Gypenoside Pretreatment Alleviates the Cerebral Ischemia Injury via Inhibiting the Microglia-Mediated Neuroinflammation.

Publisher: Humana Press Country of Publication: United States NLM ID: 8900963 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1559-1182 (Electronic) Linking ISSN: 08937648 NLM ISO Abbreviation: Mol Neurobiol Subsets: MEDLINE

Original Publication: Clifton, NJ : Humana Press, c1987-

Brain Ischemia*/complications ; Brain Ischemia*/drug therapy ; Brain Ischemia*/metabolism ; Brain Injuries*/metabolism ; Ischemic Stroke*/metabolism; Mice ; Animals ; Neuroinflammatory Diseases ; Microglia/metabolism ; Ischemia/metabolism ; Infarction, Middle Cerebral Artery/complications ; Infarction, Middle Cerebral Artery/drug therapy ; Infarction, Middle Cerebral Artery/metabolism ; Anti-Inflammatory Agents/pharmacology ; Plant Extracts ; Gynostemma

Neuroinflammation is closely related to prognosis in ischemic stroke. Microglia are the main immune cells in the nervous system. Under physiological conditions, microglia participate in clearance of dead cells, synapse pruning and regulation of neuronal circuits to maintain the overall health of the nervous system. Once ischemic stroke occurs, microglia function in the occurrence and progression of neuroinflammation. Therefore, the regulation of microglia-mediated neuroinflammation is a potential therapeutic strategy for ischemic stroke. The anti-inflammatory activity of gypenosides (GPs) has been confirmed to be related to the activity of microglia in other neurological diseases. However, the role of GPs in neuroinflammation after ischemic stroke has not been studied. In this study, we investigated whether GPs could reduce neuroinflammation by regulating microglia and the underlying mechanism through qRT-PCR and western blot. Results showed that GPs pretreatment mitigated blood-brain barrier (BBB) damage in the mice subjected to middle cerebral artery occlusion (MCAO) and improved motor function. According to the results of immunofluorescence staining, GPs pretreatment alleviated neuroinflammation in MCAO mice by reducing the number of microglia and promoting their phenotypic transformation from M1 to M2. Furthermore, GPs pretreatment reduced the number of astrocytes in the penumbra and inhibited their polarization into the A1 type. We applied oxygen and glucose deprivation (OGD) on BV2 cells to mimic ischemic conditions in vitro and found similar effect as that in vivo. At the molecular level, the STAT-3/HIF1-α and TLR-4/NF-κB/HIF1-α pathways were involved in the anti-inflammatory effects of GPs in vitro and in vivo. Overall, this research indicates that GPs are potential therapeutic agents for ischemic stroke and has important reference significance to further explore the possibility of GPs application in ischemic stroke.
(© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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ZR2021MH205 Natural Science Foundation of Shandong Province

Keywords: Gypenoside; Ischemic stroke; MCAO; Neuroinflammation

0 (gypenoside)
0 (Anti-Inflammatory Agents)
0 (Plant Extracts)

Date Created: 20230909 Date Completed: 20240214 Latest Revision: 20240725

20240726

10.1007/s12035-023-03624-0

37688709