Nrf2 signaling pathway: current status and potential therapeutic targetable role in human cancers

Frontiers in Oncology, Год журнала: 2023, Номер 13

Опубликована: Сен. 22, 2023

Cancer is a borderless global health challenge that continues to threaten human health. Studies have found oxidative stress (OS) often associated with the etiology of many diseases, especially aging process and cancer. Involved in OS reaction as key transcription factor, Nrf2 pivotal regulator cellular redox state detoxification. can prevent damage by regulating gene expression antioxidant response elements (ARE) promote process. generated an imbalance promotes accumulation mutations genome instability, thus establishment development different cancers. activation regulates plethora processes inducing proliferation, differentiation death, strongly OS-mediated What’s more, also involved anti-inflammatory effects metabolic disorders, neurodegenerative multidrug resistance. highly expressed multiple body parts digestive system, respiratory reproductive system nervous system. In oncology research, has emerged promising therapeutic target. Therefore, certain natural compounds drugs exert anti-cancer through signaling pathway, blocking pathway reduce some types tumor recurrence rates increase sensitivity chemotherapy. However, Nrf2’s dual role controversial impact cancer are inevitable consideration factors when treating this review, we summarized current biological characteristics its mechanism cells, discussed Keap1/Nrf2/ARE downstream genes, elaborated related pathways such AMPK/mTOR NF-κB. Besides, main target strategies using inhibitors or activators, well possible positive negative were reviewed. It be concluded serves important factor formation development, provides basis for targeted therapy

Язык: Английский

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Ellagic acid ameliorates arsenic-induced neuronal ferroptosis and cognitive impairment via Nrf2/GPX4 signaling pathway

Ecotoxicology and Environmental Safety, Год журнала: 2024, Номер 283, С. 116833 - 116833

Опубликована: Авг. 10, 2024

Язык: Английский

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A Mechanism Study on the Antioxidant Pathway of Keap1-Nrf2- ARE Inhibiting Ferroptosis in Dopaminergic Neurons

Current Molecular Medicine, Год журнала: 2024, Номер 25(1), С. 37 - 44

Опубликована: Янв. 5, 2024

The pathology of Parkinson's disease (PD) indicates that iron deposition exists in dopaminergic neurons, which may be related to the death cellular lipid peroxide. extracellular autophagy adaptor SQSTM1(p62) dopamine (DA) neurons can activate intracellular Keap1-Nrf2-ARE signaling pathway inhibit ferroptosis, has a protective effect on DA neurons. objective this study was investigate mechanism antioxidant against experiment divided into control group (Control group), 1-methyl-4-phenylpyridiniumion (MPP+ Control p62 overexpression (MPP+OV-p62), and no-load OV-P62-NC). inhibitors brusatol ZnPP inhibited activation NF-E2-related factor 2(Nrf2) Heme oxygenase-1(HO-1), respectively, were (MPP+OV-p62+brusatol) (MPP+OV-p62+ZnPP). RT-qPCR used detect transfection efficiency, Cell Counting Kit-8 (CCK8) cell activity. FerroOrange, 2,7-Dichlorodihydrofluorescein diacetate (DCFH-DA), Liperfluo probes iron, reactive oxygen species (ROS), peroxidation (LPO) levels. Western Blotting detected levels Nrf2, HO-1, Kelch-like ECH-associated protein1 (Keap1), their downstream Glutathione peroxidase 4(GPX4) Acyl-CoA synthetase long-chain family member 4(ACSL4). L-Glutathione (GSH) Malondialdehyde (MDA) by GSH MDA kits, verified at level have an (1) results showed compared with group, expression gene significantly increased MPP+OV-p62 groups (p = 0.039), groups, indicating successful =0.002; p=0.008). (2) immunofluorescence probe flow normal contents three kinds MPP+ model =0.001; p <0.001; p<0.001), decreased =0.004). indicated ROS, LPO group. (3) Compared expressions GPX4 =0.007; =0.004; p=0.010), Keap1 ACSL4 MPP+p62 =0.017; =0.005). Nrf2 =0.041; <0.001). kit content < 0.01), 0.01). (P 0.003), 0.001). but Based P62 plasmid, it found plasmid nerve cells activating pathway, thus playing role cells.

Язык: Английский

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The Role of Vitamins in Mitigating the Effects of Various Stress Factors in Pigs Breeding

Animals, Год журнала: 2024, Номер 14(8), С. 1218 - 1218

Опубликована: Апрель 18, 2024

Good practices in farm animal care are crucial for upholding well-being, efficiency, and health. Pigs, like other animals, exposed to various stressors, including environmental, nutritional, chemical, psychological, physiological, metabolic which can disrupt their internal balance compromise well-being. Oxidative stress adversely affect performance, fertility, immunity, leading economic losses farmers. Dietary considerations hugely important attaining these objectives. This paper reviews studies investigating the impact of additional vitamin supplementation on reduction pigs. Vitamin A be beneficial counteracting viral parasitic threats. B a potential solution reproductive issues, but it might also reducing effects inappropriate nutrition. C plays vital role heat or exposure toxins D proves addressing induced mostly by infections weaning, while E has been shown mitigate toxins, stress, transport stress. review highlights benefits dietary antioxidants maintaining pig health, enhancing productivity, adverse stressors. Understanding vitamins nutrition management is optimising welfare production efficiency.

Язык: Английский

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Ellagic acid alleviates DSS–induced ulcerative colitis by inhibiting ROS/NLRP3 pathway activation and modulating gut microbiota in mice

European Journal of Nutrition, Год журнала: 2025, Номер 64(1)

Опубликована: Янв. 7, 2025

Язык: Английский

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Inflammasomes in Alzheimer’s Progression: Nrf2 as a Preventive Target

Antioxidants, Год журнала: 2025, Номер 14(2), С. 121 - 121

Опубликована: Янв. 21, 2025

Current knowledge about Alzheimer’s disease highlights the accumulation of β-amyloid plaques (Aβ1–42) and neurofibrillary tangles composed hyperphosphorylated Tau, which lead to loss neuronal connections. Microglial activation release inflammatory mediators play a significant role in progression pathology. Recent advances have identified involvement inflammasomes, particularly NOD-like receptor NLR family pyrin domain containing 3 (NLRP3), whose promotes proinflammatory cytokines triggers pyroptosis, exacerbating neuroinflammation. Aggregates Aβ1–42 Tau been shown activate these while apoptosis-associated speck-like protein (ASC) components form aggregates that further accelerate Aβ aggregation. Defects autophagic clearance inflammasomes also implicated disease, contributing sustained inflammation. This review explores strategies counteract inflammation Alzheimer’s, emphasizing degradation ASC specks inhibition NLRP3 inflammasome activation. Notably, nuclear factor erythroid 2-related 2 (Nrf2) transcription emerges as promising therapeutic target due its dual mitigating oxidative stress directly inhibiting formation. By reducing inflammasome-driven inflammation, Nrf2 offers potential for addressing neuroinflammatory aspects disease.

Язык: Английский

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The Protective Effect of Ellagic Acid and Its Metabolites Against Organ Injuries: A Mitochondrial Perspective

Food Science & Nutrition, Год журнала: 2025, Номер 13(4)

Опубликована: Апрель 1, 2025

ABSTRACT Mitochondria are essential for maintaining health, and dysfunction of them leads to various diseases. Their role is not limited energy production but serves multiple mechanisms varying from calcium hemostasis, reactive oxygen species production, regulation apoptotic cell death. In recent years, several strategies have been developed preserve mitochondria. Ellagic acid (EA) a polyphenol extracted many plants. The intestinal microflora converts EA urolithins with high bioavailability. exhibit mitochondrial‐protective effects by regulating mitochondrial complexes, sirtuins, mitophagy, antioxidant enzymes. This review highlights the mito‐protective on injuries induced drugs toxic compounds.

Язык: Английский

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Ellagic acid alleviates PM2.5-induced senescence of lung epithelial cells by mediating autophagy

Toxicology Research, Год журнала: 2025, Номер 14(2)

Опубликована: Март 1, 2025

Abstract Fine particulate matter (PM2.5) exposure is significantly linked to lung epithelial cell senescence, and autophagy dysfunction being a key contributor the aging process. Although anti-aging properties of ellagic acid (EA) are well-documented, its specific protective effect on PM2.5-induced senescence still needs be studied in depth. To investigate impacts PM2.5 cells, 16HBE A549 cells were exposed suspension. Additionally, explore potential intervention EA, pretreated with EA before Cell morphology, proliferation, senescence-related markers, senescence-associated secretory phenotype (SASP), autophagy-related markers then assessed. Our results showed that proliferation inhibited induced under exposure. However, pretreatment can improve obstruction flux caused by PM2.5, thereby effectively alleviating senescence. This study reveals mechanism which induces confirms role this

Язык: Английский

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Icariside II Suppresses Ferroptosis to Protect Against MPP+-Induced Parkinson's Disease through Keap1/Nrf2/GPX4 Signaling

The Chinese Journal of Physiology, Год журнала: 2023, Номер 66(6), С. 437 - 445

Опубликована: Ноя. 1, 2023

Parkinson's disease (PD) is recognized as a degenerative and debilitating neurodegenerative disorder. The novel protective role of icariside II (ICS II) plant-derived flavonoid compound in diseases has aroused much attention. Herein, the definite impacts ICS on process PD relevant action mechanism were studied. Human neuroblastoma SK-N-SH cells challenged with 1-methyl-4-phenylpyridinium ion (MPP + ) to construct cell model. MTT assay flow cytometry analysis, respectively, appraised viability apoptosis. Caspase 3 Activity Assay examined caspase activity. Corresponding kits oxidative stress levels. BODIPY 581/591 C11 evaluated lipid reactive oxygen species. Iron Kit assessed iron content. Western blot tested expression apoptosis-, ferroptosis- Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related 2 (Nrf2)/glutathione peroxidase 4 (GPX4) signaling-associated proteins. Molecular docking verified binding Keap1. existing experimental results unveiled that elevated whereas reduced apoptosis, stress, ferroptosis MPP -treated concentration-dependent manner. Furthermore, declined Keap1 while raised Nrf2, heme oxygenase 1, GPX4 expression. In addition, had strong Nrf2 inhibitor ML385 partially abolished suppressive -triggered cells. To summarize, might inhibit -stimulated model, which be due activation Keap1/Nrf2/GPX4 signaling.

Язык: Английский

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New Insight into the Potential Protective Function of Sulforaphene against ROS−Mediated Oxidative Stress Damage In Vitro and In Vivo

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(17), С. 13129 - 13129

Опубликована: Авг. 23, 2023

Sulforaphene (SFE) is a kind of isothiocyanate isolated from radish seeds that can prevent free-radical-induced diseases. In this study, we investigated the protective effect SFE on oxidative-stress-induced damage and its molecular mechanism in vitro vivo. The results cell experiments show alleviate D-gal-induced cytotoxicity, promote cycle transformation by inhibiting production reactive oxygen species (ROS) apoptosis, cells with H2O2-induced oxidative damage. Furthermore, mice D-galactose-induced kidney ROS, malondialdehyde (MDA), 4-hydroxyalkenals (4-HNE) production; protect against stress-induced increasing antioxidant enzyme activity upregulating Nrf2 signaling pathway; inhibit pro-inflammatory factors downregulating expression Toll-like receptor 4 (TLR4)-mediated inflammatory response. conclusion, research shows has effects, providing new perspective for studying anti-aging properties natural compounds.

Язык: Английский

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