Investigating the Multi-Target Pharmacological Mechanism of Hedyotis diffusa Willd Acting on Prostate Cancer: A Network Pharmacology Approach

Abstract

Hedyotis diffusa Willd (HDW) is one of the most well-known herbs used in the treatment of prostate cancer. However, the potential mechanisms of its anti-tumor effects have not been fully explored. Here, we applied a network pharmacology approach to explore the potential mechanisms of HDW against prostate cancer (PCa). We obtained 14 active compounds from HDW and 295 potential PCa related targets in total to construct a network, which indicated that quercetin and ursolic acid served as the main ingredients in HDW. Mitogen-activated Protein Kinase 8 (MAPK8), Interleukin 6 (IL6), Vascular Endothelial Growth Factor A (VEGFA), Signal Transducer and Activator of Transcription 3 (STAT3), Jun Proto-Oncogene (JUN), C-X-C Motif Chemokine Ligand 8 (CXCL8), Interleukin-1 Beta (IL1B), Matrix Metalloproteinase-9 (MMP9), C-C Motif Chemokine Ligand 2 (CCL2), RELA Proto-Oncogene (RELA), and CAMP Responsive Element Binding Protein 1 (CREB1) were identified as key targets of HDW in the treatment of PCa. The protein–protein interaction (PPI) cluster demonstrated that CREB1 was the seed in this cluster, indicating that CREB1 plays an important role in connecting other nodes in the PPI network. This enrichment demonstrated that HDW was highly related to translesion synthesis, unfolded protein binding, regulation of mitotic recombination, phosphatidylinositol and its kinase-mediated signaling, nucleotide excision repair, regulation of DNA recombination, and DNA topological change. The enrichment results also showed that the underlying mechanism of HDW against PCa may be due to its coordinated regulation of several cancer-related pathways, such as angiogenesis, cell differentiation, migration, apoptosis, invasion, and proliferation.