Global Mapping of Traditional Chinese Medicine into Bioactivity Space and Pathways Annotation Improves Mechanistic Understanding and Discovers Relationships between Therapeutic Action (Sub)classes

• Published in: Evidence-based Complementary and Alternative Medicine
• Main Author: Mohamad Zobir S.Z.; Mohd Fauzi F.; Liggi S.; Drakakis G.; Fu X.; Fan T.-P.; Bender A.
• Format: Article
• Language: English
• Published: Hindawi Limited 2016
• Online Access: https://www.scopus.com/inward/record.uri?eid=2-s2.0-84959279537&doi=10.1155%2f2016%2f2106465&partnerID=40&md5=7501c92cab5b19f9268083169911046c

Traditional Chinese medicine (TCM) still needs more scientific rationale to be proven for it to be accepted further in the West. We are now in the position to propose computational hypotheses for the mode-of-actions (MOAs) of 45 TCM therapeutic action (sub)classes from in silico target prediction algorithms, whose target was later annotated with Kyoto Encyclopedia of Genes and Genomes pathway, and to discover the relationship between them by generating a hierarchical clustering. The results of 10,749 TCM compounds showed 183 enriched targets and 99 enriched pathways from Estimation Score ≤ 0 and ≥ 5% of compounds/targets in a (sub)class. The MOA of a (sub)class was established from supporting literature. Overall, the most frequent top three enriched targets/pathways were immune-related targets such as tyrosine-protein phosphatase nonreceptor type 2 (PTPN2) and digestive system such as mineral absorption. We found two major protein families, G-protein coupled receptor (GPCR), and protein kinase family contributed to the diversity of the bioactivity space, while digestive system was consistently annotated pathway motif, which agreed with the important treatment principle of TCM, "the foundation of acquired constitution" that includes spleen and stomach. In short, the TCM (sub)classes, in many cases share similar targets/pathways despite having different indications. Copyright © 2016 Siti Zuraidah Mohamad Zobir et al.