Objective To explore the potential mechanism of Zhizi Dahuang Decoction in the prevention and treatment of liver injury based on network pharmacology.

Methods The chemical constituents of each herb in Zhizi Dahuang Decoction were retrieved from the databases and then subjected to preliminary screening; the potential action targets of Zhizi Dahuang Decoction and the therapeutic targets for liver injury were collected. After taking the intersection, the composition-target interaction was analyzed, the protein-protein interaction (PPI) network was constructed, and the key target genes were screened. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were carried out to determine the key action targets and pathways of Zhizi Dahuang Decoction in the treatment of liver injury. Finally, the binding activity of key constituents to key targets was assessed by molecular docking.

Results A total of 71 phytochemical components were identified as potential active components from Zhizi Dahuang Decoction. A total of 47 intersection targets were generated after 341 disease-related targets were intersected with 138 compound targets. After further screening, seven key target genes of Zhizi Dahuang Decoction in the treatment of liver injury were obtained, including tumor necrosis factor (TNF), heme oxygenase-1 (HMOX1), interleukin-6 (IL6), mitogen-activated protein kinase 8 (MAPK8), prostaglandin intra peroxidase synthase 2 (PTGS2), and heat shock protein 90 alpha family class A member 1 (HSP90AA1) and Caspase 3 (CASP3). GO and KEGG pathway analysis showed that Zhizi Dahuang Decoction could reduce the level of lipid peroxidation in the liver and increase the level of antioxidant enzymes, thereby exerting an anti-oxidative stress effect; it could also play an anti-inflammatory effect by inhibiting the TNF signaling pathway. The molecular docking results showed that the three key active components in the Zhizi Dahuang Decoction had a very high binding activity to the key proteins(emodin-TNF, aloe emodin-HSP90AA1, obakunone-CASP3).

Conclusion Zhizi Dahuang Decoction could exert its medicinal effect on liver injury by inhibiting oxidative stress, inflammatory response and hepatocyte apoptosis.