Network Pharmacology-Based Approach to Investigate the Mechanisms of Hedyotis diffusa Willd. in the Treatment of Gastric Cancer.

Xinkui Liu,Ziqi Meng,Kaihuan Wang,Xiaomeng Zhang,Xiaojiao Duan,Jiarui Wu,Dan Zhang

doi:10.1155/2018/7802639

Abstract

Background Hedyotis diffusa Willd. (HDW) is one of the renowned herbs often used in the treatment of gastric cancer (GC). However, its curative mechanism has not been fully elucidated. Objective To systematically investigate the mechanisms of HDW in GC. Methods A network pharmacology approach mainly comprising target prediction, network construction, and module analysis was adopted in this study. Results A total of 353 targets of the 32 bioactive compounds in HDW were obtained. The network analysis showed that CA isoenzymes, p53, PIK3CA, CDK2, P27Kip1, cyclin D1, cyclin B1, cyclin A2, AKT1, BCL2, MAPK1, and VEGFA were identified as key targets of HDW in the treatment of GC. The functional enrichment analysis indicated that HDW probably produced the therapeutic effects against GC by synergistically regulating many biological pathways, such as nucleotide excision repair, apoptosis, cell cycle, PI3K/AKT/mTOR signaling pathway, VEGF signaling pathway, and Ras signaling pathway. Conclusions This study holistically illuminates the fact that the pharmacological mechanisms of HDW in GC might be strongly associated with its synergic modulation of apoptosis, cell cycle, differentiation, proliferation, migration, invasion, and angiogenesis.

Highlights

Gastric cancer (GC) is one of the most common gastrointestinal malignancies and among the most frequent causes of cancer-related deaths internationally [1]
The present research discovered that it interacted with seven known gastric cancer (GC)-related targets, including cytochrome P450 2A6 (CYP2A6), cytochrome P450 3A4 (CYP3A4), epidermal growth factor receptor (EGFR), receptor tyrosine-protein kinase erbB-2 (ERBB2), vascular endothelial growth factor receptor 1 (FLT1/VEGFR1), mitogen-activated protein kinase 1 (MAPK1), and prostaglandin G/H synthase 2 (PTGS2), which suggested that coumarin may exert some positive impacts on the treatment of GC
A total of 353 targets affected by 32 bioactive compounds in Hedyotis diffusa Willd. (HDW) were obtained, demonstrating a synergistic treatment strategy of traditional Chinese medicine (TCM) featured by multicomponent, multitarget, and multipathway

Summary

Introduction

Gastric cancer (GC) is one of the most common gastrointestinal malignancies and among the most frequent causes of cancer-related deaths internationally [1]. A network pharmacology approach mainly comprising target prediction, network construction, and module analysis was adopted in this study. The network analysis showed that CA isoenzymes, p53, PIK3CA, CDK2, P27Kip, cyclin D1, cyclin B1, cyclin A2, AKT1, BCL2, MAPK1, and VEGFA were identified as key targets of HDW in the treatment of GC. The functional enrichment analysis indicated that HDW probably produced the therapeutic effects against GC by synergistically regulating many biological pathways, such as nucleotide excision repair, apoptosis, cell cycle, PI3K/AKT/mTOR signaling pathway, VEGF signaling pathway, and Ras signaling pathway. This study holistically illuminates the fact that the pharmacological mechanisms of HDW in GC might be strongly associated with its synergic modulation of apoptosis, cell cycle, differentiation, proliferation, migration, invasion, and angiogenesis

Methods

Results

Conclusion