Systems pharmacology in drug discovery and therapeutic insight for herbal medicines

Abstract

Systems pharmacology is an emerging field that integrates systems biology and pharmacology to advance the process of drug discovery, development and the understanding of therapeutic mechanisms. The aim of the present work is to highlight the role that the systems pharmacology plays across the traditional herbal medicines discipline, which is exemplified by a case study of botanical drugs applied in the treatment of depression. First, based on critically examined pharmacology and clinical knowledge, we propose a large-scale statistical analysis to evaluate the efficiency of herbs used in traditional medicines. Second, we focus on the exploration of the active ingredients and targets by carrying out complex structure-, omics- and network-based systematic investigations. Third, specific informatics methods are developed to infer drug-disease connections, with purpose to understand how drugs work on the specific targets and pathways. Finally, we propose a new systems pharmacology method, which is further applied to an integrated platform (Herbal medicine Systems Pharmacology) of blended herbal medicine and omics data sets, allowing for the systematization of current and traditional knowledge of herbal medicines and, importantly, for the application of this emerging body of knowledge to the development of new drugs for complex human diseases.

Quantitative Evaluation of the Compatibility Effects of Huangqin Decoction on the Treatment of Irinotecan-Induced Gastrointestinal Toxicity Using Untargeted Metabolomics

“…Due to the complexity of chemical composition, only using a single index or a simple superposition method could not be feasible to unveil the multi-herb synergistic characteristics of TCM (Jin et al, 2016). Thus, recently, researchers tried to use knockout/knockin chromatography, bioactive equivalence oriented feedback screening method (Song et al, 2016) and system pharmacology strategy (Huang et al, 2014; Zhang W.J. et al, 2016) to recognize the bioactive equivalent combinatorial components (BECCs) or the most effective chemicals in one formula.…”

A New Strategy for Deleting Animal drugs from Traditional Chinese Medicines based on Modified Yimusake Formula

“…To understand the underlying mechanism of such synergistic effect, it is important to search the knowledge about the therapeutic targets of drugs. Network pharmacology has undergone a rapid development in recent years and emerged as an invaluable tool for describing and analyzing complex systems in pharmacology studies 78, 79 . In this section, the network approach was applied to analyze the active compounds and their targets for the modified Yimusake formula from a network point of view.…”

Systems pharmacology exploration of botanic drug pairs reveals the mechanism for treating different diseases

“…Current studies have indicated that two or more herbs interact with multiple targets simultaneously at reasonably close affinities in the biological network and then the biological system would attain new equilibrium in order to reduce the harmful impact26. In such an interlinked network, it would have some effects on the body through this network when a drug targets at a protein.…”

“…Finally, these methods only focus on the prediction of drug-target or drug-disease interactions individually, they ignored the concept that TCM emerged and were considered as a holistic view of the human being which included the integration and dissection of pharmacokinetics profiles, pharmacological features and underlying synergistic mechanisms of action associated with drugs, as well as the investigation of various complex relationships, such as drug-target interactions, drug-disease connections, target-disease associations, drug-pathway connections and from molecular to system level. In comparison with these approaches, systems pharmacology is likely to be a comprehensive method in providing a wealth of information for integrated multi-scale analysis of synergistic mechanisms of multi-component drugs and interrelationships of complex networks by using both computational and experiments techniques242526. With this understanding, the application of systems pharmacology in herb pairs may effectively and systematically help to elucidate the synergistic mechanism of drug combinations, including the build-up of pharmacological networks, so as to promote the discovery of new therapeutic indication of existing drugs and potential synergistic drug combinations.…”