Lecture 9 TCM Herbs in Traditionally
Defined Properties
Y.Z. Chen
Department of Pharmacy
National University of Singapore
Tel: 65-6616-6877; Email: phacyz@nus.edu.sg ; Web: http://bidd.nus.edu.sg
Content
• TCM herbs in traditionally defined properties
• Digitization of TCM herbs in traditionally defined properties
• Classification methods for identifying TCM recipes
• TCM herb pairs
• TCM combination therapy
TCM herbs in traditionally defined properties
Herb Property
• 1. Four Characters （四性）
• 2. Five Taste （五味）
• 3. Meridian （归经）
• 4. Lifting, lowering, floating and sinking （升降浮沉）
TCM herbs in traditionally defined properties
1. Four Characters 四性 (Qi) ( The temperature Characteristic )
Cold & Cool
Hot & Warm
Even
TCM
treat
ment
Clear Heat;
Cool the heat toxin in Blood;
Clear Empty Heat;
Phlegm-heat;
Promote defecating;
Promote urination;
Nourish Yin;
Calm down liver wind;
Warm the internal cold;
Expel the external cold;
Tonify the Yang Qi;
Warm up the meridian;
Rescue the exhausted Yang;
Could be
widely used;
Herb
Shi Gao; Jin Yin Hua; Qin Hao; Gua Lou;
Da Huang; Shen Di; Ling Yang Jiao
Gang Jiang; Gui Zhi; Ma Huang;
Fu Zi; Du Huo; Rou Gui;
Gan Cao;
Clinic Practicing
•
•
•
•
Treating cold syndrome with hot-natured drugs (or heating the cold).
Treating heat syndrome with cold-natured drugs ( or cooling the heat)
Identify the “Real cold syndrome with fake heat syndromes” or “Real heat
syndromes with fake cold syndromes”
According to the development of disease to choose proper herbs
Treating both heat & cold symptoms with both cold & hot natured drugs
TCM herbs in traditionally defined properties
2. Five Taste 五味
Spicy
Function
Sweet
Bitter
Tonifying
Down bearing
Disperse
Moving
Sour
Salty
Softening
Astringing
Moderating
Moistening
Draining
Dampness
Pregnant
women
Prolapse
ContraIndication
All types
of Def.
Exterior
Wind
Diarrhea,
Profuse urine
Sp. Def. ,
Blood Def. ,
Yin def.
Any
condition
of excess:
Damp or
Stagnation
Fluid
accumulation
Damp
Loose
stools
TCM herbs in traditionally defined properties
3. Meridian 归经
Herb agents target specific channels within the body to
effect a change in that channel
Clear heat from heart:
irritability, restlessness, insomnia
The herb which enter the small intestine are cold
to treat damp heat urinary problem or expel water
through intestine
Transform damp and treat wind damp, phlegm,
diarrhea or toxic swelling
TCM herbs in traditionally defined properties
Many herbs which enter the stomach channel clear
heat, especially toxic heat
All herbs in the surface releasing categories enter
lung channels
Treat damp heat diarrhea or intestinal abscess
Tonify Yin, Yang or essence; Clear empty heat in
kidney; or help drain damp
TCM herbs in traditionally defined properties
Treat jaundice or to guide the herb to the shao yang
energetic level
Treat wind syndromes like inchy skin, bloody diarrhea,
or tremors, drain liver fire, relieve liver Qi stagnation,
or treat eye problem due to heat
Treat edema; Drain damp heat from the lower burner;
TCM herbs in traditionally defined properties
• 4. lifting, lowering, floating and sinking 升降浮沉
Varying disease often appear to bear a tendency to move
upward, downward, towards the exterior or the interior.
Corresponding to the above, the direction of actions of medicinal
herbs on human body also have the lifting, lowering, floating and
sinking
distinction Lowering
lifting
Floating
Sinking
The direction of
herbal actions is
toward the upper
parts, which are
indicated for a
disease in a lower
and deeper parts
They function toward
the lower parts and
possess the action
of descending
adverse Qi and are
indicated for the
disease due to
adverse ascending
of pathogenic factors
Floating herbs
function toward the
upper and outward
parts, generally
exert the effects of
sweating and
dispersing and are
indicated for the
disease in the upper
and superficial parts
Sinking herbs
function toward the
lower and inward
parts, have the
effects of lowering
the adverse flow of
Qi and relaxing
bowels and are
indicated for the
disease in the lower
and interior
Huang Qi + Sheng Ma:
Dai Zhe Shi; Cheng
Xiang; Shi Jue Ming
MaHuang; Zi Su; Fang
Feng; Du Huo
Da Huang; Mu Tong
Prolapse disease
Cough, dizziness,
vomiting
Exterior cold
Constipation; dysuria
TCM herbs in traditionally defined properties
TCM herbs in traditionally defined properties
Digitization of TCM herbs in traditionally defined properties
Digitization of TCM herbs in traditionally defined properties
Digitization of TCM herbs in traditionally defined properties
Digitization of TCM herbs in traditionally defined properties
Geometric Picture of Digital Representation
Feature vectors:
A=(1, 1, 1)
B=(0, 1, 1)
C=(1, 1, 1)
D=(0, 1, 1)
E=(0, 0, 0)
F=(1, 0, 1)
Descriptor
Feature vector
Positive
examples
Negative
examples
Geometric Picture of Digital Representation
Feature vectors in input space:
Z
Input space
Feature vector
A=(1, 1, 1)
B=(0, 1, 1)
C=(1, 1, 1)
D=(0, 1, 1)
E=(0, 0, 0)
F=(1, 0, 1)
F
E A
B
Y
X
Classification methods for identifying TCM recipes
kNN method
Classification methods for identifying TCM recipes
Support Vector Machines
(SVM) method
Classification methods for identifying TCM recipes
Support Vector Machines
(SVM) method
Classification methods for identifying TCM recipes
Classification methods for identifying TCM recipes
TCM Herb Pairs
Compatibility of TCM Herb Pairs
• 1. Mutual reinforcement （相须）
• 2. Mutual assistance （相使 ）
• 3. Mutual restraint or detoxication（相畏 or相杀）
• 4. Mutual Antagonism （相恶）
• 5. Mutual Incompatibility （相反）
TCM Herb Pairs
• 1. Mutual reinforcement （相须）
• That is, two or more ingredients with similar properties and
effects are used in combination to reinforce each other’s
action
Mutual reinforcement
Effects & Action
•
Da Huang + Mang Xiao
Purgating action
Tao Ren + Hong Hua
Invigorating the blood
Zhi Mu + Huang Bai
Clear deficient fever
Ru Xiang + Mo Yao
Invigorating the blood
Fu Zi + Gan Jiang
Warm up the Yang Qi
Quan Xie +Wu Gong
Stop muscle Spasm
TCM Herb Pairs
2. Mutual assistance （相使 ）
• That is, Chinese medicinal herbs that are not certainly
similar but have some relationship in the aspect of
medicinal properties and actions are used in combination,
in which one herb is taken as the dominate factor and the
others as its assistants to raise its therapeutic effects.
•
Dominate herb
Assistant herbs
Effects & Action
Huang Qi
Fang Ji
Promote water circulation &
permeating the dampness
Huang Lian
Mu Xiang
Stop diarrhea & abdomen
pain
Da Huang
Huang Qin
Clear damp-heat
TCM Herb Pairs
3. Mutual restraint or detoxification（相畏or相杀）
• That is, mutual restraining effect of different medicines to
weaken or neutralize each other’s harmfulness, such as
toxicity or side-effects.
•
Mutual restraint
Ban Xia; Dan Nan Xing
Sheng Jiang
Ren Sheng
Wu Ling Zhi
Fu Zi
Gan Jiang
Fu Zi
Gan Cao
TCM Herb Pairs
• Mutual Antagonism (相恶)
•
The ability of two substances to minimize or
neutralize each other’s positive effects
Ba Dou
Qian Niu Zi
Gan Yin Wan ( 感应丸 )
Ding Xiang
Yu Jin
Shi Xiang Fan Hun San ( 十香反魂散 )
Chuan Wu &
Cao Wu
Xi Jiao
Da Huo Luo Wan ( 大活络丸 )
Ren Shen
Wu Ling Zhi
Rou Gui
Chi Shi Zhi
*Liu Huang
*Pu Xiao
*Shui Yin
*Pi Shuang
*Lang Du
*Mi Tuo Shen
*Ya Xiao
*San Leng
TCM Herb Pairs
• Mutual Incompatibility (相反)
Cause side effects or toxicity if use together
Gan Cao
Gan Sui
Da Ji
Yuan Hua
Hai Zao
Dosage: Gan Cao>= Gan Sui
Wu Tou
( Fu Zi )
Ban Xia
Gua Lou
Bei Mu
Bai Ji
Bai Lian
Bei Mu or Ban Xia + Fu Zi ( No
evidence support it )
Li Lu
Ren Shen
Dang Shen
Dan Shen
Xuan Shen
Sha Shen
Ku Shen
Xi Xin
Bai Shao
Xi Xin + Li Lu: cause animal death
in the lab
TCM Herb Pairs
TCM Herb Pairs
Method Training Testing Testing Herb-Pair Non-HerbSet
Set
Method Accuracy Pair
Accuracy
PNN
kNN
SVM
360
39
10-fold
CV
87.9%
91.6%
72.1%
97.1%
78.1%
97.6%
TCM Herb Pairs
TCM herbal ingredient pairs displaying
pharmacokinetic synergism
By inhibiting the actions of the drug efflux transporters,
resulting in an accumulation of the TCM herbal ingredients
and thus a potentiation of their effects in the target cells.
An example is the combination of genistein (from Semen
Sojae Praeparata, Oleum Glycines, Radix Sophorae
Japoniae, Flos Sophorae, Fructus Sophorae, Folium
Sophorae Japoniae, Semen Glycines Max, Caulis
Spatholobi, Radix Sophorae Tonkinensis) and paclitaxel
(from Taxus Chinensis)
TCM Herb Pairs
Mechanism of synergistic actions of paclitaxel
and genistein
TCM Herb Pairs
TCM herbal ingredient pairs displaying pharmacokinetic
synergism
By modulating its metabolism, resulting in an accumulation of
the TCM herbal ingredient and thus a potentiation of their effects
in the target cells.
An example is the combination of TCM herbal ingredient pair
comprising of caffeine (from Radix Camellia Sinensis, Folium
Camelliae Sinensis, Fructus Camellia Sinensis, Folium Ilicis
Cornutae, Cortex Firmianae Plantanifoliae, Radix Firmianae
Plantanifoliae, Flos Firmianae Plantanifoliae, Folium Firmianae
Plantanifoliae, Semen Firmianae) and apigenin (from Herba
Lagotidis, Flos Campsis, Herba Artemisiae Anomalae, Herba
Ephedrae, Flos Buddlejae, Herba Artemisiae Anomalae, Flos
Genkwa, Radix seu Cortex Daphnes Genkwae, Radix Campsis
Grandiflorae)
TCM Herb Pairs
Mechanism of synergistic actions of caffeine
and apigenin
TCM Herb Pairs
TCM herbal ingredient pairs displaying
pharmacodynamic synergism
The combination of eugenol (from Fructus Artemisiae Argyi,
Folium Artemisiae Argyi, Caulis Perillae Frutescentis, Folium
Perillae Frutescentis, Dianthus Superbus, Fructus Perillae
Preparata, Alpinia Galangae, Flos Caryophylli, Radix Syzygii
Aromatic, Liquor Destillata Caryophylli, Cortex Syzygii
Aromatic, Ramulus Syzygii Aromatic, Fructus Galangae,
Pericarpium Zanthoxyli, Flos Lonicerae, Herba Asari) and low
concentration of quercetin (from Herba Patriniae
Scabiosaefoliae, Herba Patriniae, Radix Bupleuri, Herba
Euphorbiae Humifusae, Radix Lamiophlomidis Rotatae,
Rhizoma Alpiniae Officinarum, Herba Hyperici, Herba
Lagotidis, Cannabis Sativa L.,
TCM Herb Pairs
TCM herbal ingredient pairs displaying
pharmacodynamic synergism
Radix Astragali, Fructus Ligustri Lucidi, Herba Artemisiae
Annuae, Radix Artemiiae Annua, Semen Artemisiae, Herba
Taxilli, Fructus Quisqualis, Radix Quisqualis Indica, Herba
Pyrolae Chinensis, Herba Ephedrae) exerts an anti-allergic
and anti-inflammatory effect that alleviates allergic rhinitis,
which is congruous to the therapeutic effect of the TCM herbal
pair, Herba Asari and Herba Ephedrae, containing eugenol and
quercetin respectively. This TCM herbal pair has been used to
treat allergic rhinitis. The similarity in therapeutic effect of the
TCM herbal ingredient pair and the TCM herbal pair can be a
sign of possible synergism between the ingredients in the TCM
herbal ingredient pair.
TCM Herb Pairs
Mechanism of synergistic actions of eugenol
and quercetin (low concentration)
TCM Combination Therapy
Case study 1: Antidepressant activity of St.
John’s Wort
St. John’s Wort (SJW) is an extract from the plant Hypericum
perforatum L. Numerous clinical trials have shown that SJW
had significant antidepressant efficacy and lower side effects
than standard antidepressants. In many countries, it has been
widely used for the treatment of mild to moderate forms of
depression. SJW has been included in the pharmacopoeias of
Germany and the US.
The main active ingredients of SJW are hyperforin (HP),
hypericin (HY), pseudohypericin (PH), amentoflavone (AF),
and several flavonoids (FL)
TCM Combination Therapy
Case study 1: Antidepressant activity of St. John’s Wort
TCM Combination Therapy
Case study 1: Antidepressant activity of St. John’s Wort
TCM Combination Therapy
Case study 2: The effect of Realgar-Indigo naturalis
formula (RIF) on acute promyelocytic leukemia (APL)
TCM formula RIF has been used in China to treat APL since
1980s.
RIF consists of four herbs, realgar, Indigo naturalis, Salvia
miltiorrhiza, and Radix pseudostellariae. In TCM theory,
multiple agents contained in one formula must work
synergistically. Realgar is regarded as the principal component
of the formula RIF, and the other three are adjuvant
components to assist the effect of realgar.
The main active compounds of realgar, Indigo naturalis and
Salvia miltiorrhiza are tetraarsenic tetrasulfide (As4S4, A),
indirubin (I) and tanshinone IIA (T), respectively.
TCM Combination Therapy
Case study 2: The effect of Realgar-Indigo naturalis
formula (RIF) on acute promyelocytic leukemia (APL)
A) Protein interaction network. (B) Protein-pathway association network.
TCM Combination Therapy
Case study 2: The effect of Realgar-Indigo naturalis
formula (RIF) on acute promyelocytic leukemia (APL)
TCM Combination Therapy
Comparison with combination therapy in Western medicine
TCM Combination Therapy
Comparison with combination therapy in Western medicine
TCM Combination Therapy
Comparison with combination therapy in Western medicine
TCM Combination Therapy
Comparison with combination therapy in Western medicine
Acknowledgement
Current Group Members:
•
•
•
•
•
Computer-Aided Drug Design: CY Ung, XH Ma, XH Liu, Pankaj Kumar, F Zhu, X Liu, J Jia
Protein Function, Interaction, Network: HL Zhang, CY Ung, XH Ma, F Zhu, WK Teo, Z Shi
Databases and Servers: J Jia
Medicinal Herb: CY Ung, Pankaj Kumar, Cao Jinyi(undergraduate students)
Microarray and biomarkers: J Jia, ZQ Tang
Former Members:
PhD:
ZW Cao (Prof SCBIT, Tongji U), ZL Ji (Assoc Prof Xiamen U), X Chen (Assoc Prof Zhejiang U),
CW Yap (Assist Prof NUS), LY Han (Postdoc NIH), CJ Zheng (Postdoc NIH),
HH Lin (Postdoc Harvard ), J Cui (Postdoc U Georgia), H Li (Postdoc Einstein College Med)
Research Fellow/Assistant:
ZR Li (Assoc Prof SiChuan U), Y Xue (Prof SiChuan U), W Liu (Assoc Prof DUT),
D Mi (Assoc Prof DUT), CZ Cai (Prof ChongQing U), DG Zhi (Postdoc, Berkeley),
MSc:
Y.J. Guo (Postdoc NIH), L.Z. Sun (RA, U Tenn.), J. F. Wang (MSU), L.X. Yao (Columbia),
S Ong (Washington U), H Zhou (local company), B Xie (local company)
BSc:
W.K. Yeo (IMCB, Novartis)