Based on network pharmacology and molecular docking to explore the mechanisms of the action of Tribulus terrestris in the treatment of vitiligo

Abstract

Objective This study was based on the network pharmacology to explore the mechanisms whereby Tribulus terrestris affects vitiligo. Methods The screening criteria for oral bioavailability (OB) and drug-likeness (DL) were set as OB≥30% and DL≥0.18, respectively. The databases of Traditional Chinese Medicine Systems Pharmacology and analysis platforms of OMIM, Swiss Target Prediction and GeneCards were used to screen out target genes of main active ingredients of Tribulus terrestris and construct an "active ingredients-target" network using Cytoscape 3.9.1 software. Then the target genes of the main active ingredients of Tribulus terrestris and the target genes of vitiligo were intersected to construct a "disease-pathway-target-component-drug" network. In addition, the intersection targets were respectively imported into the STRING platform to construct Protein-Protein Interaction (PPI) Networks, and into the DAVID database for GO and KEGG pathway enrichment analyses. The structure of small molecules of key drug components and vitiligo-related protein structure were searched on PubChem and PBD. After setting up receptors and ligands, the molecular docking of these two was performed. Results Through screening, we identified 12 active ingredients, including kaempferol, terrestramide, isorhamnetin, sitosterol, which possibly affect 71 targets. PPI network analysis showed ten major targets, including AKT1, TNF, ESR1, PPARG, HPGDS, CASP3, and PTGS2. These targets were involved in many biological processes, such as apoptosis, peptide serine phosphorylation, and cell response to reactive oxygen species, through various signaling pathways, including apoptosis, tumor necrosis factor and reactive oxygen species signaling. Molecular docking results showed that the main active components such as kaverol and isorhamnetin were stably bound to the core targets, such as AKT1, TNF and ESR1, the core components regulating key targets. Conclusion Tribulus terrestris may improve vitiligo through regulating inflammation, apoptosis, immune function and oxidative stress.

Keywords

• tribulus terrestris
• vitiligo
• network pharmacology
• inflammation
• cell apoptosis
• oxidative stress
• action mechanism