Elucidating the Mechanism of Action of Salvia miltiorrhiza for the Treatment of Acute Pancreatitis Based on Network Pharmacology and Molecular Docking Technology

Abstract

Using network pharmacology and molecular docking, this study investigated the molecular mechanisms by which the active components in Salvia miltiorrhiza can alleviate acute pancreatitis. Initially, the active components of Salvia miltiorrhiza and the targets collected from the GeneCards database were screened based on the platform of systematic pharmacology analysis of traditional Chinese medicine. Subsequently, the active components were intersected with the disease targets. Also, interactions among the targets were computed using the STRING database. Biological function and pathway enrichment were analyzed using the Cluster Profiler package in the R software. Protein-protein interaction and component target pathway network were constructed using the Cytoscape software. Ultimately, the key targets and their corresponding components in the network were verified using the AutoDock Vina software. The results showed Salvia miltiorrhiza had 111 targets for acute pancreatitis. The biological process (BP) analysis showed that the active components of Salvia miltiorrhiza induced a drug response, positive regulation of transcription by RNA polymerase II promoter, signal transduction, positive regulation of cell proliferation, and negative regulation of apoptosis. Furthermore, the KEGG enrichment analysis screened 118 (P < 0.05) signaling pathways, such as the pathways related to cancer, neuroactive ligand-receptor interaction, PI3K-Akt signaling pathway, and cAMP signaling pathway, to name a few. Finally, molecular docking showed that the active components of Salvia miltiorrhiza had a good binding affinity with their corresponding target proteins. Through network pharmacology, this study predicted the potential pharmacodynamic material basis and the mechanisms by which Salvia miltiorrhiza can treat acute pancreatitis. Moreover, this study provided a scientific basis for mining the pharmacodynamic components of Salvia miltiorrhiza and expanding the scope of its clinical use.

Figure 1

The component-target network of SM.

Figure 2

Venn map of “Danshen” target and acute pancreatitis target. Note: the blue part represents the target genes of acute pancreatitis, the red part represents the target genes of the active components of Salvia miltiorrhiza to be modified, and the intersection represents the common target genes.

Figure 3

The analysis diagram of target-protein interaction network.

Figure 4

GO functional enrichment analysis: Bubble diagram of the analysis of the biological processes.

Figure 5

GO functional enrichment analysis: Bubble diagram of the analysis of the cell components.

Figure 6

GO functional enrichment analysis: Bubble diagram of the analysis of the molecular functions.

Figure 7

GO functional enrichment analysis: histogram of the analysis of the biological processes.

Figure 8

GO functional enrichment analysis: cellular components analysis.

Figure 9

GO functional enrichment analysis: histogram of the analysis of the molecular functions.

Figure 10

Bubble diagram of the KEGG pathway enrichment analysis.

Figure 11

Histogram of the KEGG pathway enrichment analysis.

Figure 12

Component-target pathway network of Salvia miltiorrhiza.

Figure 13

Schematic diagram of molecular docking between core components of Salvia miltiorrhiza and key targets. Note: (a)–(d) are molecular docking diagrams of Salvia miltiorrhiza new quinone D and PTGS2, Salvia miltiorrhiza new quinone D and CHRM1, tanshinone IIA and NCOA1, and tanshinone IIA and OPRM1, respectively.