Systems Biology: The bridge between Traditional Medicine and Western Science

Transcription

1 Systems Biology: The bridge between Traditional Medicine and Western Science TNO GRA-workshop Nutrition and SA 9-11, 2005 Food Feb Research Mei Wang Jan van der Greef Traditional Chinese Medicine 1 Western Medicine

2 The perspectives Traditional Chinese Medicine Holistic Disease is an energetic disbalance Personalized Cure instead of treatment Synergetic active components 2

3 The perspectives Western Pharmaceutical Medicine Reductionistic, molecular mechanisms Disease : emphasis on single defect Generic approach Treatment of symptoms Focus 1 drug 1 target but this perspective has changed by Systems Biology 3

4 Systems Biology, a holistic approach, basis of studying Traditional Healing Systems Biology : the study of biology as an integrated system of genetic, protein, metabolite, cellular, and pathway events that are in flux and interdependent. 4

5 taurine Reading the patterns : diagnosis creatininecreatine hipuric acid dihydroxyacetone glycine creatine citric acid 1 H-NMR Fingerprint of MS patient (urine) betaine glucuronide trimethylamine -N-oxide adenosine lactic acid betaine choline carnitine N,N-dimethylamine Dimethylamine a-ketoglutarate barnsteenzuur/\succinate pyruvate acetoacetate glutamaat propionylglycine glutamine a-ketoglutaarzuur N-acetyl acetate alanine lactic acid 3-hydroxyisovalerianic acid hydroxybutyric acid a-keto-isovalerianic acid aceetamide lysine valine ppm

6 D2(33.06%) Male H Female H Healthy PCDA Score Plot D1 vs D2 Biomarker profiles for Diabetes II Male D Diabetes II Female D D1(34.52%) Winlin V1.11 6

7 Heme Oxygenase 2 Inositol First demonstration of early onset of disease detection in a mammalian system by Systems Biology Protein Kinase C e (cell signaling) Monophosphatase Glutathione S-transferase Apolipoprotein A1 DKK 1 Fatty Acid Binding Protein Pyruvate Kinase PPAR? Fatty Acid Binding Gene Murinoglobulin 2 Diacylglycerol LysoPC Nuclear Ribonucleoprotein H1 (transcription splicing) Apoptosis Inhibitory Protein 6 Translation Initiation Factor 2 (protein synthesis) PC C18 18:O PLA 2 VII TG Hemopoietic Cell Phosphatase C ij >0.8 GENE PROTEIN METABOLITE Up-regulated Down-regulated 7

8 PLA 2 VII Hemopoietic Cell Phosphatase DKK 1 Fatty Acid Binding Protein Pyruvate Kinase Conclusions Heme : Protein Kinase C e Oxygenase 2 (cell signaling) Inositol Monophosphatase Glutathione S-transferase PPAR? PC C18 18:O First demonstration of early onset of disease detection in a mammalian system by Systems Biology TG Apolipoprotein A1 Translation Initiation Factor 2 (protein synthesis) C ij >0.8 Up-regulated Fatty Acid Binding Gene Murinoglobulin 2 Diacylglycerol LysoPC Nuclear Ribonucleoprotein H1 1. Onset of disease is described as an imbalance in homeostasis reflected in changes in multiple pathways that are interconnected and interdependent (transcription splicing) Apoptosis Inhibitory Protein 6 Systems Biology offers the unique option to demonstrate the mechanistic impact of complex mixtures such as TCM on disease. Systems Biology offers the option to perform QA/QC based on biological efficacy! GENE PROTEIN METABOLITE Down-regulated 8

9 Vision in Life Sciences Human health is based on a balance between multiple pathways/networks, curing or prevention of disease is only effective when based on synergetic multi-component strategies 9

10 Life s Complexity Pyramid Systems Pharmacology based intervention concepts TNO Nutrition and Food Research Bodyfluids : Communication & Control Organizational information at system level Oltvai 10 et al Science 298 (2002) 763

11 The technology platform: From Plant to Patient < From Plant to Patient > Herbal QA/QC Profiling-PARC PP-Platform TM Biological Effect Discovery Multidimensional Pharmacology MDP-Platform Human Efficacy Phase IIa, Clin. Trial MDP-Systems Biology Cultivar database Extract-mixtures Unique Animal Models Longitudional Biomarkers Multifactorial effect monitoring < Systems Biology > technology platform 11

12 Metabolic Syndrome Obesity Diabesity Healthy Diabetes II Metabolic Syndrome Insulin Resistance Dyslipidemia Hypertension Heart Diseases 12

13 The history of Diabetes in Chinese Medicine The name Xiao ke appears in the Nei Jing (Inner Classic, 400 BC), where several different though related conditions are mentioned : Xiao ke, wasting and thirsting, Xiao dan, pure heat wasting, Ge xiao, diaphragm wasting and Xiao zhong, central wasting. In terms of disease cause, the authors of the Nei Jing recognized that overeating of sweets and fats, emotional stress, weakness of the five viscera and obesity are all closely related to this disease. 13

14 Metabolic Syndrome Yang-deficiency Obesity Damp etc. Healthy Metabolic Syndrome Diabesity Ying-def. Diabetes Body II fluid Depletion & vacuity (Ying & Qi) Ying Dyslipidemia deficiency Dry heat Hypertension Obstruction in heart & stagnation Heart of lung Diseases Qi 14

15 Effects of TCM on insulin resistance Low High Insuline resistance GIR (µl/min.kg) Control (pre-diabetic) SUB 881 SUB 882 SUB 885 Control #1 #2 #5 T =4 weeks Liver damage (ALAT) T = 7 weeks

16 Lipid profiles Controls versus SUB885 at 0, 4 and 7 weeks (APOE3 Leiden mouse plasma) 0.5 Scores for D# 1 versus D# weeks 0.2 SUB885 Control 0 weeks Control at t=0 SUB885 at t=0 Scores on D# Control at t=4 SUB885 at t=4 Control at t=7-0.1 SUB885 at t= weeks Scores on D# 1 16

17 SUB product optimization : Traditional Medicine driven! Low High Insuline resistance GIR (µl/min.kg) Control (pre-diabetic) Metformin SUB 885 SUB 885A SUB 885B SUB 885C 17

18 Systems Biology : Bridging the Seen and the Unseen 18

19 Qi BaiShi ( ) 19

20 Moving forward Building on Excellence In honour of his great teacher Qi Baishi Lotus and Dragonfly by Lou Shibai 20

21 As difficult, therefore, as it is to bridge the gap between Western and Asian art, Lou Shibai has achieved, at the age of 83, something which few others have even attempted. Without abandoning his roots, he has both innovated China s traditional painting while reaching out to the kind of symbolism that is able to touch a chord in the mind of the western observer. 21

22 Important issues for the future 22

23 Important issues for the future Roadmap suggestions for the science part: # Bridge Traditional Medicine with the same Scientific philosophy > Systems Science # Bridge TM Diagnostics with Western Diagnostics (bodyfluid System fingerprints) # Use herbal fingerprints related to bioactivity of groups of components for QC # Design separate registration system for TM 23

24 Important issues for the future Roadmap Dream : Create/enhance worldwide around important IK-domains Integrative Research & Knowledge Centers, connected via an GRA-web to stimulate, exchange and build a Global future together. 24