AEBP1 Silencing Protects Against Cerebral Ischemia/Reperfusion Injury by Regulating Neuron Ferroptosis and Microglia M2 Polarization Through PRKCA‐PI3K‐Akt Axis DOI
Yafen Zhang, Yan Li,

Fengli Liu

et al.

Drug Development Research, Journal Year: 2024, Volume and Issue: 85(8)

Published: Dec. 1, 2024

ABSTRACT Cerebral ischemia/reperfusion injury is one of the main causes neuronal damage. Neuron ferroptosis and microglia polarization are considered as critical processes during cerebral ischemia/reperfusion. Adipocyte enhancer‐binding protein 1 (AEBP1) usually acts a transcriptional repressor which involved in various diseases. However, it still remains unknown whether AEBP1 could have important roles regulating neuron injury. The oxygen‐glucose deprivation reperfusion (OGD/R)‐treated cells middle artery occlusion (MCAO)‐treated mice were used vitro vivo models. differentially expressed factors analyzed according to GEO datasets. Relative mRNA expression levels detected by qRT‐PCR western blot analysis. Cell viability was measured CCK‐8 assay. ROS, GSH iron contents using specifical assay kits. CD26 CD206 immunofluorescence Inflammatory cytokines ELISA. association between PRKCA assessed luciferase reporter ChIP analyses. damage TTC staining neurological deficit score. Transcription factor increased OGD/R‐treated HT22 BV2 cells. silencing attenuated OGD/R‐induced cell through increasing viability, GPX4 levels, decreasing ACSL4 levels. knockdown promoted M2 CD206‐positive Arg‐1 level, reducing iNOS, TNF‐α, IL‐1β IL‐6 transcriptionally repressed expression, further regulated PI3K/Akt signaling activation. Inhibition or reversed effects on polarization. downregulation infarct size scores MCAO‐treated mice. mitigated activating signaling, indicating potentially protective action

Language: Английский

Current Advances in the Therapeutic Potential of Scutellarin: Novel Applications, Mechanisms, and Future Challenges. DOI Creative Commons
Great Iruoghene Edo, Alice Njolke Mafe, Patrick Othuke Akpoghelie

et al.

Phytomedicine Plus, Journal Year: 2025, Volume and Issue: unknown, P. 100754 - 100754

Published: Jan. 1, 2025

Language: Английский

Citations

2
Decoding Ischemic Stroke: Perspectives on the Endoplasmic Reticulum, Mitochondria, and Their Crosstalk DOI Creative Commons
Chuxin Zhang, Xin Lan, Qingguo Wang

et al.

Redox Biology, Journal Year: 2025, Volume and Issue: unknown, P. 103622 - 103622

Published: March 1, 2025

Stroke is known for its high disability and mortality rates. Ischemic stroke (IS), the most prevalent form, imposes a considerable burden on affected individuals. Nevertheless, existing treatment modalities are hindered by limitations, including narrow therapeutic windows, substantial adverse effects, suboptimal neurological recovery. Clarifying pathological mechanism of IS prerequisite developing new strategies. In this context, functional disruption mitochondria, endoplasmic reticulum (ER), crosstalk mechanisms between them have garnered increasing attention their contributory roles in progression IS. Therefore, review provides comprehensive summary current pathomechanisms associated with involvement ER mitochondria IS, emphasising Ca2+ destabilization homeostasis, stress, oxidative disordered mitochondrial quality control, transfer. Additionally, article highlights interaction as well mitochondrial-ER contacts (MERCs) that structurally connect ER, aiming to provide ideas references research

Language: Английский

Citations

1
Mechanism of P-Hydroxy Benzyl Alcohol Against Cerebral Ischemia Based on Metabonomics Analysis DOI Open Access
Tian Xiao, Xian Yu, Jie Tao

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(1), P. 317 - 317

Published: Jan. 1, 2025

Stroke is the leading cause of death and disability worldwide, with ischemic stroke accounting for majority these. HBA active ingredient in Gastrodia elata has potential therapeutic effects on central nervous system diseases. In this study, cell model cerebral ischemia was replicated by culture method oxygen-glucose deprivation/reoxygenation, rat vascular dementia established two-vessel occlusion method. Metabolomics technology employed to analyze metabolic changes neurons induced HBA, targets were verified. The protective their mitochondria examined through multiple indicators, related mechanisms can improve post-ischemic cognitive impairment rats, its mechanism regulation choline-activated phospholipase D2/Sirtuin 1/peroxisome proliferator-activated receptor-γ coactivator 1α pathway mitochondrial function reduce autophagic activity maintain homeostasis. It concluded that a effect neuronal damage caused regulating key metabolites signaling pathways, it provides new molecular target treatment ischemia.

Language: Английский

Citations

0
N-acetylserotonin derivative ameliorates hypoxic-ischemic brain damage by promoting PINK1/Parkin-dependent mitophagy to inhibit NLRP3 inflammasome-induced pyroptosis DOI

Fang Fang,

Jiaxin Tang,

Jiaqing Geng

et al.

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 153, P. 114469 - 114469

Published: March 18, 2025

Language: Английский

Citations

0
Baicalin Ameliorates L‐Glutamate‐Induced Hippocampal Oxidative Stress Injury and Apoptosis in Mice by Regulating Nrf2/HO‐1 Signalling Pathway DOI Open Access

Feng Li,

Zishan Huang,

Huiyang Gou

et al.

Basic & Clinical Pharmacology & Toxicology, Journal Year: 2025, Volume and Issue: 136(4)

Published: March 20, 2025

This study aimed to explore the effect and mechanism of baicalin on L-glutamate-induced oxidative stress injury in hippocampus mice. Forty mice were divided into five groups:Sham, model, N-acetyl-L-cysteine (NAC) (BA-7.5 mg/kg BA-15 mg/kg). A model excitatory amino acid toxicity with was induced by injecting L-glutamate lateral ventricle. Drugs administered intraperitoneally post-modelling. Six hours later, behavioural tests performed. Brain lesions observed via HE staining, neuronal apoptosis evaluated using TUNEL staining. The levels superoxide dismutase (SOD) malondialdehyde (MDA) determined biochemical methods. Fluorescent staining employed detect expression reactive oxygen species (ROS). Cytochrome C (CytC) assessed immunohistochemistry. Nrf2, HO-1, SOD2 catalase (Cat) detected qPCR WB. showed that motion distance pain threshold reduced group. MDA, ROS CytC increased, while SOD Cat decreased after modelling. CA3 region exhibited pathological changes, rate TUNEL-positive increased. Baicalin could reverse these especially BA-7.5 mg/kg. can reduce L-glutamate, might be related activation Nrf2/HO-1 pathway.

Language: Английский

Citations

0
Mechanisms Associated with Mitophagy and Ferroptosis in Cerebral Ischemia-reperfusion Injury DOI Creative Commons

Yuping Ma,

X Wang,

Yahui Li

et al.

Journal of Integrative Neuroscience, Journal Year: 2025, Volume and Issue: 24(3)

Published: March 18, 2025

Ischemic stroke (IS) constitutes a major threat to human health. Vascular recanalization by intravenous thrombolysis and mechanical remain the most significant effective methods for relief of ischemia. Key elements these treatments include achieving blood-vessel recanalization, restoring brain-tissue reperfusion, preserving ischemic penumbra. However, in therapeutic goals vascular secondary damage brain tissue from cerebral ischemia-reperfusion injury (CIRI) must also be addressed. Despite advancements understanding pathological processes associated with CIRI, interventions prevent its onset progression are still lacking. Recent research has indicated that mitophagy ferroptosis critical mechanisms development significantly contribute IS CIRI because common targets co-occurrence mechanisms. Therefore, exploring summarizing potential connections between during is crucial. In present review, we mainly focused on mitochondrial autophagy ferroptosis, their interaction, CIRI. We believe data show strong relationship interactive regulation. This information may underpin new approaches prevention treatment subsequent

Language: Английский

Citations

0
Scutellarin: pharmacological effects and therapeutic mechanisms in chronic diseases DOI Creative Commons

Shanshan Nie,

Shan Zhang, Ruipeng Wu

et al.

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

Published: Nov. 7, 2024

Scutellarin (SCU), a flavonoid glucuronide derived from Scutellaria barbata and Erigeron breviscapus , exhibits broad pharmacological effects with promising therapeutic potential in treating various chronic diseases. It has demonstrated efficacy modulating multiple biological pathways, including antioxidant, anti-inflammatory, anti-apoptotic, vasodilatory mechanisms. These protective roles make SCU valuable compound diseases such as cerebrovascular diseases, cardiovascular neurodegenerative disorders, metabolic Despite its multi-targeted effects, faces challenges low bioavailability limited clinical data, which hinder widespread application. Current research supports to prevent oxidative stress, reduce inflammatory responses, enhance cell survival cells rats. However, more comprehensive studies are required clarify molecular mechanisms develop strategies that for use. could emerge potent agent the treatment of complex pathophysiological This review examines current literature on provide understanding activity, action,

Language: Английский

Citations

3
CDC42 Regulates the ERK Pathway to Improve Oxygen‒Glucose Deprivation/Reoxygenation-Induced Neural Oxidative Stress and Apoptosis DOI
Lina Hao, Hongmei Jia, Feifei Wei

et al.

Molecular Neurobiology, Journal Year: 2025, Volume and Issue: unknown

Published: March 4, 2025

Language: Английский

Citations

0
DKS26 Alleviates Ischemia-Reperfusion Injury-Induced Acute Kidney Injury by Stabilizing Vitamin D Receptors to Inhibit the Inflammatory Pathway of NF-κB P65 DOI Open Access
Luqun Liang, Yuanyuan Ruan,

Yu Xiong

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(7), P. 2985 - 2985

Published: March 25, 2025

Acute kidney injury (AKI) is a common critical clinical disease with high morbidity and mortality rates. Ischemia-reperfusion (IR) the main cause of AKI, there no effective treatment or prevention. Therefore, it to screen for therapeutic agents find targets. DKS26 derivative oleanolic acid (OA) optimized bioavailability while retaining anti-inflammatory, antioxidant, anti-apoptotic properties OA. This study aimed investigate effects on AKI its underlying molecular mechanisms. We established an model in vivo vitro observed that had ameliorative effect IR H/R-induced renal tubular epithelial cell reduced oxidative stress, inflammation, apoptosis. Meanwhile, Swiss TargetPrediction AutoDock Vina analysis revealed may interact vitamin D receptors (VDR) through hydrogen bonding, suggesting exert VDR. In this study, we found enhanced stability VDR protein, promoted binding p-NF-κB P65Ser311, entry P65Ser311 into nucleus, inhibited transcription downstream inflammatory genes as well their own expression, thus exerting protective effect. summary, these findings suggest be promising preventive strategy provide theoretical experimental basis treatment.

Language: Английский

Citations

0
AEBP1 Silencing Protects Against Cerebral Ischemia/Reperfusion Injury by Regulating Neuron Ferroptosis and Microglia M2 Polarization Through PRKCA‐PI3K‐Akt Axis DOI
Yafen Zhang, Yan Li,

Fengli Liu

et al.

Drug Development Research, Journal Year: 2024, Volume and Issue: 85(8)

Published: Dec. 1, 2024

ABSTRACT Cerebral ischemia/reperfusion injury is one of the main causes neuronal damage. Neuron ferroptosis and microglia polarization are considered as critical processes during cerebral ischemia/reperfusion. Adipocyte enhancer‐binding protein 1 (AEBP1) usually acts a transcriptional repressor which involved in various diseases. However, it still remains unknown whether AEBP1 could have important roles regulating neuron injury. The oxygen‐glucose deprivation reperfusion (OGD/R)‐treated cells middle artery occlusion (MCAO)‐treated mice were used vitro vivo models. differentially expressed factors analyzed according to GEO datasets. Relative mRNA expression levels detected by qRT‐PCR western blot analysis. Cell viability was measured CCK‐8 assay. ROS, GSH iron contents using specifical assay kits. CD26 CD206 immunofluorescence Inflammatory cytokines ELISA. association between PRKCA assessed luciferase reporter ChIP analyses. damage TTC staining neurological deficit score. Transcription factor increased OGD/R‐treated HT22 BV2 cells. silencing attenuated OGD/R‐induced cell through increasing viability, GPX4 levels, decreasing ACSL4 levels. knockdown promoted M2 CD206‐positive Arg‐1 level, reducing iNOS, TNF‐α, IL‐1β IL‐6 transcriptionally repressed expression, further regulated PI3K/Akt signaling activation. Inhibition or reversed effects on polarization. downregulation infarct size scores MCAO‐treated mice. mitigated activating signaling, indicating potentially protective action

Language: Английский

Citations

0