Title:Molecular Targets and Mechanisms of Hedyotis diffusa Willd. for
Esophageal Adenocarcinoma Treatment Based on Network Pharmacology
and Weighted Gene Co-expression Network Analysis
Volume: 25
Issue: 6
Author(s): Yu Zhuang, Yun-Gang Sun, Chen-Guang Wang, Qiang Zhang, Chao Che and Feng Shao*
Affiliation:
- Department of Thoracic Surgery, Nanjing Chest Hospital, Nanjing, Jiangsu, China
- Department of Thoracic Surgery,
Affiliated Nanjing Brain Hospital, Nanjing Medical University, Nanjing, Jiangsu, China
Keywords:
Esophageal adenocarcinoma, weighted gene co-expression network analysis, network pharmacology, chemotherapy, Hedyotis Diffusa Willd. (HDW), Protein-Protein Interaction (PPI).
Abstract:
Background: Hedyotis diffusa Willd. (HDW) is a common anticancer herbal medicine
in China, and its therapeutic effectiveness has been demonstrated in a range of cancer patients.
There is no consensus about the therapeutic targets and molecular mechanisms of HDW, which
contains many active ingredients.
Aim: To clarify the mechanism of HDW for esophageal adenocarcinoma (EAC), we utilized network
pharmacology and weighted gene co-expression network analysis methods (WGCNA).
Methods: The gene modules that were linked with the clinical features of EAC were obtained
through the WGCNA method. Then, the potential target genes were retrieved through the network
pharmacology method in order to determine the targets of the active components. After enrichment
analysis, a variety of signaling pathways with significant ratios of target genes were found,
including regulation of trans-synaptic signaling, neuroactive ligand-receptor interaction and modulation
of chemical synaptic transmission. By means of protein-protein interaction (PPI) network
analysis, we have successfully identified the hub genes, which were AR, CNR1, GRIK1, MAPK10,
MAPT, PGR and PIK3R1.
Result: Our study employed molecular docking simulations to evaluate the binding affinity of the
active components with the hub gene. The identified active anticancer constituents in HDW are
scopoletol, quercetin, ferulic acid, coumarin, and trans-4-methoxycinnamyl alcohol.
Conclusion: Our findings shed light on the molecular underpinnings of HDW in the treatment of
EAC and hold great promise for the identification of potential HDW compounds and biomarkers
for EAC therapy.
