Mechanism of Shen Shuai II Recipe against Renal Hypoxia in Chronic Kidney Disease: Based on Network Pharmacology and Molecular Docking Study

Background: Renal hypoxia is prevalent in chronic kidney disease (CKD), and aggravates renal failure. Shen Shuai II Recipe (SSR) is our common herbal formula for the treatment of CKD. However, the molecular mechanism of SSR under the efficacy remains unclear. This study aims to systematically explore the potential mechanism of SSR in the improvement of renal hypoxia in CKD using network pharmacology prediction and molecular docking validation. Methods The bioactive compounds and targets of SSR were mined from TCMSP database and employed to construct compounds-targets network by Cytoscape 3.8.2. The corresponding targets reflecting CKD-associated renal hypoxia were retrieved from GeneCards, OMIM and DrugBank databases. The intersection of compound target and disease target was obtained and imported into STRING database to build a PPI network. Metascape was used for GO and KEGG pathway enrichment analyses on screened coincident targets. We further constructed compounds-targets-pathways network using Cytoscape 3.8.2, and the Autodock was adopted for molecular docking validation on the core active compounds and targets. Results A total of 145 active compounds and 249 targets of SSR were identified. Furthermore, 8 compounds and 10 targets were screened as the key roles in the therapeutic effect of SSR. GO and KEGG analysis showed that the mechanisms of SSR against renal hypoxia in CKD were closely related to the regulation of proliferation, differentiation, apoptosis, inflammation, and oxidative stress through AGE-RAGE, p53, JAK-STAT, HIF-1 as well as IL-1β/c-Myc signaling pathway. The molecular docking results indicated good binding activities of the predicted compounds with targets. Conclusion This study reveals the multi-compounds, multi-targets, and multi-pathways synergistic mechanism of SSR against CKD-associated renal hypoxia, which provides a reference for subsequent basic research of SSR in CKD treatment.