Abstract:

Drug-induced liver injury (DILI) is one of the most common adverse drug reactions. Therefore, using computational biology and artificial intelligence modeling to explore the material basis and mechanisms underlying adverse drug reactions from traditional Chinese medicine compounds is of great significance in enhancing the safety of clinical medication. In this study, we retrieved the chemical composition and target information of Compound Polygonum multiflorum and Rehmannia glutinosa Pills (CPRP), along with DILI-related targets. A CPRP-DILI protein-protein interaction network containing 362 nodes and 1 518 interactions was constructed based on this information. Gene ontology analysis indicated that in terms of molecular function CPRP-DILI primarily involves reactions to chemical substances, chemical stimuli, and organic compounds. Cellular components are primarily localized to the extracellular region, plasma membrane, and cell surface. The biological processes of CPRP-DILI involve the binding of enzymes, proteins, small molecules, and signaling receptors. Kyoto encyclopedia of genes and genomes signaling pathway analysis revealed the involvement of the PI3K-Akt and MAPK signaling pathways. The key miRNAs in the miRNA regulatory network include hsa-mir-34a-5p and has-mir-155-5p. The HubGenes of the two core subnetworks include AKT1, CTNNB1, MAPK3, HIF1A, JUN, TP53, and STAT3. The clinical drugs associated with DILI include antitumor drugs, nonsteroidal anti-inflammatory drugs (NSAIDs), and immunosuppressants. Fourteen high-risk DILI compounds were predicted to be present in CPRP, including emodin, rhein, and gallic acid. The chemical components in CPRP may affect certain biological pathways in susceptible populations, interfering with hepatic angiogenesis and autophagy balance, thereby impeding liver repair processes and exacerbating liver injury. The chemical compounds may also exhibit cross-hepatotoxicity with pyrimidine-containing antitumor drugs, NSAIDs, and immunosuppressants, suggesting that caution is needed when co-administering CPRP with the aforementioned drugs in clinical settings.

Key words: drug-induced liver injury, Polygonum multiflorum, Compound Polygonum multiflorum and Rehmannia glutinosa Pills, computational biology, angiogenesis