Natural products targeting Nrf2/ARE signaling pathway in the treatment of inflammatory bowel disease DOI Open Access
Botong Li, Yixuan Wang, Xiaolin Jiang

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 164, P. 114950 - 114950

Published: May 30, 2023

Inflammatory bowel disease (IBD) is a special chronic intestinal inflammatory disease, which mainly divided into Crohn's (CD) and ulcerative colitis (UC). Its occurrence complex process that regulated by multiple signaling pathways, including nuclear factor erythroid 2-related (Nrf2)/ antioxidant response element (ARE) pathway. Nrf2/ARE pathway as the central defense mechanism against oxidative stress controls expression of many anti-inflammatory genes in nucleus, plays crucial role treatment IBD. Various studies have proved natural compounds target to treat Here, we introduced regulatory pathway, its IBD complications (intestinal fibrosis colorectal cancer (CRC)); summarized research progress Nrf2 targeted extracts IBD; finally described microbiota alleviate or via activating This review highlights potential for targeting

Language: Английский

Nrf2 and Oxidative Stress: A General Overview of Mechanisms and Implications in Human Disease DOI Creative Commons
Vy Ngo, Martin L. Duennwald

Antioxidants, Journal Year: 2022, Volume and Issue: 11(12), P. 2345 - 2345

Published: Nov. 27, 2022

Organisms are continually exposed to exogenous and endogenous sources of reactive oxygen species (ROS) other oxidants that have both beneficial deleterious effects on the cell. ROS important roles in a wide range physiological processes; however, high levels associated with oxidative stress disease progression. Oxidative has been implicated nearly all major human diseases, from neurogenerative diseases neuropsychiatric disorders cardiovascular disease, diabetes, cancer. Antioxidant defence systems evolved as means protection against stress, transcription factor Nrf2 key regulator. is responsible for regulating an extensive panel antioxidant enzymes involved detoxification elimination extensively studied contexts. This review aims provide reader general overview Nrf2, including basic mechanisms activation regulation, implications various diseases.

Language: Английский

Citations

384
Mitochondrial dysfunction in neurodegenerative disorders DOI Creative Commons

Madelyn Klemmensen,

Seth H. Borrowman,

Colin Pearce

et al.

Neurotherapeutics, Journal Year: 2023, Volume and Issue: 21(1), P. e00292 - e00292

Published: Dec. 19, 2023

Recent advances in understanding the role of mitochondrial dysfunction neurodegenerative diseases have expanded opportunities for neurotherapeutics targeting mitochondria to alleviate symptoms and slow disease progression. In this review, we offer a historical account biology disease. Additionally, summarize current knowledge normal physiology pathogenesis dysfunction, disease, therapeutics recent therapeutic advances, as well future directions function. A focus is placed on reactive oxygen species their disruption telomeres effects epigenome. The etiology progression Alzheimer's amyotrophic lateral sclerosis, Parkinson's Huntington's are discussed depth. Current clinical trials mitochondria-targeting discussed.

Language: Английский

Citations

79
Metformin decelerates aging clock in male monkeys DOI
Yuan‐Han Yang,

Xiaoyong Lu,

Ning Liu

et al.

Cell, Journal Year: 2024, Volume and Issue: 187(22), P. 6358 - 6378.e29

Published: Sept. 12, 2024

Language: Английский

Citations

49
Ferroptosis regulation through Nrf2 and implications for neurodegenerative diseases DOI Creative Commons
Yao Xiang, Xiaohua Song,

Dingxin Long

et al.

Archives of Toxicology, Journal Year: 2024, Volume and Issue: 98(3), P. 579 - 615

Published: Jan. 24, 2024

Abstract This article provides an overview of the background knowledge ferroptosis in nervous system, as well key role nuclear factor E2-related 2 (Nrf2) regulating ferroptosis. The takes Alzheimer's disease (AD), Parkinson's (PD), Huntington's (HD), and amyotrophic lateral sclerosis (ALS) starting point to explore close association between Nrf2 ferroptosis, which is clear significant importance for understanding mechanism neurodegenerative diseases (NDs) based on oxidative stress (OS). Accumulating evidence links pathogenesis NDs. As progresses, damage antioxidant excessive OS, altered expression levels, especially inhibition by lipid peroxidation inhibitors adaptive enhancement signaling, demonstrate potential clinical significance detecting identifying targeted therapy neuronal loss mitochondrial dysfunction. These findings provide new insights possibilities treatment prevention

Language: Английский

Citations

28
Electroacupuncture attenuates ferroptosis by promoting Nrf2 nuclear translocation and activating Nrf2/SLC7A11/GPX4 pathway in ischemic stroke DOI Creative Commons

Xichen Yang,

Ying Jin,

Rong Ning

et al.

Chinese Medicine, Journal Year: 2025, Volume and Issue: 20(1)

Published: Jan. 4, 2025

Abstract Objective Electroacupuncture has been shown to play a neuroprotective role following ischemic stroke, but the underlying mechanism remains poorly understood. Ferroptosis key in injury process. In present study, we wanted explore whether electroacupuncture could inhibit ferroptosis by promoting nuclear factor erythroid-2-related 2 (Nrf2) translocation. Methods The stroke model was established middle cerebral artery occlusion/reperfusion (MCAO/R) adult rats. These rats have randomly divided into EA + MCAO/R group, Brusatol group (the inhibitor of Nrf2), and DMSO Sham group. received intervention 24 h after modeling for 7 consecutive days. behavioral function evaluated Neurologic severity score (NSS), Garcia score, Foot-fault Test, Rotarod Test. infarct volume detected TTC staining, neuronal damage observed Nissl staining. levels Fe 2+ , reactive oxygen species (ROS), superoxide dismutase (SOD), malondialdehyde (MDA) were measured ELISA. immunofluorescence Western blotting used detect expression Total Nrf2, p-Nrf2, Nuclear Cytoplasmic essential proteins, including glutathione peroxidase 4 (GPX4), solute carrier family member 11 (SLC7A11) ferritin heavy chain 1 (FTH1). mitochondria transmission electron microscopy (TEM). Results improved neurological deficits MCAO/R, decreased brain volume, alleviated damage, inhibited ROS, MDA accumulation, increased SOD levels, GPX4, SLC7A11 FTH1, rescued injured mitochondria. Especially, found that up-regulated promoted phosphorylation Nrf2 translocation, However, reversed effect electroacupuncture. Conclusion can alleviate I/R injury-induced It is expected these data will provide novel insights mechanisms protecting against potential targets stroke. Graphical

Language: Английский

Citations

3
The Regulatory Effect of Phytochemicals on Chronic Diseases by Targeting Nrf2-ARE Signaling Pathway DOI Creative Commons
Wenjiang He, Chenghao Lv, Zhong Chen

et al.

Antioxidants, Journal Year: 2023, Volume and Issue: 12(2), P. 236 - 236

Published: Jan. 20, 2023

Redox balance is essential to maintain the body’s normal metabolism. Once disrupted, it may lead various chronic diseases, such as diabetes, neurodegenerative cardiovascular inflammatory cancer, aging, etc. Oxidative stress can cause or aggravate a series of pathological processes. Inhibition oxidative and related processes help ameliorate these which have been found be associated with Nrf2 activation. activation not only regulate expression antioxidant genes that reduce its damage, but also directly above-mentioned counter corresponding changes. Therefore, targeting has great potential for prevention treatment many natural phytochemicals reported activators although defined mechanisms remain elucidated. This review article focuses on possible mechanism by in diseases regulation stress. Moreover, current clinical trials phytochemical-originated drug discovery Nrf2-ARE pathway were summarized; outcomes relationship between are finally analyzed propose future research strategies prospective.

Language: Английский

Citations

39
Procyanidin B2: A promising multi-functional food-derived pigment for human diseases DOI
Junren Chen, Kexin Zhong, Yiqi Jing

et al.

Food Chemistry, Journal Year: 2023, Volume and Issue: 420, P. 136101 - 136101

Published: April 7, 2023

Language: Английский

Citations

39
GSK3: A potential target and pending issues for treatment of Alzheimer's disease DOI Creative Commons
Jiahui Zhao, Mengying Wei,

Min‐Song Guo

et al.

CNS Neuroscience & Therapeutics, Journal Year: 2024, Volume and Issue: 30(7)

Published: July 1, 2024

Abstract Glycogen synthase kinase‐3 (GSK3), consisting of GSK3α and GSK3β subtypes, is a complex protein kinase that regulates numerous substrates. Research has observed increased GSK3 expression in the brains Alzheimer's disease (AD) patients models. AD neurodegenerative disorder with diverse pathogenesis notable cognitive impairments, characterized by Aβ aggregation excessive tau phosphorylation. This article provides an overview GSK3's structure regulation, extensively analyzing its relationship factors. overactivation disrupts neural growth, development, function. It directly promotes phosphorylation, amyloid precursor (APP) cleavage, leading to formation, or indirectly triggers neuroinflammation oxidative damage. We also summarize preclinical research highlighting inhibition activity as primary therapeutic approach for AD. Finally, pending issues like lack highly specific affinity‐driven inhibitors, are raised expected be addressed future research. In conclusion, represents target treatment, filled hope, challenges, opportunities, obstacles.

Language: Английский

Citations

13
Interplay among Oxidative Stress, Autophagy, and the Endocannabinoid System in Neurodegenerative Diseases: Role of the Nrf2- p62/SQSTM1 Pathway and Nutraceutical Activation DOI Creative Commons
Federica Armeli, Beatrice Mengoni, Debra L. Laskin

et al.

Current Issues in Molecular Biology, Journal Year: 2024, Volume and Issue: 46(7), P. 6868 - 6884

Published: July 2, 2024

The onset of neurodegenerative diseases involves a complex interplay pathological mechanisms, including protein aggregation, oxidative stress, and impaired autophagy. This review focuses on the intricate connection between stress autophagy in disorders, highlighting as pivotal disease pathogenesis. Reactive oxygen species (ROS) play dual roles cellular homeostasis regulation, with disruptions redox signaling contributing to neurodegeneration. activation Nrf2 pathway represents critical antioxidant mechanism, while maintains by degrading altered cell components. interaction among p62/SQSTM1, Nrf2, Keap1 forms regulatory essential for response, whose dysregulation leads aggregate accumulation. Targeting Nrf2-p62/SQSTM1 holds promise therapeutic intervention, mitigating preserving functions. Additionally, this explores potential synergy endocannabinoid system neuroprotection. Further research is needed elucidate involved molecular mechanisms develop effective strategies against

Language: Английский

Citations

12
Inhibition of MST1 ameliorates neuronal apoptosis via GSK3β/β-TrCP/NRF2 pathway in spinal cord injury accompanied by diabetes DOI Creative Commons
Weijun Huang,

Depeng Wu,

Chaoyang Cai

et al.

Redox Biology, Journal Year: 2024, Volume and Issue: 71, P. 103104 - 103104

Published: Feb. 28, 2024

Spinal cord injury (SCI) is a devastating neurological disease that often results in tremendous loss of motor function. Increasing evidence demonstrates diabetes worsens outcomes for patients with SCI due to the higher levels neuronal oxidative stress. Mammalian sterile 20-like kinase (MST1) key mediator stress central nervous system; however, mechanism its action still not clear. Here, we investigated role MST1 activation induced both and diabetes. Diabetes was established mice by diet induction combined intraperitoneal injection streptozotocin (STZ). performed at T10 level through weight dropping. Advanced glycation end products (AGEs) were applied mimic diabetic conditions PC12 cell line vitro. We employed HE, Nissl staining, footprint assessment Basso mouse scale evaluate functional recovery after SCI. Moreover, immunoblotting, qPCR, immunofluorescence protein-protein docking analysis used detect mechanism. Regarding vivo experiments, resulted up-regulation MST1, excessive apoptosis weakened function mice. Furthermore, impeded NRF2-mediated antioxidant defense neurons damaged spinal cord. Treatment AAV-siMST1 could restore properties facilitate reactive oxygen species (ROS) clearance, which subsequently promoted survival improve locomotor recovery. In vitro model found AGEs worsened mitochondrial dysfunction increased cellular While inhibition chemical inhibitor XMU-MP-1 or MST1-shRNA infection restored NRF2 nuclear accumulation transcription downstream enzymes, therefore preventing ROS generation. However, these effects reversed knockdown. Our in-depth studies showed over-activation directly hindered neuroprotective AKT1, fostered ubiquitination degradation via GSK3β/β-TrCP pathway. significantly restores preexisting diabetes, largely attributed GSK3β(Ser 9)/β-TrCP/NRF2 may be promising pharmacological target effective treatment

Language: Английский

Citations

10