Active components and molecular mechanisms of Sagacious Confucius’ Pillow Elixir to treat cognitive impairment based on systems pharmacology

Background: Sagacious Confucius’ Pillow Elixir (SCPE) is a common clinical prescription to treat cognitive impairment (CI) in East Asia. Objective: To predict the active components of SCPE, identify the associated signaling pathway, and explore the molecular mechanism using systems pharmacology and an animal study. Methods: Systems pharmacology and Python programming language-based molecular docking were used to select and analyze the active components and targets. Senescence-accelerated prone 8 mice were used as a CI model. The molecular mechanism was evaluated using the water maze test, neuropathological observation, cerebrospinal fluid microdialysis, and Western blotting. Results: Thirty active components were revealed by screening relevant databases and performing topological analysis. Additionally, 376 differentially expressed genes for CI were identified. Pathway enrichment analysis, protein–protein interaction (PPI) network analysis and molecular docking indicated that SCPE played a crucial role in modulating the PI3K/Akt/mTOR signaling pathway, and 23 SCPE components interacted with it. In the CI model, SCPE improved cognitive function, increased the levels of the neurotransmitter 5-hydroxytryptamine (5-HT) and metabolite 5-hydroxyindole acetic acid (5-HIAA), ameliorated pathological damage and regulated the PI3K/AKT/mTOR signaling pathway. SCPE increased the LC3-II/LC3-I, p-PI3K p85/PI3K p85, p-AKT/AKT, and p-mTOR/mTOR protein expression ratios and inhibited P62 expression in the hippocampal tissue of the CI model. Conclusion: Our study revealed that 23 active SCPE components improve CI by increasing the levels of the neurotransmitter 5-HT and metabolite 5-HIAA, suppressing pathological injury and regulating the PI3K/Akt/mTOR signaling pathway to improve cognitive function.