The Interplay between Ferroptosis and Neuroinflammation in Central Neurological Disorders

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

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Engeletin alleviates cerebral ischemia reperfusion‐induced neuroinflammation via the HMGB1/TLR4/NF‐κB network

Journal of Cellular and Molecular Medicine, Journal Year: 2023, Volume and Issue: 27(12), P. 1653 - 1663

Published: May 2, 2023

Abstract High‐mobility group box1 (HMGB1) induces inflammatory injury, and emerging reports suggest that it is critical for brain ischemia reperfusion. Engeletin, a natural Smilax glabra rhizomilax derivative, reported to possess anti‐inflammatory activity. Herein, we examined the mechanism of engeletin‐mediated neuroprotection in rats having transient middle cerebral artery occlusion (tMCAO) against reperfusion injury. Male SD were induced using 1.5 h tMCAO, following by 22.5 h. Engeletin (15, 30 or 60 mg/kg) was intravenously administered immediately 0.5 ischemia. Based on our results, engeletin, dose‐dependent fashion, reduced neurological deficits, infarct size, histopathological alterations, edema factors, namely, circulating IL‐1β, TNF‐α, IL‐6 IFN‐γ. Furthermore, engeletin treatment markedly neuronal apoptosis, which, turn, elevated Bcl‐2 protein levels, while suppressing Bax Cleaved Caspase‐3 levels. Meanwhile, significantly reduces overall expressions HMGB1, TLR4, NF‐κB attenuated nuclear transfer factor kappa B (NF‐κB) p65 ischemic cortical tissue. In conclusion, strongly prevents focal via suppression HMGB1/TLR4/NF‐κB network.

Language: Английский

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Engeletin alleviates depression‐like phenotype by increasing synaptic plasticity via the BDNF‐TrkB‐mTORC1 signalling pathway

Journal of Cellular and Molecular Medicine, Journal Year: 2023, Volume and Issue: 27(23), P. 3928 - 3938

Published: Oct. 6, 2023

Abstract Major depressive disorder (MDD) is a severe mental associated with high rates of morbidity and mortality. Current first‐line pharmacotherapies for MDD are based on enhancement monoaminergic neurotransmission, but these antidepressants still insufficient produce significant side‐effects. Consequently, the development novel therapeutic targets desired. Engeletin, natural Smilax glabra rhizomilax derivative, compound proven efficacy in treating ischemic stroke, yet its effects mechanisms depression remain unexplored. The engeletin were assessed forced swimming test (FST) tail suspension (TST) mice. Engeletin was also investigated chronic restraint stress (CRS) mouse model fluoxetine (FLX) as positive control. Changes prefrontal cortex (PFC) spine density, synaptic plasticity‐linked protein expressions brain‐derived neurotrophic factor (BDNF)‐tyrosine kinase B (TrkB)‐ mammalian target rapamycin complex 1 (mTORC1) signalling pathway after treatment then investigated. TrkB mTORC1 selective inhibitors, ANA‐12 rapamycin, respectively, utilized to assess engeletin's antidepressive mechanisms. Our data shows that exhibited antidepressant‐like activity FST TST mice without affecting locomotor activity. Furthermore, it efficiency against CRS model. Moreover, enhanced BDNF‐TrkB‐mTORC1 PFC during altered reduction dendritic density levels induced by CRS. In conclusion, has antidepressant via activation upregulation plasticity.

Language: Английский

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Engeletin attenuates the inflammatory response via inhibiting TLR4-NFκB signaling pathway in Crohn's disease-like colitis

Journal of Ethnopharmacology, Journal Year: 2024, Volume and Issue: 336, P. 118733 - 118733

Published: Aug. 23, 2024

Smilax glabra rhizome has a long history been used for clinical purposes in traditional Chinese medicinal treating various inflammatory conditions. Engeletin

Language: Английский

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Maternal separation stress through triggering of the neuro‐immune response in the hippocampus induces autistic‐like behaviors in male mice

International Journal of Developmental Neuroscience, Journal Year: 2023, Volume and Issue: 84(2), P. 87 - 98

Published: Dec. 18, 2023

Abstract Autism spectrum disorder (ASD) is the fastest‐growing neurodevelopmental disease throughout world. Neuro‐immune responses from prenatal to adulthood stages of life induce developmental defects in synaptic signaling, neurotransmitter imbalance, and even structural changes brain. In this study, we aimed focus on possible role neuroinflammatory response hippocampus development autistic‐like behaviors following maternal separation (MS) stress mice. To do this, mice neonates daily separated their mothers postnatal day (PND) 2 PND 14 for 3 h. During PND45–60, behavioral tests related including three‐chamber sociability, Morris water maze (MWM), shuttle box, resident‐intruder, marble burying were performed. Then, hippocampi dissected out, gene expression inflammatory mediators TNF‐α, IL‐1β, TLR4, HMGB1, NLRP3 was assessed using RT‐PCR. Results showed that MS exerted impaired sociability preference, repetitive behaviors, passive avoidance, spatial memories. The significantly increased We concluded probably via activating HMGB1/TLR4 signaling cascade induced

Language: Английский

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Mechanism of Astragalus mongholicus Bunge ameliorating cerebral ischemia-reperfusion injury: Based on network pharmacology analysis and experimental verification

Journal of Ethnopharmacology, Journal Year: 2024, Volume and Issue: 329, P. 118157 - 118157

Published: April 6, 2024

Language: Английский

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Engeletin alleviates depressive‐like behaviours by modulating microglial polarization via the LCN2/CXCL10 signalling pathway

Journal of Cellular and Molecular Medicine, Journal Year: 2024, Volume and Issue: 28(8)

Published: April 1, 2024

Microglial polarization and associated inflammatory activity are the key mediators of depression pathogenesis. The natural Smilax glabra rhizomilax derivative engeletin has been reported to exhibit robust anti-inflammatory activity, but no studies date have examined mechanisms through which it can treat depressive symptoms. We showed that treatment for 21 days with significantly alleviated depressive-like behaviours in chronic stress social defeat (CSDS) model mice. T1-weighted imaging (T1WI), T2-weighted (T2WI) revealed significant differences between groups, bilateral prefrontal cortex CSDS mice exhibited increases apparent diffusion coefficient T2 values relative normal control mice, a corresponding reduction fractional anisotropy, while reversed all these changes. resulted higher levels IL-1β, IL-6, TNF-a production, enhanced microglial activation, greater M1 concomitant decrease M2 mPFC, whereas effectively abrogated CSDS-related pathological Engeletin was further found suppress LCN2/C-X-C motif chemokine ligand 10 (CXCL10) signalling axis such adeno-associated virus-induced LCN2 overexpression ablated antidepressant effects its beneficial on M1/M2 microglia. In conclusion, alleviate CSDS-induced by regulating LCN2/CXCL10 pathway thereby altering These data suggest correlated microglia, highlighting potential avenue future design strategies specifically target

Language: Английский

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MicroRNA-155 Inhibition Activates Wnt/β-catenin Signaling to Restore Th17/Treg Balance and Protect against Acute Ischemic Stroke

eNeuro, Journal Year: 2025, Volume and Issue: unknown, P. ENEURO.0347 - 24.2024

Published: Jan. 9, 2025

Acute ischemic stroke (AIS) is a dangerous neurological disease associated with an imbalance in Th17/Treg cells and abnormal activation of the Wnt/β-catenin signaling pathway. This study aims to investigate whether inhibition miR-155 can activate pathway improve provide neuroprotective effects against stroke. We employed multi-level experimental design. Firstly, we analyzed differential gene expression between antagomir-treated group control using high-throughput sequencing identify potential target genes. Subsequently, conducted functional enrichment analysis differentially expressed genes bioinformatics tools. Next, performed vivo animal experiments mouse model validate impact antagomir treatment on improvement cell ratios. Lastly, vitro our findings further. High-throughput results showed significant (BioProject: PRJNA1152758, SRA IDs: SRR30410532, SRR30410531, SRR30410530 for group; SRR30410529, SRR30410528, SRR30410527 group). Bioinformatics revealed imbalance. In demonstrated that significantly activated improved vivo, experiment indicated exhibited AIS. demonstrates by activating exhibiting AIS model. These crucial support as therapeutic strategy lay foundation further research. Significance Statement identifies pivotal regulator balance By inhibiting miR-155, demonstrate enhance neuroprotection modulate immune responses, offering promising avenue management. contribute growing understanding molecular mechanisms developing miR-155-targeted therapies.

Language: Английский

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Engeletin Targets Mitochondrial Dysfunction to Attenuate Oxidative Stress and Experimental Colitis in Intestinal Epithelial Cells Through AMPK/SIRT1/PGC-1α Signaling

Antioxidants, Journal Year: 2025, Volume and Issue: 14(5), P. 524 - 524

Published: April 27, 2025

Inflammatory bowel disease (IBD), encompassing Crohn's and ulcerative colitis, is characterized by chronic intestinal inflammation epithelial barrier disruption. Emerging evidence highlights mitochondrial dysfunction as a pivotal contributor to IBD pathogenesis, where impaired homeostasis in cells (IECs) disrupts redox balance, exacerbates oxidative stress, triggers apoptosis, further compromising integrity. This study investigated the therapeutic effects of Engeletin (Eng), dihydroflavonoid from Smilax glabra Roxb., dextran sulfate sodium (DSS)-induced colitis mice colonic organoid models. Eng administration (10, 20, 40 mg/kg) significantly alleviated symptoms, including weight loss, activity index (DAI) scores, colon shortening, while restoring integrity through upregulation tight junction proteins (ZO-1, claudin-1) goblet cell preservation. suppressed NF-κB-mediated activated Nrf2 antioxidant pathway, well reduced stress markers (MDA, CAT, GSH, SOD). It attenuated apoptosis balancing pro- anti-apoptotic (Bax/Bcl2, c-caspase3) ameliorated via enhanced ATP production, mtDNA levels, complex I/IV activity. Mechanistically, AMPK/SIRT1/PGC-1α axis, pharmacological inhibition PGC-1α abolished its protective effects. These findings demonstrate that alleviates targeting signaling, offering multitargeted strategy for therapy.

Language: Английский

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Paeoniflorin as a potential agent for urticaria treatment: Suppressing mast cell degranulation through HMGB1/TLR4/NF-κB signaling inhibition

Molecular Immunology, Journal Year: 2025, Volume and Issue: 183, P. 33 - 43

Published: May 2, 2025

Language: Английский

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