Exploring the anti-Alzheimer's disease mechanisms of edible medicinal plant Polygonum cuspidatum by integrating network pharmacology and molecular docking

Alzheimer's disease (AD) is a recognized neurodegenerative disease requiring long-term medication, so it is imperative to develop new drugs that are safe and medicine-food homologous. Previous studies have demonstrated that edible medicinal plant Polygonum cuspidatum possesses substantial neuroprotective properties, while the specific mechanisms through which it operates remain largely unexplored. This study explored the mechanisms by which Polygonum cuspidatum exerts anti-AD effects, utilizing an integration of network pharmacology coupled with molecular docking techniques. Firstly, we screened 456 targets from the 10 active ingredients of Polygonum cuspidatum, with 156 of these targets being relevant to AD. Through topological analysis of these 156 targets, we determined that core targets such as TP53, AKT1, EGFR, IL6, TNF, JUN, IL1B, BCL2, HIF1A, CASP3, MYC, MMP9, PTGS2, CXCL8, and ESR1 play central roles in the against AD of Polygonum cuspidatum. Secondly, it was found that the anti-AD mechanism was closely linked to the PI3K-Akt signaling pathway, a critical component in the regulation of oxidative stress. Thirdly, molecular docking studies indicated that the principal ingredients of Polygonum cuspidatum - quercetin, luteolin, and rhein - exhibit strong binding affinities with the targets MMP9, PTGS2, AKT1, and TNF, establishing them as the main ingredients responsible for its anti-AD properties. Notably, quercetin, luteolin, and rhein demonstrated superior docking affinities compared to other constituents. In summary, these findings suggest that Polygonum cuspidatum may combat AD through various pathways and molecular targets. Polygonum cuspidatum has the potential to alleviate AD symptoms by restoring blood-brain barrier integrity and modulating the PI3K-Akt signaling pathway through its constituents, thereby reducing inflammatory factor activity and mitigating the inflammatory response.