Mechanistic insights into Guizhi Fuzi decoction for lumbar disc herniation: Integrating network pharmacology and bioinformatics approach

The ancient Chinese medical texts have recorded Guizhi Fuzi decoction (GZFZT) as a therapeutic intervention for lumbar disc herniation (LDH), and its clinical efficacy has been validated in medical practice. This research endeavor is specifically designed to delve into and elucidate its precise underlying mechanisms of action, leveraging the sophisticated methodologies of network pharmacology and bioinformatics. In this study, we used the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform to extract active compounds and targets from the traditional Chinese medicine GZFZT. Subsequently, we integrated LDH disease target information from DisGeNET, GeneCards, OMIM, and GEO database. By combining this with drug-effective targets, we screened for common targets. Based on these, we conducted protein-protein interaction network analysis and performed gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses on core targets to explore LDH treatment pathways. Finally, we used molecular docking to evaluate potential targets and compounds, identifying the optimal core protein-compound complex. Our study identified 154 active compounds and 230 corresponding targets of GZFZT. Additionally, we collected a total of 1492 LDH disease targets. Topological analysis of the protein-protein interaction network for common drug-disease targets revealed 6 core targets: TNF, STAT3, MAPK1, IL6, MAPK3, and AKT1. Gene ontology enrichment analysis indicated that the mechanism of action of GZFZT is associated with inflammatory responses, apoptotic processes, and oxidative stress states. Kyoto Encyclopedia of Genes and Genomes enrichment analysis suggested that the mechanism of action of GZFZT is closely related to genes involved in the AGE-RAGE and IL-17 signaling pathways. Molecular docking results demonstrated that the selected compounds exhibit strong binding affinity to the targets, indicating their good biological activity. This study unveils novel insights into the active ingredients, targets, and signaling pathways of Guizhi Fuzi decoction in the treatment of lumbar disc herniation. Furthermore, this study suggests that the 3 bioactive components of Guizhi Fuzi decoction (naringenin, β-sitosterol, and stigmasterol) may exert their therapeutic effects on lumbar disc herniation by specifically targeting MAPK3.