Cynaroside improved depressive-like behavior in CUMS mice by suppressing microglial inflammation and ferroptosis

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 173, P. 116425 - 116425

Published: March 14, 2024

Depression is a common mental health disorder, and in recent years, the incidence of various forms depression has been on rise. Most medications for are highly dependency-inducing can lead to relapse upon discontinuation. Therefore, novel treatment modalities therapeutic targets urgently required. Traditional Chinese medicine (TCM) offers advantages owing its multi-target, multi-dimensional approach that addresses root cause by regulating organ functions balancing Yin Yang, with minimal side effects. Cynaroside (CNS), an extract from traditional herb honeysuckle, flavonoid compound antioxidant properties. In this study, network pharmacology identified 44 potential CNS associated several correlated inflammatory signaling pathways. alleviated LPS-induced M1 polarization release factors BV-2 cells. Transcriptomic analysis validation revealed reduced polarization, lipid peroxidation, ferroptosis via IRF1/SLC7A11/GPX4 pathway. vivo experiments showed had effects similar those fluoxetine (FLX). It effectively ameliorated anxiety-, despair-, anhedonia-like states chronic unpredictable mild stress (CUMS)-induced mice microglial activation hippocampus. Thus, we conclude exerts effect inhibiting cells polarizing into phenotype reducing inflammation levels. This study provides further evidence antidepressant, offering new avenues depression.

Language: Английский

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Current Trends on the Involvement of Zinc, Copper, and Selenium in the Process of Hepatocarcinogenesis

Nutrients, Journal Year: 2024, Volume and Issue: 16(4), P. 472 - 472

Published: Feb. 6, 2024

Numerous nutritional factors increase the risk of hepatocellular carcinoma (HCC) development. The dysregulation zinc, copper, and selenium homeostasis is associated with occurrence HCC. impairment these essential trace elements results in oxidative stress, DNA damage, cell cycle progression, angiogenesis, finally leading to hepatocarcinogenesis. These can affect microenvironment carrier proteins for zinc copper selenium-containing enzymes play important roles prevention or progression enhance alleviate chemosensitivity anticancer agents patients may other each other. Novel types death including ferropotosis cupropotosis are also Therapeutic strategies HCC that target have been developed vitro vivo studies. use zinc-, copper- selenium-nanoparticles has considered as novel therapeutic indicate become promising targets clinical application an urgent unmet requirement. This review article highlights correlation between development summarizes current trends on pathogenesis

Language: Английский

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Targeting ferroptosis: a new therapeutic opportunity for kidney diseases

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: July 3, 2024

Ferroptosis is a form of non-apoptotic regulated cell death (RCD) that depends on iron and characterized by the accumulation lipid peroxides to lethal levels. involves multiple pathways including redox balance, regulation, mitochondrial function, amino acid, lipid, glycometabolism. Furthermore, various disease-related signaling also play role in regulating process oxidation. In recent years, with emergence concept ferroptosis in-depth study its mechanisms, closely associated biological conditions related kidney diseases, organ development, aging, immunity, cancer. This article reviews development ferroptosis, mechanisms (including GSH-GPX4, FSP1-CoQ1, DHODH-CoQ10, GCH1-BH4, MBOAT1/2 pathways), latest research progress involvement diseases. It summarizes diseases within frameworks metabolism, reactive oxygen biology, biology. The introduces key regulatory factors as well important concepts major open questions natural compounds. hoped future research, further breakthroughs can be made understanding regulation mechanism utilizing promote treatments for such acute injury(AKI), chronic disease (CKD), diabetic nephropathy(DN), renal carcinoma. paves way new approach prevent, treat clinical

Language: Английский

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CD4 T cell-secreted IFN-γ in Sjögren's syndrome induces salivary gland epithelial cell ferroptosis

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Journal Year: 2024, Volume and Issue: 1870(4), P. 167121 - 167121

Published: March 11, 2024

Language: Английский

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Ferroptosis in Cancer Therapy: Mechanisms, Small Molecule Inducers, and Novel Approaches

Drug Design Development and Therapy, Journal Year: 2024, Volume and Issue: Volume 18, P. 2485 - 2529

Published: June 1, 2024

Abstract: Ferroptosis, a unique form of programmed cell death, is initiated by an excess iron accumulation and lipid peroxidation-induced damage. There growing body evidence indicating that ferroptosis plays critical role in the advancement tumors. The increased metabolic activity higher levels tumor cells make them particularly vulnerable to ferroptosis. As result, targeted induction becoming increasingly promising approach for cancer treatment. This review offers overview regulatory mechanisms ferroptosis, delves into mechanism action traditional small molecule inducers their effects on various In addition, latest progress inducing using new means such as proteolysis-targeting chimeras (PROTACs), photodynamic therapy (PDT), sonodynamic (SDT) nanomaterials summarized. Finally, this discusses challenges opportunities development ferroptosis-inducing agents, focusing discovering targets, improving selectivity, reducing toxic side effects. Keywords: inducers, molecules, PROTACs, PDT, SDT,

Language: Английский

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Different types of cell death and their interactions in myocardial ischemia–reperfusion injury

Cell Death Discovery, Journal Year: 2025, Volume and Issue: 11(1)

Published: March 5, 2025

Myocardial ischemia-reperfusion (I/R) injury is a multifaceted process observed in patients with coronary artery disease when blood flow restored to the heart tissue following ischemia-induced damage. Cardiomyocyte cell death, particularly through apoptosis, necroptosis, autophagy, pyroptosis, and ferroptosis, pivotal myocardial I/R injury. Preventing death during of vital for improving ischemic cardiomyopathy. These multiple forms can occur simultaneously, interact each other, contribute complexity In this review, we aim provide comprehensive summary key molecular mechanisms regulatory patterns involved these five types We will also discuss crosstalk intricate interactions among mechanisms, highlighting interplay between different death. Furthermore, explore specific molecules or targets that participate pathways elucidate their action. It important note manipulating distinct processes may have significant impact on reducing By enhancing researchers' understanding injury, review aims pave way development novel interventions cardio-protection affected by

Language: Английский

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Iron and Targeted Iron Therapy in Alzheimer’s Disease

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(22), P. 16353 - 16353

Published: Nov. 15, 2023

Alzheimer’s disease (AD) is the most common neurodegenerative worldwide. β-amyloid plaque (Aβ) deposition and hyperphosphorylated tau, as well dysregulated energy metabolism in brain, are key factors progression of AD. Many studies have observed abnormal iron accumulation different regions AD which closely correlated with clinical symptoms AD; therefore, understanding role brain major pathological aspects critical for its treatment. This review discusses main mechanisms recent advances involvement above processes, including iron-induced oxidative stress-dependent non-dependent directions, summarizes hypothesis that dysregulation may be an initiating factor AD, based on available evidence, further therapeutic perspectives targeting iron.

Language: Английский

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Manganese overexposure results in ferroptosis through the HIF-1α/p53/SLC7A11 pathway in ICR mouse brain and PC12 cells

Ecotoxicology and Environmental Safety, Journal Year: 2024, Volume and Issue: 279, P. 116481 - 116481

Published: May 23, 2024

Manganese (Mn) overexposure has been associated with the development of neurological damage reminiscent Parkinson's disease, while underlying mechanisms have yet to be fully characterized. This study aimed investigate leading injury in dopaminergic neurons induced by Mn and identify novel treatment approaches. In vivo vitro models, ICR mice neuron-like PC12 cells were exposed Mn, respectively. We treated them anti-ferroptotic agents ferrostatin-1 (Fer-1), deferoxamine (DFO), HIF-1α activator dimethyloxalylglycine (DMOG) inhibitor LW6. also used p53-siRNA verify mechanism Mn-induced neurotoxicity. Fe concentrations increased brains overexposed Mn. Additionally, Mn-exposed exhibited movement impairment encephalic pathological changes, decreased HIF-1α, SLC7A11, GPX4 proteins p53 protein levels. Fer-1 protective effects against both behavioral biochemical changes. Consistently, vitro, exposure caused ferroptosis-related changes levels, all ameliorated Fer-1. Upregulation DMOG alleviated Mn-associated ferroptosis, LW6 exacerbated neurotoxicity through downregulating HIF-1α. knock-down rescued ferroptosis without altering expression. resulted neurons, mediated HIF-1α/p53/SLC7A11 pathway.

Language: Английский

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Ferroptosis and myocardial ischemia-reperfusion: mechanistic insights and new therapeutic perspectives

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: Oct. 1, 2024

Myocardial ischemia-reperfusion injury (MIRI) is a significant factor in the development of cardiac dysfunction following myocardial infarction. Ferroptosis, type regulated cell death driven by iron and marked lipid peroxidation, has garnered growing interest for its crucial involvement pathogenesis MIRI.This review comprehensively examines mechanisms ferroptosis, focusing on regulation through metabolism, VDAC signaling, antioxidant system dysregulation. We also compare ferroptosis with other forms to highlight distinct characteristics. Furthermore, MIRI examined focus recent discoveries concerning ROS generation, mitochondrial impairment, autophagic processes, ER stress, non-coding RNA regulation. Lastly, emerging therapeutic strategies that inhibit mitigate are reviewed, providing new insights into potential clinical applications.

Language: Английский

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Tungsten-based polyoxometalate nanoclusters as ferroptosis inhibitors modulating S100A8/A9-mediated iron metabolism pathway for managing intracerebral haemorrhage

Journal of Nanobiotechnology, Journal Year: 2025, Volume and Issue: 23(1)

Published: Feb. 19, 2025

Intracerebral haemorrhage (ICH) is a devastating neurological disorder with high morbidity and mortality rates, largely owing to the lack of effective therapeutic strategies. Growing evidence has underscored pivotal role ferroptosis in intracerebral haemorrhage, its contribution neuronal death exacerbation brain injury, thus establishing it as crucial target for intervention. In recent years, polyoxometalate nanoclusters (NCs) have been applied various neurodegenerative diseases, demonstrating neuroprotective effects. However, their impact on iron content function following ICH yet be reported. Here, we explored potential tungsten-based (W-POM) NCs inhibitors targeting metabolic pathway mediated by S100A8/A9 treatment ICH. We successfully synthesized ultra-small reduced W-POM that can rapidly cross blood-brain barrier are cleared through kidney. vitro experiments demonstrated exhibit significant stable ROS scavenging activity while effectively alleviating overload associated damage. vivo, restored metabolism homeostasis, suppressed neuroinflammation oxidative stress, ultimately severe damage motor deficits mice. Proteomic combined bioinformatic analyses identified two core genes, S100A8 S100A9, most intervention Further confirmed act modulating toll-like receptor 4/hepcidin/ferroportin signaling pathway, thereby regulating reducing secondary injury. This study pioneers application polyoxometalates offering novel promising approach management ferroptosis-related injuries.

Language: Английский

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