Nephrotoxicity and carcinogenesis of aristolochic acids and their derivates

Aristolochic acids （AAs）, a natural mixture of 8-methoxy-6-nitro-phenanthro-（3,4-d）-1,3-dioxolo-5-carboxylic acid （AAI）and 6-nitro-phenanthro-（3,4-d）-1,3-dioxolo-5-carboxylic acid （AAII）, derived from aristolochiaceae species, has beenreported to cause AAS-induced nephropathy and upper urothelial cancer. In this review, we summarize the informationon the nephrotoxicity and carcinogenesis of AAs and their derivatives. AAs nephrotoxicity can lead to apoptosis andoxidative stress of renal tubular cells, and inhibition of the expression of aquaporins. AAs can also reduce the capabilityfor renal tubular epithelial cell repair after acute injury and further produce renal fibrosis by activating TGF-β-Smadsignaling and promoting the migration of macrophages. Moreover, AAs-induced carcinogenesis may be due to theformation of covalent adducts with DNA which can lead to the mutation in certain tumor suppressor genes orproto-oncogenes and the different catalyzing capacity of the microsomal cytochrome P450 of individuals in AAImetabolism.

Mechanism prediction analysis of an epidemic prevention sachet in preventing new coronavirus pneumonia

Objective:To explore the prevention mechanism of an anti-epidemic sachet on the new coronavirus pneumonia(COVID-19)based on the network pharmacology and molecular docking method.Methods:The chemical constituents and action targets of wormwood leaves,white peony,borneol,Rhizoma atracylodis,and Herba pogostemonis in the epidemic-preventive sachet were retrieved in TCMSP database.Query the genes of targets through the Uniprot database,and then use Cytoscape 3.7.2 software to build a medicinal drugs-active ingredients-targets(genes)network for visualization.Then we used DAVID to perform gene ontology(GO)function enrichment analysis and genome encyclopedia(KEGG)pathway analysis to predict the mechanisms of action.Draw histograms and bubble charts for visualization with Excel software and Omicshare database.The crystal structure of ACE2 was searched in the RCSB PDB database,and the compounds and proteins were molecularly docked with the help of PyMOL,AutoDockTool,and Vina software.Results:Sixty-seven effective chemical components in the anti-epidemic sachet were screened and a drugs-chemical components-targets network was constructed to obtain 948 targets,and 18 core targets and 28 core target pathways were predicted.6 compounds in Folium artemisiae argyi,13 compounds in Radix angelicae dahuricae,3 compounds in Rhizoma atracylodis,4 compounds in Fructus tsaoko,8 compounds in Herba pogostemonis,and 3 compounds in Rhizoma acori talarinowii have less binding energy with 1R42 than the ligand.Conclusion:It is predicted that the anti-epidemic sachet has prevention effects on new coronavirus pneumonia.