Exploring the Anti-aging Mechanism of Gallic Acid on Caenorhabditis elegans Based on Network Pharmacology

Objective: To explore the anti-aging effect of gallic acid on Caenorhabditis elegans through network pharmacological methods. Methods: The nematodes were treated with different concentrations of gallic acid, and their natural lifespan, stress resistance, locomotor activity, antioxidant enzyme activity, and malondialdehyde (MDA) content were observed in both the treated and control groups to investigate the anti-aging effect of gallic acid on nematodes. Drug targets were obtained from the Pharmmapper and Swisstargetprediction databases, while aging targets were retrieved from the Genecards database. The PPI (Protein-Protein Interaction) network was constructed using the STRING database and Cytoscape. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analyses were performed using the DAVID database and the Microarray Bioinformatics platform. Molecular docking validation was conducted using AutoDock to explore the anti-aging mechanism of gallic acid. Results: Compared to the control group, the treated group exhibited varying degrees of improvement in the survival of nematodes under natural conditions. The nematodes in the treated group also enhanced survival abilities under ultraviolet radiation, oxidative stress, and high temperature conditions. Furthermore, the activities of superoxide dismutase (SOD) and catalase (CAT) within the nematodes were increased, while the content of malondialdehyde (MDA) was decreased. Additionally, the PPI network revealed that AKT1, MMP9, SRC, PIK3R1, and HSP90AA1 might be key targets of gallic acid in its anti-aging effect. Analysis of the KEGG pathways showed that most of the relevant targets were enriched in cancer pathways and metabolic pathways, suggesting that these two pathways were closely related to the anti-aging process of gallic acid. The results of molecular docking validation indicated that the docking effect between gallic acid and these key targets was relatively good. Conclusion: Gallic acid exhibits relatively good anti-aging effects on Caenorhabditis elegans, and its anti-aging action may be mediated through its interaction with the aforementioned five key targets, regulating metabolic pathways and cancer pathways, thereby exerting its anti-aging effects.