To explore the potential mechanism of a drug pair of Ramulus Uncariae Cum Uncis (RUCU)-Achyranthis Bidentatae Radix (ABR) in the treatment of renovascular hypertension through the network pharmacology and molecular docking technology.

The chemical components and potential targets of RUCU and ABR were obtained by searching the database of Traditional Chinese Medicine Systems Pharmacology (TCMSP). By retrieving the Online Mendelian Inheritance in Man (OMIM) database, human gene proteome database (GeneCards), drug information database (DrugBank), and human disease gene database (DisGeNET), renovascular hypertension-related targets were obtained. By means of the Cytoscape 3.8.2 software, a "component-target-disease" network was established. The STRING platform was used to draw the interaction network of the key target proteins. For the key targets, the gene ontology (GO) database was used for gene protein enrichment analysis, while the Kyoto Encyclopedia of Genes and Genomes (KEGG) was used for signal pathway enrichment analysis. The AutoDock 4.2.3 software was used to verify the molecular docking of 8 active components and 6 core targets of the RUCU-ABR drug pair.

Through the retrieving, 54 active ingredients and 199 potential targets were obtained from the RUCU-ABR drug pair, among which 38 key targets were related to renovascular hypertension. Analysis of the protein-protein interaction network (PPI) showed that IL-6, vascular endothelial growth factor A (VEGFA), matrix metalloproteinase 9 (MMP9), nitric-oxide synthase 3 (NOS3), prostaglandin-endoperoxide synthase 2 (PTGS2), FOS, and heme oxygenase 1 (HMOX1) might be core targets for treatment of renal vascular hypertension with RUCU-ABR drug pair. GO enrichment analysis disclosed cell components (such as endoplasmic reticulum cavity and collagen containing extracellular matrix), molecular functions (such as heme binding and cytokine receptor binding), and biological processes (such as oxidative stress and inflammatory response regulation). KEGG enrichment analysis showed signaling pathways (such as advanced glycation end products, tumor necrosis factor, and hypoxia-inducible factor). Molecular docking found that the absolute value of binding energy of active ingredients such as coptisine and uncarine with NOS3 was relatively high.

Among the active ingredients of RUCU-ABR drug pair for treatment of renal vascular hypertension, coptisine and uncarine could all combine well with NOS3. NOS3 may be the potential target of RUCU-ABR drug pair in treating renal vascular hypertension.