Effects and Mechanisms of Andrographolide for COVID-19: A Network Pharmacology-Based and Experimentally Validated Study

Objective: This study aimed to elucidate the therapeutic effects and underlying mechanisms of andrographolide against COVID-19 through a network pharmacology approach and experimental validation. Methods: Network pharmacology approaches were employed to elucidate potential targets of andrographolide, investigating their overlap with proteins implicated in SARS-CoV-2 infection. The identified targets underwent further analysis through protein-protein interaction (PPI) mapping, gene ontology (GO) categorization, and pathway enrichment within the framework of the Kyoto Encyclopedia of Genes and Genomes (KEGG). Subsequent molecular docking studies provided insights into the binding dynamics between andrographolide and the relevant protein targets. To validate these findings, a series of experimental procedures were conducted, including cytotoxicity assays, quantitative PCR analyses, and the deployment of a SARS-CoV-2 pseudovirus system, using BEAS-2B lung epithelial cells as a model. Results: Bioinformatics analysis revealed that andrographolide potentially modulates proinflammatory cytokines, JAK-STAT signaling, and antiviral immunity pathways in COVID-19. Molecular docking showed favorable binding interactions between andrographolide and its putative targets. In vitro studies confirmed that andrographolide suppressed the mRNA expression of IL-6, TNF-α, IL-1β, and STAT3 and inhibited pseudovirus entry and infection at pharmacologically relevant concentrations. Conclusion: The findings suggest that andrographolide could be a promising candidate for the treatment of COVID-19 due to its capacity to both inhibit SARS-CoV-2 and modulate harmful inflammation. Our findings highlight the potential therapeutic value of andrographolide in treating COVID-19, warranting further exploration in clinical trials.