Ferulic Acid Activates SIRT1-Mediated Ferroptosis Signaling Pathway to Improve Cognition Dysfunction in Wilson’s Disease DOI Creative Commons
Xie Wang, Nan Shao, Xiaoyan Zhang

et al.

Neuropsychiatric Disease and Treatment, Journal Year: 2023, Volume and Issue: Volume 19, P. 2681 - 2696

Published: Dec. 1, 2023

Background: Wilson's disease (WD), an autosomal recessive genetic disease, is characterized by copper metabolism disorder. WD patients may have a series of cognitive deficits in terms neurological symptoms. Ferroptosis (FPT), type programmed cell death, involved the pathological progression various disorders, and silent information regulator 1 (SIRT1) considered to be key factor FPT. Ferulic acid (FA) traditional Chinese medicine monomer, with remarkable effect clinical treatment impairment-related disease. However, its intrinsic on FPT still unclear. This study aims investigate protective FA impairment animal models WD, whether pharmacological mechanism related SIRT1-mediated signaling pathway. Methods: Copper-loaded rats PC12 cells were used as dysfunction vivo vitro, respectively. Morris Water Maze (MWM) was evaluate spatial exploration memory abilities rats. HE staining observe neuronal damage CA1 region rat hippocampus. Immunofluorescence (IF) detect expression GPX4 protein. Transmission electron microscopy (TEM) ultrastructure neurons. The levels Fe2+, MDA, SOD, GSH, 4HNE, ROS detected. Western blot qRT-PCR protein mRNA SIRT1, Nrf2, SCL7A11, GPX4. Results: In copper-loaded model rats, MWM, TEM, IF results showed that could promote repair learning function, improve morphological hippocampal neurons, maintain mitochondria integrity. experiment, MTT method increased viability copper-overloaded models. confirmed significantly proteins addition, reversed oxidative stress-related indicators, including ROS. Conclusion: alleviates injury activating FPT, providing valuable candidate for monomer therapeutics impairment. Keywords: ferulic acid, impairment, ferroptosis,

Language: Английский

A novel anti-atherosclerotic mechanism of quercetin: Competitive binding to KEAP1 via Arg483 to inhibit macrophage pyroptosis DOI Creative Commons
Xing Luo,

Xiuzhu Weng,

Xiaoyi Bao

et al.

Redox Biology, Journal Year: 2022, Volume and Issue: 57, P. 102511 - 102511

Published: Oct. 14, 2022

Natural antioxidants represented by quercetin have been documented to be effective against atherosclerosis. However, the related mechanisms remain largely unclear. In this study, we identified a novel anti-atherosclerotic mechanism of inhibiting macrophage pyroptosis activating NRF2 through binding Arg483 site KEAP1 competitively. ApoE-/- mice fed with high fat diet, administration attenuated atherosclerosis progression reducing oxidative stress level and suppressing pyroptosis. At cellular level, suppressed THP-1 induced ox-LDL, demonstrated NLRP3 inflammasome activation ROS while these effects were reversed specific inhibitor (ML385). Mechanistically, promoted dissociate from KEAP1, enhanced nuclear translocation as well transcription downstream antioxidant protein. Molecular docking results suggested that could bind at Arg415 Arg483. order verify sites, mutated Ser (R415S R483S) was transfected into macrophages, anti-pyroptotic effect abrogated mutation, but not mutation. Furthermore, after adeno associated viral vector (AAV) AAV-KEAP1-R483S, almost abolished in mice. These findings proved quercetins targeting KEAP1/NRF2 interaction, provided reliable data on underlying natural protect

Language: Английский

Citations

71
Quercetin: A promising therapy for diabetic encephalopathy through inhibition of hippocampal ferroptosis DOI
Xin Cheng, Jianhua Huang, Hongli Li

et al.

Phytomedicine, Journal Year: 2023, Volume and Issue: 126, P. 154887 - 154887

Published: May 20, 2023

Language: Английский

Citations

49
Quercetin induces ferroptosis in gastric cancer cells by targeting SLC1A5 and regulating the p-Camk2/p-DRP1 and NRF2/GPX4 Axes DOI

Lixian Ding,

Shuwei Dang, Mingjun Sun

et al.

Free Radical Biology and Medicine, Journal Year: 2024, Volume and Issue: 213, P. 150 - 163

Published: Jan. 6, 2024

Language: Английский

Citations

23
The Interplay between Ferroptosis and Neuroinflammation in Central Neurological Disorders DOI Creative Commons

Yejia Xu,

Bowen Jia,

Jing Li

et al.

Antioxidants, Journal Year: 2024, Volume and Issue: 13(4), P. 395 - 395

Published: March 26, 2024

Central neurological disorders are significant contributors to morbidity, mortality, and long-term disability globally in modern society. These encompass neurodegenerative diseases, ischemic brain traumatic injury, epilepsy, depression, more. The involved pathogenesis is notably intricate diverse. Ferroptosis neuroinflammation play pivotal roles elucidating the causes of cognitive impairment stemming from these diseases. Given concurrent occurrence ferroptosis due metabolic shifts such as iron ROS, well their critical central nervous disorders, investigation into co-regulatory mechanism has emerged a prominent area research. This paper delves mechanisms along with interrelationship. It specifically emphasizes core molecules within shared pathways governing neuroinflammation, including SIRT1, Nrf2, NF-κB, Cox-2, iNOS/NO·, how different immune cells structures contribute dysfunction through mechanisms. Researchers’ findings suggest that mutually promote each other may represent key factors progression disorders. A deeper comprehension common pathway between cellular holds promise for improving symptoms prognosis related

Language: Английский

Citations

17
In defence of ferroptosis DOI Creative Commons
Francesca M. Alves, Darius J.R. Lane,

Triet Phu Minh Nguyen

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: Jan. 2, 2025

Abstract Rampant phospholipid peroxidation initiated by iron causes ferroptosis unless this is restrained cellular defences. Ferroptosis increasingly implicated in a host of diseases, and unlike other cell death programs the physiological initiation conceived to occur not an endogenous executioner, but withdrawal guardians that otherwise constantly oppose induction. Here, we profile key ferroptotic defence strategies including regulation, modulation enzymes metabolite systems: glutathione reductase (GR), suppressor protein 1 (FSP1), NAD(P)H Quinone Dehydrogenase (NQO1), Dihydrofolate (DHFR), retinal reductases dehydrogenases (RDH) thioredoxin (TR). A common thread uniting all metabolites combat lipid during dependence on reductant, nicotinamide adenine dinucleotide phosphate (NADPH). We will outline how cells control central carbon metabolism produce NADPH necessary precursors defend against ferroptosis. Subsequently discuss evidence for dysregulation different disease contexts glucose-6-phosphate dehydrogenase deficiency, cancer neurodegeneration. Finally, several anti-ferroptosis therapeutic spanning use radical trapping agents, dependent redox support highlight current landscape clinical trials focusing

Language: Английский

Citations

2
Quercetin inhibits DNA damage responses to induce apoptosis via SIRT5/PI3K/AKT pathway in non-small cell lung cancer DOI Open Access

Baochen Zhou,

Ye Yang, Xuemeng Pang

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 165, P. 115071 - 115071

Published: June 28, 2023

SIRT5 is a mitochondrial NAD+ -dependent lysine deacylase. Downregulation of has been linked to several primary cancers and DNA damage. In clinical therapy for non-small cell lung cancer (NSCLC), the Feiyiliu Mixture (FYLM) an experience effective Chinese herb prescription. And we found that quercetin important ingredient in FYLM. However, whether regulates damage repair (DDR) induces apoptosis through NSCLC remains unknown. The present study revealed directly binds inhibits phosphorylation PI3K/AKT interaction between PI3K, thus inhibiting process homologous recombination (HR) non-homologous end-joining (NHEJ) NSCLC, which raise mitotic catastrophe apoptosis. Our provided novel mechanism action treatment NSCLC.

Language: Английский

Citations

35
Quercetin Alleviates Acrylamide-Induced Liver Injury by Inhibiting Autophagy-Dependent Ferroptosis DOI
Tongwen Huang, Ke Zhang, Junqiao Wang

et al.

Journal of Agricultural and Food Chemistry, Journal Year: 2023, Volume and Issue: 71(19), P. 7427 - 7439

Published: May 3, 2023

Acrylamide (ACR) generated in carbohydrate-rich foods during thermal processing has been demonstrated to exhibit hepatotoxicity. As one of the most consumed flavonoids with diet, quercetin (QCT) possesses ability protect against ACR-induced toxicity, albeit its mechanism is unclear. Herein, we discovered that QCT alleviated elevated levels reactive oxygen species (ROS), AST, and ALT mice. RNA-seq analysis revealed reversed ferroptosis signaling pathway upregulated by ACR. Subsequently, experiments indicated inhibited through reduction oxidative stress. With autophagy inhibitor chloroquine, further confirmed suppressed inhibiting stress-driven autophagy. Additionally, specifically reacted autophagic cargo receptor NCOA4, blocked degradation iron storage protein FTH1, eventually downregulated intracellular consequent ferroptosis. Collectively, our results presented a unique approach alleviate liver injury targeting QCT.

Language: Английский

Citations

29
Quercetin attenuates cerebral ischemic injury by inhibiting ferroptosis via Nrf2/HO-1 signaling pathway DOI
Caiwang Peng, Qidi Ai, Fengyan Zhao

et al.

European Journal of Pharmacology, Journal Year: 2023, Volume and Issue: 963, P. 176264 - 176264

Published: Dec. 18, 2023

Language: Английский

Citations

25
Recent Advances in the Inhibition of Membrane Lipid Peroxidation by Food-Borne Plant Polyphenols via the Nrf2/GPx4 Pathway DOI
Mengmeng Zhang, Jingbo Liu,

Yiding Yu

et al.

Journal of Agricultural and Food Chemistry, Journal Year: 2024, Volume and Issue: 72(22), P. 12340 - 12355

Published: May 22, 2024

Lipid peroxidation (LP) leads to changes in the fluidity and permeability of cell membranes, affecting normal cellular function potentially triggering apoptosis or necrosis. This process is closely correlated with onset many diseases. Evidence suggests that phenolic hydroxyl groups food-borne plant polyphenols (FPPs) make them effective antioxidants capable preventing diseases triggered by membrane LP. Proper dietary intake FPPs can attenuate oxidative stress, especially damage phospholipids, activating Nrf2/GPx4 pathway. Nuclear factor E2-related 2 (Nrf2) an stress antagonist. The signaling pathway regulated Nrf2 a defense transduction organism against external stimuli such as reactive oxygen species exogenous chemicals. Glutathione peroxidase 4 (GPx4), under regulation Nrf2, only enzyme reduces lipid peroxides specificity, thus playing pivotal role regulating ferroptosis counteracting stress. study explored mechanism, antioxidant activity FPPs, mechanism It also highlighted bioprotective properties LP its associated mechanisms, including (i) activation pathway, GPx4 serving central target protein, (ii) activities, leading reduction production ROS other peroxides, (iii) effects on downstream phospholipid structure. In conclusion, play crucial natural However, further in-depth analysis coregulation multiple pathways required, combined these mechanisms need evaluation experimental models. Human trials could provide valuable insights into new directions for research application.

Language: Английский

Citations

13
Natural product-derived ferroptosis mediators DOI
Yili Chen,

Lin-An Xiong,

Lie‐Feng Ma

et al.

Phytochemistry, Journal Year: 2024, Volume and Issue: 219, P. 114002 - 114002

Published: Jan. 27, 2024

Language: Английский

Citations

12