Network Pharmacology and Bioinformatics of Flavonoids from Scutellaria baicalensis stems: Mitigating Aβ-Induced Cognitive Impairment in Rats via the MEK-ERK-CREB Pathway.

Introduction: This study investigates the effects and mechanisms of Scutellaria baicalensis flavonoids (SSF) on passive avoidance learning and memory deficits induced by composite amyloid-β proteins (Aβ) via the MEK-ERK-CREB signaling pathway in rats based on network pharmacology and bioinformatics.

Methods: Network pharmacology and bioinformatics identified target pathways. An Alzheimer's disease model was induced in male wistar rats using Aβ_25-35, AlCl₃, and RHTGF-β₁(referred to as compound Aβ). Memory impairment was confirmed with the Morris water maze. Modeled rats were assigned to a control group and three SSF-treated groups for 33 days. Passive avoidance learning abilities were assessed with a step-down test, and p-crebser133 expression in the hippocampus was detected via immunohistochemistry. Real-time qPCR and western blotting measured mRNA and protein levels of c-Raf, MEKs, Rsk, and zif268 in the hippocampus and cortex.

Results: Pathways such as the calcium signaling pathway, Apelin signaling pathway and cAMP signaling pathway were highlighted by KEGG analysis. The model had an 83.30% success rate. Model rats showed dry coats and unresponsiveness, while SSF treatment improved appearance and behavior. In passive avoidance tests, model rats made more errors and had shorter latencies (P < 0.01). They also showed decreased p-CREBSer133 and increased c-Raf, Rsk, and P-MEKs levels (P < 0.01), with reduced Zif268 (P < 0.01). SSF reversed these effects, enhancing p-CREBSer133 and Zif268 while regulating c-Raf, Rsk, and P-MEKs (P < 0.01).

Conclusion: SSF ameliorates learning and memory impairments induced by composite Aβ, acting through the MEK-ERK-CREB pathway in rats.