Astragaloside IV Attenuates Cerebral Ischemia-Reperfusion Injury via PI3K/Akt/NF-κB Pathway

02 Apr 20264 min read0 viewsJournal Feed

GIST

AimThis study aimed to systematically investigate the therapeutic effects and underlying mechanisms of ASIV against cerebral ischemia-reperfusion injury (CIRI) using an integrated approach combining network pharmacology and experimental validation.MethodsPotential targets of Astragaloside IV (ASIV) were predicted using SwissTargetPrediction, PharmMapper and Comparative Toxicogenomics Database (CTD). Ischemic stroke-related targets were collected from GeneCards, DisGeNET and DrugBank.

Overlapping targets were used to construct a protein-protein interaction (PPI) network via STRING and visualized in Cytoscape. Functional enrichment analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways was performed using DAVID.

The neuroprotective effects of ASIV were evaluated in a mouse model of middle cerebral artery occlusion/reperfusion (MCAO/R), assessing neurological function, infarct volume, blood brain barrier (BBB) integrity, inflammatory markers, and PI3K/Akt/NF-κB pathway activity. In vitro, LPS-stimulated BV-2 microglia were used to examine the effects of ASIV on cell viability, inflammatory cytokine expression, and PI3K/Akt/NF-κB signaling.ResultsNetwork pharmacology analysis identified 166 overlapping targets, and enrichment analysis emphasized the PI3K/Akt pathway as a key mechanism.

Clinical Editorial

Study design and analytical pipeline

Ischemia-related targets were gathered from GeneCards, DisGeNET, and DrugBank.

Functional contexts were explored with GO and KEGG enrichment using DAVID.

The investigation combined network pharmacology with experimental validation to explore astragaloside IV (ASIV) effects on cerebral ischemia-reperfusion injury (CIRI).
Potential ASIV targets were predicted with multiple in silico resources (SwissTargetPrediction, PharmMapper, and CTD).
Overlapping targets formed a protein-protein interaction (PPI) network analyzed in STRING and depicted via Cytoscape.

Key mechanistic signal and in vivo model

Network analyses highlighted multiple overlapping targets, with enrichment underscoring the PI3K/Akt axis as a central mechanism linked to ASIV action.
The in vivo component employed a middle cerebral artery occlusion/reperfusion (MCAO/R) mouse model to assess neuroprotection conferred by ASIV.

Primary outcomes and findings

In LPS-stimulated BV-2 microglia, ASIV also mitigated inflammatory markers.

In MCAO/R mice, ASIV yielded improvements in neurological function, accompanied by reductions in infarct size and neuronal apoptosis.
Blood-brain barrier (BBB) integrity was better preserved, as evidenced by decreased Evans blue leakage and lowered MMP-9 expression, along with restored levels of tight junction proteins ZO-1 and Occludin.
Proinflammatory cytokines were dampened, with reduced mRNA expression of IL-6, IL-1β, and TNF-α observed in vivo.
Anti-inflammatory shifts were noted in vitro, with upregulation of IL-10 and Arg-1 in BV2 cells treated with ASIV.
Mechanistically, ASIV appeared to inhibit NF-κB activation via stimulation of the PI3K/Akt signaling cascade.

Limitations and scope of evidence

The study design integrates predictive network pharmacology with targeted experimental work, but explicit limitations regarding translational applicability or potential off-target effects were not detailed in the provided content.
Some outcomes (e.g., numerical values for infarct size, BBB metrics, and cytokine measurements) are not reported in the synopsis and thus not transcribed here.