Study of the Anti-Inflammatory Mechanism of β-Carotene Based on Network Pharmacology

Abstract

β-carotene is known to have pharmacological effects such as anti-inflammatory, antioxidant, and anti-tumor properties. However, its main mechanism and related signaling pathways in the treatment of inflammation are still unclear. In this study, component target prediction was performed by using literature retrieval and the SwissTargetPrediction database. Disease targets were collected from various databases, including DisGeNET, OMIM, Drug Bank, and GeneCards. A protein-protein interaction (PPI) network was constructed, and enrichment analysis of gene ontology and biological pathways was carried out for important targets. The analysis showed that there were 191 unique targets of β-carotene after removing repeat sites. A total of 2067 targets from the three databases were integrated, 58 duplicate targets were removed, and 2009 potential disease action targets were obtained. Biological function enrichment analysis revealed 284 biological process (BP) entries, 31 cellular component (CC) entries, 55 molecular function (MF) entries, and 84 cellular pathways. The biological processes were mostly associated with various pathways and their regulation, whereas the cell components were mainly membrane components. The main molecular functions included RNA polymerase II transcription factor activity, DNA binding specific to the ligand activation sequence, DNA binding, steroid binding sequence-specific DNA binding, enzyme binding, and steroid hormone receptors. The pathways involved in the process included the TNF signaling pathway, sphingomyelin signaling pathway, and some disease pathways. Lastly, the anti-inflammatory signaling pathway of β-carotene was systematically analyzed using network pharmacology, while the molecular mechanism of β-carotene was further explored by molecular docking. In this study, the anti-inflammatory mechanism of β-carotene was preliminarily explored and predicted by bioinformatics methods, and further experiments will be designed to verify and confirm the predicted results, in order to finally reveal the anti-inflammatory mechanism of β-carotene.

Keywords: inflammatory; molecular docking; network pharmacology; β-carotene.

Figure 1

Venn diagram of β-carotene–inflammation effective targets.

Figure 2

β-carotene-targets map. The middle diamond node represents the beta-carotene, and the surrounding circular nodes represent the targets that interact with the beta-carotene.

Figure 3

Candidate target protein interaction network. Nodes represent different targets, and the connections between nodes represent different interactions between them.

Figure 4

PPI network diagram of β-carotene-protein interaction of inflammation. The nodes are sorted by degree value. The larger the node, the darker the color, the higher the degree value, and vice versa. Nodes represent different targets, the connections between nodes represent the interaction between them, and the size of nodes represents the different possibility of binding with β-carotene.

Figure 5

GO analysis of the biological process. The significance of the enrichment result is measured by the −log10 (p-value). The higher the −log10 (p-value), the more significant the enrichment result, and vice versa.

Figure 6

GO analysis of cell components. The significance of the enrichment result is measured by the −log10 (p-value). The higher the −log10 (p-value), the more significant the enrichment result, and vice versa.

Figure 7

GO analysis of molecular function. The significance of the enrichment result is measured by the −log10 (p-value). The higher the −log10 (p-value), the more significant the enrichment result, and vice versa.

Figure 8

Bubble diagram of the KEGG pathway. The significance of the enrichment result is measured by the −log10 (p-value). The higher the −log10 (p-value), the more significant the enrichment result, and vice versa.

Figure 9

Docking pattern between β-carotene and the core target protein. (A) β-carotene–TNF, (B) β-carotene–IL1B, (C) β-carotene–PPARG, (D) β-carotene–LEP, (E) β-carotene–IGF1, (F) β-carotene–APOE, (G) β-carotene–PPARA, (H) β-carotene–ESR1, (I) β-carotene–CAT, (J) β-carotene–MAPK1; Cyan represents van der Waals, yellow for pi-sulfur, green for conventional hydrogen bond, gray for covalent bond, blue for halogen, and pink for pi-alkyl.