Exploring the potential mechanism of Andrographis paniculata compounds against neurodegenerative diseases based on network pharmacology and molecular docking

Abstract

Although research indicates that Andrographis paniculata (A. paniculata) and its bioactive components contribute to the therapeutic potential for Alzheimer's disease (AD) and Parkinson's disease (PD), the underlying mechanism still needs to be better understood. In the present study, the multi-target mechanism of A. paniculata was investigated using integrative research methods, and its potential application in preventing AD and PD was further explored. By using network pharmacology methods such as compound-target and target-pathway networks, 29 active compounds were screened from A. paniculata, resulting in 116 targets for AD and 90 targets for PD. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses uncovered the pathways linking active compounds to AD and PD. These constituents involve multiple pathways, such as the response to drugs, response to lipopolysaccharide (LPS), negative regulation of apoptotic process, synaptic transmission. Molecular docking analysis revealed that wogonin had greater affinity for AD-related targets CYP1B1, PTGS2, and PTGS1, while oroxylin A had great affinity for PD-related targets ADORA1 and NOS2. Additionally, density functional theory calculations conducted on the bioactive compounds indicated that receptor-ligand interactions were the primary contributors to the electronic structure (HOMO, LUMO, HOMO-LUMO energy gap). Furthermore, in vitro experimental data indicated that andropanolide and deoxyelephantopin showed good anti-neuroinflammatory activity and neurotrophic activity, respectively. Overall, A. paniculata combats neurodegenerative diseases through its multi-component, multi-target, and multi-pathway actions. The repurposing and repositioning of traditional herbal medicines hold considerable significance. This study demonstrates that, in addition to its use in treating influenza, the traditional medicine A. paniculata also possesses significant potential in the treatment of neurodegenerative diseases.