In this study, we explored the cytoprotective potential of silibinin against oxygen-glucose deprivation (OGD)-induced neuronal cell damages, and studied underling mechanisms. In vitro model of ischemic stroke was created by keeping neuronal cells (SH-SY5Y cells and primary mouse cortical neurons) in an OGD condition followed by re-oxygenation. Pre-treatment of silibinin significantly inhibited OGD/re-oxygenation-induced necrosis and apoptosis of neuronal cells. OGD/re-oxygenation-induced reactive oxygen species (ROS) production and mitochondrial membrane potential (MMP) reduction were also inhibited by silibinin. At the molecular level, silibinin treatment in SH-SY5Y cells and primary cortical neurons led to significant AMP-activated protein kinase (AMPK) signaling activation, detected by phosphorylations of AMPKα1, its upstream kinase liver kinase B1 (LKB1) and the downstream target acetyl-CoA Carboxylase (ACC). Pharmacological inhibition or genetic depletion of AMPK alleviated the neuroprotective ability of silibinin against OGD/re-oxygenation. Further, ROS scavenging ability by silibinin was abolished with AMPK inhibition or silencing. While A-769662, the AMPK activator, mimicked silibinin actions and suppressed ROS production and neuronal cell death following OGD/re-oxygenation. Together, these results show that silibinin-mediated neuroprotection requires activation of AMPK signaling.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bbrc.2014.10.080 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Mechanisms of Autophagy in Ineffective Reperfusion After Ischemic Stroke.
J Neurosci Res
January 2025
Luhe Institute of Neuroscience, Capital Medical University, Beijing, China.
Despite significant advancements in achieving high recanalization rates (80%-90%) for large vessel occlusions through mechanical thrombectomy, the issue of "futile recanalization" remains a major clinical challenge. Futile recanalization occurs when over half of patients fail to experience expected symptom improvement after vessel recanalization, often resulting in severe functional impairment or death. Traditionally, this phenomenon has been attributed to inadequate blood flow and reperfusion injury.
View Article and Find Full Text PDFImpact of LITAF on Mitophagy and Neuronal Damage in Epilepsy via MCL-1 Ubiquitination.
CNS Neurosci Ther
January 2025
Department of Neurology, School of Medicine, Guangzhou First People's Hospital, South China University of Technology, Guangzhou, China.
Objective: This study aims to investigate how the E3 ubiquitin ligase LITAF influences mitochondrial autophagy by modulating MCL-1 ubiquitination, and its role in the development of epilepsy.
Methods: Employing single-cell RNA sequencing (scRNA-seq) to analyze brain tissue from epilepsy patients, along with high-throughput transcriptomics, we identified changes in gene expression. This was complemented by in vivo and in vitro experiments, including protein-protein interaction (PPI) network analysis, western blotting, and behavioral assessments in mouse models.
Parkinsons disease (PD) is considered one of the most frequent neurological diseases in the world. There is a need to study the early and efficient biomarkers of Parkinsons, such as changes in structural disorders like DNA and chromatin, especially at the subcellular level in the human brain. We used two techniques, Partial wave spectroscopy (PWS) and Inverse Participation Ratio (IPR), to detect the changes in structural disorder in the human brain tissue samples.
View Article and Find Full Text PDFNeuroprotective role of sialic-acid-binding immunoglobulin-like lectin-11 in humanized transgenic mice.
Front Neurosci
December 2024
Institute of Reconstructive Neurobiology, Medical Faculty and University Hospital of Bonn, University of Bonn, Bonn, Germany.
Brain aging is a chronic process linked to inflammation, microglial activation, and oxidative damage, which can ultimately lead to neuronal loss. Sialic acid-binding immunoglobulin-like lectin-11 (SIGLEC-11) is a human lineage-specific microglial cell surface receptor that recognizes -2-8-linked oligo-/polysialylated glycomolecules with inhibitory effects on the microglial inflammatory pathways. Recently, the gene locus was prioritized as a top tier microglial gene with potential causality to Alzheimer's disease, although its role in inflammation and neurodegeneration remains poorly understood.
View Article and Find Full Text PDFCombination of tauroursodeoxycholic acid, co-enzyme Q10 and creatine demonstrates additive neuroprotective effects in models of Parkinson's disease.
Front Neurosci
December 2024
The Neuro's Early Drug Discovery Unit (EDDU), McGill University, Montreal, QC, Canada.
This study aimed to evaluate different combinations of three dietary supplements for potential additive or synergistic effects in an Parkinson's Disease model. The complex and diverse processes leading to neurodegeneration in each patient with a neurodegenerative disorder cannot be effectively addressed by a single medication. Instead, various combinations of potentially neuroprotective agents targeting different disease mechanisms simultaneously may show improved additive or synergistic efficacy in slowing the disease progression and allowing the agents to be utilized at lower doses to minimize side effects.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!