Network Pharmacology-Based Strategy to Reveal the Mechanism of Cassiae Semen against Cataracts

Abstract

Cassiae semen (CS) is one of the most well-known herbs used in the treatment of cataracts in China. However, the potential mechanisms of its anticataract effects have not been fully explored. In this study, network pharmacology was used to investigate the potential mechanism underlying the actions of CS against cataracts, and molecular docking was performed to analyze the binding activity of proteins and compounds. qPCR was performed to detect the mRNA level of genes, and the cell apoptotic rate was measured using flow cytometry. We identified 13 active compounds from CS and 105 targets, as well as 238 cataract-related targets. PPI networks were constructed, and fifty key targets were obtained. These key targets were enriched in the regulation of transcription, apoptotic process, and signal transduction pathways. Molecular docking demonstrated that the compounds of CS exhibited good affinity to some critical targets. Furthermore, CS prevented the apoptosis of human lens epithelial cells induced by UVB lights by decreasing the gene expression of CASP3, ESR1, and TP53 and increasing the CRYAB gene expression. The present study attempted to explain the mechanisms for the effects of CS in the prevention and treatment of cataracts and provided an effective strategy to investigate active ingredients from natural medicines. Further studies are required to verify these findings via in vivo and in vitro experiments.

Figure 1

The characteristics of active compounds in CS and their targets: (a) the network of active compounds and their targets; (b) the PPI network of active compounds' targets; (c) top 10 enriched GO terms of compounds' targets; (d) the top 20 enriched pathways of compounds' targets.

Figure 2

The characteristics of cataract-related targets: (a) the PPI network of the cataract-related targets; (b) KEGG and GO analysis of the cataract-related targets; (c) a subnetwork from module analysis with score = 5.60; (d) GO and KEGG results of the subnetwork from module analysis.

Figure 3

The central network analysis and bioinformatic analysis: (a) the merged PPI network of compound targets and cataract-related targets; (b) central network obtained from the merged network; (c) top 10 enriched GO terms of the key targets from the central network; (d) the top 20 enriched pathways of the key targets from the central network. In (a) and (b), green circles represented compound targets, cyan circles represented disease targets, and orange circles represented shared targets.

Figure 4

Molecular docking results of the proteins and compounds or inhibitors (1). A sphere and a cartoon chain represent a ligand and a protein, respectively.

Figure 5

Molecular docking results of the proteins and compounds or inhibitors (2). A sphere and a cartoon chain represent a ligand and a protein, respectively.

Figure 6

The effect of CS on the gene expression and apoptosis of human lens epithelial cells. (a) The effect of CS on the mRNA expression of AKR1B1, CASP3, MAPK14, ESR1, TP53, and CRYAB. (b) The effects of CS on the apoptosis of human lens epithelial cells. The groups were identified as follows: (i) CS: apoptosis cell model of human lens epithelial cells treated with CS, (ii) model: apoptosis cell model of human lens epithelial cells, and (iii) control: human lens epithelial cells. ^∗p < 0.05 compared to the control group, ^#p < 0.05 compared to the model group.