Saikosaponin B2 ameliorates depression-induced microglia activation by inhibiting ferroptosis-mediated neuroinflammation and ER stress

Journal of Ethnopharmacology, Journal Year: 2023, Volume and Issue: 316, P. 116729 - 116729

Published: June 3, 2023

Language: Английский

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Biomimetic Remodeling of Microglial Riboflavin Metabolism Ameliorates Cognitive Impairment by Modulating Neuroinflammation

Advanced Science, Journal Year: 2023, Volume and Issue: 10(12)

Published: Feb. 17, 2023

Abstract Neuroinflammation, for which microglia are the predominant contributors, is a significant risk factor cognitive dysfunction. Riboflavin (also known as vitamin B2) ameliorates impairment via anti‐oxidative stress and anti‐inflammation properties; however, underlying mechanisms linking riboflavin metabolism microglial function in remain unclear. Here, it demonstrated that kinase (RFK), critical enzyme metabolism, specifically expressed microglia. An intermediate product of riboflavin, flavin mononucleotide (FMN), inhibited RFK expression regulation lysine‐specific methyltransferase 2B (KMT2B). FMN supplementation attenuated pro‐inflammatory TNFR1/NF‐ κ B signaling pathway, this effect abolished by KMT2B overexpression. To improve limited anti‐inflammatory efficiency free FMN, biomimetic nanoparticle strategy (designated MNPs@FMN) established, penetrated blood brain barrier with enhanced microglial‐targeted delivery efficiency. Notably, MNPs@FMN ameliorated dysfunctional synaptic plasticity lipopolysaccharide‐induced inflammatory mouse model 5xFAD Alzheimer's disease. Taken together, may serve potential therapeutic approach inflammation‐dependent decline.

Language: Английский

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Revitalizing Ancient Mitochondria with Nano‐Strategies: Mitochondria‐Remedying Nanodrugs Concentrate on Disease Control

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(18)

Published: Jan. 15, 2024

Abstract Mitochondria, widely known as the energy factories of eukaryotic cells, have a myriad vital functions across diverse cellular processes. Dysfunctions within mitochondria serve catalysts for various diseases, prompting widespread demise. Mounting research on remedying damaged indicates that constitute valuable target therapeutic intervention against diseases. But less clinical practice and lower recovery rate imply limitation traditional drugs, which need further breakthrough. Nanotechnology has approached favorable regiospecific biodistribution high efficacy by capitalizing excellent nanomaterials targeting drug delivery. Mitochondria‐remedying nanodrugs achieved ideal effects. This review elucidates significance in cells organs, while also compiling mortality data related Correspondingly, nanodrug‐mediate strategies applicable mitochondria‐remedying disease are detailed, with full understanding roles dysfunction advantages nanodrugs. In addition, future challenges directions discussed. conclusion, this provides comprehensive insights into design development nanodrugs, aiming to help scientists who desire extend their fields engage interdisciplinary subject.

Language: Английский

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Biomimetic Nanovesicles as a Dual Gene Delivery System for the Synergistic Gene Therapy of Alzheimer’s Disease

ACS Nano, Journal Year: 2024, Volume and Issue: 18(18), P. 11753 - 11768

Published: April 22, 2024

The association between dysfunctional microglia and amyloid-β (Aβ) is a fundamental pathological event increases the speed of Alzheimer's disease (AD). Additionally, pathogenesis AD intricate single drug may not be enough to achieve satisfactory therapeutic outcome. Herein, we reported facile effective gene therapy strategy for modulation function intervention Aβ anabolism by ROS-responsive biomimetic exosome-liposome hybrid nanovesicles (designated as TSEL). codelivery β-site amyloid precursor protein cleaving enzyme-1 (BACE1) siRNA (siBACE1) TREM2 plasmid (pTREM2) efficiently penetrate blood-brain barrier enhance accumulation at lesions with help exosomes homing ability angiopep-2 peptides. Specifically, an upregulation expression can reprogram from pro-inflammatory M1 phenotype anti-inflammatory M2 while also restoring its capacity phagocytose nerve repair function. In addition, reduces production plaques source knocking out BACE1 gene, which expected further effect AD. in vivo study suggests that TSEL through synergistic two drugs ameliorate APP/PS1 mice cognitive impairment regulating activated microglial phenotype, reducing Aβ, preventing retriggering neuroinflammation. This employs delivery dual nucleic acids, achieving AD, thus offering more options treatment

Language: Английский

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Microglial‐Biomimetic Memantine‐Loaded Polydopamine Nanomedicines for Alleviating Depression

Advanced Materials, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 21, 2025

Abstract Depression is a common psychiatric disorder, and monoamine‐based antidepressants as first‐line therapy remain ineffective in some patients. The synergistic modulation of neuroinflammation neuroplasticity could be major strategy for treating depression. In this study, an inflammation‐targeted microglial biomimetic system, PDA‐Mem@M, reported Microglial membrane‐coated nanoparticles penetrate the blood‐brain barrier facilitate targeting. Subsequently, owing to excellent free radical‐scavenging capacity, PDA‐Mem@M attenuate brain inflammatory microenvironment. After on‐demand release from nanoparticles, memantine increases expression brain‐derived neurotrophic factors reverses loss synaptic dendritic spines. Further, vivo studies demonstrate that effectively alleviate depression‐like behaviors greater extent than or polydopamine (PDA) monotherapy. This strategy, with satisfactory biosafety strong anti‐inflammatory plasticity restoration effects, conducive advances depression therapy.

Language: Английский

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Myocardia‐Injected Synergistically Anti‐Apoptotic and Anti‐Inflammatory Poly(amino acid) Hydrogel Relieves Ischemia‐Reperfusion Injury

Advanced Materials, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 5, 2025

Abstract Reperfusion therapy is the most effective treatment for acute myocardial infarction, but its efficacy frequently limited by ischemia‐reperfusion injury (IRI). While antioxidant and anti‐inflammatory therapies have shown significant potential in alleviating IRI, these strategies not yielded satisfactory clinical outcomes. For that, a thermo‐sensitive myocardial‐injectable poly(amino acid) hydrogel of methoxy poly(ethylene glycol) 45 ‐poly(L‐methionine 20 ‐ co ‐L‐alanine 10 ) (mPEG ‐P(Met ‐Ala ), PMA) loaded with FTY720 (PMA/FTY720) developed to address IRI through synergistic anti‐apoptotic effects. Upon injection into ischemic myocardium, PMA aqueous solution undergoes sol‐to‐gel phase transition gradually degrades response reactive oxygen species (ROS), releasing on demand. acts synergistically inhibit cardiomyocyte apoptosis modulate pro‐inflammatory M1 macrophage polarization toward M2 macrophages clearing ROS, thereby mitigating inflammatory promoting vascular regeneration. In rat model, PMA/FTY720 reduces apoptotic cell ratio 81.8%, increases density 34.0%, enhances left ventricular ejection fraction (LVEF) 12.8%. rabbit gel‐based sustained release enhanced LVEF an additional 7.2% compared individual treatment. summary, engineered effectively alleviates anti‐apoptosis anti‐inflammation actions, offering valuable treating IRI.

Language: Английский

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Hybrid Membrane‐Coated Nanoparticles for Precise Targeting and Synergistic Therapy in Alzheimer's Disease

Advanced Science, Journal Year: 2024, Volume and Issue: 11(24)

Published: April 22, 2024

Abstract The blood brain barrier (BBB) limits the application of most therapeutic drugs for neurological diseases (NDs). Hybrid cell membrane‐coated nanoparticles derived from different types can mimic surface properties and functionalities source cells, further enhancing their targeting precision efficacy. Neuroinflammation has been increasingly recognized as a critical factor in pathogenesis various NDs, especially Alzheimer's disease (AD). In this study, novel membrane coating is designed by hybridizing platelets chemokine (C–C motif) receptor 2 (CCR2) cells are overexpressed to cross BBB target neuroinflammatory lesions. Past unsuccessful endeavors AD drug development underscore challenge achieving favorable outcomes when utilizing single‐mechanism drugs.Two with mechanisms actions into liposomes successfully loaded realize multitargeting treatment. transgenic mouse model familial (5xFAD), administration these drug‐loaded hybrid results significant reduction amyloid plaque deposition, neuroinflammation, cognitive impairments. Collectively, nanomaterials offer new opportunities precise delivery disease‐specific targeting, which represent versatile platform targeted therapy AD.

Language: Английский

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Choline alleviates cognitive impairment in sleep-deprived young mice via reducing neuroinflammation and altering phospholipidomic profile

Redox Biology, Journal Year: 2025, Volume and Issue: 81, P. 103578 - 103578

Published: March 1, 2025

Cognitive impairment resulting from insufficient sleep poses a significant public health concern, particularly in children. The effects and mechanisms of choline on cognitive caused by deprivation are unknown. Chronic is induced young mice this study, followed feeding diet containing 11.36 g/kg bitartrate. Choline supplementation significantly improves spatial learning ability. Functional MRI results reveal the hippocampus as key region affected deprivation, where notably preserves hippocampal structural integrity enhanced connectivity. Additionally, ameliorates pathological injury, reduces blood-brain barrier permeability serum brain injury biomarkers. also inflammation oxidative stress biomarkers, mitigates microglial activation hippocampus, which synaptic plasticity. A finding changes phospholipidomic profile along with function, total 313 phospholipid molecules identified. increases levels sub-classes (particularly PC), strongly correlated reduced neuroinflammation well improved outcomes. Furthermore, there similar findings some such PC 36:1, O-33:0, p-38:3, PE 36:3, p-42:4 PS 44:12. These highlight that alleviates via reducing altering profile. This study suggests could develop into functional food or medicine ingredient to prevent treat disturbances, children adolescents.

Language: Английский

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Associations of prenatal metal exposure with child neurodevelopment and mediation by perturbation of metabolic pathways

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 1, 2025

Prenatal exposure to metals has been associated with impaired neurodevelopment in children, but the detailed molecular mechanisms remain largely unknown. Based on Wuhan Healthy Baby Cohort, China (N = 1088), eleven were measured maternal urine during early pregnancy (13.1 ± 1.1 weeks) and metabolomics profiling was conducted cord blood. Neurodevelopment evaluated using Bayley Scales of Infant Development 2-year-old children obtain mental development index (MDI) psychomotor (PDI). After false discovery rate correction, higher urinary levels manganese, nickel, aluminum, rubidium, gallium, summary score only significantly lower MDI scores. The weighted quantile sum metal mixture showed a significant inverse association PDI scores, aluminum contributing most associations. Histidine, beta-alanine, purine, pyrimidine metabolism mediated above associations, suggesting that disturbances amino acids, neurotransmitter neuroendocrine may be important mediators children. linked underlying are unclear. Here, authors show neurotransmitters, mediate association.

Language: Английский

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Association of vitamin B2 intake with cognitive performance in older adults: a cross-sectional study

Journal of Translational Medicine, Journal Year: 2023, Volume and Issue: 21(1)

Published: Nov. 30, 2023

To scrutinize the relationship between vitamin B2 consumption and cognitive function based on NHANES database.

Language: Английский

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