Mechanism of ASTRAGALI RADIX in Reducing the Nephrotoxicity of Tripterygium Wilfordii Based on Network Toxicology Combined with Network Pharmacology and Experimental Verification?
Objective:Network toxicology was used to screen the nephrotoxic targets of Tripterygium wilfordii.Network pharmacology and molecular docking were used to explore the mechanism of ASTRAGALI RADIX in reducing the nephrotoxicity of Tripterygium wilfordii,and an animal experiment was performed for verification.Methods:The nephrotoxicity-related targets were collected in OMIM,PharmGKB,and GeneCards,and the nephrotoxic targets of Tripterygium wilfordii were searched in the CTD database.Venny2.1.0 was used to take the intersection of nephrotoxic targets of Tripterygium wilfordii.TCMSP,ETCM,and literature were searched to collect the chemical components of ASTRAGALI RADIX.The action targets of the chemical components of ASTRAGALI RADIX were collected by Swiss Target Prediction.The intersection targets of ASTRAGALI RADIX interfering with the nephrotoxicity of Tripterygium wilfordii were obtained by Venny2.1.0.The network map was constructed by Cytoscape 3.9.1.GO function and KEGG pathway were enriched by Metascape for the intersection targets.Autodock 4.2 was used for molecular docking.According to the predicted results,the experimental verification was carried out,and the serum was detected.In addition,the pathological changes were observed,and the path in KEGG analysis was verified.Results:A total of 46 chemical components of ASTRAGALI RADIX,425 nephrotoxic targets of Tripterygium wilfordii,and 83 potential targets of ASTRAGALI RADIX interfering with Tripterygium wilfordii nephrotoxicity were collected.The enrichment analysis suggested that the common targets were involved in bioengineer-ing,such as the response of cells to chemical stress,cell migration,and cell movement.KEGG signaling pathway was mainly enriched in AGE-RAGE,HIF-1,C-type lectin receptor,IL-17,PI3K/AKT,and other signaling pathways after exclusion of extensive pathways.The PPI results showed that AKT1,IL6,and VEGFA might be the core targets of ASTRAGALI RADIX interfering with Tripterygium wilfordii nephro-toxicity,in which AKT1 was the most important core target.The results of traditional Chinese medicine-component-target-pathway showed that isorhamnetin,huperzine,kaempferol,quercetin,3-hydroxy-9,and 10-dimethoxypyrantel might be the core components of ASTRAGALI RADIX in interfering with the nephrotoxicity of Tripterygium wilfordii.The molecular docking results showed that after the core targets were bound with core components of ASTRAGALI RADIX,they all had good binding activity with AKT1.The results of animal experiments indicated that acute renal injury occurred in the model control group.The serum contents of SCr and BUN were significantly increased (P<0.01).Triptery-gium wilfordii water extract significantly down-regulated the mRNA expressions of PI3K and AKT,while combined with ASTRAGALI RADIX water extract,the mRNA expressions of PI3K and AKT were up-regulated.Conclusion:Core components of ASTRAGALI RADIX may act on the core targets of AKT1,and they may interfere with the nephrotoxicity of Tripterygium wilfordii by regulating the PI3K/AKT pathway.
ASTRAGALI RADIXTripterygium wilfordiiNetwork Toxicology Combined with Network PharmacologyMechanism of nephro-toxicity
NETL
NSTL
万方数据
