Network Toxicological Analysis and Verification of Liver Injury Induced by Dioscorea Bulbifera L.

OBJECTIVE To predict the toxicological effects and mechanisms of Dioscorea bulbifera L. causing liver damage by the network toxicology method, and verify the prediction results through animal experiments. METHODS TCMSP combined with TOXNET was used to screen the toxic components of Dioscorea bulbifera L. that caused liver damage, and the Pharm Mapper database was used to predict the target of the toxic components of Dioscorea bulbifera L.. Gene Cards and CTD were used to screen liver damage targets, and Cytoscape software was used to construct a network of "toxic components-targets" and "toxic components-liver damage targets" of Dioscorea bulbifera L.. The STRING database was used to construct a protein interaction network and analyze the key targets of Dioscorea bulbifera L. induced liver damage. Pathway enrichment analysis was performed on the targets of Dioscorea bulbifera L. induced liver damage through the DAVID platform. The mechanism of Dioscorea bulbifera L. induced liver damage was verified through animal experiments. RESULTS The 63 components of Dioscorea bulbifera L. were obtained through TCMSP. The TOXNET website screened out 8 toxic components of Dioscorea bulbifera L. that caused liver damage. The key targets of Dioscorea bulbifera L. caused liver damage were Akt1, INS, VEGFA. Its mechanism included many signal pathways, such as PI3K/Akt, HIF-1, Ras, Rap1, etc. The results of animal experiments showed that decoction of Dioscorea bulbifera L. could increase serum ALT, AST and ALP levels, increase the content of MDA in liver tissue and decrease SOD and GSH activities. Dioscorea bulbifera L. could reduce p-Akt and p-PI3K protein expression in liver. CONCLUSION The liver damage caused by Dioscorea bulbifera L. is the result of multiple signal pathways through multiple components and multiple targets. It is related to the reduction of the PI3K/Akt signal pathway in liver tissue.