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

Abstract

Multi-herb therapy has been widely used in Traditional Chinese medicine and tailored to meet the specific needs of each individual. However, the potential molecular or systems mechanisms of them to treat various diseases have not been fully elucidated. To address this question, a systems pharmacology approach, integrating pharmacokinetics, pharmacology and systems biology, is used to comprehensively identify the drug-target and drug-disease networks, exemplified by three representative Radix Salviae Miltiorrhizae herb pairs for treating various diseases (coronary heart disease, dysmenorrheal and nephrotic syndrome). First, the compounds evaluation and the multiple targeting technology screen the active ingredients and identify the specific targets for each herb of three pairs. Second, the herb feature mapping reveals the differences in chemistry and pharmacological synergy between pairs. Third, the constructed compound-target-disease network explains the mechanisms of treatment for various diseases from a systematic level. Finally, experimental verification is taken to confirm our strategy. Our work provides an integrated strategy for revealing the mechanism of synergistic herb pairs, and also a rational way for developing novel drug combinations for treatments of complex diseases.

A Systems Pharmacology Approach for Identifying the Multiple Mechanisms of Action for the Rougui‐Fuzi Herb Pair in the Treatment of Cardiocerebral Vascular Diseases

“…To verify the reliability of compound-target binding interactions, molecular docking program was in progress using AutoDock software (version 4.2), which employs the Lamarckian genetic algorithm (LGA) for each progress [42]. All the 3D structures of target proteins were downloaded from the RCSB PDB database (http://www.pdb.org), so that proteins and ligands could be prepared in the AutoDock tools before performing the docking progress [43]. e auxiliary program Autogrid was used to generate the docking area, which was defined as a 60 × 60 × 60 3D grid centered around the ligand-binding site with a 0.375Å grid space.…”

“…All bond rotations for the ligands were ignored in this study. Finally, the docking binding energy was calculated to explore binding interactions Evidence-Based Complementary and Alternative Medicine between the compounds and their targets in our studies, the potential protein targets of TCM were successfully predicted with a good compound-protein binding affinity based on the threshold level of − 5.0 kcal/mol [43].…”

A system-level investigation into the pharmacological mechanisms of flavor compounds in Maotai liquor

“…Thus, it is imperative to develop network-based method for interpreting the complicated relationships between multi-component and multi-target that are involved in complex diseases at a system level. Fortunately, network pharmacology has emerged as a powerful tool for predicting and analyzing complex systems in pharmacology studies [6]. Particularly, the C-T-D network is widely applicable for interpreting pharmacological mechanism of compound action by employing compounds, targets and diseases.…”

“…The successful application of systems pharmacology is not only helpful to promote systems-level understanding of the mechanism of drug action and therapeutics, but also critical for facilitating the drug discovery and development of complex disease therapy. In recent years, systems pharmacology plays a significant role in the research of herbal and western medicines, including predicting bioactive drug ingredients and potential targets, revealing pharmacological synergy and therapeutic mechanisms, resolving the Chinese tradition medicine theory and identifying multiple toxin-target interactions based on chemical, genomic, and toxicological data and so on [5,6].…”

Systematic Analysis of the Pharmacological Effects of Alcoholic Components in Maotai

“…Systems pharmacology is a multidisciplinary approach that aims to elucidate multiple mechanisms of the networks between compounds and targets, targets and diseases, and targets and pathways, thus providing a new perspective on the pharmacological effects of candidate compounds and promoting drug discovery at the systems level (Zhou, Wang, Lu, & Zhang, ). Recently, several system pharmacology models were applied to identify the active compounds, targets protein, and their interactions of functional food, resolving the Chinese tradition medicine theory, revealing the pharmacological synergy and therapeutic mechanisms of herb pairs, and so on ( Zhou et al., ; Zhou & Wang, ).…”