Complementary Therapies in Medicine (2012) 20, 9399

Available online at www.sciencedirect.com

journal homepage: www.elsevierhealth.com/journals/ctim

Future perspectives of personalized medicine in

traditional Chinese medicine: A systems biology
approach
Aihua Zhang, Hui Sun, Ping Wang, Ying Han, Xijun Wang

National TCM Key Lab of Serum Pharmacochemistry, Heilongjiang University of Chinese Medicine, and Key
Pharmacometabolomics Platform of Chinese Medicines, Heping Road 24, Harbin 150040, China
Available online 30 November 2011

KEYWORDS Summary Deconstruction of molecular pathways and advances in enabling technology plat-
forms have opened new horizons for disease management, exploring therapeutic solutions
Personalized
to each individual patient beyond the one-size ts all practice. Application of personalized
medicine;
medicine paradigms aims to achieve the right diagnosis and right treatment for the right patient
Traditional Chinese
at the right time at the right cost. With the potential to transform medical practice across
medicine;
global communities, personalized medicine is emerging as the agship of modern medicine.
Systems biology;
In recent years, the health care paradigm has shifted from a focus on diseases to a major
Omics;
hot of personalized traditional Chinese medicine (TCM) with holistic approach. TCM focuses on
Biomarkers;
health maintenance, emphasizes on enhancing the bodys resistance to diseases and especially
Treatment of
showes great advantages in early intervention, personalized and combination therapies, etc.
differential
Systems biology, a new science of the 21st century, becomes practically available and resem-
syndrome;
bles TCM in many aspects such as study method and design, and is current key component
Individualized
technologies that serves as the major driving force for translation of the personalized medicine
medicine
revolution of TCM principles into practice, will advance personalized therapy principles into
healthcare management tools for individuals and populations. Such system approach concepts
are transforming principles of TCM to modern therapeutic approaches, enable a predictive and
preventive medicine and will lead to personalized medicine. To realise the full potential of
personalized TCM, we describe the current status of principles and practice of TCM integrated
with systems biology platform. Some characteristic examples are presented to highlight the
application of this platform to personalized TCM research and development as well as some of
the necessary milestones for moving TCM into mainstream health care.
2011 Elsevier Ltd. All rights reserved.

Contents

Introduction............................................................................................................... 94
Basic principles of personalized TCM ...................................................................................... 94

Corresponding author. Tel.: +86 451 82110818; fax: +86 451 82110818.
E-mail addresses: phar research@hotmail.com, xijunwangls@126.com (X. Wang).

0965-2299/$ see front matter 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.ctim.2011.10.007
94 A. Zhang et al.

Personalized characteristics of TDS: translating the promise into practice ............................................ 95

Combinatorial formulae for personalized therapy..................................................................... 95
TDS corresponding formulae .......................................................................................... 95
Physique characteristics .............................................................................................. 95
A systems biology technology platform for practice of personalized medicine ........................................ 96
Genomics platform ................................................................................................... 96
Proteomics platform.................................................................................................. 96
Metabolomics platform ............................................................................................... 96
Conclusion and future perspective.................................................................................... 97
Competing nancial interests......................................................................................... 97
Acknowledgements ................................................................................................... 97
References ........................................................................................................... 97

Introduction holistic approach to cure human diseases through estab-

One important special feature of biology is its diversity, its
variation.1 That is why personalized medicine is signicant.
Personalized medicine refers to the right treatment for
the right individual at the right time in the health-care
world and has the potential to diminish the incidence
of drug adverse reactions, eliminate invalid therapy,
improve the efcacy of treatments, ultimately, achieve
optimal health outcomes.24 During recent years, most
people seem to agree that personalized medicine is the
trend of the future.5 The personalized medicine market
is estimated at about $232 billion, and is projected to
grow 11% annually, expected to nearly double in size by
2015 to more than $450 billion, according to a recent Price
Waterhouse Coopers report.6 The health-care paradigm
has shifted from a focus on diseases to a holistic approach
to health care.7,8 Owing to the accomplishment of the
Human Genome Project (HGP), personalized medicine
is looming in the horizon and modern medicine moves
towards a new individualized health-care model with
biologicalpsychologicalsocialenvironmentalspiritual
characteristics that reect the thinking of patient-
centred care. Fortunately, the personalized traditional
Chinese medicine (TCM) affords new signicance of
personalized health care and advances the practice
research.
The area of integrating TCM with systems biology
approach has become a major hot topic of personalized
medicine research. TCM, a key approach to the practice
of personalized medicine in the future, has been used in
Asian countries for thousands of years, based on the indi-
viduals physiology and the holistic characteristics. Recent
advances in systems biology technology have enabled the
discovery of biomarkers, provided the basis for the develop-
ment of new targeted drugs, potentially offered the right
therapy for the right patient.9 Such technologies, for exam-
ple, genomics, proteomics and metabolomics, have been
able to identify biomarkers of a particular disease within the
set of genes, proteins and metabolites of a given organism.10
TCM has developed its own coherent theories with regard
to diagnosis and treatment of disease and accrued a myr-
iad of valuable clinical observations, some of which have
provided the basis for successful personalized medicines.11
TCM pays attention to the whole and individual parts of
the body, the general and specic character, uses a unique
lishment of equilibrium in the human life, body, mind,
intellect and soul, so satisfactory treatment results could be
achieved. As one of the most important parts of medicine,
TCM has been accepted by patients as superior value in the
treatment of multiple organ system disorders, chronic dis-
eases and metabolic syndromes, and should play a key role
in the formation of personalized medicine.12
Systems biology, a new science of the 21st century,
becomes practically available and resembles TCM in many
aspects such as study method and design.13 Combining
the systems biology with in-depth investigations of TCM
mechanisms will enable a revolution in our understand-
ing of disease pathology and will advance personalized
medicine.14 Systems biology studies living systems from
whole systems instead of isolated parts, opening up a
novel opportunity to reinvestigate TCM.15 As an important
part of life science, the notions of the whole or sys-
tem of TCM rather than the isolated parts are important
concepts, which t well to the systems biology theory. Adop-
tion of systems biology approach would do much to help
explore the scientic connotation of treatment of differ-
ential syndrome (TDS, diagnosis and treatment based on
over-all symptoms and signs) and revolutionize personal-
ized TCM.13,1618 As World Health Organization proposed
Health for All, we should be able to promote the use
of traditional medicine. There are new signs that the pur-
suit of both personalized TCM and systems biology will be
a priority for people and pave the way towards personal-
ized health care.19,20 Together with new technologies, such
systems approaches are transforming current therapeutic
approaches to enable a predictive and preventive medicine
that will lead to personalized medicine.2124 In order to
realise the potential role of personalized medicine, our spe-
cial article describes the increasing importance of principles
and practice of TCM integrated with the systems biology
platform, and discusses some of the ongoing challenges for
integrating personalized medicine into mainstream health
care.
Basic principles of personalized TCM
TCM has been used for thousands of years to treat diseases
and has many benecial effects for disease control.25,26 The
focus of TCM science is on the patient rather than the dis-
ease. The key theories of TCM comprise the yinyang, the
Future perspectives of personalized medicine in traditional Chinese medicine: A systems biology approach
ve elements, Qi and Blood, Zang-fu organ and four natures.
Consistent with the homeostasis, the holistic adjustment to
pursuit system balance of the yin and yang is the principle
of TCM syndrome. In a mainstream therapeutic manner, sys-
tem balance has been practiced for centuries in TCM and
has attracted worldwide interest. Based on thinking of sys-
tem medicine, making system balance is the aim for disease
treatment; combination therapy is the challenging method
for performing the purpose in modern medicine.27 TCM views
the human body as a dynamic energy system with yinyang
balance, and disease as an unbalanced state. Combination
therapy is the main strategy of TCM to adjust a disease
state to system balance of a dynamic state. The biological
effects of the four natures of TCM, including cold, hot, warm
and cool, have an effect on the central nervous system,
endocrine system, on the activity of sympathetic nerves,
basal metabolic rate, the function of organs and tissues and
secretion of cytokines out of the body.28 Four natures of TCM
will be a multi-factor and target research, connecting Chi-
nese medicine theory. Water, earth, metal, wood and re
are the ve elements of the material world. The internal
Zang-fu organ systems play an important role in the yin and
yang balance. The clinical diagnosis and treatment in TCM
are mainly based on the above theories. Based on the fron-
tier science and key approaches, establishing the direction
for personalized medicine with TCM properties was essential
for the health of mankind.
Personalized characteristics of TDS: translating the
promise into practice
Personalized treatment of TCM was rst recorded in The
Yellow Emperors Classic of Internal Medicine, which is
a classical Chinese medicine book. For improving health,
TCM applies multiple natural therapeutic methods, such
as acupuncture, moxibustion and herbal medicine. All TCM
therapeutic approaches come from the effective TDS.29
Holistic, spacetime dynamics and individual variance are
three personalized characteristics of TCM syndrome. The
external information should appear something of intrinsic
disease. From these points of view, syndrome should play
an important role in impacting on disease pathogenesis that
directly inuences the therapeutic effect. Modern medicine
aims to explore the specicity of morbidity, while TCM
mainly explores the reality of the morbidity by checking
the external appearance (that is TDS). Disease treatment
based on the syndrome differentiation is to determine the
appropriate treatment. TCM treatment of disease does not
primarily focus on the similarities and differences of dis-
ease, but rather on the difference of syndrome through
TDS and better understanding of the disease. TDS is a typi-
cal individualized treatment method of TCM diagnosis and
treatment process, and focusses on discrimination of the
personality characteristics. Individualized treatment high-
lights personalized features with the specic clinical and
appropriate diagnosis treatment. TDS in the treatment pro-
cess not only pays attention to common features of the
human body, but also focusses on the analysis of personality
characteristics. Therefore, the individualized treatment is
closely related to the TDS process.
95
Combinatorial formulae for personalized therapy
As a unique medical system, TCM advocates combinatory
therapeutic strategies by prescriptions called formulae.
Typically, formulae are comprised of several types of crude
herbs or minerals, in which one represents the key com-
ponent, and others serve as adjuvant ones to assist the
effects or facilitate the delivery of the key component.30 It
is believed that formulae can hit multiple targets and pro-
duce a synergistic therapeutic effect. The pharmaceutical
industry has shifted from the search of disease treatments
with the one disease-one target-one drug and the one-
drug-ts-all concepts to the pursuit of combination therapy
that comprise more than one active ingredient.31,32 Com-
bination medicine with multi-effect-pathway targets have
better efcacy than a single drug alone, and can change the
current predicament state in the therapy. Modern medicine
has acknowledged that combination application of TCM can
achieve a synergistic interaction capable of yielding a suf-
cient effect at low doses that has increased signicantly in
recent years. On the basis of characteristics of patients and
guided by the TDS, formulae contain a combination of dif-
ferent herbal or mineral medicine to improve efcacy. TDS is
the basis for Chinese medicine, and formulae compatibility
is the core of prescriptions; they both are complementary
and mutually dependent. Formulae compatibility is the goal
to achieve overall balance and regulation of the holistic fea-
tures. Modern pharmacology from the multi-target effects
mainly refers to a drug molecule that can occur on multiple
metabolic aspects of the key role of efcacy, but it ignores
the overall balance adjustment. Fortunately, the systems
biology approach may contribute to explain individual dif-
ferences in response to treatment, as well as adverse drug
response differences.
TDS corresponding formulae
TDS corresponding formulae (TCF), a unique dialectical
model, refers to the collection, analysis, comparison and
identication of clinical data, to nd out the relation-
ship between the syndrome and corresponding prescription
and understand the effect and mechanism of the prescrip-
tion. Syndromes and prescriptions are two important parts
of TCM. Syndrome is a certain stage of a comprehensive
response of patients with body condition, whereas prescrip-
tion is the primary means of TCM treatment. Seizing the
corresponding relationship between the syndrome and pre-
scription and clarifying the mechanism of prescription has
great clinical value for the patient. As one of the key prin-
ciples of TCM prescription, each prescription has its specic
syndrome and treatment. As an important part of TDS, TCF
is the embodiment of the principles of TDS diagnosis and
treatment. The combination of syndrome and formulae will
set up a bridge to explore the intrinsic link between clinical
and efcacy.
Physique characteristics
Physique characteristics are often the best embodiment of
TDS, and play an important role in certain diseases. Human
physique is considered as a special state of an individual
96
with relative stability in function, structure and metabolism,
formed during growth, development and ageing, undering
effects of the environment and on the basis of individ-
ual heredity. Physique theory of TCM is based on various
human physical characteristics, physical type of physiologi-
cal and pathological characteristics, and thus the response
and development of disease status, to guide disease pre-
vention, treatment and health rehabilitation. It emphasizes
regulating the overall function of the human body based on
the physical characteristics and more attention is given to
differences between individuals, and at the same time, due
to individual differences of physique in the dose response
and tolerability, which should be based on physical dif-
ferences, are adopting different methods and principle of
treatment and dosage. The physical characteristics are the
innate and relatively stable endowments and form the basis
of morphological, physiological and psychological status
comprehensively, with the natural and social environment
suited to human personality characteristics. Some think that
attention in the 21st century will develop in both macro-
scopic and microscopic directions. The former is about how
humans go into the universe and rule the universe and the
latter includes how humans know themselves and reshape
themselves. It could be seen that humans will gradually
focus on themselves in the future. This trend is getting ever
clear from developments in biology, genetics and immunol-
ogy; certainly, it will be the favourite of the times.
A systems biology technology platform for practice
of personalized medicine
Systems biology has developed from a technology-driven
enterprise to a new strategic tool in life sciences, particu-
larly for innovative TCM development.3338 A systems biology
approach has been explored to nd subtypes of rheumatoid
arthritis patients enabling a development towards more per-
sonalized medicine.39 The identied biomarkers have the
potential to bring increased accuracy in disease diagnosis
and monitoring. Combining systems biology with in-depth
investigations of personalized TCM will enable a revolution
in our understanding of disease and will advance person-
alized medicine.40 A prerequisite for deriving the benets
of such a systems approach is a well-validated bioana-
lytical platform, especially a genomics, proteomics and
metabolomics platform.
Genomics platform
Genomics, which is the use of information from genomes
and their derivatives to guide medical decision making,
is a key component of personalized medicine, which uses
genetic information to tailor strategies for each patient.41,42
Researchers believe that genomics has the potential to
revolutionize the practice of personalized medicine, and
improve the diagnosis, prevention and treatment of disease,
and reduce adverse drug reactions.43,44 With the completion
of the HGP in May 2006, genetic testing for every per-
son is rapidly becoming a reality.45 Personalized medicine
can take advantage of the genetic framework to provide
the health-care system with useful tools that can opti-
mize the effectiveness of treatment.4648 The combined
A. Zhang et al.
genome-wide expression analysis with methods of systems
biology can identify the functional gene networks for the
sets of clinical symptoms that comprise the major infor-
mation for pattern classication related to hot and cold
patterns in TCM.49 Wang et al.50 studied the patients with
cold syndrome using gene chip method and found that gene
expression spectrum of the patients with cold syndrome
was signicantly different from that of normal controls.
Among the 59 differently expressed genes, most of them
were related with metabolism such as energy metabolism
or protein metabolism, etc., indicating that the metabolic
network may be the major component in differentiation
of cold syndrome. The new discoveries of genomics pro-
vide meaningful insights that will increase doctors ability
to personalize treatment in a not-too-distant future.5153
Proteomics platform
Proteomics have provided a means for molecular proling
that allows personalized therapy. It is the information of a
whole proteome, which refers to the entire complement of
proteins including the modulation made to a particular set of
proteins within an organism or system. The ability to detect
expressed proteins has enormous potential for early diag-
nostics and intervention at curable stages of disease.5456
The analysis of this extended range of biomarkers will prove
critical for the development and implementation of per-
sonalized medicine. In addition, the components of Chinese
herbal medicine, that is, either a single herb or formulae,
are complex chemical systems, and each component binds to
its own target receptor. Individual variance is the foundation
of TCM syndrome science. All these characteristics of TCM
syndromes might be related to various proteins with differ-
ences in contents, functions and structures. With the help
of functional proteomics, functions, structures and interac-
tions of proteins expressed by a cell, a tissue or body uid
in different syndromes, and the changes of proteins before
and after treatment with single herb or a formulae could
be analysed. Therefore, the characteristic of proteomics
is analysing numerous proteins; simultaneously, proteomics
could provide a platform for research of the essence of TCM
syndromes.
Metabolomics platform
Metabolomics is a novel area that promises to contribute to
the identication of personal metabolic features that can
predict response to therapies.57 It incorporates the most
advanced approaches to provide the ideal technology plat-
form for the discovery of biomarker patterns associated
with healthy and diseased states, for use in individualized
health-monitoring designs.58 From a clinical standpoint, the
metabolomics has two major potential applications. The
rst is the early diagnosis and characterisation of disease
phenotypes. The second application concerns the identi-
cation of individual characteristics able to predict drug
effectiveness or toxicity. Metabolomics, based on the sys-
tematic complement of metabolites in a biological sample,
is the best to t the holistic concept of multi-target systems
of TCM. Many claims have been attached to the promise of
personalized medicine. One example of this approach is that
Future perspectives of personalized medicine in traditional Chinese medicine: A systems biology approach
Chen et al.59 found that the metabolic network of animal
model with kidney-yang deciency was signicantly differ-
ent from that of normal controls using the metabolomics
analyses. Moreover, Chinese herbs with the property of
warming kidney-yang could normalize the metabolic chart
of the animals with kidney-yang deciency, showing that
changes of metabolic network could be repaired with proper
herbal treatment. The future goals for metabolomics are the
validation of existing biomarkers, in terms of mechanism
and translation to man, together with a focus on character-
ising the individual health care. Metabolomics will pave the
way for a better understanding of the mechanisms of dis-
ease, ultimately advance the personalized TCM and lay the
groundwork for the application of personalized medicine in
the 21st century.60,61 The rapid advances in systems biology
are making these dreams come true.
Conclusion and future perspective
With the recent understanding of systems biology, the era of
one size ts all therapy concepts has passed and a new era
of personalized medicine has started.62,35,63 Several omics
technologies are being increasingly used for this purpose
and personalized medicine efforts are in progress in major
therapeutic areas.64,65 The individualisation of medicine and
health care appears to be following a general societal trend.
Hence, the main rationale of personalized medicine could
focus on treating disease by relying on relevant structure
and state of patients whole molecular network, thus imply-
ing right therapy for the patient at the right dose and time.
The future of personalized TCM should therefore rely on
the methods of systems biology to develop the efcient
and effective diagnostic, prognostic and predictive biomark-
ers. Personalized medicine introduces the promise to use
biomarkers that signal the risk of disease or its presence
before clinical signs and symptoms appear. This information
underlies a new health-care strategy focussed on prevention
and early intervention, rather than reaction to advanced
stages of disease. Systems biology approaches identifying
molecular drivers and biomarkers will facilitate the practice
of personalized TCM. It is conceivable that the applica-
tion of technologies developed in proteomic, genomic and
metabolomic platforms will eventually lead to the reconcil-
iation and integration of TCM with contemporary medicine.
TCM is fundamentally a highly personalized medicine; per-
haps it is time to embrace the arrival of TCM-OMICS era. We
are at the dawn of a new era of personalized medicine.
Competing nancial interests
The authors declare no competing nancial interests.
Acknowledgements
This work was supported by grants from the Key Program
of the Natural Science Foundation of the State (Grant No.
90709019), the National Key Program on the Subject of Drug
Innovation (Grant No. 2009ZX09502-005), the National Spe-
cic Program on the Subject of Public Welfare (Grant No.
97
200807014) and the National Program for Key Basic Research
Projects in China (Grant No. 2005CB523406).
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