The mechanism of peach kernel and safflower herb-pair for the treatment of liver fibrosis based on network pharmacology and molecular docking technology: A review

Abstract

Peach kernel and safflower herb-pair (PKSH) are widely used in traditional Chinese medicine for the treatment of liver fibrosis. Therefore, network pharmacology was performed to explore potential therapeutic targets and pharmacological mechanisms of PKSH. The active components of PKSH from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform database and potential targets of liver fibrosis from the Online Mendelian Inheritance in Man, Pharmacogenetics and Pharmacogenomics Knowledge Base, GeneCards, and DrugBank Database were identified. The protein-protein interaction network was constructed using Cytoscape (v3.8.0). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed for the treatment of liver fibrosis, and molecular docking was carried out to verify the results of network pharmacology analysis. After screening disease-related genes, 179 intersection genes overlapped between 196 target proteins of the active compound and 9189 potential disease targets. Furthermore, we obtained 15 hub nodes and 146 edges to establish a related network diagram using CytoNCA. 2559 Gene Ontology biological processes underlying PKSH have been explored for the treatment of liver fibrosis, in which the response to oxidative stress plays a vital role. Furthermore, Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that PKSH might play a role in inhibiting liver fibrosis, mainly through the PI3K-Akt signaling pathway. PKSH can regulate the response to oxidative stress through the PI3K-Akt signaling pathway for the treatment of liver fibrosis. The main bioactive components in PKSH, including quercetin and luteolin, can activate the PI3K-Akt signaling pathway by binding with the hub targets of the disease, which may provide insights into drug development for liver fibrosis.

Figure 1.

Overlapped genes between targets of active compounds in peach kernel and safflower herb-pair and liver fibrosis-related genes from the GeneCards, DrugBank, OMIM, and PharmGkb databases. (A) Liver fibrosis-related genes. (B) overlapped genes. PharmGkb = Pharmacogenetics and Pharmacogenomics Knowledge Base.

Figure 2.

The construction of the network diagram. (A) Herbal-compounds-target network diagram. (B) Compounds-core targets-GO biological processes-signal pathways network diagram. GO = Gene Ontology.

Figure 3.

Map of protein interaction network and the identification of hub genes.

Figure 4.

GO function analysis of the target proteins including BP, CC, and MF terms. (A) Bar chart. (B) Bubble chart. BP = biological process, CC = cellular component, GO = Gene Ontology, MF = molecular function.

Figure 5.

KEGG pathway enrichment analysis of the target proteins. (A) Bar chart. (B) Bubble chart. KEGG = Kyoto Encyclopedia of Genes and Genomes.

Figure 6.

Molecular docking of the hub targets with bioactive compounds. (A) Binding poses of quercetin complexed with AKT1, affinity = −4.5 kcal/mol. (B) Binding poses of luteolin complexed with CCND1, affinity = −7.9 kcal/mol. (C) Binding poses of luteolin complexed with EGFR, affinity = −8.4 kcal/mol. (D) Binding poses of luteolin complexed with MAPK1, affinity = −9.1 kcal/mol. (E) Binding poses of quercetin complexed with MYC, affinity = −7.8 kcal/mol. (F) Binding poses of luteolin complexed with RELA, affinity = −8.4 kcal/mol.