Network Pharmacology-Based Prediction of the Active Compounds, Potential Targets, and Signaling Pathways Involved in Danshiliuhao Granule for Treatment of Liver Fibrosis

Abstract

This study aims to predict the active ingredients, potential targets, signaling pathways and investigate the “ingredient-target-pathway” mechanisms involved in the pharmacological action of Danshiliuhao Granule (DSLHG) on liver fibrosis. Pharmacodynamics studies on rats with liver fibrosis showed that DSLHG generated an obvious anti-liver fibrosis action. On this basis, we explored the possible mechanisms underlying its antifibrosis effect using network pharmacology approach. Information about compounds of herbs in DSLHG was collected from TCMSP public database and literature. Furthermore, the oral bioavailability (OB) and drug-likeness (DL) were screened according to ADME features. Compounds with OB≥30% and DL≥0.18 were selected as active ingredients. Then, the potential targets of the active compounds were predicted by pharmacophore mapping approach and mapped with the target genes of the specific disease. The compound-target network and Protein-Protein Interaction (PPI) network were built by Cytoscape software. The core targets were selected by degree values. Furthermore, GO biological process analysis and KEGG pathway enrichment analysis were carried out to investigate the possible mechanisms involved in the anti-hepatic fibrosis effect of DSLHG. The predicted results showed that there were 108 main active components in the DSLHG formula. Moreover, there were 192 potential targets regulated by DSLHG, of which 86 were related to liver fibrosis, including AKT1, EGFR, and IGF1R. Mechanistically, the anti-liver fibrosis effect of DSLHG was exerted by interfering with 47 signaling pathways, such as PI3K-Akt, FoxO signaling pathway, and Ras signaling pathway. Network analysis showed that DSLHG could generate the antifibrosis action by affecting multiple targets and multiple pathways, which reflects the multicomponent, multitarget, and multichannel characteristics of traditional Chinese medicine and provides novel basis to clarify the mechanisms of anti-liver fibrosis of DSLHG.

Byakangelicin protects against carbon tetrachloride–induced liver injury and fibrosis in mice

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Network Pharmacology Study of Heat-Clearing and Detoxifying Traditional Chinese Medicine for Alzheimer's Disease

“…DL represents the ability of potential ingredients to become effective drugs by calculating the similarity with a known drug, which is beneficial to optimize pharmacokinetic properties to affect ADME [17,21]. e active ingredients were considered viable according to ADME features with OB ≥ 30% and DL ≥ 0.18, two critical value that indicate acceptable oral bioavailability and drug-likeness as previously described [22]. All targets (including the validated and predicted targets) related to these active ingredients were extracted from the TCMSP database and entered into the UniProt database [23] (http:// www.uniprot.org/) to obtain target-relevant gene names.…”

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