Lecture 9 TCM Herbs in Traditionally Lecture 9 TCM Herbs in Traditionally Defined PropertiesDefined Properties
Y.Z. ChenY.Z. Chen Department of PharmacyDepartment of Pharmacy
National University of SingaporeNational University of Singapore Tel: 65-6616-6877; Email: [email protected] ; Web: http://bidd.nus.edu.sgTel: 65-6616-6877; Email: [email protected] ; Web: http://bidd.nus.edu.sg
ContentContent
• TCM herbs in traditionally defined propertiesTCM herbs in traditionally defined properties
• Digitization of TCM herbs in traditionally defined propertiesDigitization of TCM herbs in traditionally defined properties
• Classification methods for identifying TCM recipesClassification methods for identifying TCM recipes
• TCM herb pairsTCM herb pairs
• TCM combination therapyTCM combination therapy
Herb PropertyHerb 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 propertiesTCM herbs in traditionally defined properties
1. Four Characters 四性 (Qi) ( The temperature Characteristic )
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
Cold & Cool Hot & Warm Even
TCM treatment
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;
TCM herbs in traditionally defined propertiesTCM herbs in traditionally defined properties
2. Five Taste 五味Spicy Sweet Bitter Sour Salty
FunctionFunction DisperseDisperse
TonifyingTonifying Down bearingDown bearing
AstringingAstringing
SofteningSoftening
ModeratingModeratingMovingMoving
MoisteningMoisteningDrainingDraining
Contra-
IndicationAll types of Def.
DampnessPregnant women
Any condition of excess: Damp or
Stagnation
Fluid accumulat-
ion
Exterior Wind
Prolapse
Diarrhea, Profuse urine
Damp
Sp. Def. , Blood Def. ,
Yin def.
Loose stools
TCM herbs in traditionally defined propertiesTCM herbs in traditionally defined properties
3. Meridian 3. Meridian 归经Herb agents target specific channels within the body to Herb agents target specific channels within the body to
effect a change in that channeleffect 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 propertiesTCM 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 propertiesTCM 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 propertiesTCM 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 distinctionlifting Lowering 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 propertiesTCM herbs in traditionally defined properties
TCM herbs in traditionally defined propertiesTCM herbs in traditionally defined properties
TCM herbs in traditionally defined propertiesTCM herbs in traditionally defined properties
Digitization of TCM herbs in traditionally defined propertiesDigitization of TCM herbs in traditionally defined properties
Digitization of TCM herbs in traditionally defined propertiesDigitization of TCM herbs in traditionally defined properties
Digitization of TCM herbs in traditionally defined propertiesDigitization of TCM herbs in traditionally defined properties
Digitization of TCM herbs in traditionally defined propertiesDigitization of TCM herbs in traditionally defined properties
Geometric Picture of Digital RepresentationGeometric Picture of Digital Representation
A=(1, 1, 1)B=(0, 1, 1)C=(1, 1, 1)D=(0, 1, 1)E=(0, 0, 0)F=(1, 0, 1)
Feature vectors: Descriptor
Feature vector
Positive examples
Negative examples
Geometric Picture of Digital RepresentationGeometric Picture of Digital Representation
Feature vectors in input space:
A=(1, 1, 1)B=(0, 1, 1)C=(1, 1, 1)D=(0, 1, 1)E=(0, 0, 0)F=(1, 0, 1)
Z
Input space
X
Y
BAE
F
Feature vector
Classification methods for identifying TCM recipesClassification methods for identifying TCM recipeskNN method
Classification methods for identifying TCM recipesClassification methods for identifying TCM recipesSupport Vector Machines(SVM) method
Classification methods for identifying TCM recipesClassification methods for identifying TCM recipes
Support Vector Machines(SVM) method
Classification methods for identifying TCM recipesClassification methods for identifying TCM recipes
Classification methods for identifying TCM recipesClassification methods for identifying TCM recipes
Compatibility of TCM Herb PairsCompatibility 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 PairsTCM 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 PairsTCM 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 PairsTCM 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 PairsTCM 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 PairsTCM 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 PairsTCM Herb Pairs
TCM Herb PairsTCM Herb Pairs
TCM Herb PairsTCM Herb Pairs
Method Training Set
Testing Set
Testing Method
Herb-Pair Accuracy
Non-Herb-Pair Accuracy
PNN 360 39 10-fold CV
87.9% 91.6%
kNN 72.1% 97.1%
SVM 78.1% 97.6%
TCM Herb PairsTCM 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 PairsTCM Herb PairsMechanism of synergistic actions of paclitaxel and genistein
TCM Herb PairsTCM Herb PairsTCM 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 PairsTCM Herb PairsMechanism of synergistic actions of caffeine and apigenin
TCM Herb PairsTCM 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 PairsTCM Herb PairsTCM 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 PairsTCM Herb PairsMechanism of synergistic actions of eugenol and quercetin (low concentration)
TCM Combination TherapyTCM 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)
Case study 1: Antidepressant activity of St. John’s WortTCM Combination TherapyTCM Combination Therapy
Case study 1: Antidepressant activity of St. John’s Wort
TCM Combination TherapyTCM Combination Therapy
TCM Combination TherapyTCM 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 TherapyTCM Combination TherapyCase 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 TherapyTCM Combination TherapyCase study 2: The effect of Realgar-Indigo naturalis formula (RIF) on acute promyelocytic leukemia (APL)
TCM Combination TherapyTCM Combination TherapyComparison with combination therapy in Western medicine
TCM Combination TherapyTCM Combination TherapyComparison with combination therapy in Western medicine
TCM Combination TherapyTCM Combination TherapyComparison with combination therapy in Western medicine
TCM Combination TherapyTCM Combination TherapyComparison with combination therapy in Western medicine
AcknowledgementAcknowledgement
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)