Synergistic Effect of Network-Based Multicomponent Drugs: An Investigation on the Treatment of Non-Small-Cell Lung Cancer with Compound Liuju Formula

Xing Su,Jinglin Zhu,Wei Xiao,Yueping Li,Chunli Zheng,Xuetong Chen,Yan Li,Jun Zhou,Yonghua Wang,Meng Jiang

doi:10.1155/2019/9854047

Abstract

Lung cancer is the most common cause of cancer death with high morbidity and mortality, which non-small-cell lung cancer (NSCLC) accounting for the majority. Traditional Chinese Medicine (TCM) is effective in the treatment of complex diseases, especially cancer. However, TCM is still in the conceptual stage. The interaction between different components remains unknown due to its multicomponent and multitarget characteristics. In this study, compound Liuju formula was taken as an example to isolate compounds with synergistic biological activity through systems pharmacology strategy. Through pharmacokinetic evaluation, 37 potentially active compounds were screened out. Meanwhile, 116 targets of these compounds were obtained by combing with the target prediction model. Through network analysis, we found that multicomponent drugs can present a synergistic effect through regulating inflammatory signaling pathway, invasion pathway, proliferation, and apoptosis pathway. Finally, it was confirmed that the bioactive compounds of compound Liuju formula have not only a killing effect on NSCLC tumor cells but also a synergistic effect on inhibiting the secretion of correlative inflammatory mediators, including TNF-α and IL-1β. The systems pharmacology method was applied in this study, which provides a new direction for analyzing the mechanism of TCM.

Highlights

With increasing incidence and mortality, cancer has become the leading cause of death and has caused serious public health problems worldwide
To explore the target of compounds for Nonsmall-cell lung cancer (NSCLC), we enriched the targets of the compounds. erefore, we identified 116 targets of these active compounds by means of the weighted integration similarity (WES) and system drug targeting tool (SysDT) algorithms. e results indicated that most compounds act on more than one target and exhibit multiple pharmacological effects of biologically active molecules
Target peroxisome proliferatoractivated receptor gamma (PPARG) corresponds to 23 compounds accounting for 62% of the total active compound

Summary

Introduction

With increasing incidence and mortality, cancer has become the leading cause of death and has caused serious public health problems worldwide. The main effective methods in reducing the mortality of non-small-cell lung cancer include chemotherapy, radiotherapy, targeted therapy, and surgery [4]. Traditional Chinese Medicine (TCM) is widely used all over the world. TCM has been effective to relieve complex diseases for over 4000 years due to Evidence-Based Complementary and Alternative Medicine multicomponent, multitarget, and multilevel characteristics [6]. Compound Liuju formula is widely used in the treatment of lung diseases in China. Clinical medicines such as clinical compound Liuju tablets and compound Liuju granules contain leaves of Hanliuye (Salix matsudana Koidz., SMK), Yejuhua (Chrysanthemum indicum L., CIL), and Baihuasheshecao (Hedyotis diffusa Willd, HDW). It is very hard to explain the interaction among the collaborative compositions that we confront a huge complex system for TCM formula

Methods

Results

Conclusion