An Integration of Network Pharmacology and Experimental Verification to Investigate the Mechanism of Guizhi to Treat Nephrotic Syndrome

Background: Guizhi has the pharmacological activity of anti-inflammatory. However, the effect mechanism of Guizhi against nephrotic syndrome (NS) remains unclear. A network pharmacological approach with experimental verification in vitro was performed to investigate the potential mechanisms of Guizhi against NS. Methods: Active compounds and potential targets of Guizhi, as well as the related targets of NS were obtained from the public databases. The intersecting targets of Guizhi and NS were obtained through Venny 2.1.0. The key targets and signaling pathways were determined by protein-protein interaction (PPI), genes ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) analysis. And the drug-compound-target-pathway-disease network was constructed with Cytoscape. Molecular docking verification was carried out by AutoDock Vina. Finally, in vitro experiment was performed to verify the anti-NS mechanism of Guizhi. Results: 63 intersecting targets were obtained, and the top 5 key targets mainly involed in NF- Kappa B and MAPK signaling pathway. In the drug-compound-target-pathway-disease network, cinnamaldehyde (CA) was the top one active compound with the highest degree value. The molecular docking showed that the top 5 key targets were of good binding activity with the active components of Guizhi. To in vitro experiment, CA, the main active component of Guizhi, inhibited the secretion of IL-1β, IL-6, TNF-α in LPS challenged RAW264.7 cells, and down regulated the protein expression of NF-κB p65, p-NF-κB p65 and p-p38 MAPK in LPS challenged RAW264.7 cells. Conclusion: CA might be the main active component of Guizhi against NS, and the underlying mechanism might mainly be achieved by inhibiting NF- Kappa B and MAPK signaling pathway.