Alessandro Di Michele, Simona Boncompagni, Marco Dell'Omo, Kerstin Leopold, Ivo Iavicoli, Vincenzo Nicola Talesa, Cinzia Antognelli

引用次数: 0

Corynoxeine Supplementation Ameliorates Colistin-Induced Kidney Oxidative Stress and Inflammation in Mice. 补充紫杉醇可改善粘菌素诱导的小鼠肾脏氧化应激和炎症。

IF 6 2区医学

Antioxidants Pub Date : 2025-05-15 DOI: 10.3390/antiox14050593

Yue Liu, Ruichen Zhang, Tony Velkov, Jianzhong Shen, Shusheng Tang, Chongshan Dai

{"title":"Corynoxeine Supplementation Ameliorates Colistin-Induced Kidney Oxidative Stress and Inflammation in Mice.","authors":"Yue Liu, Ruichen Zhang, Tony Velkov, Jianzhong Shen, Shusheng Tang, Chongshan Dai","doi":"10.3390/antiox14050593","DOIUrl":"10.3390/antiox14050593","url":null,"abstract":"This study investigated the protective effects of corynoxeine, a natural alkaline compound, on colistin-caused nephrotoxicity using a murine model. Forty mice were divided randomly into control, corynoxeine-only (20 mg/kg/day, intraperitoneal injection), colistin-only (20 mg/kg/day, intraperitoneal injection), and colistin (20 mg/kg/day) + corynoxeine (5 and 20 mg/kg/day) groups (8 mice in each group). All treatments were maintained for seven consecutive days. Results showed that colistin treatment at 20 mg/kg/day for seven days significantly increased serum urea nitrogen and creatinine levels and induced the loss and degeneration of renal tubular epithelial cells, which were markedly ameliorated by corynoxeine co-treatment at 5 or 20 mg/kg/day. Corynoxeine supplementation also markedly attenuated colistin-induced increases in malondialdehyde levels and decreases in reduced glutathione levels and superoxide dismutase and catalase activities in the kidneys. Furthermore, corynoxeine supplementation significantly decreased the expression of transforming growth factor β (TGF-β) and nicotinamide adenine dinucleotide phosphate hydrogen oxidase 4 (NOX4) proteins and nuclear factor kappa B (NF-κB), interleukin-1beta (IL-1β), IL-6, and tumor necrosis factor-α mRNAs, while it significantly increased the expression of erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) proteins in the kidneys. In conclusion, these results reveal that corynoxeine can protect against colistin-induced nephrotoxicity in mice by inhibiting oxidative stress and inflammation, which may partly be attributed to its ability on the activation of the Nrf2/HO-1 pathway and the inhibition of the TGF-β/NOX4 and NF-κB pathways.","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 5","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12108663/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144155794","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}

引用次数: 0

The Extract from the Stem and Leaf of Paeonia lactiflora Pall Has Demonstrated an Anti-Oxidative Stress Effect in Alleviating Diarrhea by Regulating the Gut-Liver Axis. 芍药茎叶提取物通过调节肠肝轴具有抗氧化应激缓解腹泻作用。

IF 6 2区医学

Antioxidants Pub Date : 2025-05-15 DOI: 10.3390/antiox14050592

Ming-Hua Wang, Ling Liu, Jun Li, Wei-Wei Zhou, Wei Tian, Jin-Hua Zhao, Xiu-Mei Li

{"title":"The Extract from the Stem and Leaf of Paeonia lactiflora Pall Has Demonstrated an Anti-Oxidative Stress Effect in Alleviating Diarrhea by Regulating the Gut-Liver Axis.","authors":"Ming-Hua Wang, Ling Liu, Jun Li, Wei-Wei Zhou, Wei Tian, Jin-Hua Zhao, Xiu-Mei Li","doi":"10.3390/antiox14050592","DOIUrl":"10.3390/antiox14050592","url":null,"abstract":"This study investigated the preventive effects and mechanisms of Paeonia lactiflora pall stem and leaf extract (PLE) on oxidative stress-induced diarrhea in broilers, using a Diquat (DQ)-induced model. Results indicated that PLE significantly improved growth performance, increased average daily gain (ADG), reduced feed-to-gain ratio (F/G), and enhanced liver and kidney indices. PLE alleviated DQ-induced oxidative stress diarrhea by reducing the diarrhea rate by 63.84%, upregulating mRNA expression of MUC2, Claudin-1, ZO-1, and Occludin, and decreasing AST and ALT activities in serum. Additionally, PLE increased levels of CAT, SOD, GSH-Px, and GSH while reducing PCO and MDA levels in serum, intestine, and liver tissues. Furthermore, PLE increased acetic acid content and decreased propionic acid, butyric acid, and isobutyric acid contents. PLE also altered gut microbiota by up-regulated Bacteroidetes and Barnesiella and down-regulated Firmicutes and unclassified_o__Eubacteriales. Network pharmacology suggested that PLE acts via the PI3K-Akt-Nrf2 pathway, confirmed by up-regulated mRNA expression of PI3K, AKT, Nrf2, NQO1, and HO-1, and down-regulated Keap1 in intestinal and liver tissues. Correlation analysis revealed significant associations between Barnesiella and unclassified_o__Eubacteriales with short-chain fatty acids and PI3K-Akt-Nrf2 pathway-related genes. Thus, PLE prevents and alleviates oxidative stress-induced diarrhea in broilers by modulating the PI3K-Akt-Nrf2 pathway, regulating gut microbiota, and influencing short-chain fatty acids.","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 5","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12108339/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144155874","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}

引用次数: 0

Manganese Porphyrin Treatment Improves Redox Status Caused by Acute Compressive Spinal Cord Trauma. 锰卟啉治疗可改善急性脊髓压缩性损伤引起的氧化还原状态。

IF 6 2区医学

Antioxidants Pub Date : 2025-05-14 DOI: 10.3390/antiox14050587

Raquel Vieira Niella, Janaína Maria Xavier Corrêa, Claire Souza da Costa Marques, Álvaro José Chávez Silva, Luciano Cardoso Santos, Iago Santos de Oliveira, Gilson DeFreitas-Silva, Júlio Santos Rebouças, Juneo Freitas Silva, Mário Sérgio Lima de Lavor

{"title":"Manganese Porphyrin Treatment Improves Redox Status Caused by Acute Compressive Spinal Cord Trauma.","authors":"Raquel Vieira Niella, Janaína Maria Xavier Corrêa, Claire Souza da Costa Marques, Álvaro José Chávez Silva, Luciano Cardoso Santos, Iago Santos de Oliveira, Gilson DeFreitas-Silva, Júlio Santos Rebouças, Juneo Freitas Silva, Mário Sérgio Lima de Lavor","doi":"10.3390/antiox14050587","DOIUrl":"10.3390/antiox14050587","url":null,"abstract":"There is increasing interest in identifying drugs that can prevent or delay neurological complications following spinal cord injury, thus expanding the therapeutic window for other potential neuroprotective agents. In this context, manganese porphyrins (MnPs) have shown high antioxidant and anti-inflammatory potential in various experimental disease models, including stroke, cancer, diabetes, ischemia, and radiotherapy. However, they have been little evaluated in spinal cord injuries. This study aimed to assess the therapeutic potential of the manganese porphyrins [MnTE-2-PyP]5+ (MnPI) and [MnT(5-Br-3-E-Py)P]5+ (MnPII) in acute compressive spinal cord trauma in rats. Twenty-four animals were used (six animals/group). Following general inhalation anesthesia, acute compressive spinal cord trauma was induced in all groups except for the negative control (SHAM). Treatment commenced 60 min post-trauma, with animals receiving treatment for seven days at 24 h intervals. While no improvement in motor capacity was observed, MnPs effectively blocked the increase in oxidative stress and endoplasmic reticulum (ER) stress mediators caused by trauma, maintaining the protein expression levels of Hifα, 8-OHdG and MDA, as well as the expression of the genes Grp78, Chop, Ho1, and Perk, similar to those of the control group. Moreover, there was an increase in protein expression of SOD1, Cat, and GPX1, along with a restoration of SOD and CAT enzymatic activity. Additionally, MnPs improved the expression of IL-6, neurotrophic markers, and apoptotic factors. In conclusion, treatment with MnPs attenuated the oxidative stress and ER stress caused by acute compressive spinal cord trauma and restored spinal expression of neurotrophic mediators.","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 5","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12108513/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144155769","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}

引用次数: 0

Enhancing the Bioactive Properties of Sugarcane Vinegar Through Caesalpinia sappan Extract Supplementation: A Novel Approach for Functional Beverage Development. 添加仙人掌提取物提高甘蔗醋的生物活性：功能饮料开发的新途径。

IF 6 2区医学

Antioxidants Pub Date : 2025-05-14 DOI: 10.3390/antiox14050590

Preekamol Klanrit, Haruthairat Kitwetcharoen, Kanit Vichitphan, Sukanda Vichitphan, Sudarat Thanonkeo, Mamoru Yamada, Pornthap Thanonkeo

{"title":"Enhancing the Bioactive Properties of Sugarcane Vinegar Through Caesalpinia sappan Extract Supplementation: A Novel Approach for Functional Beverage Development.","authors":"Preekamol Klanrit, Haruthairat Kitwetcharoen, Kanit Vichitphan, Sukanda Vichitphan, Sudarat Thanonkeo, Mamoru Yamada, Pornthap Thanonkeo","doi":"10.3390/antiox14050590","DOIUrl":"10.3390/antiox14050590","url":null,"abstract":"Functional vinegars have been produced from various ingredients worldwide, yet there remains a notable gap in utilizing herbal plants as complementary ingredients to sugar-based materials. This study investigates the innovative combination of Caesalpinia sappan extract with sugarcane juice for functional vinegar production. The results demonstrate that C. sappan-supplemented vinegars exhibited significantly enhanced quality parameters compared to control vinegar made from sugarcane juice alone. Specifically, the supplemented vinegars showed increased total acidity and total phenolic content (TPC), with the improvement directly proportional to the concentration of plant extract used. Gas chromatography-mass spectrometry (GC-MS) analysis revealed unique volatile organic compounds (VOCs) that were present exclusively in the C. sappan-supplemented vinegars but absent in the control. Most notably, the supplementation of C. sappan extract at concentrations of 2 and 4 g/L substantially enhanced both the antioxidant capacity and antimicrobial activity of the resulting vinegars. These biochemical improvements highlight the synergistic potential of combining sugarcane juice with C. sappan extract for developing novel functional vinegar beverages with enhanced bioactive properties. Our findings open new possibilities for creating value-added products that leverage traditional medicinal plants in modern functional beverages, potentially offering consumers additional health benefits beyond conventional vinegars.","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 5","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12108335/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144155705","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}

引用次数: 0

Physicochemical Characterization of Kynurenine Pathway Metabolites. 犬尿氨酸途径代谢产物的理化性质。

IF 6 2区医学

Antioxidants Pub Date : 2025-05-14 DOI: 10.3390/antiox14050589

Luca Buzásy, Károly Mazák, Balázs Balogh, Balázs Simon, Anna Vincze, György Tibor Balogh, Tamás Pálla, Arash Mirzahosseini

{"title":"Physicochemical Characterization of Kynurenine Pathway Metabolites.","authors":"Luca Buzásy, Károly Mazák, Balázs Balogh, Balázs Simon, Anna Vincze, György Tibor Balogh, Tamás Pálla, Arash Mirzahosseini","doi":"10.3390/antiox14050589","DOIUrl":"10.3390/antiox14050589","url":null,"abstract":"The kynurenine pathway is a significant metabolic route involved in the catabolism of tryptophan, producing various bioactive metabolites with crucial roles as antioxidants in immune regulation and neurobiology. This study investigates the acid-base properties of picolinic acid, kynurenic acid, kynurenine, and 3-hydroxykynurenine, utilizing computational simulations and experimental techniques, including potentiometric and nuclear magnetic resonance titrations. The results reveal distinct pKa values, with kynurenic acid exhibiting a single dissociation step around 2.4, while kynurenine displays three dissociation steps governed by interactions between its functional groups. Additionally, 3-hydroxykynurenine shows overlapping dissociations in two separate pH regions, suggesting nuanced behavior influenced by its molecular structure. The analysis of intramolecular hydrogen bonding in protonation microspecies across varying pH highlights the relevance of the charge state and hydrogen transfer potential of these metabolites in the context of their radical scavenging ability. At physiological pH, most kynurenine and 3-hydroxykynurenine entities exist in zwitterionic form, with hydrogen bonding stabilizing the aromatic amino group, which may significantly influence their interactions with proteins and reactive oxygen species. This study provides critical insights into the acid-base equilibria of kynurenine pathway metabolites.","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 5","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12108296/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144155845","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}

引用次数: 0

Success and Controversy of Natural Products as Therapeutic Modulators of Wnt Signaling and Its Interplay with Oxidative Stress: Comprehensive Review Across Compound Classes and Experimental Systems. 天然产物作为Wnt信号的治疗调节剂及其与氧化应激的相互作用的成功和争议：跨化合物类别和实验系统的综合综述。

IF 6 2区医学

Antioxidants Pub Date : 2025-05-14 DOI: 10.3390/antiox14050591

Alexey Koval, Nilufar Z Mamadalieva, Rano Mamadalieva, Fazliddin Jalilov, Vladimir L Katanaev

{"title":"Success and Controversy of Natural Products as Therapeutic Modulators of Wnt Signaling and Its Interplay with Oxidative Stress: Comprehensive Review Across Compound Classes and Experimental Systems.","authors":"Alexey Koval, Nilufar Z Mamadalieva, Rano Mamadalieva, Fazliddin Jalilov, Vladimir L Katanaev","doi":"10.3390/antiox14050591","DOIUrl":"10.3390/antiox14050591","url":null,"abstract":"The highly conserved Wnt signaling pathway, a complex network critical for embryonic development and adult tissue homeostasis, regulates diverse cellular processes, ultimately influencing tissue organization and organogenesis; its dysregulation is implicated in numerous diseases, and it is known to be affected by oxidative pathways. This report reviews the recent literature on major classes of natural products with pronounced anti-oxidant properties, such as cardiac glycosides, steroid saponins, ecdysteroids, withanolides, cucurbitacins, triterpenes, flavonoids, and iridoids, that modulate its activity in various pathological conditions, summarizing and critically analyzing their effects on the Wnt pathway in various therapeutically relevant experimental models and highlighting the role of ROS-mediated crosstalk with Wnt signaling in these studies. Models reviewed include not only cancer but also stroke, ischemia, bone or kidney diseases, and regenerative medicine, such as re-epithelialization, cardiac maintenance, and hair loss. It highlights the paramount importance of modulating this signaling by natural products to define future research directions. We also discuss controversies identified in the mode of action of several compounds in different models and directions on how to further improve the quality and depth of such studies.","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 5","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12108534/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144155863","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}

引用次数: 0

Hydrogen Peroxide-Induced Re-Expression of Repressor Element 1-Silencing Transcription Factor Contributes to Cardiac Vagal Dysfunction in Type 2 Diabetes Mellitus. 过氧化氢诱导的抑制元件1-沉默转录因子的重新表达与2型糖尿病心脏迷走神经功能障碍有关

IF 6 2区医学

Antioxidants Pub Date : 2025-05-14 DOI: 10.3390/antiox14050588

Dongze Zhang, Huiyin Tu, Wenfeng Hu, Yu Li, Michael C Wadman, Yu-Long Li

{"title":"Hydrogen Peroxide-Induced Re-Expression of Repressor Element 1-Silencing Transcription Factor Contributes to Cardiac Vagal Dysfunction in Type 2 Diabetes Mellitus.","authors":"Dongze Zhang, Huiyin Tu, Wenfeng Hu, Yu Li, Michael C Wadman, Yu-Long Li","doi":"10.3390/antiox14050588","DOIUrl":"10.3390/antiox14050588","url":null,"abstract":"Diabetes mellitus, especially type 2 diabetes mellitus (T2DM), is a major health problem worldwide and has become a leading cause of mortality. As a common complication of patients with T2DM, cardiac autonomic dysfunction (including sympathetic overactivation and reduced vagal tone) is associated with a higher risk of arrhythmia-related sudden cardiac death. Our previous study found that T2DM-elevated hydrogen peroxide (H2O2) levels in atrioventricular ganglion (AVG) neurons contribute to the decrease in cardiac vagal function and ventricular arrhythmogenesis through inhibition of N-type Ca2+ channels (Cav2.2). In the present study, treatment with exogenous H2O2 in differentiated NG108-15 cells increased REST expression and decreased Cav2.2-α expression. Adenoviral catalase gene transfection into the AVG neurons significantly reduced the REST levels elevated by a high-fat diet plus streptozotocin-induced T2DM. Lentiviral REST shRNA transfection markedly increased Cav2.2-α expression in the AVG neurons from T2DM rats. REST shRNA also activated N-type Ca2+ channels and increased cell excitability of AVG neurons in T2DM rats. Additionally, REST shRNA markedly improved cardiac vagal activation in T2DM rats. The present study suggests that the H2O2-REST-Cav2.2 channel signaling axis could be a potential therapeutic target to normalize cardiac vagal dysfunction and its related cardiac complications in T2DM.","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 5","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12108343/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144155711","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}

引用次数: 0