Modernization of traditional oriental medicine using a systems approach

A systems approach using metabolite structural similarity helps elucidate the mechanisms of action of traditional oriental medicine.

Article  |  Fall 2015

Traditional oriental medicine (TOM) has been practiced in Asian countries for centuries, and is gaining popularity around the world. Despite its efficacy in treating various symptoms, TOM has been practiced without precise knowledge of its mechanisms of action. Use of TOM largely comes from empirical knowledge based on experience over a long period of time. However, the fact that some of the compounds found in TOM have led to successful modern drugs, such as artemisinin for malaria and taxol (Paclitaxel) for cancer, highly motivates the modernization of TOM.

A research team led by Distinguished Professor Sang Yup Lee at the Korea Advanced Institute of Science and Technology (KAIST) focused on structural similarities between compounds in TOM and human metabolites in an initial attempt to elucidate the mechanisms of action at a global scale. This systems approach using structural similarities is based on a hypothesis that the compounds that are structurally similar to metabolites would affect metabolic reactions by biosynthesizing those structurally-similar metabolites.

This chemical structural analysis provides two important implications. First, the identification of metabolites that are structurally similar to TOM compounds helped narrow down candidate target pathways that can potentially be affected by the TOM compounds. Second, the chemical structural analysis indicates that the TOM compounds have a great potential to interact with diverse metabolic pathways with strong efficacy, and might be advantageous for multitargeting that is required to cure complex diseases.

One distinctive feature of TOM is its multicomponent, multitarget approach wherein multiple components show synergistic effects to treat symptoms. A set of TOM compounds that have appeared in the literature since 2000, with known mechanisms of action and synergistic effects, were investigated. The identified synergistic combinations of TOM compounds largely appeared to consist of a major compound providing the intended efficacy to the target site and a supporting compound maximizing the efficacy of the major compound. The synergistic combinations of TOM compounds reported in the literature showed four different types of synergisms: complementary action, neutralizing action, facilitating action, and pharmacokinetic potentiation. Additional structural analyses for these compounds with synergism show that they appeared to affect the metabolism of amino acids, cofactors, and vitamins as major targets.

This study is a starting point for the modernization of TOM, which should be followed by further rigorous studies. Such continued efforts will ultimately enable the integration of TOM with the modern drug discovery pipeline.

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The present work was published in Nature Biotechnology (2015, 33, pp264).