Antioxidants & redox signaling最新文献

{"title":"Liposomes-Loaded miR-9-5p Alleviated Hypoxia-Ischemia-Induced Mitochondrial Oxidative Stress by Targeting ZBTB20 to Inhibiting Nrf2/Keap1 Interaction in Neonatal Mice.","authors":"Yijing Zhao, Chengcheng Gai, Shuwen Yu, Yan Song, Bing Gu, Qian Luo, Xixi Wang, Quan Hu, Weiyang Liu, Dexiang Liu, Zhen Wang","doi":"10.1089/ars.2024.0640","DOIUrl":"https://doi.org/10.1089/ars.2024.0640","url":null,"abstract":"<p><p><b><i>Aims:</i></b> Hypoxia ischemia (HI) is a leading cause of cerebral palsy and long-term neurological sequelae in infants. Given that mitochondrial dysfunction in neurons contributes to HI brain damage, this study aimed to investigate the regulatory role of miR-9-5p in mitochondrial function following HI injury. <b><i>Results:</i></b> Overexpression of miR-9-5p in HI mice or H₂O₂-exposed PC12 cells suppressed neuronal injury, associated with increased mitochondrial copy number, normalizing mitochondrial membrane potential, improved nuclear factor-erythroid factor 2-related factor 2 (Nrf2) activation, and downregulation of Keap1. This was mediated, in part, through the ability of this miR-9-5p to bind and regulate the transcriptional activity of zinc finger and BTB domain-containing protein 20 (ZBTB20). Further study suggested that the knockdown of ZBTB20 exerts neuroprotection by inhibiting Nrf2/Keap1 interaction to promote the translocation of Nrf2 from the cytoplasm to the nucleus and the consequent expression of antioxidant proteins. Notably, the protective effects of miR-9-5p overexpression against HI-induced mitochondrial damage were reversed by the Nrf2 inhibitor ML385. Finally, the utilization of liposomes for the delivery of miR-9-5p (miR-9-5p@Lip) presents a promising therapeutic strategy for the treatment of HI injury. <b><i>Innovation:</i></b> miR-9-5p is a potential therapeutic agent for ischemic stroke through its modulation of the ZBTB20/Nrf2/Keap1 signaling pathway, influencing mitochondrial function and antioxidant response. Furthermore, the use of liposomal delivery for miR-9-5p offers a promising therapeutic strategy for HI injury. <b><i>Conclusion:</i></b> Overexpression of miR-9-5p protects against cerebral HI injury by modulating mitochondrial function through the ZBTB20/Nrf2/Keap1 signaling pathway. <i>Antioxid. Redox Signal.</i> 00, 000-000.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual Oxygen-Responsive Control by RegSR of Nitric Oxide Reduction in the Soybean Endosymbiont <i>Bradyrhizobium diazoefficiens</i>.","authors":"Andrea Jiménez-Leiva, Raquel A Juárez-Martos, Juan J Cabrera, María J Torres, Socorro Mesa, María J Delgado","doi":"10.1089/ars.2024.0710","DOIUrl":"https://doi.org/10.1089/ars.2024.0710","url":null,"abstract":"<p><p><b><i>Aims:</i></b> To investigate the role of the RegSR-NifA regulatory cascade in the oxygen control of nitric oxide (NO) reduction in the soybean endosymbiont <i>Bradyrhizobium diazoefficiens</i>. <b><i>Results:</i></b> We have performed an integrated study of <i>norCBQD</i> expression and NO reductase activity in <i>regR</i>, <i>regS</i>₁, <i>regS</i>₂, <i>regS</i>_1/2, and <i>nifA</i> mutants in response to microoxia (2% O₂) or anoxia. An activating role of RegR and NifA was observed under anoxia. In contrast, under microaerobic conditions, RegR acts as a repressor by binding to a RegR box located between the -10 and -35 regions within the <i>norCBQD</i> promoter. In addition, both RegS₁ and RegS₂ sensors cooperated with RegR in repressing <i>norCBQD</i> genes. <b><i>Innovation:</i></b> NO is a reactive gas that, at high levels, acts as a potent inhibitor of symbiotic nitrogen fixation. In this paper, we report new insights into the regulation of NO reductase, the major enzyme involved in NO removal in rhizobia. This knowledge will be crucial for the development of new strategies and management practices in agriculture, in particular, for improving legume production. <b><i>Conclusion:</i></b> Our results demonstrate, for the first time, a dual control of the RegSR two-component regulatory system on <i>norCBQD</i> genes control in response to oxygen levels. <i>Antioxid. Redox Signal.</i> 00, 000-000.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Molecular Interplay Between Oxygen Transport, Cellular Oxygen Sensing, and Mitochondrial Respiration.","authors":"Sirsendu Jana, Abdu I Alayash","doi":"10.1089/ars.2023.0428","DOIUrl":"https://doi.org/10.1089/ars.2023.0428","url":null,"abstract":"<p><p><b><i>Significance:</i></b> The mitochondria play a key role in maintaining oxygen homeostasis under normal oxygen tension (normoxia) and during oxygen deprivation (hypoxia). This is a critical balancing act between the oxygen content of the blood, the tissue oxygen sensing mechanisms, and the mitochondria, which ultimately consume most oxygen for energy production. <b><i>Recent Advances:</i></b> We describe the well-defined role of the mitochondria in oxygen metabolism with a special focus on the impact on blood physiology and pathophysiology. <b><i>Critical Issues:</i></b> Fundamental questions remain regarding the impact of mitochondrial responses to changes in overall blood oxygen content under normoxic and hypoxic states and in the case of impaired oxygen sensing in various cardiovascular and pulmonary complications including blood disorders involving hemolysis and hemoglobin toxicity, ischemia reperfusion, and even in COVID-19 disease. <b><i>Future Directions:</i></b> Understanding the nature of the crosstalk among normal homeostatic pathways, oxygen carrying by hemoglobin, utilization of oxygen by the mitochondrial respiratory chain machinery, and oxygen sensing by hypoxia-inducible factor proteins, may provide a target for future therapeutic interventions. <i>Antioxid. Redox Signal.</i> 00, 000-000.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Physiological Fatty Acid-Stimulated Insulin Secretion and Redox Signaling <i>Versus</i> Lipotoxicity.","authors":"Petr Ježek","doi":"10.1089/ars.2024.0799","DOIUrl":"https://doi.org/10.1089/ars.2024.0799","url":null,"abstract":"<p><p><b><i>Significance:</i></b> Type 2 diabetes as a world-wide epidemic is characterized by the insulin resistance concomitant to a gradual impairment of β-cell mass and function (prominently declining insulin secretion) with dysregulated fatty acids (FAs) and lipids, all involved in multiple pathological development. <b><i>Recent Advances:</i></b> Recently, redox signaling was recognized to be essential for insulin secretion stimulated with glucose (GSIS), branched-chain keto-acids, and FAs. FA-stimulated insulin secretion (FASIS) is a normal physiological event upon postprandial incoming chylomicrons. This contrasts with the frequent lipotoxicity observed in rodents. <b><i>Critical Issues</i></b>: Overfeeding causes FASIS to overlap with GSIS providing repeating hyperinsulinemia, initiates prediabetic states by lipotoxic effects and low-grade inflammation. In contrast the protective effects of lipid droplets in human β-cells counteract excessive lipids. Insulin by FASIS allows FATP1 recruitment into adipocyte plasma membranes when postprandial chylomicrons come late at already low glycemia. <b><i>Future Directions:</i></b> Impaired states of pancreatic β-cells and peripheral organs at prediabetes and type 2 diabetes should be revealed, including the inter-organ crosstalk by extracellular vesicles. Details of FA/lipid molecular physiology are yet to be uncovered, such as complex phenomena of FA uptake into cells, postabsorptive inactivity of G-protein-coupled receptor 40, carnitine carrier substrate specificity, the role of carnitine-O-acetyltransferase in β-cells, and lipid droplet interactions with mitochondria. <i>Antioxid. Redox Signal.</i> 00, 000-000.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sulfur Dioxide Alleviates Aortic Dissection Through Inhibiting Vascular Smooth Muscle Cell Phenotype Switch, Migration, and Proliferation <i>via</i> miR-184-3p/Cyp26b1 Axis.","authors":"Jie He, Kan Huang, Xiaoping Fan, Guangqi Chang","doi":"10.1089/ars.2023.0471","DOIUrl":"https://doi.org/10.1089/ars.2023.0471","url":null,"abstract":"<p><p><b><i>Aims:</i></b> Abnormal migration and proliferation of vascular smooth muscle cells (VSMCs) are considered early events in the onset of thoracic aortic dissection (TAD). Endogenous sulfur dioxide (SO₂), primarily produced by aspartate aminotransferase (AAT1) in mammals, has been reported to inhibit the migration and proliferation of VSMCs. However, the role of SO₂ in the development of TAD remains unclear. <b><i>Results:</i></b> Endogenous SO₂ production was decreased in aortic samples from patients with TAD. Supplementation with SO₂ ameliorated β-aminopropionitrile-induced vascular injury in mice. Increasing the expression of SO₂ pathway might reverse the abnormal migration, proliferation, and phenotypic switching in VSMCs. MicroRNA sequencing revealed miR-184-3p as the miRNA with the most significant increased expression level after AAT1 knockdown, and Cyp26b1 was predicted to be its potential target. A decrease in the SO₂ pathway resulted in reduced Cyp26b1 expression, impairing VSMCs function, while restoring Cyp26b1 expression with miR-184-3p inhibitors could improve the VSMCs function. <b><i>Innovation:</i></b> This research extends the application of endogenous SO₂ to the aortic diseases and elucidates the role of miRNA in endogenous SO₂ regulatory network, highlighting its potential as a target for clinical practice. <b><i>Conclusion:</i></b> Endogenous SO₂ inhibits the migration and proliferation of VSMCs in TAD progression <i>via</i> the miR-184-3p/Cyp26b1 axis. <i>Antioxid. Redox Signal.</i> 00, 000-000.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic Control of Redox Pathways in Cancer Progression.","authors":"Vandit Shah, Hiu Yan Lam, Charlene Hoi-Mun Leong, Reo Sakaizawa, Jigna S Shah, Alan Prem Kumar","doi":"10.1089/ars.2023.0465","DOIUrl":"https://doi.org/10.1089/ars.2023.0465","url":null,"abstract":"<p><p><b><i>Significance:</i></b> Growing evidence indicates the importance of redox reactions homeostasis, mediated predominantly by reactive oxygen species (ROS) in influencing the development, differentiation, progression, metastasis, programmed cell death, tumor microenvironment, and therapeutic resistance of cancer. Therefore, reviewing the ROS-linked epigenetic changes in cancer is fundamental to understanding the progression and prevention of cancer. <b><i>Recent Advances:</i></b> We review in depth the molecular mechanisms involved in ROS-mediated epigenetic changes that lead to alteration of gene expression by altering DNA, modifying histones, and remodeling chromatin and noncoding RNA. <b><i>Critical Issues:</i></b> In cancerous cells, alterations of the gene-expression regulatory elements could be generated by the virtue of imbalance in tumor microenvironment. Various oxidizing agents and mitochondrial electron transport chain are the major pathways that generate ROS. ROS plays a key role in carcinogenesis by activating pro-inflammatory signaling pathways and DNA damage. This loss of ROS-mediated epigenetic regulation of the signaling pathways may promote tumorigenesis. We address all such aspects in this review. <b><i>Future Directions:</i></b> Developments in this growing field of epigenetics are expected to contribute to further our understanding of human health and diseases such as cancer and to test the clinical applications of redox-based therapy. Recent studies of the cancer-epigenetic landscape have revealed pervasive deregulation of the epigenetic factors in cancer. Thus, the study of interaction between ROS and epigenetic factors in cancer holds a great promise in the development of effective and targeted treatment modalities. <i>Antioxid. Redox Signal.</i> 00, 000-000.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ALOX15 Aggravates Metabolic Dysfunction-Associated Steatotic Liver Disease in Mice with Type 2 Diabetes via Activating the PPARγ/CD36 Axis.","authors":"Wenhui Yan, Xin Cui, Tingli Guo, Na Liu, Zhuanzhuan Wang, Yuzhuo Sun, Yuanrui Shang, Jieyun Liu, Yuanyuan Zhu, Yangyang Zhang, Lina Chen","doi":"10.1089/ars.2024.0670","DOIUrl":"https://doi.org/10.1089/ars.2024.0670","url":null,"abstract":"<p><p><b><i>Aims:</i></b> Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent hepatic disorder worldwide. Arachidonic acid 15-lipoxygenase (ALOX15), an enzyme catalyzing the peroxidation of polyunsaturated fatty acids, plays a crucial role in various diseases. Here, we sought to investigate the involvement of ALOX15 in MASLD. <b><i>Results:</i></b> In this study, we observed upregulation of ALOX15 in the liver of high-fat diet (HFD)- and streptozotocin (STZ)-induced mice. Metabolomic analysis revealed elevated levels of ALOX15 metabolites, 12(S)-hydroperoxyeicosatetraenoic acid and 15(S)-hydroperoxyeicosatetraenoic acid. Transcriptomic analysis showed that the increased fatty acid uptake regulated by the PPARγ/CD36 pathway predominated in lipid accumulation. To elucidate the mechanism underlying ALOX15-induced lipid accumulation, HepG2 cells were transfected with a lentivirus expressing ALOX15 or small interfering RNA targeting ALOX15 and exposed to palmitic acid (PA). Both ALOX15 overexpression and PA exposure led to increased intracellular free fatty acid and triglyceride, resulting in lipotoxicity. ALOX15 overexpression aggravated the effect of PA, while the knockdown of ALOX15 attenuated PA-induced lipotoxicity. Moreover, the treatment with PPARγ antagonist GW9662 or CD36 inhibitor sulfosuccinimidyl oleate sodium effectively reduced lipid accumulation and lipotoxicity resulting from ALOX15 overexpression and PA exposure, indicating the involvement of the PPARγ/CD36 pathway in ALOX15-mediated lipid accumulation. Furthermore, liraglutide, a widely used glucagon-like peptide 1 receptor (GLP-1R) agonist (GLP-1RA), improved hepatic lipid accumulation in HFD/STZ-induced mice by suppressing the ALOX15/PPARγ/CD36 pathway. <b><i>Innovation and Conclusion:</i></b> Our study underscores the potential of ALOX15 as an emerging therapeutic target for MASLD. In addition, the GLP-1RA may confer hepatoprotection by regulating ALOX15, enhancing our comprehension of the mechanisms underpinning their protection on MASLD. <i>Antioxid. Redox Signal.</i> 00, 000-000.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Oxidoreductase Retinol Saturase in Thyroid Gland Is Regulated by Hypothyroidism and Iodide Overload and Its Deletion Impairs Metabolic Homeostasis in Mice.","authors":"Na Yang, Lisa Wessoly, Yueming Meng, Marie F Kiefer, Yingfu Chen, Madita Vahrenbrink, Sascha Wulff, Chen Li, Jonah W Schreier, Julia S Steinhoff, Moritz Oster, Manuela Sommerfeld, Sylvia J Wowro, Konstantin M Petricek, Roberto E Flores, Panos G Ziros, Gerasimos P Sykiotis, Eva K Wirth, Michael Schupp","doi":"10.1089/ars.2023.0458","DOIUrl":"https://doi.org/10.1089/ars.2023.0458","url":null,"abstract":"<p><p><b><i>Aims:</i></b> Thyroid hormones (TH) are major regulators of cell differentiation, growth, and metabolic rate. TH synthesis in the thyroid gland requires high amounts of H₂O₂ to oxidize iodide for the iodination of thyroglobulin (TG). Retinol Saturase (RetSat) is an oxidoreductase implicated in dihydroretinol formation and cellular sensitivity toward peroxides and ferroptosis. RetSat is highly expressed in metabolically active organs where it regulates lipid metabolism and the production of reactive oxygen species. Due to the high expression of RetSat in the thyroid gland and its role in peroxide sensitivity, we investigated the regulation and function of RetSat in the thyroid gland in appropriate mouse models. <b><i>Results:</i></b> RetSat is strongly expressed in thyrocytes, induced by hypothyroidism, and decreased by iodide overload in mice. Thyrocyte-specific deletion of <i>RetSat</i> increased circulating thyroid-stimulating hormone levels, altered thyroid morphology, and disturbed metabolic homeostasis in a diet- and sex-dependent manner without major effects on the concentrations of circulating TH. Moreover, deletion of <i>RetSat</i> increased TG protein levels but lowered TG iodination upon iodide overload. In cultured thyrocytes, acute RetSat depletion altered the expression of genes involved in TH biosynthesis and the response to endoplasmic reticulum stress. <b><i>Innovation:</i></b> This is the first report that specifically dissects the regulation and function of the oxidoreductase RetSat in the thyroid gland. <b><i>Conclusion:</i></b> Deletion of <i>RetSat</i> in thyrocytes induces compensatory feedback mechanisms to maintain TH homeostasis in mice. We conclude that RetSat in the thyroid gland is required for TH biosynthesis and secretion and metabolic homeostasis in mice. <i>Antioxid. Redox Signal.</i> 00, 000-000.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Emerging Role of Herbal Medicines in Cancer by Interfering with Posttranslational Modifications.","authors":"Rui Wang, Yu Li, Jiahui Ji, Lingwei Kong, Yukai Huang, Zhongqiu Liu, Linlin Lu","doi":"10.1089/ars.2023.0418","DOIUrl":"10.1089/ars.2023.0418","url":null,"abstract":"<p><p><b><i>Significance:</i></b> Herbal medicines have a long history of comprehensive cancer treatment through various posttranslational modifications (PTMs). Recently, emerging evidence revealed that dysregulation of reactive oxygen species (ROS) and ROS-regulated signaling pathways influence cancer initiation, growth, and progression in a paradoxical role with either low levels or increasing levels of basal ROS. However, ROS-triggered modifications of target proteins in the face of ROS-mediated signal transduction are not fully understood in the anticancer therapies of herbal medicines. In this review, we briefly introduce the PTM-dependent regulations of herbal medicines, and then focus on the current ideals that targeting ROS-dependent PTMs <i>via</i> antioxidant and redox signaling pathways can provide a promising strategy in herbal-based anticancer effects. <b><i>Recent Advances:</i></b> Advanced development in highly sensitive mass spectrometry-based techniques has helped utilize ROS-triggered protein modifications in numerous cancers. Accumulating evidence has been achieved in laboratory to extensively ascertain the biological mechanism of herbal medicines targeting ROS in cancer therapy. Two general mechanisms underlining ROS-induced cell signaling include redox state and oxidative modification of target protein, indicating a new perspective to comprehend the intricate dialogues between herbal medicines and cancer cellular contexts. <b><i>Critical Issues:</i></b> Complex components of herbal medicines limit the benefits of herbal-based cancer therapies. In this review, we address that ROS-dependent PTMs add a layer of proteomic complexity to the cancer through altering the protein structure, expression, function, and localization. Elaborating ROS-triggered PTMs implicated in cell signaling, apoptosis, and transcriptional regulation function, and the possible cellular signaling, has provided important information about the contribution of many ROS targeting herbal therapies in anticancer effects. Continued optimization of proteomic strategies for PTM analysis in herbal medicines is also briefly discussed. <b><i>Future Directions:</i></b> Rigorous evaluations of herbal medicines and proteomic strategies are necessary to explore the aberrant regulation of ROS-triggered antioxidant and redox signaling contributing to the novel protein targets and herbal-associated pharmacological issues. These efforts will eventually help develop more herbal drugs as modern therapeutic agents. <i>Antioxid. Redox Signal.</i> 42, 150-164.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"150-164"},"PeriodicalIF":5.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141544476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Asperuloside as a Novel NRF2 Activator to Ameliorate Endothelial Dysfunction in High Fat Diet-Induced Obese Mice.","authors":"Chufeng He, Ruiwen Zhu, Lei He, Chui Yiu Bamboo Chook, Huixian Li, Fung Ping Leung, Gary Tse, Zhen-Yu Chen, Yu Huang, Wing Tak Wong","doi":"10.1089/ars.2024.0593","DOIUrl":"10.1089/ars.2024.0593","url":null,"abstract":"<p><p><b><i>Aims:</i></b> Current treatments are inadequate in alleviating obesity-associated vascular diseases. The development of effective therapies to ameliorate endothelial dysfunction and attenuate oxidative stress is of utmost importance. Asperuloside (ASP), a bioactive compound extracted from <i>Eucommia species</i>, exhibits antiobesity properties. However, the effects of ASP on vasculopathy have not been investigated. Therefore, the effects of ASP on vascular dysfunction and related mechanisms were elucidated. <b><i>Results:</i></b> ASP significantly reversed the impaired endothelium-dependent relaxations (EDRs) in obese mice and interleukin (IL)-1β-treated aortas. ASP suppressed endothelial activation in obese mice aortas and IL-1β-treated endothelial cells. ASP attenuated oxidative stress, scavenged mitochondrial reactive oxygen species (ROS), and upregulated heme oxygenase-1 (HO-1) expression in endothelium, independent of its anti-inflammatory properties. HO-1 knockdown diminished the protective effects of ASP against impaired EDRs, ROS overproduction, and endothelial activation. Endothelial cell-specific nuclear factor erythroid 2-related factor 2 (Nrf2) knockdown eliminated the ASP-mediated vascular protective effects and endothelial HO-1 upregulation, emphasizing that ASP improves endothelial function by activating Nrf2/HO-1 signaling. ASP facilitated Nrf2 nuclear translocation and the direct binding of Nrf2 to antioxidant response element, thereby enhancing HO-1 transcription and scavenging ROS. The cellular thermal shift assay results provide the first experimental characterization of the direct binding of ASP to Nrf2. <b><i>Conclusions:</i></b> These findings demonstrate that ASP ameliorates obesity-associated endothelial dysfunction by activating Nrf2/HO-1 signaling and thereby maintaining redox hemostasis, suggesting its potential as a novel Nrf2-targeted therapeutic agent and dietary supplement for vasculopathy. <i>Antioxid. Redox Signal.</i> 42, 77-96.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"77-96"},"PeriodicalIF":5.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141905678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}