Abstract
Background Qingdu Decoction (QDD) is a traditional Chinese medicine formula for treating chronic liver injury (CLI). Materials and methods. A network pharmacology combining experimental validation was used to investigate potential mechanisms of QDD against CLI. We firstly screened the bioactive compounds with pharmacology analysis platform of the Chinese medicine system (TCMSP) and gathered the targets of QDD and CLI. Then, we constructed a compound-target network and a protein-protein interaction (PPI) network and enriched core targets in Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathways. At last, we used a CLI rat model to confirm the effect and mechanism of QDD against CLI. Enzyme-linked immunosorbent assay (ELISA), western blot (WB), and real-time quantitative polymerase chain reaction (RT-qPCR) were used. Results 48 bioactive compounds of QDD passed the virtual screening criteria, and 53 overlapping targets were identified as core targets of QDD against CLI. A compound-CLI related target network containing 94 nodes and 263 edges was constructed. KEGG enrichment of core targets contained some pathways related to CLI, such as hepatitis B, tumor necrosis factor (TNF) signaling pathway, apoptosis, hepatitis C, interleukin-17 (IL-17) signaling pathway, and hypoxia-inducible factor (HIF)-1 signaling pathway. Three PPI clusters were identified and enriched in hepatitis B and tumor necrosis factor (TNF) signaling pathway, apoptosis and hepatitis B pathway, and peroxisome pathway, respectively. Animal experiment indicated that QDD decreased serum concentrations of alanine aminotransferase (ALT), aspartate aminotransferase (AST), endotoxin (ET), and IL-17 and increased prothrombin time activity (PTA) level. WB and RT-qPCR analyses indicated that, compared with the model group, the expression of cysteinyl aspartate specific proteinase-9 (caspase-9) protein, caspase-3 protein, B-cell lymphoma-2 associated X protein (Bax) mRNA, and cytochrome c (Cyt c) mRNA was inhibited and the expression of B-cell lymphoma-2 (Bcl-2) mRNA was enhanced in the QDD group. Conclusions QDD has protective effect against CLI, which may be related to the regulation of hepatocyte apoptosis. This study provides novel insights into exploring potential biological basis and mechanisms of clinically effective formula systematically.
Highlights
Chronic liver disease (CLD) usually results from iterative liver injury, such as excessive alcohol consumption, viral hepatitis, nonalcoholic fatty liver disease, autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis, and causes approximately 2 million deaths per year worldwide [1]
We focused on the multiple target effect of Qingdu Decoction (QDD) on apoptosis pathway and visualized these target data in a Kyoto Encyclopedia of Genes and Genomes (KEGG) diagram
After KEGG pathway enrichment, we found that cluster 1 was enriched in the hepatitis B and tumor necrosis factor (TNF) signaling pathway, cluster 2 was enriched in the apoptosis and hepatitis B pathway, and cluster 3 was enriched in the peroxisome pathway
Summary
Chronic liver disease (CLD) usually results from iterative liver injury, such as excessive alcohol consumption, viral hepatitis, nonalcoholic fatty liver disease, autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis, and causes approximately 2 million deaths per year worldwide [1]. Evidence-Based Complementary and Alternative Medicine molecular pathways in chronic liver injury would help the development of clinical therapies to prevent or improve the prognosis of CLDs. Traditional Chinese medicine has been around for thousands of years. Ere is increasing evidence that certain Chinese medicine prescriptions have beneficial effects on experimental liver injury [2]. Our previous clinical studies have confirmed that the prescription has a good effect on improving clinical symptoms, protecting liver function, and reducing endotoxin absorption in CLI patients [3, 4]. Qingdu Decoction (QDD) is a traditional Chinese medicine formula for treating chronic liver injury (CLI). KEGG enrichment of core targets contained some pathways related to CLI, such as hepatitis B, tumor necrosis factor (TNF) signaling pathway, apoptosis, hepatitis C, interleukin-17 (IL-17) signaling pathway, and hypoxiainducible factor (HIF)-1 signaling pathway. QDD has protective effect against CLI, which may be related to the regulation of hepatocyte apoptosis. is study provides novel insights into exploring potential biological basis and mechanisms of clinically effective formula systematically
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