Chinese Medicine in the omics era

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1 Chinese Medicine in the omics era Prof. Giovanna Franconi Systems Medicine Department Tor Vergata University, Rome, Italy

2 Western Medicine crisis: Exponential increase of costs, Treatment side effects, Fewer new drugs on the market, etc

3 Western Medicine P2P Point to Point methodology (a single small molecule acting on a single target)

4 Western Medicine great success, especially for single - factor infectious diseases no satisfying solutions for multi - factor complex chronic diseases

5 Western Medicine Variability is the law of life, and as no two faces are the same, so no two bodies are alike, and no two individuals react alike and behave alike under the abnormal conditions which we know as disease. Sir William Osler ( )

6 Systems Medicine After the Human Genome Project The study of how a biological system responds to a given disturbance or stimulant of the environment

7 Systems Medicine Organism = integrated and interactive network of genes (genomics and transcriptomics), proteins (proteomics) and biochemical reactions (metabolomics)

8 Systems Medicine Identification of new biomarkers: an increasingly essential element of predictive, preventive and personalized medicine.

Systems Medicine Biomarkers can be objectively

intervention Breast Cancer Type 1 susceptibility

9 Systems Medicine Biomarkers can be objectively measured can be indicators of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention Breast Cancer Type 1 susceptibility protein (BRCA1) Vitamin K epoxide reductase complex protein 1 (VKORC1)

10 Chinese Medicine S2S System to System methodology TCM is concerned with the body as a system

11 Chinese Medicine syndrome (Zheng 征 ) a set of symptoms of both pathological and physiological states

12 Chinese Medicine

13 Chinese Medicine (macro level ) syndrome = special clinical phenotype differentiated according to symptoms and signs COLD Feels cold Lack of thirst Pale complexion Profuse urine Clear urine Loose stool Pale tongue White coating HEAT Feels hot Thirsty Red face Scanty urine Dark urine Constipation Red tongue Yellow coating

14 Chinese Medicine (micro level ) Biomarkers identified by functional genomics can be aggregated into different syndromes specific imbalance at the level of the microscopic network

15 Cold and Hot gene expression = Network model Li et al. Sci. Rep. 2013; 3:1543

16 Li et al. Sci. Rep. 2013; 3:1543

particularly yin deficiency; DQY -PQ, deficiency of both qi

17 CM and diabetic nephropathy DM, diabetes mellitus; DN, diabetic nephropathy; DQY - PY, deficiency of both qi and yin, particularly yin deficiency; DQY -PQ, deficiency of both qi and yin, particularly qi deficiency; DYY, deficiency of both yin and yang

18 CM and diabetic nephropathy Metabolic fingerprint of a plasma sample.

19 CM and diabetic nephropathy Score plot of all the plasma fingerprints Western diagnosis TCM diagnosis

20 CM and diabetic nephropathy Tangshen formula is a TCM formula for the treatment of Diabetic Nephropathy it supplements qi and nourishes Yin, and activates blood circulation to dissipate blood stasis. Huangqi (Astragali Radix), Dihuang (Rehmanniae Rhizoma), Sanqi (Notoginseng Radix et Rhizoma), Weimao (Euonymi Ramulus), Dahuang (Rhei Radix et Rhizoma), Shanzhuyu (Corni Fructus).

21 CM and diabetic nephropathy Score plot of patient plasma fingerprints after treatment in DN III (a) and DN IV (b). G Luo,YM Wang,QL Liang,QF Liu. Systems Biology for Traditional Chinese Medicine. Wiley 2012

Omics and acupuncture acupuncture exerts physical (mechanical) stimulations, produces endogenous biological effects and nonlinear results

22 Omics and acupuncture acupuncture exerts physical (mechanical) stimulations, produces endogenous biological effects and nonlinear results not only relying on the anatomical structure of meridians / acupoints, but also on the combined effects of all acting factors in the human body.

23 Omics and acupuncture Lin et al. ecam 2012; doi: /2012/372670

24 Genomics and acupuncture Hypercholesterolemia ST40 Allergic rhinitis LI4, ST36, LI20, EX-HN3 Knee osteoarthritis CV4, CV6, ST36, EX32, GB34 Parkinson s disease GB34, LR3 Spinal cord injury ST36, GB39, ST32, SP6 Neuropathic pain ST36 Immunomodulation ST36 Yang et al 2014 ecam, Article ID ,

25 Genomics and acupuncture Hippocampus gene expression profiles in senescence accelerated mice (CV17, CV12, CV6, ST36, SP10) => alteration of the expression of genes related to oxidative damage => acupuncture may retard aging in mammals Ding et al. Neurosci Lett. 2006; 399(1-2):11-6

26 Genomics and acupuncture Sensitivity to acute thermal nociception before and after acupuncture (on LI4) in 15 males In the responder group 375 genes showed significant variation. New potential targets identified for investigating the mechanisms behind acupuncture-induced analgesia Chae et al. J Physiol Sci 2006; 56 (6):

Proteomics and acupuncture Hypertension LR3 Acute ischemic stroke BL10, GB20, LI4, PC6, BL40, SP6, ST36, MS6 (scalp acu motor area) Parkinson s disease

27 Proteomics and acupuncture Hypertension LR3 Acute ischemic stroke BL10, GB20, LI4, PC6, BL40, SP6, ST36, MS6 (scalp acu motor area) Parkinson s disease Parkinson s disease Spinal cord injury GB34, GB39 GB34, SI3, BL62, ST36 Gv6, GV9 Yang et al 2014 ecam, Article ID ,

28 Proteomics and acupuncture Treatment at the Taichong LR3 acupoint in spontaneously hypertensive rats (SHRs). Compared with nonacupoint treatment, Taichong treatment reduced significantly the rat s systolic pressure (P=0.01) Lai et al PLoS ONE 7(9): e doi: /journal.pone

29 Proteomics and acupuncture The different treatment groups showed different proteomic response in the nervous system Taichong acupuncture increased the expression of antioxidant enzymes Lai et al PLoS ONE 7(9): e doi: /journal.pone

Proteomics and acupuncture 35 acute ischemic stroke patients: all received Erigeron breviscapus, 24 pts also received acupuncture Xingnao Kaiqiao acupuncture therapy principle: MS6 (scalp acu motor

30 Proteomics and acupuncture 35 acute ischemic stroke patients: all received Erigeron breviscapus, 24 pts also received acupuncture Xingnao Kaiqiao acupuncture therapy principle: MS6 (scalp acu motor areas), BL10, GB20, LI4, PC6, BL40, SP6, and ST36 of the affected side. EA (6 V, 10 Hz) 30 min a day for 10 days Pan et al. Exp Biol Med (Maywood) 2011 Mar;236(3): doi: /ebm

31 Proteomics and acupuncture Muscle strength recovered only after EA treatment, and was accompanied by differential effects of EA on the expression of a number of serum proteins (SerpinG1, Gelsolin, C3) Pan et al. Exp Biol Med (Maywood) 2011 Mar;236(3): doi: /ebm

32 Metabolomics and acupuncture Aging Chronic emotional stress Functional dyspepsia Carpal tunnel syndrome Depression GV20, KI1 GV20, SP6 BL21, CV12 PC7, TE5, SP6, LR4 LR8 (laser and needle acupuncture) Yang et al 2014 ecam, Article ID ,

33 Metabolomics and acupuncture positron emission tomography (PET) functional magnetic resonance imaging (fmri) magnetoencephalography (MEG)

34 Metabolomics and acupuncture acupuncture affects a network of systems in the brain, including decreasing activity in the limbic system, the emotional part of the brain, and activating it in the parts of the brain that typically light up when the brain is at rest.

35 Metabolomics and acupuncture GV20, ear Shenmen, LI4, LI11, SP6, LRv3, GB34, bilateral ST36

36 Metabolomics and acupuncture Short term effects Long term effects

37 Conclusions

38 THANK YOU FOR YOUR ATTENTION Long life

Contents. Basic Theory of Acupuncture. (Page 1) Acupuncture Points. (Page 31) Side Effects of Acupuncture. (Page 51)

Contents. Basic Theory of Acupuncture. (Page 1) Acupuncture Points. (Page 31) Side Effects of Acupuncture. (Page 51) VII Contents Basic Theory of Acupuncture (Page 1) Scientific Aspects of Acupuncture..................... 2 Indication and Direction of Action of Acupuncture.................................... 12 Relative