Potential Mechanism of Qinggong Shoutao Pill Alleviates Age-associated Memory Decline in D-Galactose-Injured Mice Based on Network Pharmacology, Molecular Docking, and Experimental Verification Integration Strategy

AbstractBackground Qinggong Shoutao Pill (QGSTW) is extensively used as a traditional medicine to prevent and treat age-associated memory decline. However, its potential therapeutic mechanisms and targets are unclear. Methods Network pharmacology and molecular Docking approach was utilized to identified the main active components of QGSTW, the potential pathway and target of QGSTW effect on memory decline. Age-associated memory impairment of mouse model induced by D-galactose was established to verified the pathway and target of QGSTW effectiveness on memory decline, as shown by behavioral tests, immunofluorescence staining and western blot. Results By retrieving, 206 chemical components were identified in QGSTW. Based on these chemical components, network pharmacology demonstrated that the targets of active components were significantly enriched in the pathways in neuroactive ligand-receptor interaction, cAMP signaling pathway and calcium signaling pathway, which were closely related with signal transduction and chemical synaptic transmission. The interrelationships between common targets were analyzed by PPI network and ten biomarkers were discovered. Ten QGSTW active components were revealed furtherly. The affinity between the top five targets and their corresponding active ingredients was predicted by molecular docking. Finally, experiments showed that QGSTW could upregulate the expression of cAMP signaling pathway related targets PKA, CREB, and synaptic plasticity related proteins GluN1, GluA1, CaMKⅡ-α, c-Fos and SYN, contributing to the recovery of memory decline in D-galactose-injured mice. Conclusions This paper revealed the key nodes of QGSTW effect on anti-memory decline are cAMP signaling pathway and synaptic plasticity.