Exploring the pharmacodynamic substance basis of Ginseng-Polygala-Poria-Cervi Cornu compound prescription against Alzheimer’s disease based on HPLC-MS and network pharmacologyOA

Background:As global aging intensifies,the incidence of cognitive disorders,such as Alzheimer’s disease(AD),has significantly increased.This study optimized the classical formula Ginseng and Polygala Formula(RSYZF)to develop the compound GPPC,which is composed of Ginseng Radix et Rhizoma,Poria,Polygalae Radix,Cervi Cornu Pantotrichum,with the aim of enhancing its neuroprotective activity.However,the synergistic mechanisms underlying the combination remain unclear.Methods:GPPC’s chemical composition was identified using UPLC-Q/TOF-MS.Its active components were screened for AD-related targets through network pharmacology,followed by GO and KEGG enrichment analysis.Using a scopolamine-induced memory impairment mouse model,its cognitive-enhancing effects and mechanisms were validated via the Morris water maze,biochemical indicator assays,and Western blot analysis.Results:Fifty-nine chemical constituents were identified from GPPC,including major bioactive components such as ginsenosides Rg1,Re,Rb1,and tenuifolin.Network pharmacology prediction yielded 61 active components and 300 AD-related targets,with core targets including AKT1,TNF,and STAT3.KEGG analysis indicated the PI3K/AKT signaling pathway as a key pathway.Animal experiments demonstrated that GPPC significantly shortened the escape latency in model mice,regulated acetylcholine levels and cholinergic system-related enzyme activities in the brain,and improved oxidative stress status.Western blot results showed that GPPC significantly increased p-PI3K and p-AKT protein expression in hippocampal tissue and modulated apoptosis-related proteins such as Bcl-2,Bax,and cleaved Caspase-3.Conclusion:GPPC exerts neuroprotective effects through multiple targets and pathways via core components such as ginsenosides Rg1,Re,Rb1,and tenuifolin.Its mechanism is closely associated with activating the PI3K/AKT signaling pathway,thereby regulating oxidative stress,the cholinergic system,and apoptosis.This study clarifies the pharmacological basis and underlying mechanisms of GPPC for treating AD,presenting a novel strategy for the creation of innovative anti-AD medications derived from traditional Chinese medicine.