Protective effect of baicalein from Pinellia ternate on Alzheimer's disease cell injury: a network pharmacology, molecular docking, and molecular dynamics study.

INTRODUCTION

Alzheimer's disease (AD) constitutes the primary leading cause of dementia. Pinellia ternata (Thunb.) Breit. is a traditional Chinese herb with unclarified potential therapeutic effects against AD. This study aimed to explore the therapeutic potential and underlying mechanism of Pinellia ternata (Thunb.) Breit. in the treatment of AD.

METHODS

The bioactive components and corresponding targets of Pinellia ternata (Thunb.) Breit. were screened from TCMSP, Herb, and SymMap databases. AD-related targets were retrieved from OMIM, GeneCards, and TTD databases, and key targets were obtained via target intersection analysis. Functional enrichment analyses were performed to identify the main signaling pathways involved in the targets. Core targets and major bioactive components were further screened, and molecular docking as well as dynamics simulations were conducted to verify the binding affinity between key components and core targets. In vitro cell experiments using BV2 cells were implemented to validate the therapeutic effect of the core bioactive component.

RESULTS

A total of 13 bioactive components and 99 corresponding targets of Pinellia ternata (Thunb.) Breit. were identified, and 29 key AD-related targets were screened out through target intersection. Enrichment analysis results showed that these key targets were mainly enriched in neuroactive ligand-receptor interaction and calcium signaling pathways. PTGS2, CASP2, and AKT1 were determined as core therapeutic targets, with β-sitosterol and baicalein identified as the principal bioactive components of Pinellia ternata (Thunb.) Breit. against AD. Molecular docking and dynamics simulations verified the strong binding affinity between baicalein and PTGS2. In vitro experimental results further demonstrated that baicalein pretreatment could relieve the inhibitory effect of Aβ1-42 on BV2 cell proliferation.

DISCUSSION: Pinellia ternata (Thunb.) Breit. exerts therapeutic effects on AD via a synergistic mechanism characterized by multi-component, multi-target, and multi-pathway regulation. The active ingredient baicalein targeting PTGS2 is a crucial material basis for its anti-AD effect. The findings of this study elucidate the potential mechanism of Pinellia ternata (Thunb.) Breit. in AD treatment and provide a reliable theoretical foundation for subsequent in-depth research and clinical exploration of the herb as a therapeutic agent for AD.