tcm herbs in traditionally defined properties

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 EvenTCM 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;


2. Five Taste 五味Spicy Sweet Bitter Sour Salty

FunctionFunction DisperseDisperse

TonifyingTonifying Down bearingDown bearing

AstringingAstringing

SofteningSoftening

ModeratingModeratingMovingMoving

MoisteningMoisteningDrainingDraining

Contra-Indication

All types of Def.

Dampness Pregnant 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


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


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


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;


• 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


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

XY

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

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 & ActionDa 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


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 & ActionHuang Qi Fang Ji Promote water circulation &

permeating the dampness

Huang Lian Mu Xiang Stop diarrhea & abdomen pain

Da Huang Huang Qin Clear damp-heat


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


• 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 ZhiRou Gui Chi Shi Zhi

*Liu Huang *Pu Xiao

*Shui Yin *Pi Shuang

*Lang Du *Mi Tuo Shen

*Ya Xiao *San Leng


• Mutual Incompatibility ( 相反 )Cause side effects or toxicity if use together

Gan Cao Gan SuiDa Ji

Yuan HuaHai Zao

Dosage: Gan Cao>= Gan Sui

Wu Tou( Fu Zi )

Ban XiaGua LouBei MuBai Ji

Bai Lian

Bei Mu or Ban Xia + Fu Zi ( No evidence support it )

Li Lu Ren ShenDang ShenDan Shen

Xuan ShenSha ShenKu ShenXi Xin

Bai Shao

Xi Xin + Li Lu: cause animal death in the lab



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 PairsTCM 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 PairsTCM 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 TherapyCase 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

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

AcknowledgementAcknowledgementCurrent 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)

tcm herbs in traditionally defined properties

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