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System Approach Using Metabolite Structural Similarity Toward TOM Suggested
A Korean research team at KAIST suggests that a system approach using metabolite structural similarity helps to elucidate the mechanisms of action of traditional oriental medicine.
Traditional oriental medicine (TOM) has been practiced in Asian countries for centuries, and is gaining increasing popularity around the world. Despite its efficacy in various symptoms, TOM has been practiced without precise knowledge of its mechanisms of action. Use of TOM largely comes from empirical knowledge practiced over a long period of time. 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 has spurred modernization of TOM.
A research team led by Sang-Yup Lee at KAIST has focused on structural similarities between compounds in TOM and human metabolites to help explain TOM’s mechanisms of action. This systems approach using structural similarities assumes that compounds which are structurally similar to metabolites could affect relevant metabolic pathways and reactions by biosynthesizing structurally similar metabolites.
Structural similarity analysis has helped to identify mechanisms of action of TOM. This is described in a recent study entitled “A systems approach to traditional oriental medicine,” published online in Nature Biotechnology on March 6, 2015. In this study, the research team conducted structural comparisons of all the structurally known compounds in TOM and human metabolites on a large-scale. As a control, structures of all available approved drugs were also compared against human metabolites. This structural analysis provides two important results. First, the identification of metabolites structurally similar to TOM compounds helped to narrow down the candidate target pathways and reactions for the effects from TOM compounds. Second, it suggested that a greater fraction of all the structurally known TOM compounds appeared to be more similar to human metabolites than the approved drugs. This second finding indicates that TOM has a great potential to interact with diverse metabolic pathways with strong efficacy. This finding, in fact, shows that TOM compounds might be advantageous for the multitargeting required to cure complex diseases. “Once we have narrowed down candidate target pathways and reactions using this structural similarity approach, additional in silico tools will be necessary to characterize the mechanisms of action of many TOM compounds at a molecular level,” said Hyun Uk Kim, a research professor at KAIST.
TOM’s multicomponent, multitarget approach wherein multiple components show synergistic effects to treat symptoms is highly distinctive. The researchers investigated previously observed effects recorded since 2000 of a set of TOM compounds with known mechanisms of action. TOM compounds’ synergistic combinations largely consist of a major compound providing the intended efficacy to the target site and supporting compounds which maximize the efficacy of the major compound. In fact, such combination designs appear to mirror the Kun-Shin-Choa-Sa design principle of TOM.
That principle, Kun-Shin-Choa-Sa (君臣佐使 or Jun-Chen-Zuo-Shi in Chinese) literally means “king-minister-assistant-ambassador.” In ancient East Asian medicine, treating human diseases and taking good care of the human body are analogous to the politics of governing a nation. Just as good governance requires that a king be supported by ministers, assistants and/or ambassadors, treating diseases or good care of the body required the combined use of herbal medicines designed based on the concept of Kun-Shin-Choa-Sa. Here, the Kun (king or the major component) indicates the major medicine (or herb) conveying the major drug efficacy, and is supported by three different types of medicines: the Shin (minister or the complementary component) for enhancing and/or complementing the efficacy of the Kun, Choa (assistant or the neutralizing component) for reducing any side effects caused by the Kun and reducing the minor symptoms accompanying major symptom, and Sa (ambassador or the delivery/retaining component) which facilitated the delivery of the Kun to the target site, and retaining the Kun for prolonged availability in the cells.
The synergistic combinations of TOM compounds reported in the literature showed four different types of synergisms: complementary action (similar to Kun-Shin), neutralizing action (similar to Kun-Choa), facilitating action or pharmacokinetic potentiation (both similar to Kun-Choa or Kun-Sa). Additional structural analyses for these compounds with synergism show that they appeared to affect metabolism of amino acids, co-factors and vitamins as major targets.
Professor Sang Yup Lee remarks, “This study lays a foundation for the integration of traditional oriental medicine with modern drug discovery and development. The systems approach taken in this analysis will be used to elucidate mechanisms of action of unknown TOM compounds which will then be subjected to rigorous validation through clinical and in silico experiments.”
Sources: Kim, H.U. et al. “A systems approach to traditional oriental medicine.” Nature Biotechnology. 33: 264-268 (2015).
This work was supported by the Bio-Synergy Research Project (2012M3A9C4048759) of the Ministry of Science, ICT and Future Planning through the National Research Foundation. This work was also supported by the Novo Nordisk Foundation.
The picture below presents the structural similarity analysis of comparing compounds in traditional oriental medicine and those in all available approved drugs against the structures of human metabolites.
2015.03.09 View 13341 -
Late Dr. Ryu Geun Chul's Achievements and Generous Contributions
First Doctor in the field of Korean Traditional Medicine
The late Dr. Ryu was born in 1926 and is the father figure of Korea’s Traditional Medicine and is its First Doctor (1976 Kyung Hee University), and was the vice-professor of Kyung Hee University of Medicine, Vice-Director of Kyung Hee Institute of Korean Traditional Medicine, and was the first chairman of the Association of Korea Oriental Medicine. He developed the painless acupuncture administering device for the first time in Korea in 1962, and succeeded in anesthetizing a patient for cesarean procedure using acupuncture in 1972.
He even was the first to receive a medical engineering doctorate degree from the Moscow National Engineering School in April of 1996 and developed a stroke rehabilitation machine.
Korea’s Most Generous Donor
Dr. Ryu surprised the world by donating 57.8billion Won worth of real estate to KAIST in August of 2008. Dr. Ryu revealed that his reason for donating such a huge sum to KAIST was due to its focused students giving him the belief that the future of Korea is at KAIST and that the development of science and technology is necessary for Korea to develop into a world class nation and KAIST is the institute most suitable to lead Korea in the field.
Dr. Ryu lived on KAIST campus after donating his entire fortune and even established ‘KAIST scholars and spacemen health research center’ and ‘Dr. Ryu Health Clinic’ as he also wanted to donate his knowledge.
Even when he was a professor at Moscow National Engineering University in the late 1990s he carried out free medical work throughout Korea and in recognition of his devoted work, he was named honorary citizen from Chun Ahn city, San Chung city, and DaeJeon city. In 2007 he donated 450million Won to Cheon Dong Elementary School in Chun Ahn city to build a gymnasium and an indoor golf practice range.
Role as Science and Technology Public Relations Officer
Dr. Ryu volunteered to numerous lectures and interviews after donation to advertise science and technology. His belief that the development of science and technology is necessary for Korea’s development was the driving force behind his efforts at increasing interest and support for the field of science and technology.
In addition, through interviews with MBC, KBS, SBS, KTV, Joong Ang Newspapers, Dong Ah Newspaper and other media mediums, Dr. Ryu improved the public perception on donations whilst increasing the pride of scientists and researchers by highlighting their importance and the importance of science and technology.
In recognition of Dr. Ryu’s efforts, he received the 43rd Science Day Science and Technology Creation Award, 2010 MBC Social Service Special Award, and 2010 ‘Proud Chung Cheong Citizen’ Award.
2011.03.22 View 26547 -
KAIST, KRIBB Agree to Cooperate in Research of Convergence Technologies
Oct. 15, 2008 -- KAIST and Korea Research Institute of Bioscience and Biotechnology (KRIBB) have agreed to cooperate in the research of convergence fields of biotechnology, information technology and nanotechnology.
To this end, the two institutions concluded a memorandum of understanding to create a new academia-institute cooperative model in the convergence fields on Oct. 15 in Seoul, with KAIST President Nam-Pyo Suh, KRIBB Director Young-Hoon Park and Vice Minister of Education, Science and Technology Jong-Koo Park in attendance.
Under the agreement, the two institutions will set up the tentatively-named KAIST-KRIBB BINT Convergence Institute for the development of technologies and nurturing skilled manpower in the convergence fields.
The partnership of the two institutions is expected to bring broad-based cooperation opportunities and create a massive synergy effect by combining their resources and infrastructure for the development of convergence technologies, KAIST officials said..
The proposed institute is also designed to build a world-class research hub in systems biotechnology by combining strengths of the two institutions with initiatives to achieve the Korean government"s new vision for "low carbon, green growth."
The institute will also serve as a base for domestic brain convergence by concentrating the nation"s research capacities in genetics and brain technology.
KAIST also signed a memorandum of understanding for cooperation in researches in Oriental medicine with three institutions, KRIBB, Daegu Hanny University and Korea Institute of Oriental Medicine.
The agreement calls for the four institutions to conduct joint researches in traditional sciences and Oriental medicine based on systems biology, develop manpower in related fields and share academic and research information.
The agreement is expected to provide impetus to reinforcing competitiveness in compound and convergence technologies and discover new properties in Oriental medicine, according to KAIST authorities.
2008.10.16 View 24004