Astragaloside's Role in Microglial Neuroinflammation: A Multi-Method Study Combining Experimental and Computational...

Area of Science:

• Neuroscience
• Pharmacology
• Biochemistry

Background:

• Ischemic brain injury, modeled by oxygen-glucose deprivation/reoxygenation (OGD/R), triggers microglial inflammatory responses.
• Microglial metabolic reprogramming plays a critical role in OGD/R-induced inflammatory injury.
• Astragaloside (AST), a compound from Astragalus, is explored for its therapeutic potential.

Purpose of the Study:

• To elucidate the mechanism by which astragaloside (AST) modulates microglial metabolism to alleviate inflammatory injury following OGD/R.
• To investigate AST's effects on microglial polarization and inflammatory mediator release.
• To identify the molecular targets and signaling pathways affected by AST.

Main Methods:

• Cell injury assessed by CCK-8 assay; microglial M1 polarization by flow cytometry.
• Inflammatory markers (TNF-α, IL-1β, IL-10) measured by ELISA and PCR.
• Network pharmacology, molecular docking, Western blotting, and metabolomics used to identify targets and pathways.

Main Results:

• AST significantly reduced OGD/R-induced microglial injury and inflammatory cytokine expression (TNF-α, IL-1β).
• AST inhibited M1 microglial polarization and increased anti-inflammatory IL-10 mRNA.
• Network pharmacology identified SRC, AKT, and mTOR as key targets; AST modulated SRC/AKT pathways and reversed metabolic shifts.

Conclusions:

• Astragaloside mitigates OGD/R-induced inflammatory brain injury by reprogramming microglial metabolism via SRC and AKT signaling.
• AST demonstrates potential as a therapeutic agent for neuroinflammatory diseases like ischemic stroke.