Background and objective Hepatic ischemia-reperfusion injury (HIRI) is a key factor leading to complications and poor prognosis after hepatobiliary surgery, but its pathogenesis remains unclear. Hence, it is a very necessary discovery the prevention and treatment methods and pathological mechanism of HIRI.
Methods Our animal experiments indicated that two doses of dogwood alcohol extract (DAX) at 5 g/kg and 2.5 g/kg (crude drug/mouse body mass) could significantly reduce serum alamine aminotransferase (AST) and aspartate aminotransferase (ALT) in HIRI mice. The level of these two transaminases determined the pharmacodynamic effect of DAX on HIRI. Next, we used the results of network pharmacology and transcriptome sequencing to obtain important prevention and cure target genes, and applied molecular docking to simulate receptor and ligand binding. Finally, immunohistochemical method was made use of verifying the results.
Results When the model group vs control group, administration group vs model group, set padj < 0.05, | log2FoldChange | >1.0 filter condition, the intersection between the obtained transcriptome sequencing data set and the network pharmacological target was only heparin-binding epidermal growth factor (HBEGF). Then DockThor online software was applied to make loganin and ursolic acid, small molecular compounds contained in DAX, form complexes with HBEGF active sites through hydrogen bonding to interfere with HIRI. Meanwhile, immunohistochemical test results showed that HBEGF expression decreased in the administration group compared with the model group (*P < 0.05).
Conclusions DAX interferes with the occurrence and development of HIRI by down-regulating HBEGF. Our experimental results not only highlight the advantages of traditional Chinese medicine in treating difficult diseases, but also provide a reference for clinical exploration of new methods to prevent and treat HIRI.
Acknowledgments
Authors thank the Central Laboratory of Tianjin First Central Hos-pital of China for providing the experimental site.
Funding
This work was financially supported by the Health Commission of Tianjin, China (ZC20215).
Conflict of interest
Hongsheng Liu is the editorial board member of Future Integrative Medicine. Other authors declare that they do not have competing interests regarding this publication.
Author contributions
HL conceived the overall idea of this project and completed the simulation experiment of receptor-ligand molecular docking. CG and ZL completed the data mining experiment of network phar-macology and RNA-seq. CG wrote the manuscript and HL cor-rected it. In short, all the authors agreed on the final version of the manuscript.
Ethical statement
The animal study was reviewed and approved by the Animal Ethics Committee of Nankai University (license number: SCXK (Jing) 2014-0004). All animal handling procedures and experimental protocols were performed in accordance with the guidelines for the care and use of laboratory animals as outlined in the “Pharma-cological Experimental Methodology, 3rd Edition” edited by Xu Shuyun. All surgical procedures were conducted under anesthesia induced by pentobarbital sodium, and every effort was made to minimize animal suffering.
Data sharing statement
The data used in support of the findings of this study are available from the corresponding author upon request.
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