Sedum sarmentosum Bunge Attenuates Drug-Induced Liver Injury via Nrf2 Signaling Pathway: An Experimental Verification Based on Network Pharmacology Prediction

PURPOSE: Using network pharmacology and in vivo experiments, we investigated the antidrug-induced liver injury components and functional processes of Sedum sarmentosum Bunge (SSBE). METHODS: The effective components, primary active ingredients, and possible target in the therapy of DILI were predicted using network pharmacology and bioinformatics. APAP was inducing the DILI model. In vivo testing of the pharmacodynamic foundation of SSBE in the treatment of DILI was performed. RESULTS: The TCMSP database evaluated five main active components and 299 related targets. In addition, 707 differential genes for DILI were obtained from the DisGeNET database, DigSee database, and OMIM database. 61 related targets were mapped to predict the targets of SSBE acting on DILI. The protein-protein interaction (PPI) core network contained 59 proteins, including IL-β, MARK14, SSP1, and MMP9. These genes are closely related to the Nrf2/ARE signaling pathway, and they may play a key role in the hepatoprotective effect of SSBE. Verification experiment results showed that, in the DILI mouse model, SSBE promoted inflammation diminution and regulation of Nrf2-ARE cascade. SSBE protected normal hepatocyte growth and inhibited apoptosis of normal liver cells induced by APAP. SSBE inhibited the expression of Nrf2 and ARE proteins in the liver tissue of the DILI mouse model in vivo. CONCLUSION: By modulating the Nrf2 signaling pathway, the active components in SSBE may protect against drug-induced liver damage.