Systems Pharmacology for Investigation of the Mechanisms of Action of Traditional Chinese Medicine in Drug Discovery.

Wenjuan Zhang,Ying Huai,Airong Qian,Zhiping Miao,Yonghua Wang

doi:10.3389/fphar.2019.00743

Abstract

As a traditional medical intervention in Asia and a complementary and alternative medicine in western countries, traditional Chinese medicine (TCM) has attracted global attention in the life science field. TCM provides extensive natural resources for medicinal compounds, and these resources are generally regarded as effective and safe for use in drug discovery. However, owing to the complexity of compounds and their related multiple targets of TCM, it remains difficult to dissect the mechanisms of action of herbal medicines at a holistic level. To solve the issue, in the review, we proposed a novel approach of systems pharmacology to identify the bioactive compounds, predict their related targets, and illustrate the molecular mechanisms of action of TCM. With a predominant focus on the mechanisms of actions of TCM, we also highlighted the application of the systems pharmacology approach for the prediction of drug combination and dynamic analysis, the synergistic effects of TCMs, formula dissection, and theory analysis. In summary, the systems pharmacology method contributes to understand the complex interactions among biological systems, drugs, and complex diseases from a network perspective. Consequently, systems pharmacology provides a novel approach to promote drug discovery in a precise manner and a systems level, thus facilitating the modernization of TCM.

Highlights

Traditional Chinese medicine (TCM) plays important roles in the prevention and treatment of complex diseases, which has been developed in China for thousands of years (Tang et al, 2009)
Given the multiple compounds, multiple targets, and synergetic effects of traditional Chinese medicine (TCM), we have proposed a mathematical model called prediction of oral drug bioavailability (PreOB), which integrated the effects of Pgp efflux and P450 metabolism to ensure the accuracy of oral bioavailability (OB) prediction of drugs (Xu et al, 2012)
There are two key problems: 1) If the compound and the person are considered as whole entities, how do they interact with each other? 2) How do the molecules, tissues, and organs of the body respond to different molecules or molecule groups in a formula under holistic frameworks? To solve these problems, in the previous studies, we have examined the molecular basis of some diseases associated with different organs, such as cardio-cerebral diseases and cardiovascular diseases (CVDs) and gastrointestinal disorders (GIDs)

Summary

INTRODUCTION

Traditional Chinese medicine (TCM) plays important roles in the prevention and treatment of complex diseases, which has been developed in China for thousands of years (Tang et al, 2009). To enhance the systems pharmacology platform, theoretic calculations and experimental methods were integrated into the models for the discovery of bioactive molecules, the identification of new drug targets, the prediction of adverse drug reactions, the exploration of therapeutic mechanisms, and the elucidation of the rules of drug combination (Huang et al, 2013a). This platform allows the large-scale analysis of simulation methodology and optimization algorithms, which can be applied to determine the molecular mechanisms of TCM and to assist the development of novel drugs

METHODOLOGY OF SYSTEMS PHARMACOLOGY IN TCM

Findings

CONCLUSIONS AND PROSPECTS