Multi-level association rule mining and network pharmacology to identify the polypharmacological effects of herbal materials and compounds in traditional medicine.

Abstract

Many cultures worldwide have widely used traditional medicine (TM) to prevent or treat diseases. Herbal materials and their compounds used in TM offer many advantages for drug discovery, including cost-effectiveness, fewer side effects, and improved metabolism. However, the multi-compound and multi-target characteristics of TM prescriptions complicate drug discovery; meanwhile, previous studies have been limited by a lack of high-quality data, complex interpretation, and/or narrow analytical ranges. Thus, this study proposed a framework to identify potential therapeutic combinations of herbal materials and their compounds currently used in TM by integrating association rule mining (ARM) and network pharmacology analysis across multiple TM and biological levels. Subsequently, we collected prescriptions, herbal materials, compounds, genes, phenotypes, and all ensuing interactions to identify effective combinations of herbal materials and compounds using ARM for various symptoms and diseases. This proposed analytical approach was also applied to screen effective herbal material combinations and compounds for five phenotypes: asthma, diabetes, arthritis, stroke, and inflammation. The potential pharmacological effects of the inferred candidates were identified at the molecular level using structural network analysis and a literature review. In addition, compounds from Morus alba, Ephedra sinica, Perilla frutescens, and Pinellia ternata, which were strongly associated with asthma, were validated in vitro. Collectively, our study provides ethnopharmacological and biological evidence for the polypharmacological effects of herbal materials and their compounds, thus enhancing the understanding of the mechanisms involved in TM and suggesting potential candidates for prescriptions, dietary supplements, and drug combinations. The source code and results are available at https://github.com/bmil-jnu/InPETM.