Iron homeostasis and ferroptosis in human diseases: mechanisms and therapeutic prospects

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Окт. 14, 2024

Iron, an essential mineral in the body, is involved numerous physiological processes, making maintenance of iron homeostasis crucial for overall health. Both overload and deficiency can cause various disorders human diseases. Ferroptosis, a form cell death dependent on iron, characterized by extensive peroxidation lipids. Unlike other kinds classical unprogrammed death, ferroptosis primarily linked to disruptions metabolism, lipid peroxidation, antioxidant system imbalance. Ferroptosis regulated through transcription, translation, post-translational modifications, which affect cellular sensitivity ferroptosis. Over past decade or so, diseases have been as part their etiology, including cancers, metabolic disorders, autoimmune diseases, central nervous cardiovascular musculoskeletal Ferroptosis-related proteins become attractive targets many major that are currently incurable, some regulators shown therapeutic effects clinical trials although further validation potential needed. Therefore, in-depth analysis its molecular mechanisms may offer additional strategies prevention treatment. In this review, we discuss significance contribution etiology development along with evidence supporting targeting approach. Importantly, evaluate recent promising interventions, providing guidance future targeted treatment therapies against

Язык: Английский

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The Role of Quercetin, a Flavonoid in the Management of Pathogenesis Through Regulation of Oxidative Stress, Inflammation, and Biological Activities

Biomolecules, Год журнала: 2025, Номер 15(1), С. 151 - 151

Опубликована: Янв. 20, 2025

Quercetin, a flavonoid found in vegetables and fruits, has been extensively studied for its health benefits disease management. Its role the prevention of various pathogenesis well-documented, primarily through ability to inhibit oxidative stress, inflammation, enhance endogenous antioxidant defense mechanisms. Electronic databases such as Google Scholar, Scopus, PubMed, Medline, Web Science were searched information regarding quercetin pathogeneses. The included literature comprised experimental studies, randomized controlled trials, epidemiological studies related quercetin, while editorials, case analyses, theses, letters excluded. It reported have wide range including hepatoprotective, antidiabetic, anti-obesity, neuroprotective, cardioprotective, wound healing, antimicrobial, immunomodulatory effects, achieved modulation biological activities. Additionally, numerous vitro vivo shown that quercetin’s efficacies cancer management involve inhibiting cell signaling pathways, cycle, angiogenesis, activating pathways tumor suppressor genes, inducing apoptosis. This review aims provide comprehensive understanding this outlines sources nanoformulations, applications management, along with key findings from important clinical trial studies. Limited data safety mechanism action are available. is conduct more trials gain deeper disease-preventive potential, mechanisms action, safety, optimal therapeutic dosages. Furthermore, research based on nanoformulations should be performed minimize/overcome hindrance associated bioavailability, rapid degradation, toxicity.

Язык: Английский

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Electroacupuncture suppresses neuronal ferroptosis to relieve chronic neuropathic pain

Journal of Cellular and Molecular Medicine, Год журнала: 2024, Номер 28(7)

Опубликована: Март 20, 2024

Growing evidence supports the analgesic efficacy of electroacupuncture (EA) in managing chronic neuropathic pain (NP) both patients and NP models induced by peripheral nerve injury. However, underlying mechanisms remain incompletely understood. Ferroptosis, a novel form programmed cell death, has been found to be activated during development, while EA shown potential promoting neurological recovery following acute cerebral injury targeting ferroptosis. In this study, investigate detailed mechanism intervention on NP, male Sprague-Dawley rats with constriction (CCI)-induced model received treatment at acupoints ST36 GV20 for 14 days. Results demonstrated that effectively attenuated CCI-induced hypersensitivity mitigated neuron damage loss spinal cord rats. Moreover, reversed oxidative stress-mediated ferroptosis phenotype upregulating reduced expression xCT, glutathione peroxidase 4 (GPX4), ferritin heavy chain (FTH1) superoxide dismutase (SOD) levels, downregulating increased acyl-CoA synthetase long-chain family member (ACSL4), malondialdehyde levels iron overload. Furthermore, immunofluorescence co-staining GPX4 neurons cells CCI Mechanistic analysis unveiled inhibition antioxidant pathway Nrf2 signalling via its specific inhibitor, ML385, significantly countered EA's protective effect against neuronal marginally diminishing effect. These findings suggest may protect inhibiting cord, partially through activation signalling.

Язык: Английский

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Nrf2-Keap1 in Cardiovascular Disease: Which Is the Cart and Which the Horse?

Physiology, Год журнала: 2024, Номер 39(5), С. 288 - 301

Опубликована: Апрель 30, 2024

High levels of oxidant stress in the form reactive species are prevalent circulation and tissues various types cardiovascular disease including heart failure, hypertension, peripheral arterial disease, stroke. Here we review role nuclear factor erythroid 2-related 2 (Nrf2), an important widespread antioxidant anti-inflammatory transcription that may contribute to pathogenesis maintenance diseases. We studies showing downregulation Nrf2 exacerbates autonomic function. Finally, discuss potential for using modulation as a therapeutic strategy diseases dysfunction.

Язык: Английский

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Therapeutic potential of dihydroartemisinin in mitigating radiation‐induced lung injury: Inhibition of ferroptosis through Nrf2/HO‐1 pathways in mice

Immunity Inflammation and Disease, Год журнала: 2024, Номер 12(2)

Опубликована: Фев. 1, 2024

Radiation-induced lung injury (RILI) is a common consequence of thoracic radiation therapy that lacks effective preventative and treatment strategies. Dihydroartemisinin (DHA), derivative artemisinin, affects oxidative stress, immunomodulation, inflammation. It uncertain whether DHA reduces RILI. In this work, we investigated the specific mechanisms action in

Язык: Английский

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Panaxadiol Attenuates Neuronal Oxidative Stress and Apoptosis in Cerebral Ischemia/Reperfusion Injury via Regulation of the JAK3/STAT3/HIF‐1α Signaling Pathway

CNS Neuroscience & Therapeutics, Год журнала: 2025, Номер 31(2)

Опубликована: Фев. 1, 2025

ABSTRACT Background Cerebral ischemic stroke (CIS) is a debilitating neurological condition lacking specific treatments. ischemia/reperfusion injury (CIRI) critical pathological process in CIS. Purpose This study aimed to explore the protective effects of panaxadiol (PD) against oxidative stress‐induced neuronal apoptosis CIS/CIRI and its underlying mechanisms. Method An MCAO mouse model was established investigate therapeutic PD vivo. Network pharmacology molecular docking techniques were used predict PD's anti‐CIS targets. The further validated vitro using oxygen–glucose deprivation/reoxygenation (OGD/R)‐treated HT22 cells. Finally, core targets verified through combined vivo experiments elucidate mechanisms treating Result exhibited significant neuroprotective activity, demonstrated by restoration behavioral performance, reduced infarct volume, decreased mice. analysis identified 24 overlapping target genes between CIS‐related hub genes, PTGS2, SERPINE1, ICAM‐1, STAT3, MMP3, HMOX1, NOS3, associated with HIF‐1α pathway, which may play crucial role effects. Molecular confirmed stable binding these genes. Both that significantly mitigates stress induced CIS/CIRI. Conclusion counteracts modulating JAK3/STAT3/HIF‐1α signaling making it promising agent for

Язык: Английский

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Flavonoids serve as a promising therapeutic agent for ischemic stroke

Brain Research, Год журнала: 2025, Номер unknown, С. 149528 - 149528

Опубликована: Фев. 1, 2025

Язык: Английский

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Roles of Oxidative Stress and Autophagy in Alcohol-Mediated Brain Damage

Antioxidants, Год журнала: 2025, Номер 14(3), С. 302 - 302

Опубликована: Фев. 28, 2025

Excessive alcohol consumption significantly impacts human health, particularly the brain, due to its susceptibility oxidative stress, which contributes neurodegenerative conditions. Alcohol metabolism in brain occurs primarily via catalase, followed by CYP2E1 pathways. Excess metabolized generates reactive oxygen/nitrogen species (ROS/RNS), leading cell injury altering many different Elevated stress impairs autophagic processes, increasing post-translational modifications and further exacerbating mitochondrial dysfunction ER death. The literature highlights that alcohol-induced disrupts autophagy mitophagy, contributing neuronal damage. Key mechanisms include dysfunction, epigenetics, accumulation of oxidatively modified proteins, lead neuroinflammation impaired cellular quality control. These processes are exacerbated chronic exposure, resulting suppression protective pathways like NRF2-mediated antioxidant responses increased changes brain. Alcohol-mediated neurotoxicity involves complex interactions between metabolism, regulation, influenced various factors such as drinking patterns, nutritional status, genetic/environmental factors, highlighting need for molecular studies unravel these develop targeted interventions.

Язык: Английский

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Investigating the Protective Mechanism of the Zha-Chong-Shi-San-Pill Ethanol Extract on Cerebral Stroke Based on Network Pharmacology, Molecular Docking, and In Vitro Experiments

Pharmacognosy Magazine, Год журнала: 2025, Номер unknown

Опубликована: Март 25, 2025

Objectives To study the anti-oxidant effects of traditional Mongolian medicine Zha-Chong-Shi-San-Pill ethanol extract (EEZC) on cerebral stroke for future clinical use. Materials and Methods Active components mechanisms EEZC against were predicted analyzed via ultra-performance liquid chromatography-electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS), network pharmacology, molecular docking. Next, an oxidative damage model was established in bEnd.3 cells using H 2 O to simulate damage. Multiple cellular tests performed verify mechanisms, including cell counting kit-8 (CCK-8), flow cytometry, terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining, enzyme-linked immunosorbent assay (ELISA), Western blotting. Results It found that conferred protection -treated cells. Moreover, vitro experiments revealed increased survival rates suppressed apoptosis reactive oxygen species (ROS) release. reduced levels interleukin-6 (IL-6) MMP-9, interleukin-10 (IL-10), superoxide dismutase (SOD), glutathione (GSH), vascular endothelial growth factor (VEGF), phospho-endothelial nitric oxide synthase (p-eNOS), phospho-phosphatidylinositide 3-kinases (p-pi3k), phospho-protein kinase B (p-AKT). Conclusion These results strongly suggested might protect PI3K/Akt/eNOS signaling pathway.

Язык: Английский

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Apigenin Alleviates Intestinal Ischemia/Reperfusion Injury via Upregulating Nrf2‐Mediated Tight Junction Integrity

Molecular Nutrition & Food Research, Год журнала: 2025, Номер unknown

Опубликована: Март 27, 2025

ABSTRACT Epithelial barrier dysfunction, critically involved in intestinal ischemia/reperfusion (I/R) injury, is significantly regulated by Nrf2‐mediated oxidative stress. Apigenin, a flavonoid commonly found fruits and vegetables with diverse biological properties, has an unclear impact on I/R injury. We hypothesize that apigenin improves dysfunction activating Nrf2 signaling. Thirty rats were randomly divided into five groups to establish model using superior mesenteric artery occlusion. Hypoxia re‐oxygenation (H/R) was developed utilizing Caco‐2 IEC‐6 cells, which exposed hypoxic conditions followed re‐oxygenation. Apigenin protected against mucosal damage suppressing inflammatory cytokines release (TNF‐α, IL‐1β, IL‐6, MPO, p < 0.01), ameliorating stress (MDA, SOD, GSH, GSH‐Px, improving (DAO TEER, 0.01) both vivo vitro, without causing significant changes the corresponding normal controls ( > 0.05). up‐regulated protein expression of Nrf2, HO‐1, tight junction (TJ) proteins 0.01). Furthermore, knockdown abrogated apigenin‐enhanced TJ expression. pretreatment alleviates I/R‐induced through activation upregulation, offering new strategies for preventing or treating I/R‐associated diseases.

Язык: Английский

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