Based on network pharmacology and molecular docking to explore the mechanism of Achyranthis bidentate radix in the treatment of Renal cell carcinoma

Abstract

Background: Renal cell carcinoma (RCC) is a common malignant tumor of the urinary system.The incidence rate was increasing year by year, which has become a worldwide health problem. Achyranthis bidentate radix（ABR) is a traditional Chinese medicine that has been commonly reported on the prevention and treatment of RCC. However, the detailed mechanism of ABR is unclear. Therefore, this study aims to explore the possible molecular mechanism of ABR in the treatment of RCC based on network pharmacology and molecular docking.Methods: The main active compounds of ABR were obtained from pharmacology analysis platform of the Chinese Medicine System (TCMSP). The targets of ABR active compounds were obtained from TCMSP and Swiss Target Prediction. The targets of RCC were then screened in the Gene Cards and Online Mendelian Inheritance in Man (OMIM). The network of “medicine-ingredients-disease-targets” was established employing network pharmacology, and the key targets and core pathways were determined by R analysis. The molecular docking method was used to evaluate the binding activity between the target and the active compounds of ABR.Results: Twenty active compounds were found from ABR and are involving in 164 targets. The results of network analysis indicated that the targets mainly involve biological processes such as active oxygen metabolism, oxidative stress, cell proliferation, and apoptosis. ABR was able to treat RCC through regulating AGE-RAGE, PI3K-Akt, MAPK, JAK-STAT, NF-KB, and other major signaling pathways. Quercetin, baicalein, kaempferol had a strong binding to the target proteins of and MAPK1, AKT1, HSP90AA1.Conclusion: Flavonoids in ABR may be the material basis for its treatment of RCC. The mechanisms of action were through regulating active oxygen metabolism, inhibiting oxidative stress, cell proliferation, activating tumor cell apoptosis pathway, regulating protein kinase activity and nuclear receptor Activity, etc.