A Network Pharmacology Approach to Uncover the Multiple Mechanisms of Hedyotis diffusa Willd. on Colorectal Cancer

Abstract

Background: As one of the most frequently diagnosed cancer diseases globally, colorectal cancer (CRC) remains an important cause of cancer-related death. Although the traditional Chinese herb Hedyotis diffusa Willd. (HDW) has been proven to be effective for treating CRC in clinical practice, its definite mechanisms have not been completely deciphered.

Objective: The aim of our research is to systematically explore the multiple mechanisms of HDW on CRC.

Methods: This study adopted the network pharmacology approach, which was mainly composed of active component gathering, target prediction, CRC gene collection, network analysis, and gene enrichment analysis.

Results: The network analysis showed that 10 targets might be the therapeutic targets of HDW on CRC, namely, HRAS, PIK3CA, KRAS, TP53, APC, BRAF, GSK3B, CDK2, AKT1, and RAF1. The gene enrichment analysis implied that HDW probably benefits patients with CRC by modulating pathways related to cancers, infectious diseases, endocrine system, immune system, nervous system, signal transduction, cellular community, and cell motility.

Conclusions: This study partially verified and predicted the pharmacological and molecular mechanism of HDW against CRC from a holistic perspective, which will also lay a foundation for the further experimental research and clinical rational application of HDW.

Figure 1

Compound-compound target network (green diamonds represent compounds contained in HDW. Red hexagons represent compound targets).

Figure 2

CRC targets' PPI network (orange hexagons represent targets related to colorectal cancer acquired from DisGeNET. Red hexagons represent other human proteins that are directly or indirectly interacting with the CRC targets).

Figure 3

Compound-compound target-CRC target-other human proteins' PPI network (green diamonds represent compounds that have effects on intersection targets between compound targets and CRC targets. Orange hexagons represent intersection targets between compound targets and CRC targets. Red circles represent other human proteins that are directly or indirectly interacting with the intersection targets).

Figure 4

GO analysis for the major targets of HDW. The y-axis shows significantly enriched GO categories of the target genes, and the x-axis shows the enrichment scores of these terms or the counts of targets (FDR < 0.01).

Figure 5

KEGG analysis for the major targets of HDW. The y-axis shows significantly enriched KEGG pathways of the target genes, and the x-axis shows the Rich factor (FDR < 0.01). Rich factor stands for the ratio of the number of target genes belonging to a pathway to the number of all the annotated genes located in the pathway. The higher Rich factor represents the higher level of enrichment. The size of the dot indicates the number of target genes in the pathway, and the color of the dot reflects the different FDR range.