The protective effect of Dogwood preparation on hepatic ischemia-reperfusion injury in mice by down-regulating PTGS2

Hepatic ischemia - reperfusion injury (HIRI) is a major cause of postoperative complications and mortality after hepatobiliary surgery, but there is currently no effective treatment strategy. Dogwood is a valuable Chinese Medicine which helps to protect the liver. Our animal experiments showed that ethanol extract (DD) of Dogwood could significantly lower the levels of Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) in HIRI mice serum. The findings revealed that DD had protective effect against HIRI in mice. Furthermore, we used network pharmacology to screen 613 target genes corresponding to Loganin, Ursolic acid and Oleanolic acid of the main active components contained in DD and 1117 target genes corresponding to HIRI, with 87 common target genes among them. The STRING database was then used to generate a protein-protein interaction (PPI) dataset of 87 target genes, which was then imported into Cytoscape3.7.2 to generate the top 10 target genes using the MCC function of cytoHubba. Next, using the DAVID online database, 87 target genes were assigned to 35 KEGG pathways. Pathways in cancer had 17 target genes with the highest score. The top 10 target genes identified by MCC function were cross-referenced with 17 target genes identified by Pathways in cancer. HSP90AA1, MAPK3, PTGS2, MMP2, IL2, PPARG, MTOR and IL6 were identified as target genes. In the meantime, transcriptomic sequencing was performed, and a total of 165 differential genes between drug administration group and HIRI group were identified. At last PTGS2 is locked as the hub target gene of DD intervention in HIRI. Following that, immunohistochemistry and real-time fluorescence quantitative PCR were used to verify the results. The results showed that DD protected mice against HIRI by lowering the expression level of PTGS2. In conclusion, DD may protect the mice against HIRI by regulation of PTGS2 expression.