Mechanism of Action of Taohong Huazhuo Decoction the Empirical Prescription Made by Professor Yang Zhen of Master of Traditional Chinese Medicine in Treating Hepatic Fibrosis based on Network Pharmacology and Molecular Docking Techniques

Abstract

Objective: To explore the mechanism of Taohong Huazhuo Decoction, the empirical prescription made by professor Yang Zhen of master of traditional Chinese medicine(TCM) in the treatment of hepatic fibrosis based on network pharmacology and molecular docking technology. Methods: The active ingredients and their corresponding effective targets of Taohong Huazhuo Decoction were screened using the TCM pharmacology database and analysis platform; the potential targets of hepatic fibrosis were obtained from GeneCards database and OMIM database, and then were processed to obtain common potential targets of hepatic fibrosis, thereby obtaining common targets of Taohong Huazhuo Decoction and hepatic fibrosis; Cytoscape 3.8.0 software was used to plot the network map of "traditional Chinese medicine-active substance-disease potential targets"; the intersection targets of drugs and diseases were imported into the String database, and the protein-protein interaction network (PPI) map was drawn by Cytoscape 3.8.0 software, and the intersection targets were analyzed by GO enrichment analysis and KEGG pathway enrichment analysis; small molecule ligand file 2D structures were searched in the PubChem database, the UniProt database was used to find the ID of the key gene of the disease, and the corresponding three-dimensional spatial structure of the disease protein was screened from the PDB database for download. Subsequently, molecular docking of small molecule ligand files and disease protein ligands was performed. Results: A total of 182 active ingredients of Taohong Huazhuo Decoction, 240 component targets, 1,749 hepatic fibrosis-related targets, and 28 disease intersection targets were obtained through each platform. In Taohong Huazhuo Decoction, it was found that there were 144 targets for anti-hepatic fibrosis, and the top 10 key active ingredients were quercetin, luteolin, kaempferol, naringenin, nephrin irisin, baicalein, nobiletin, acacetin, β-carotene and isorhamnetin. The top 10 genes screened by PPI were AKT1, TNF, TP53, IL6, IL1B, MMP9, CASP3, HIF1A, PTGS2 and EGFR. GO functional enrichment analysis showed that the targets were enriched in the response to oxidative stress in biological process (BP); in terms of cellular component (CC), the targets were enriched in membrane rafts and membrane microdomains; In terms of molecular function (MF), targets were enriched in DNA-binding transcription factor binding and so on. The enriched KEGG pathways included TNF signaling pathway, hepatitis B, small cell lung cancer, etc. Molecular docking results showed that there was a strong interaction between the core active components of Taohong Huazhuo Decoction and the core targets of hepatic fibrosis. Conclusion: The study preliminarily uncovers the potential mechanisms of action of Taohong Huazhuo Decoction in the treatment of liver fibrosis based on network pharmacology and molecular docking technique in combination. Besides, it has identified the key bioactive ingredients of the prescription, potential protein targets associated with liver fibrosis, and elucidates the cellular pathways that they may be involved. These findings provide a theoretical basis for the clinical application of Taohong Huazhuo Decoction in the prevention and treatment of hepatic fibrosis.