The Mechanism of Liujunzi Decoction for Treatment of Age-Related Macular Degeneration Based on Network Pharmacology

  OBJECTIVE  To analyze the targets and signal pathways of Liujunzi decoction in the treatment of age-related macular degeneration (AMD) by network pharmacology, and explore the mechanism of action.

  METHODS  The chemical constituents of six herbs of Liujunzi Decoction were searched from the TCMSP, and the active ingredients were screened out. The corresponding targets of the active ingredients were searched from the Swiss Target Prediction database, the disease targets of AMD were collected through Drugbank, TTD and OMIM databases, the common targets of the active ingredients and disease were determined by Venny analysis. The protein interaction information of common targets was obtained from String database, the target protein interaction network and active ingredient-targets interaction network were constructed with Cytoscape software, the gene function GO and KEGG pathway enrichment analysis were carried out by David database.

  RESULTS  Liujunzi decoction contains 154 active ingredients and 934 corresponding targets, AMD has 266 disease targets, common targets are 92. 37 major targets were obtained by protein interaction network, 39 key active ingredients were obtained by active ingredients-target network. The gene function GO enrichment yielded 277 biological processes entries, mainly involving in transcription factor binding, serine/threonine kinase activity, protein phosphorylation, protein kinase C activity, protein kinase activity, protein deacetylase activity, protein autophosphorylation, peptidyl-tyrosine phosphorylation, NAD-dependent histone deacetylase activity, and MAP kinase activity. KEGG pathway enrichment generated 107 signal pathways, mainly involving in VEGF signaling pathway, Toll-like receptor signaling pathway, TNF signaling pathway, NOD-like receptor signaling pathway, prolactin signaling pathway, neurotrophin signaling pathway, MAPK signaling pathway and inflammatory mediator regulation of TRP channels. The serum containing Liujunzi decoction could protect ARPE-19 cells from oxidative injury, and down-regulate the expressions of VEGF, Akt, ERK1/2 and p38.

  CONCLUSION  Liujunzi decoction plays an active role through multi-component, multi-target and multi-pathway. The underlying mechanism in treatment of AMD may be to regulate cell proliferation and migration, apoptosis, angiogenesis and inflammation.