Molecular neurobiology, 2024-05, Vol.61 (5), p.2728-2744
2024
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- Autor(en) / Beteiligte
- Titel
- Gastrodin Regulates PI3K/AKT-Sirt3 Signaling Pathway and Proinflammatory Mediators in Activated Microglia
- Ist Teil von
- Molecular neurobiology, 2024-05, Vol.61 (5), p.2728-2744
- Ort / Verlag
- New York: Springer US
- Erscheinungsjahr
- 2024
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Activated microglia and their mediated inflammatory responses play an important role in the pathogenesis of hypoxic-ischemic brain damage (HIBD). Therefore, regulating microglia activation is considered a potential therapeutic strategy. The neuroprotective effects of gastrodin were evaluated in HIBD model mice, and in oxygen glucose deprivation (OGD)-treated and lipopolysaccharide (LPS)activated BV-2 microglia cells. The potential molecular mechanism was investigated using western blotting, immunofluorescence labeling, quantitative realtime reverse transcriptase polymerase chain reaction, and flow cytometry. Herein, we found that PI3K/AKT signaling can regulate Sirt3 in activated microglia, but not reciprocally. And gastrodin exerts anti-inflammatory and antiapoptotic effects through the PI3K/AKT-Sirt3 signaling pathway. In addition, gastrodin could promote FOXO3a phosphorylation, and inhibit ROS production in LPSactivated BV-2 microglia. Moreover, the level P-FOXO3a decreased significantly in Sirt3-siRNA group. However, there was no significant change after gastrodin and siRNA combination treatment. Notably, gastrodin might also affect the production of ROS in activated microglia by regulating the level of P-FOXO3a via Sirt3. Together, this study highlighted the neuroprotective role of PI3K/AKT-Sirt3 axis in HIBD, and the anti-inflammatory, anti-apoptotic, and anti-oxidative stress effects of gastrodin on HIBD.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0893-7648eISSN: 1559-1182DOI: 10.1007/s12035-023-03743-8Titel-ID: cdi_proquest_miscellaneous_2886596846
- Format
- –
- Schlagworte
- 1-Phosphatidylinositol 3-kinase, AKT protein, Animal models, Animals, Apoptosis, Apoptosis - drug effects, Benzyl Alcohols - pharmacology, Biomedical and Life Sciences, Biomedicine, Brain damage, Brain injury, Carotid arteries, Cell Biology, Cell growth, Cell Line, Cytokines, Flow cytometry, Forkhead Box Protein O3 - metabolism, FOXO3 protein, Glucose, Glucosides - pharmacology, Hypoxia, Immunofluorescence, Inflammation, Inflammation - metabolism, Inflammation - pathology, Inflammation Mediators - metabolism, Ischemia, Kinases, Lipopolysaccharides, Lipopolysaccharides - pharmacology, Male, Mice, Mice, Inbred C57BL, Microglia, Microglia - drug effects, Microglia - metabolism, Molecular modelling, Neurobiology, Neurology, Neuroprotection, Neuroprotective Agents - pharmacology, Neurosciences, Oxidative stress, Pathogenesis, Phosphatidylinositol 3-Kinases - metabolism, Phosphorylation, Proteins, Proto-Oncogene Proteins c-akt - metabolism, Reactive Oxygen Species - metabolism, RNA-directed DNA polymerase, Signal transduction, Signal Transduction - drug effects, siRNA, Sirtuin 3 - metabolism, Traumatic brain injury, Tumor necrosis factor-TNF, Western blotting