Phytotherapies E-Book

• Herausgeber: John Wiley & Sons
• Kategorie: Wissenschaft und neue Technologien
• Sprache: Englisch

Seitenzahl: 1281

Veröffentlichungsjahr: 2015

Beschreibung

Covering fundamentals and new developments in phytotherapy, this book combines pharmaceutical sciences and chemistry with clinical issues.

•    Helps readers better understand phytotherapy and learn the fundamentals of and how to analyze phytotherapeutic agents
•    Discusses phytotherapy in modern medicine, chemoprevention of disease, and  alternatives to western medicines for specific diseases
•    Chapters summarizes the uses and applications of phytomedicines, by type like Chinese, Greco-Arab, Indian, European, and Ayurvedic
•    Includes international regulatory perspectives and discusses emerging regulations for various established and emerging markets

Leseprobe

CONTENTS

COVER

TITLE PAGE

LIST OF CONTRIBUTORS

PREFACE

1 PHYTOTHERAPIES—PAST, PRESENT, AND FUTURE

1.1 OVERVIEW OF PHYTOTHERAPY

1.2 PRECLINICAL RESEARCH ON PHYTOTHERAPIES

1.3 CLINICAL RESEARCH ON PHYTOTHERAPIES

1.4 SAFETY OF PHYTOTHERAPIES

1.5 PROFILE OF RESEARCH IN COMPLEMENTARY MEDICINE

1.6 SUMMARY AND FUTURE DIRECTIONS

REFERENCES

2 QUALITY CONTROL AND QUALITY ASSURANCE OF PHYTOMEDICINES: KEY CONSIDERATIONS, METHODS, AND ANALYTICAL CHALLENGES

2.1 INTRODUCTION

2.2 KEY CONSIDERATIONS IN QC/QA OF PHYTOMEDICINES

2.3 METHODS FOR QC/QA OF PHYTOMEDICINES

2.4 CHALLENGES

2.5 CONCLUSIONS

REFERENCES

3 PRECLINICAL

(IN VIVO)

AND LABORATORY

(IN VITRO)

EVIDENCE OF PHYTOMEDICINE EFFICACY

3.1 INTRODUCTION TO DEVELOPMENT OF DRUGS FROM NATURE

3.2 USE OF

IN VITRO

AND

IN VIVO

MODELS IN HERB DRUG RESEARCH: LEARNING THUS FAR

3.3 CARDIOVASCULAR- AND STROKE-RELATED DISEASES:

IN VITRO

AND

IN VIVO

FOCUS

3.4 CONCLUSIONS

REFERENCES

4 CLINICAL EFFICACY TRIALS WITH NATURAL PRODUCTS AND HERBAL MEDICINES

4.1 INTRODUCTION

4.2 TRIALS IN VARIOUS DISEASE STATES

4.3 NATURAL PRODUCT: GREEN TEA

4.4 EGCG CLINICAL TRIALS

4.5 HUMAN CLINICAL STUDY: EGCG AND HIV-1 INFECTION

4.6 CONCLUSION

REFERENCES

5 NOVEL FORMULATIONS AND DRUG DELIVERY SYSTEMS FOR PHYTOTHERAPIES

5.1 LIMITATIONS OF CONVENTIONAL FORMULATIONS FOR HERBAL MEDICINES

5.2 CRUCIAL ISSUES OF DEVELOPING NOVEL DELIVERY SYSTEMS FOR HERBAL MEDICINES

5.3 NOVEL DELIVERY SYSTEMS OF HERBAL MEDICINES

5.4 SUMMARY

REFERENCES

6 PHYTOTHERAPIES USED BY INDIGENOUS POPULATIONS

6.1 INTRODUCTION

6.2 PHYTOTHERAPIES OF INDIGENOUS AUSTRALIANS

6.3 CHALLENGES OF A CHANGING ENVIRONMENT

6.4 CONCLUSIONS

REFERENCES

7 PHYTOTHERAPIES FROM TRADITIONAL CHINESE MEDICINE

7.1 TRADITIONAL CHINESE MEDICINE

7.2 KEY CONCEPTS IN TRADITIONAL CHINESE MEDICINE

7.3 HERBAL MEDICINE AND TRADITIONAL CHINESE MEDICINE

7.4 ISSUES IN THE DEVELOPMENT OF PHYTOTHERAPY FROM TRADITIONAL CHINESE MEDICINE

7.5 PHYTOTHERAPIES DEVELOPED FROM TRADITIONAL CHINESE MEDICINE

7.6 HUANG QIN TANG AND THE DEVELOPMENT OF PHY906

7.7 GINSENG

7.8 MOVING FORWARD

REFERENCES

8 INTEGRATING TRADITIONAL GRECO-ARAB AND ISLAMIC DIET AND HERBAL MEDICINES IN RESEARCH AND CLINICAL PRACTICE

8.1 INTRODUCTION

8.2 FOOD THERAPY IN GRECO-ARAB AND ISLAMIC MEDICINE

REFERENCES

9 EVOLUTION OF HERBAL MEDICINES IN EUROPE AND ITS RELATIONSHIP WITH MODERN MEDICINE

9.1 BACKGROUND

9.2 HISTORICAL PERSPECTIVE

9.3 EUROPEAN HERBAL MEDICINE: RELATIONSHIP WITH MODERN MEDICINE

9.4 SUMMARY

REFERENCES

10 CHEMICAL CLASSIFICATION AND CHEMISTRY OF PHYTOTHERAPEUTICS CONSTITUENTS

10.1 INTRODUCTION

10.2 PHYTOCHEMICALS

10.3 OTHER PHYTOCHEMICALS

10.4 MEDICINAL EFFECTS RELATING TO DIETARY INTAKE

10.5 NATURAL PRODUCTS AS LEADS FOR DRUG DEVELOPMENT

10.6 SUMMARY

REFERENCES

11 THERAPEUTIC POTENTIAL OF GINSENOSIDES IN MANAGEMENT OF ATHEROSCLEROSIS

11.1 INTRODUCTION

11.2 CHEMICAL DIVERSITY OF GINSENOSIDES AND DISTRIBUTION

11.3 ANTI-ATHEROSCLEROTIC EFFECTS OF GINSENOSIDES

11.4 UNDERLYING MECHANISMS OF GINSENOSIDES AGAINST ATHEROSCLEROSIS

11.5 CONCLUSIONS AND FUTURE PERSPECTIVES

ACKNOWLEDGMENTS

REFERENCES

12 PHYTOTHERAPY PHARMACOPHORES FOR MAJOR CELLULAR DRUG TARGETS

12.1 INTRODUCTION

12.2 WHAT IS A PHARMACOPHORE?

12.3 PHARMACOPHORE MODELS OF CARDIOVASCULAR DRUGS

12.4 PHARMACOPHORE MODELS FOR ANTICANCER DRUGS

12.5 PHARMACOPHORE MODELS FOR ANTI-INFLAMMATORY DRUGS

12.6 PHARMACOPHORE MODELS FOR ANTI-INFECTIVE DRUGS

12.7 PHARMACOPHORE MODELS FOR NEUROLOGICAL DRUGS

12.8 PHARMACOPHORE MODELS FOR MISCELLANEOUS DRUGS

12.9 CONCLUSIONS

REFERENCES

13 USE OF KAVA AS A PHYTOTHERAPEUTIC AGENT AND KAVA-RELATED HEPATOTOXICITY

13.1 INTRODUCTION

13.2 ACTIVE COMPONENTS IN KAVA

13.3 THERAPEUTIC APPLICATIONS OF KAVA

13.4 PHARMACOLOGY OF KAVA

13.5 SIDE EFFECTS OF KAVA

13.6 HEPATOTOXICITY OF KAVA

13.7 SUMMARY AND FUTURE CHALLENGES

REFERENCES

14 PHYTOTHERAPIES AS NEW DRUG SOURCES: GOSSYPOL AND CURCUMIN

14.1 BOTANICAL SOURCES OF GOSSYPOL AND CURCUMIN

14.2 STEREOISOMERISM, TAUTOMERISM, AND REACTIVITY

14.3 BIOLOGICAL ACTIVITY OF GOSSYPOL AND ITS ANALOGUES

14.4 BIOLOGICAL ACTIVITY OF CURCUMIN AND ITS ANALOGUES

REFERENCES

15 PHYTOTHERAPIES FOR THE MANAGEMENT OF OBESITY AND DIABETES

15.1 INTRODUCTION

15.2 PLANTS FROM THE NORTH AMERICAN PHARMACOPOEIA

15.3 PHARMACOLOGICAL SCREENING: PROVIDING EMPIRICAL EVIDENCE FOR PHYTOTHERAPIES

15.4 COMMUNITY-BASED PARTICIPATION: DEVELOPING PHYTOTHERAPIES FROM TRADITIONAL KNOWLEDGE

15.5 CONCLUSIONS

REFERENCES

16 PHYTOTHERAPEUTICS FOR CANCER THERAPY

16.1 INTRODUCTION

16.2 ANTICANCER PHYTOTHERAPEUTICS WITH NK ENHANCEMENT

16.3 CONCLUSIONS

REFERENCES

17 PHYTOMEDICINES FOR FATTY LIVER DISEASE AND FUNCTIONAL GASTROINTESTINAL CONDITIONS

17.1 INTRODUCTION

17.2 PHYTOMEDICINES FOR FLD

17.3 PHYTOMEDICINES FOR IBS

17.4 PHYTOMEDICINES FOR CONSTIPATION

17.5 SUMMARY AND FUTURE PERSPECTIVES

REFERENCES

18 PHYTOMEDICINES FOR INFLAMMATORY CONDITIONS

18.1 TRADITIONAL MEDICINES FOR INFLAMMATORY CONDITIONS IN EUROPE

18.2 TWENTY-FIRST-CENTURY UPDATE ON PAIDs

18.3 ORAL EXTRACTS FROM

SALIX

SPECIES

18.4 ORAL EXTRACTS FROM

HARPAGOPHYTUM PROCUMBENS

18.5 ORAL AVOCADO–SOYBEAN UNSAPONIFIABLES

18.6 ORAL EXTRACTS FROM

TRIPTERYGIUM WILFORDII

18.7 ORAL PAIDs CONTAINING UNSATURATED FATTY ACIDS

18.8 OTHER ORAL PAIDs

18.9 TOPICAL PAIDs

REFERENCES

19 PHYTOTHERAPIES FOR INFECTIOUS DISEASES: ARE THESE REALLY USEFUL?

19.1 INTRODUCTION

19.2 HISTORICAL PRECEDENT FOR NATURAL PRODUCTS AS ANTIMICROBIAL DRUGS

19.3 ARE PHYTOTHERAPIES USEFUL FOR THE TREATMENT OF INFECTIOUS DISEASES?

19.4 NATURALLY OCCURRING COMPOUNDS THAT MAY REDUCE ZOONOSIS

19.5 SYNERGISTIC AND ADDITIVE EFFECTS WITH ANTIBIOTICS

19.6 NEW EMERGING INFECTIOUS DISEASES AND THOSE WITH NO KNOWN TREATMENTS

19.7 SARS

19.8 REDUCING MRSA CARRIAGE

19.9 CONCLUSIONS

REFERENCES

20 PHYTOMEDICINES FOR CNS DISORDERS: SAFETY ISSUES FOR USE WITH ANTIEPILEPTIC DRUGS

20.1 INTRODUCTION

20.2 METHODOLOGY OF SYSTEMATIC LITERATURE SEARCH

20.3 PHARMACOKINETIC INTERACTIONS

20.4 PHARMACODYNAMIC INTERACTIONS

20.5 CONCLUSIONS

REFERENCES

21 PHYTOTHERAPIES: DRUG INTERACTIONS IN CANCER

21.1 INTRODUCTION

21.2 USE OF HERBAL AND COMPLEMENTARY MEDICINES BY PEOPLE LIVING WITH CANCER

21.3 MECHANISMS OF PHYTOTHERAPY–DRUG INTERACTIONS

21.4 SELECTED EXAMPLES OF PHYTOTHERAPY MEDICINES THAT HAVE THE POTENTIAL TO CAUSE DRUG INTERACTIONS IN CANCER

21.5 FUTURE PERSPECTIVES: NEED FOR EVIDENCE AND ADVICE TO CANCER PATIENTS AND PHYSICIANS

21.6 CONCLUSIONS

ACKNOWLEDGMENTS

CONFLICT OF INTEREST

REFERENCES

22 QUALITY USE OF MEDICINES

22.1 INTRODUCTION

22.2 RELEVANCE OF QUM FOR HERBAL MEDICINES

22.3 USE OF PHYTOTHERAPIES BY CONSUMERS

22.4 CONSUMER ATTITUDES AND BELIEFS ABOUT HERBAL MEDICINES

22.5 APPLYING THE QUM FRAMEWORK TO PHYTOTHERAPIES

22.6 BUILDING BLOCKS FOR QUALITY USE OF HERBAL MEDICINES

22.7 CONCLUSION

REFERENCES

23 INTELLECTUAL PROPERTY AND PATENT ISSUES WITH PHYTOTHERAPY PRODUCTS

23.1 INTRODUCTION

23.2 IP RIGHTS—PHYTO-INDUSTRY

23.3 BRIEF OVERVIEW OF PATENTS AND THE PATENTING PROCESS

23.4 OTHER TYPES OF IP RIGHTS

23.5 PATENTING TRENDS FOR PHYTOTHERAPEUTICS

23.6 TRADITIONAL KNOWLEDGE AND IP RIGHTS

DISCLAIMER

REFERENCES

24 INTERNATIONAL REGULATORY STATUS OF PHYTOTHERAPIES

24.1 INTRODUCTION

24.2 SPECIFIC COUNTRY REGULATIONS

24.3 FUTURE OF PHYTOTHERAPIES: WORLD HEALTH ORGANIZATION (WHO)

FURTHER READING

INDEX

END USER LICENSE AGREEMENT

List of Tables

Chapter 01

TABLE 1.1 Profile of Complementary and Alternative Medicine (CAM) Research from Excellence in Research for Australia (ERA) 2012

Chapter 02

TABLE 2.1 Key Considerations for Quality Assessments of Phytomedicines

TABLE 2.2 Toxic Heavy Metal and Microbial Limit Requirement in Singapore

TABLE 2.3 Methods for Quality Assessment of Phytomedicines

Chapter 03

TABLE 3.1

In Vivo

Models for Studying Cardiac Effects of Drugs or Phytomedicines

TABLE 3.2

In Vitro

Models for Studying Cardiac Effects of Drugs or Phytomedicines

TABLE 3.3

In Vitro

and

In Vivo

Evidence of Phytomedicines or Their Constituents for Efficacy in Cardiovascular Diseases

TABLE 3.4 Methods Used to Induce Strokes in Different Animals

TABLE 3.5

In Vitro

and

In Vivo

Evidence on Phytomedicines or Their Constituents for Their Efficacy in Strokes

Chapter 07

TABLE 7.1 The Five Phases: Associated Colors, Directions, Seasons, and Organs

TABLE 7.2 Characteristics of the Four Types of Herbs Used in Prescriptions of Classical Chinese Medicine

TABLE 7.3 Characteristics of Herbs Used in Traditional Chinese Medicine

TABLE 7.4 Commonly Used Chinese Herbs

Chapter 08

TABLE 8.1 Commonly Used Cultivated Edible Plants in the Mediterranean Region and Their Evidence-Based Medical Properties

Chapter 09

TABLE 9.1 Evolution of Orthodox Medicine in Europe

TABLE 9.2 A Timeline of Major Influences on European Herbal Medicines

Chapter 10

TABLE 10.1 Classifications of Alkaloids

TABLE 10.2 Common Alkaloids with Their Therapeutic Uses

TABLE 10.3 Classifications of Flavonoids

TABLE 10.4 Common Flavonoids, Plant Sources, and Major Uses

TABLE 10.5 Examples of Glycosides

TABLE 10.6 Examples of Glycosides and Saponins with Therapeutic Use and Plant Sources

TABLE 10.7 Summary of Common Saturated Fatty Acids

TABLE 10.8 Terpenes: Classifications and Characteristics

TABLE 10.9 Examples of Dietary Intake Components and Their Medicinal Effects

TABLE 10.10 Anti-proliferative and Pro-apoptotic Activities of

n

 − 3 MUFAs in COX-2 Overexpressed Breast Cancer Cells

TABLE 10.11 Effect of

n

 − 3 MUFAs on PGE2 Secretion by COX-2 Overexpressed Breast Cancer Cells

TABLE 10.12 Survival Strategies are Wide and Include Plants and Microorganisms

TABLE 10.13 IC

50

Values for Cell Growth Inhibition in K562 Cells by Compounds 1–6

Chapter 11

TABLE 11.1 Chemical Differences in Ginsenoside Composition of Notoginseng (

P. notoginseng

), Asian Ginseng (

P. ginseng

), and American Ginseng (

P. quinquefolius

)

Table 11.2

In Vivo

Anti-atherosclerotic Studies of Ginsengs and Ginsenosides

Table 11.3

In vitro

Evidence for Anti-atherosclerotic Effects of Ginsengs and Ginsenosides

Chapter 12

TABLE 12.1 Chemical structures and activity of eight compounds chosen for cellular reporter gene assay at a concentration of 30 μM

TABLE 12.2 Chemical structures of tested

G. Lucidum

constituents

TABLE 12.3 EC

50

and IC

50

values for six compounds that were found to have significant androgen receptor down-regulating activities

Chapter 13

TABLE 13.1 Pharmacological Effects of Kava

Chapter 14

TABLE 14.1 Examples of the Enantiomeric (Atropisomeric) Excesses of Gossypol in Cottonseeds (

Gossypium

Species) and

T. populnea

[2]

TABLE 14.2 Examples of the Growth Inhibitory Activity of Gossypol Atropisomers in Human Cancer Cell Lines

TABLE 14.3 Effects of Gossypol and Analogues on HIV-1 Replication in PBM Cells [46]

TABLE 14.4 Effects of Gossypol Schiff Bases 3 on HIV-1

IIIB

Replication in TZM-bl Cells and H

5

N

1

Replication in MDCK Cells [49]

TABLE 14.5 Growth Inhibition of Human Cancer Cell Lines by Curcumin 2 and GO-Y030 34

TABLE 14.6 Data from NCI-60 DTP Cell Line Screen for Curcumin 2 and EF-24 35

Chapter 15

TABLE 15.1 List of North American Plant Species Documented in the Literature for Their Traditional Uses in Treating Diabetes and Symptoms Associated with Diabetes

TABLE 15.2 Description of

In Vivo

Animal Models and

In Vitro

Bioassays Used by the CIHR-TAAM to Evaluate the Antiobesity and Antidiabetic Potential of Medicinal Plants

TABLE 15.3 Antidiabetic Activity of Medicinal Plants from the CEI Pharmacopoeia Evaluated Using the

In Vitro

and

In Vivo

Models of Table 15.2

Chapter 16

TABLE 16.1 Effects of L

. edodes

Mycelia on NK Cells

TABLE 16.2 Effects of L

. edodes

Mycelia on QoL and Survival Condition of Cancer Patients

TABLE 16.3 Effects of G

anoderma lucidum

on NK Cells

TABLE 16.4 Effects of G

anoderma lucidum

on QoL and Survival Condition of Cancer Patients

TABLE 16.5 Effects of Phytotherapeutic Formulae on NK Cells in Clinical Cancer Treatment

TABLE 16.6 Effects of Phytotherapeutic Formulae on QoL and Survival Rate in Clinical Cancer Treatment

Chapter 17

TABLE 17.1 Summary of Activities of Herbal Medicines for Fatty Liver Disease

Chapter 18

TABLE 18.1 Mechanisms of Action of PAIDs Suggested by

In Vitro

Studies

TABLE 18.2 Characteristics of Some Phytomedicines Used for the Treatment of Osteoarthritis and Rheumatoid Arthritis

Chapter 20

TABLE 20.1 Effects of Phytomedicines on Plasma Concentrations of Antiepileptic Drugs

TABLE 20.2 Effect of Phytomedicines on the Anti-epileptic Effects of Antiepileptic Drugs

TABLE 20.3 Effect of Phytomedicines on the Sedative Effects of Antiepileptic Drugs

TABLE 20.4 Effect of Phytomedicines on the Anxiolytic Effects of Antiepileptic Drugs

TABLE 20.5 Effect of Phytomedicines on the Memory Impairment Effects of Antiepileptic Drugs

TABLE 20.6 Effect of Phytomedicines on the Motor Incoordination Effects of Antiepileptic Drugs

Chapter 21

TABLE 21.1 Most Commonly used Herbal Medicines in Developed Countries Identified from a Range of Studies

Chapter 22

TABLE 22.1 Disadvantages of Complementary Medicines as Perceived by Users

TABLE 22.2 Advantages of Complementary Medicines as Perceived by Users

TABLE 22.3 Herbal Medicines Associated with Side Effects in Systemic Reviews

TABLE 22.4 High-Quality Objective Information on Herbal Medicines

Chapter 23

TABLE 23.1 International Patent Classifications Assigned to Herbal

Materia Medica

List of Illustrations

Chapter 01

FIGURE 1.1 Publication counts during the past two decades in Scopus.

FIGURE 1.2 Top 10 countries with highest publication counts during the past two decades in Scopus.

Chapter 03

FIGURE 3.1 Leading causes of death worldwide in the year 2011. .

Chapter 04

FIGURE 4.1 Structures of the polyphenolic catechins found in green tea.

Chapter 05

FIGURE 5.1 Developing novel delivery systems for herbal medicines .

Chapter 06

FIGURE 6.1

Acacia aneura

.

FIGURE 6.2 Boiling a decoction.

FIGURE 6.3

Eremophila duttonii

.

Chapter 07

FIGURE 7.1 Yin and yang. The central duality underpinning Traditional Chinese Medicine; yin is the dark area (“shady place” or “north slope”) and yang is the light area (“sunny place” or “south slope”).

FIGURE 7.2 The five phases: the arrows on the outer circle represent generation or creation while the arrows in the inner circle represent destruction [10].

FIGURE 7.3 Survival of mice with colon cancer allografts treated with control vehicle PHY-906, CPT-111, or a combination of both CPT-111 and PHY-906 [28]. There was survival at 7 and 14 days post-grafting only in mice treated with the combination.

Chapter 08

FIGURE 8.1 Development of Greco-Arab and Islamic medicine.

FIGURE 8.2 Scholars of the Greco-Arab and Islamic medicine and their contributions.

FIGURE 8.3 Greco-Arab and Islamic medicine-based herbal medicines.

FIGURE 8.4 Methods of therapy used in Greco-Arab and Islamic medicine.

Chapter 09

FIGURE 9.1 Frontispiece of “Hortus sanitatis,” 1491. The woodcut represents an imaginary conversation between classical and medieval European and Arabian physicians: Aristotle (center), Hippocrates (right), Rhazes (left), and behind them, from left to right, is Galen, Avicenna, Serapion, Dioscorides, Pandectarius, and Platearius (see Table 9.2).

Chapter 10

FIGURE 10.1 The relationships between glucose and the primary and secondary metabolites. Substrates and primary metabolites are shown in the gray boxes and the classes of secondary metabolites or natural products are shown in clear boxes with more specific examples listed nearby [1].

FIGURE 10.2 Structures of major classes of alkaloids.

FIGURE 10.3 The four basic structures of flavonoids.

FIGURE 10.4 Structures of major classes of flavonoids.

FIGURE 10.5 Structures of major classes of glycosides.

FIGURE 10.6 Structures of common sterols.

FIGURE 10.7 Structure of cholesterol.

FIGURE 10.8 Chemical structures of sterols and stanols. Unsaturated phytosterols (campesterol, β-sitosterol, stigmasterol) and hydrogenated phytosterols (campestanol and sitostanol).

FIGURE 10.9 Structure of triacylglycerols.

FIGURE 10.10 Structures of omega-9, omega-6, and omega-3 carbon 18 polyunsaturated fatty acids.

FIGURE 10.11 Structure of isoprene.

FIGURE 10.12 Structure of amylose linking glucose units together with α-1,4 glucosidic bonds.

FIGURE 10.13 Structure of amylopectin linking glucose units together with a-1,4 and a-1,6 glucosidic bonds.

FIGURE 10.14 Structure of cellulose linking glucose units together with β-1,4-glucosidic bonds.

FIGURE 10.15 Structures of polyhydroxyphenols and related compounds.

FIGURE 10.16 Chemical structures of resveratrol and piceatannol.

FIGURE 10.17 Structural analogues of

n

 − 3 mono-unsaturated fatty acids with different carbon chain lengths: 16 (a), 17 (b), 18 (c), 19 (d), 20 (e), 21 (f), and 22 (g) [63].

FIGURE 10.18 H-atom-donating reaction [38].

FIGURE 10.19 Structures and anti-oxidant activities of hydroxystilbenes. IC

50

: concentrations causing 50% quenching of DMPO/.OOH signal in the ESR experiments.

k

2

: second-order rate constants for the abstraction of H-atoms from hydroxystilbenes by DPPH. [38].

FIGURE 10.20 Redox-cycling of

ortho

-semiquinones [38].

FIGURE 10.21 Studies of prenylated tetrahydroxystilbenes showing a range of biological activities [38, 73–77].

FIGURE 10.22 Structure of analogues used in cytotoxicity test toward K562 leukemic cancer cells [78].

FIGURE 10.23 Docking of the

n

 − 3 MUFA analogues carbon 16 (upper) and carbon 22 (lower) into the COX-2 active site [63].

Chapter 11

FIGURE 11.1 Yearly trend of publications on ginsenoside-related studies in the recent two decades.

FIGURE 11.2 Chemical structures of selected ginsenosides. Araf,

α

-

L

-arabinofuranosyl; Arap,

α

-

L

-arabinopyranosyl; Glc,

β

-

D

-glucopyranosyl; GlcUA,

β

-

D

-glucuronic acid; Rha,

α

-

L

-rhamnopyranosyl; Xyl,

β

-

D

-xylopyranosyl.

Chapter 12

FIGURE 12.1 Pharmacophoric features in (+)-6-aminopenicillanic acid. Key functional groups contain negatively ionizable (anion, carboxylate) features, the positively ionizable (cation, amine) H-bond donor (amine) features, and the ring and the methyl (hydrophobe) features.

FIGURE 12.2 Chemical structure of two molecular scaffolds derived from α-santonin,

S1

and

S2

. Both scaffolds were found among the top-scoring virtual hits obtained by

LIQUID

pharmacophore searching the

AnalytiCon Discovery

compound collection.

FIGURE 12.3 Neolignans: dieugenol (a); tetrahydrodieugenol (b); magnolol (c), aligned with a structure-based pharmacophore model consisting of hydrogen bond acceptor (red arrow), hydrogen bond donor (green arrow), hydrophobic interaction (yellow sphere), and aromatic interaction (blue rings).

FIGURE 12.4 Chemical structures of neolignans dieugenol (1), tetrahydrodieugenol (2), magnolol (3), and eugenol (4).

FIGURE 12.5 Influence of the neolignans on human PPARγ-mediated reporter gene transactivation. Results are expressed as fold activation compared with negative control (dimethyl sulfoxide (DMSO) vehicle treatment). Data are shown as means ± S.D. of three independent experiments each performed in four replicates.

FIGURE 12.6 Four-point pharmacophore model for known PPARγ partial agonists superimposed on indeglitazar (RMSD = 0.50 Å). Pharmacophoric features are represented by a point encased in a sphere: hydrogen bond donor (blue), hydrophobic region (green), aromatic center (orange), and CO

2

centroid (red). Points not encased in spheres are other potential pharmacophore features on the indeglitazar structure (2D structure shown on top left).

FIGURE 12.7 Oleanonic acid docked in the ligand-binding domain of PPARγ, which shows a hydrogen bond between the carboxylic moiety with His323 and Thr327 on helix 4/5 on arm I. The remainder of the ligand is stabilized within a hydrophobic pocket formed by residues Gln286, Met364, Leu453, and Leu469.

FIGURE 12.8 Chemical structures of (S)-tryptophan-betaxanthin and berberrubine.

FIGURE 12.9 Generated structure-based pharmacophore models for PPARδ shown with inter-feature distance constraints only (a), control, ET1 (b), (S)-tryptophan-betaxanthin (c), and berberrubine (d). Pharmacophoric features are shown for hydrogen bond acceptors (green), hydrogen bond donors (magenta), and hydrophobic feature (blue).

FIGURE 12.10 Generated structure-based pharmacophore models for PPARα shown with inter-feature distance constraints only (a), control, 7HA (b), (S)-tryptophan-betaxanthin (c), and berberrubine (d). Pharmacophoric features are shown for hydrogen bond acceptors (green), hydrogen bond donors (magenta), and hydrophobic feature (blue).

FIGURE 12.11 Generated structure-based pharmacophore models for PPARγ shown with inter-feature distance constraints only (a), control, T2384 (b), (S)-tryptophan-betaxanthin (c), and berberrubine (d). Pharmacophoric features are shown for hydrogen bond acceptors (green), hydrogen bond donors (magenta), and hydrophobic feature (blue).

FIGURE 12.12 Pharmacophore model

1osh-1

comprising five hydrophobic features, 1 hydrogen bond acceptor with His294, and 27 exclusion volume spheres aligned with native ligand fexaramine.

FIGURE 12.13 Shape-constrained pharmacophore model

3bej-1-s

comprising three hydrophobic features, 2 hydrogen bond acceptors anchoring the ligand with His294 and Thr288, a negatively ionizable feature representing the interaction with Arg331, and 25 exclusion volume sphere, aligned with native ligand MFA-1.

FIGURE 12.14 Best-fitting FXR pharmacophore model

3bej-2

for

Ganoderma

constituents investigated. Crucial interactions of native ligand MFA-1 with Arg331 and His447 are highlighted in ball-and-stick style.

FIGURE 12.15 Chemical structures of the four most active triterpenoids, compound

1

,

9

,

17

, and

18

.

FIGURE 12.16 Merged features pharmacophore model derived from compounds

1

,

9

,

17

, and

18

. Chemical features include hydrophobic features (yellow) and hydrogen bond acceptors (red).

FIGURE 12.17 Alignment of top three virtual hits ZINC19924472 (a), ZINC33086616 (b), and ZINC33086598 (c) with best pharmacophore hypotheses for ACC1 (

Hypo1_ACC1

, left) and ACC2 (

Hypo1_ACC2

, right). Chemical features include hydrogen bond acceptors (green), hydrogen bond donors (magenta), hydrophobic features (blue), and exclusion volumes (gray).

FIGURE 12.18 Chemical structures of natural, biocatalytic, and semis-synthetic

Veratrum alkaloids

.

FIGURE 12.19 Pharmacophore model

Hypo2

(a), alignment with cyclopamine (b), alignment with active compounds 4, 6, 7, and 10. Chemical features include hydrogen bond acceptors (green), hydrophobic features (blue), positive ionizable features (red), and exclusion volumes (gray).

FIGURE 12.20 Chemical structures of known androgen receptor down-regulating agents (ARDAs) used to generate the pharmacophore model

Hypo1.

FIGURE 12.21 Common feature-based pharmacophore model of ARDAs

Hypo1

(left).

Hypo1

mapping all the important features of training set ARDAs (right). Chemical features include two hydrogen bond acceptors (green), one hydrophobic group (cyan), and one aromatic feature (red).

FIGURE 12.22 Chemical structures of six compounds, KM 06622, NCI-0001009, NCI-0002091, NCI-0002815, NCI-0004355, and BTB 01434, which were found to possess significant androgen down-regulating activities.

FIGURE 12.23 Chemical structures of selected caged

Garcinia

xanthones.

FIGURE 12.24 Chemical structure of compound

11a

.

FIGURE 12.25 Chemical structures of synthetic α,β-epoxyketone proteasome inhibitors YU101 and YU102 that are selective to chymotrypsin-like and caspase-like activity, respectively.

FIGURE 12.26 Chemical structure of salinosporamide A.

FIGURE 12.27 Observed interactions between 3D X-ray crystal structures with its native ligand (left) and its corresponding structure-based pharmacophore model (right), which form the final model collection for virtual screening:

1cqe-1

(a),

1pge-2-s

(b),

2ayl-1

(c),

4cox-2

(d), and

6cox-1-s

(e).

FIGURE 12.28 Ligand-based pharmacophore model for COX inhibitors based on (S)-flurbiprofen and SC-558. Chemical features include hydrogen bond acceptor (tiled sphere), hydrophobic features (full sphere), and an aromatic ring (ring).

FIGURE 12.29 Number of percentage of virtual hits that are classified as highly active (IC

50

 < 25.0 μM), moderately active (IC

50

 25.0–150.0 μM), and inactive (IC

50

 > 150.0 μM).

FIGURE 12.30 Distribution of phytochemical classes from herbs containing predicted inhibitors against COX, p38, JNK, and PDE4.

FIGURE 12.31 Some predicted multi-target inhibitors from Chinese herbs. Phytochemical class and targets are shown in the bottom left and right corners of each structure, respectively.

FIGURE 12.32 Chemical structures of active depsidones: physodic acid, perlatolic acid, and olivertoric acid.

FIGURE 12.33 Pharmacophore model for acidic mPGES-1 inhibitors. For

M1

, it is necessary to satisfy all chemical features consisting of four hydrophobic features (cyan), one aromatic ring (gold), one negatively ionizable feature (blue), and a spatial shape restriction (gray). Whereas screening with

M2

allows the omission of one hydrophobic group or aromatic ring features, inhibitors of mPGES-1, namely, 2 (green), 8 (blue), and 9 (gray) map two of the hydrophobic features with their alkyl chains.

FIGURE 12.34 Pharmacophore mapping for (a) shanciol A and (b) shanciol B, (c) castilliferol, and (d) aurantiamide acetate. Chemical features include one hydrogen bond donor (purple), one hydrophobic group (light blue), and two aromatic rings (orange).

FIGURE 12.35 Chemical structures of shanciol A and B, castilliferol, and aurantiamide acetate.

FIGURE 12.36 Chemical structure of flavone M4753.

FIGURE 12.37 Superposition of M4753 (red) and native ligands (blue) co-crystallized with WT (PDB 2ZD1, left) and mutant HIV-1 RT (PDB 3BGR, right).

FIGURE 12.38 Chemical structures of most active flavonoids YKAF01, YKAF02, YKAF03, and YKAF04.

FIGURE 12.39 Pharmacophore maps, previously determined using receptor-oriented pharmacophore-based

in silico

screening.

FIGURE 12.40 Chemical structures of highly active morphinans and isoquinolines.

FIGURE 12.41 Superposition of seven structures matching the pharmacophore template with RMS < 0.200.

FIGURE 12.42 Identified pharmacophore template for anti-convulsant activity in the MES test.

FIGURE 12.43 Chemical structures of compounds derived from Chinese herb, Semen

ziziphi spinosae

(suanzaoren), including betulin, betulin acid, jujuboside A, jujuboside B, jujubogenin,

cis

-ebelin lactone, and

trans

-ebelin lactone.

FIGURE 12.44 Overall pharmacophore model (a), and pharmacophore mapping of betulin (b), betulic acid (c), jujubogenin (d),

cis

-ebelin lactone (e), and

trans

-ebelin lactone (f). Pharmacophore features include hydrogen bond acceptors (green) and hydrogen bond donors (purple).

FIGURE 12.45 Schematic illustration of the refined H

3

pharmacophore model derived from imidazole and non-imidazole H

3

antagonists.

FIGURE 12.46 Chemical structures of dispyrin (left) and compound

24d

(right).

FIGURE 12.47 Overall pharmacophore of PDE5 binding site (a), CS01 (b), CS03 (c), ES03a (d), ES03b (e), and natural substrate cGMP (f). Chemical features include hydrogen bond acceptors (green), hydrogen bond donors (purple), and hydrophobic regions (blue).

FIGURE 12.48 Chemical structures of the most active Evo compounds

SC01-Evo4

,

SC03-Evo1

, and

ES03b-Evo48

and respective parent compounds

SC01

,

SC03

, and

ES03b

.

FIGURE 12.49 Pharmacophore models

Hopyo-1

(left) and

Hopyo-1m

(right) that consist of chemical features, which include hydrogen bond acceptors (green), hydrophobic features (blue), and aromatic rings (yellow).

FIGURE 12.50 Chemical structures of tanshinone I, tanshinone IIA, cryptotanshinone, matrine, sophoridine, and oxymatrine.

FIGURE 12.51 Chemical structures of five herbal compounds 272, 284, 300, 616, and 817 with CYP1A2 inhibitory activity.

Chapter 13

FIGURE 13.1 Chemical structures of six main kavalactones in kava root extract. These are kavain, yangonin, methysticin, 5,6-dehydrokavain, 7,8-dihydrokavain, and 7,8-dihydromethysticin.

FIGURE 13.2 Chemical structures of flavokawain A, B, and C.

FIGURE 13.3 Diagram of cellular mechanisms of kava-induced hepatotoxicity.

Chapter 14

FIGURE 14.1 (

M

)-(−)-Gossypol

1

. In the right-hand figure, the lines represent the planes of the naphthyl groups, and the groups shown are those

ortho

to the C2–C2 bond. When viewed along the C2–C2 bond from the RHS, the horizontal OH group is on the LHS, and the vertical OH is below the plane of the horizontal naphthyl system.

Scheme 14.1 Symmetrical gossypol tautomers.

Scheme 14.2 Tautomerism of gossypol Schiff’s bases; imine

3

and enamine

3

′ tautomers.

Scheme 14.3 Tautomers of curcumin.

Scheme 14.4 Partial hydrolysis of gossypol bis-Schiff’s bases

3

.

Scheme 14.5 Photoepimerization of gossypol bis-Schiff’s base

3a

.

Scheme 14.6 Proposed formation of a bis-Michael adduct

5

from curcumin and glutathione.

Scheme 14.7 Pabon synthesis of curcumin.

Scheme 14.8 Antioxidant mechanism of DMTC

27

, leading to C–C bond breaking [110].

Chapter 16

FIGURE 16.1 Flowchart of screening process for publications.

Chapter 17

FIGURE 17.1 Manifestation of fatty liver disease (adapted from [31, 32]). AMPK, AMP-activated protein kinase; ApoB, apolipoprotein B; ATGL, adipose triglyceride lipase; ChREBP, carbohydrate-responsive element-binding protein; FFA, free fatty acid; HSL, hormone-sensitive lipase; LD, lipid droplet; MTP, microsomal triglyceride transfer protein; PPARα, peroxisome proliferator-activated receptor alpha; SREBP-1c, sterol regulatory element-binding protein-1c; TG, triglyceride; VLDL, very-low-density lipoprotein.

FIGURE 17.2 The pleiotropic effects and their molecular mechanisms of herbal medicines in amelioration of FLD. AMPK, AMP-activated protein kinase; COX-2, cyclooxygenase 2; FAS, fatty acid synthase; FFA, free fatty acid; LD, lipid droplet; NEFA, nonesterified fatty acid; NF-κB, nuclear factor-kappa B; PPARα, peroxisome proliferator-activated receptor alpha; PPARγ, peroxisome proliferator-activated receptor gamma; SREBP-1c, sterol regulatory element-binding protein-1c; TG, triglyceride.

FIGURE 17.3 The pleiotropic effects of herbal medicines in amelioration of IBS. Brain–gut axis mediators involved: serotonin, calcitonin gene-related peptide, substance P, calcitonin gene-related peptide, histamine, and glucagon-like peptide 1.

FIGURE 17.4 The pleiotropic effects of herbal medicines in amelioration of constipation.

FIGURE 17.5

Aloe vera

.

Chapter 18

FIGURE 18.1 OMERACT-OARSI response considering pain and function [37, 38] during treatment with

Harpagophytum

extract (60 mg harpagoside/day) in two studies over 1 year [39, 40] and during treatment with a rose hip and seed powder (

Rosa canina

) over 1 year [41].

Chapter 19

FIGURE 19.1 Structure of mupirocin, a topical antibiotic.

FIGURE 19.2 Structure of one of the oxazolidinone classes of antibiotics, linezolid, a novel class of antibiotics that was approved by the US FDA in 2000.

FIGURE 19.3 Chemical structure of the lipopeptide antibiotic, daptomycin.

FIGURE 19.4 Structure of tetracycline.

FIGURE 19.5 Structure of nalidixic acid.

FIGURE 19.6 Example of a proanthocyanidin (proanthocyanidin trimer), compound from cranberry reported to have antibacterial effects.

FIGURE 19.7 Chemical structures of the phenolic constituents of turmeric.

FIGURE 19.8 Chemical structure of the gingerols.

FIGURE 19.9 Structure of caprylic acid. A naturally occurring compound having antibacterial effects in chickens.

FIGURE 19.10 Structure of baicalein.

FIGURE 19.11 Structure of epigallocatechin gallate (EGCG), a compound present in a tea catechin extract that as an inhalant, can reduce nasal MRSA carriage.

Chapter 20

FIGURE 20.1 How phytomedicines interact with AEDs.

Chapter 22

Figure 22.1 Faces of the QUM pyramid.

Guide

Cover

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PHYTOTHERAPIES

Efficacy, Safety, and Regulation

Edited by

IQBAL RAMZAN

Copyright © 2015 by John Wiley & Sons, Inc. All rights reserved

Published by John Wiley & Sons, Inc., Hoboken, New JerseyPublished simultaneously in Canada

No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, scanning, or otherwise, except as permitted under Section 107 or 108 of the 1976 United States Copyright Act, without either the prior written permission of the Publisher, or authorization through payment of the appropriate per-copy fee to the Copyright Clearance Center, Inc., 222 Rosewood Drive, Danvers, MA 01923, [phone], fax [phone], or on the web at www.copyright.com. Requests to the Publisher for permission should be addressed to the Permissions Department, John Wiley & Sons, Inc., 111 River Street, Hoboken, NJ 07030, [phone], fax [phone], or online at http://www.wiley.com/go/permissions.

Limit of Liability/Disclaimer of Warranty: While the publisher and author have used their best efforts in preparing this book, they make no representations or warranties with respect to the accuracy or completeness of the contents of this book and specifically disclaim any implied warranties of merchantability or fitness for a particular purpose. No warranty may be created or extended by sales representatives or written sales materials. The advice and strategies contained herein may not be suitable for your situation. You should consult with a professional where appropriate. Neither the publisher nor author shall be liable for any loss of profit or any other commercial damages, including but not limited to special, incidental, consequential, or other damages.

For general information on our other products and services or for technical support, please contact our Customer Care Department within the United States at [phone], outside the United States at [phone] or fax [phone].

Wiley also publishes its books in a variety of electronic formats. Some content that appears in print may not be available in electronic formats. For more information about Wiley products, visit our web site at www.wiley.com.

Library of Congress Cataloging-in-Publication Data:

Phytotherapies : efficacy, safety, and regulation / edited by Iqbal Ramzan.  p. ; cm. Includes bibliographical references and index.

 ISBN 978-1-118-26806-3 (cloth)I. Ramzan, Iqbal, 1951–, editor.[DNLM: 1. Phytotherapy–methods. 2. Phytotherapy–standards. 3. Quality Assurance, Health Care. WB 925] RS164 615.321–dc23

      2014049520

LIST OF CONTRIBUTORS

Mohi Iqbal Mohammed Abdul, College of Pharmacy, Taibah University, Madina, Kingdom of Saudi Arabia

Bolanle A. Adeniyi, Department of Pharmaceutical Microbiology, University of Ibadan, Ibadan, Nigeria

Maureen V. Boost, Faculty of Health and Social Sciences, The Hong Kong Polytechnic University, Hong Kong

Hak-Kim Chan, Faculty of Pharmacy, The University of Sydney, Sydney, New South Wales, Australia

Kelvin Chan, Faculty of Pharmacy, The University of Sydney; and National Institute for Complementary Medicine, University of Western Sydney, Sydney, New South Wales, Australia

Meiwan Chen, State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau, China

Jun-Lae Cho, Faculty of Pharmacy, The University of Sydney, Sydney, New South Wales, Australia

Sigrun Chrubasik-Hausmann, Institute of Forensic Medicine, University of Freiburg, Freiburg, Germany

Stephen J. Clarke, Sydney School of Medicine and Northern Clinical School, Kolling Institute of Medical Research, Royal North Shore Hospital, The University of Sydney, Sydney, New South Wales, Australia

Alain Cuerrier, Institut de recherche en biologie végétale, l’Université de Montréal, Montréal, Canada

Pei H. Cui, Faculty of Pharmacy, The University of Sydney, Sydney, New South Wales, Australia

Colin C. Duke, Faculty of Pharmacy, The University of Sydney, Sydney, New South Wales, Australia

Gabrielle Escalante, Department of Pharmacy Practice, College of Pharmacy, PAHO/WHO Collaborating Center for Traditional Medicine, University of Illinois at Chicago, Chicago, Illinois, USA

Sophia Yui Kau Fong, School of Pharmacy, The Chinese University of Hong Kong, Shatin, Hong Kong

Dong Fu, Faculty of Pharmacy, The University of Sydney, Sydney, New South Wales, Australia

Qiong Gao, School of Pharmacy, The Chinese University of Hong Kong, Shatin, Hong Kong

Cheong Hian Goh, Audit and Licensing Division, Health Products Regulation Group, Health Sciences Authority, Singapore, Republic of Singapore

Paul W. Groundwater, Faculty of Pharmacy, The University of Sydney, Sydney, New South Wales, Australia

David E. Hibbs, Faculty of Pharmacy, The University of Sydney, Sydney, New South Wales, Australia

Tom Hsun-Wei Huang, Faculty of Medicine, The University of Sydney, Sydney, New South Wales, Australia

Fangming Jin, School of Pharmacy, Shaanxi University of Chinese Medicine, Xi’an, Shaanxi, China; and Global Therapeutics Pty Ltd, Byron Bay, New South Wales, Australia

Moon-Sun Kim, Faculty of Pharmacy, The University of Sydney, Sydney, New South Wales, Australia

Hwee-Ling Koh, Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore, Republic of Singapore

Temitope O. Lawal, Department of Pharmaceutical Microbiology, University of Ibadan, Ibadan, Nigeria

George Q. Li, Faculty of Pharmacy, The University of Sydney, Sydney, New South Wales, Australia

Vivian Wan Yu Liao, Faculty of Pharmacy, The University of Sydney, Sydney, New South Wales, Australia

Ernest V. Linek, Banner & Witcoff, Ltd., Boston, Massachusetts, USA

Hao Liu, Faculty of Health and Social Sciences, The Hong Kong Polytechnic University, Hong Kong

Gail B. Mahady, Department of Pharmacy Practice, College of Pharmacy, PAHO/WHO Collaborating Center for Traditional Medicine, University of Illinois at Chicago, Chicago, Illinois, USA

Laura J. Mahady, The Barrow Neurological Institute and Arizona State University, Phoenix, Arizona, USA

Andrew J. McLachlan, Faculty of Pharmacy and Centre for Education and Research on Ageing, The University of Sydney and Concord Hospital, Sydney, New South Wales, Australia

Pooja Mikkilineni, Department of Pharmacy Practice, College of Pharmacy, PAHO/WHO Collaborating Center for Traditional Medicine, University of Illinois at Chicago, Chicago, Illinois, USA

Rosina Yau Mok, School of Pharmacy, The Chinese University of Hong Kong, Shatin, Hong Kong

Christina L. Nance, Department of Pediatrics, Baylor College of Medicine, Immunology, Allergy and Rheumatology, Texas Children’s Hospital, Houston, Texas, USA

Rajeshwar Narlawar, School of Chemistry, The University of Sydney, Sydney, New South Wales, Australia

Jennifer A. Ong, Faculty of Pharmacy, The University of Sydney, Sydney, New South Wales, Australia

Iqbal Ramzan, Faculty of Pharmacy, The University of Sydney, Sydney, New South Wales, Australia

Michel Rapinski, Institut de recherche en biologie végétale, l’Université de Montréal, Montréal, Canada

Michael Rieder, Departments of Paediatrics, Physiology and Pharmacology, and Medicine, Schulich School of Medicine & Dentistry; and Robarts Research Institute, Western University, London, Ontario, Canada

Bashar Saad, Qasemi Research Center-Al-Qasemi Academic College, Baga Algharbiya, Israel; and Faculty of Arts and Sciences, Arab American University Jenin, Jenin, Palestine

Stephen Sagar, Departments of Oncology and Medicine, McMaster University, Hamilton, Ontario, Canada

Susan J. Semple, Sansom Institute for Health Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia

Gint Silins, Cullens Patent & Trade Mark Attorneys, Brisbane, Queensland, Australia

Bradley S. Simpson, Flinders Centre for Innovation in Cancer, School of Medicine, Flinders University, Bedford Park, South Australia, Australia

Huanxing Su, State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau, China

Daniel M.-Y. Sze, School of Medical Sciences and Health Innovations Research Institute (HiRi), RMIT University, Australia

Jennifer Tan, E-TQCM Consultants Limited, Tsuen Wan, Hong Kong

Jian-Bo Wan, State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau, China

Shengpeng Wang, State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau, China

Yi-Tao Wang, State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau, China

Lynn Weekes, NPS MedicineWise, Surry Hills, New South Wales, Australia

Elizabeth M. Williamson, The School of Pharmacy, Whiteknights, Reading, Berkshire, United Kingdom

Raimond Wong, Departments of Oncology and Medicine, McMaster University, Hamilton, Ontario, Canada

Yin Cheong Wong, School of Pharmacy, The Chinese University of Hong Kong, Shatin, Hong Kong

Wai-Ping Yau, Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore, Republic of Singapore

Xiao-Jing Zhang, State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau, China

Qi (Tony) Zhou, Faculty of Pharmacy, The University of Sydney, Sydney, New South Wales, Australia

Zhong Zuo, School of Pharmacy, The Chinese University of Hong Kong, Shatin, Hong Kong

PREFACE

This book focuses on many facets of the use of Phytotherapies in preventing or treating illness and disease internationally. Phytotherapies are variously defined by practitioners and scientists but include herbal therapies, therapies used by indigenous peoples around the world and alternative medicines as opposed to classical western medicines.

I had not considered editing a book on Phytotherapies as the focus of my scientific career has not been on Phytotherapies. However, in the last 10 years I have investigated some of the pharmacological and more specifically, the hepatotoxic effects of kava. This interest has arisen from my background in that I was born and educated in Fiji where kava is widely used for social and ceremonial functions for centuries.

I was very surprised to receive an invitation from Jonathan Rose at Wiley some 2 years ago to ask if I had an interest in editing such a book. Not having edited an entire book previously, I naively agreed, of course, not realizing the magnitude of the task ahead. I realize now that editing an entire book is exponentially more challenging than contributing to a Book Chapter or even publishing numerous journal articles.

The topic interested me for several other reasons. The Faculty of Pharmacy at the University of Sydney had for many years hosted a Herbal Medicines Education and Research Centre (HMREC) and the Faculty also offered a Masters degree in Herbal Medicines. This program was moderately successful financially and the Centre was closed following an external review that I instituted as Dean of the Faculty. However, I do believe that it is important to examine in a scientific manner, the various forms of Phytotherapies used around the globe as use of such therapies continues to increase.

Phytotherapies are at the heart of disease management in countries such as China and India where they are used instead of and alongside Western medicines.

In the west, the use of Phytotherapies continues to grow at a phenomenal rate. Whether this reflects the dissatisfaction with modern western medicine or the perception that Phytotherapies are natural and thus free of any adverse effects is open to conjecture. However, there is certainly a belief especially among younger people that Phytotherapies are promising alternatives to modern drugs not only in promoting well-being and preventing disease but also in managing some conditions.

Identifying suitable Chapter authors was very challenging due to the diverse and varied nature of the field. I believed it was important to identify suitable scientists with the research and scientific credentials to bring reputational credit to such a book and to ensure balanced and erudite debate. This was confounded by language and cultural sensitivities relating to Phytotherapy use and the evidence base for use in different cultural and ethnic contexts.

Having succeeded in identifying potential Chapter authors the other interesting observation was that while these authors have individually made a strong contribution to the evidence base for the use of Phytotherapies some were also philosophically committed to clinical paradigms that promote the use of Phytotherapies. Separating this attachment to the adoption of Phytotherapies from the scientific evidence for their use was an additional challenge that I had not anticipated in accepting to edit such a book.

If you, the reader, like this book and find it informative and useful in either your practice, for your students or indeed as a resource in your scientific library, then I hope I have been able to objectively separate out the evidence base and summarise some of the science in this vast field of Phytotherapies. The other issue which I wanted to come across in the book is the rightful acknowledgment of the breath of the topic and the variety of the evidence base that is available for the use of Phytotherapies.

I want to thank Angela Teklic for her tireless effort in assisting me with the formatting of the Chapters and making sure that the Book complied with the Wiley template. Both of us underestimated this mammoth task but the attention to detail displayed by Angela made my life more bearable. Eleanor Luntao was very valuable in making sure the contributor agreements were in place and that permissions to reproduce published material were obtained. Eleanor’s dedication during the proof-reading stage was also exemplary. Finally, I would like to thank my wife, Dr Lynn Weekes AM, who had to spend many hours alone while I spent days editing this book.

Professor IQBAL RAMZAN

The University of SydneyFebruary 2015

1PHYTOTHERAPIES—PAST, PRESENT, AND FUTURE

IQBAL RAMZAN AND GEORGE Q. LI

Faculty of Pharmacy, The University of Sydney, Sydney, New South Wales, Australia

1.1 OVERVIEW OF PHYTOTHERAPY

1.1.1 Definition

Phytotherapy, or the use of herbal medicines to prevent or treat a disease, is a traditional medical practice based on medicinal plants. It is a branch of complementary and alternative medicine (CAM) or traditional medicine, which refers to traditional medicine systems and various forms of Indigenous medicine [1]. Many different cultures have developed herbal medicine systems, for example, Western herbal medicines, Chinese herbal medicines, Ayurvedic and Unani medicines, and Australian Indigenous medicines [2]. Phytotherapy is the basis of modern pharmaceutical science, with about 25% of the drugs prescribed today, such as digoxin, aspirin, and paclitaxel being derived from plants [3].

Western herbal medicine and orthodox medicine share to a large degree a common physiologic and diagnostic system, but they are different in many important ways as well. Herbs are complex mixtures of chemicals, which may have several distinct and concurrent pharmacological activities, while pharmaceutical drugs are mostly single chemical entities. Modern herbal medicines are becoming part of integrative clinical management in medical textbooks as exemplified in Natural Standard Herbal Pharmacotherapy [4].

Traditional Chinese Medicine (TCM) is another popular traditional medical system in China and worldwide. It includes various practices including Chinese herbal medicine, acupuncture, and massage, sharing a fundamental principle that the human body is part of the whole universe. The treatment goals are harmonization and balance using a holistic approach. The basic theories of TCM are Yin and Yang theory, Five-Element theory, Zang Fu (viscera and bowels) theory, Meridian, Qi, Blood and Fluid theory, Syndrome Differentiation, and Treatment theory. Detailed information on TCM can be found in textbooks on Chinese medicine [5–8]. For example, the blockage by Phlegm is closely related to excessive fat retention in metabolic syndrome and the management with herbal formulations and other modalities is to eliminate the Phlegm [9]. Treatment of diabetes with TCM focuses on nourishing Yin, clearing Heat, producing Body Fluid, and moistening Dryness using herbal formulae composed of herbs such as Rehmannia (Rehmannia glutinosa) and yam (Dioscorea opposita) [10].

Modernization of TCM and integration with orthodox medicine and science is a model accepted in China, covering education, clinical practice, and research. Modern pharmacologic and clinical studies have been used to examine claims of traditional practice; chemistry and chemical analysis are used for quality control of Chinese herbal medicines. Pharmacological and chemical studies have revealed connections between nature of herbal medicines and pharmacological activities, herbal tastes, and chemical components. For example, ephedra is warm as it contains ephedrine, a sympathomimetic amine; pungent herbs contain essential oils; sour herbs contain acid and tannins; sweet herbs contain sugars, proteins, and amino acids; bitter herbs contain alkaloids and glycosides; and salty herbs contain inorganic salts. Pharmacokinetic studies demonstrate a link between the tissue distribution of active chemical constituents and the attributive meridians of Chinese herbal medicines.

The World Health Organization (WHO) has a long-term interest in promoting traditional medicines and has produced a series of publications on global atlas [11], good agricultural practices [12], and monographs on selected medicinal plants [13], providing scientific information on the safety, efficacy, and quality control of widely used medicinal plants. The latest version of WHO Traditional Medicine Strategy (2014–2023) was developed to support Member States in harnessing the potential contribution of traditional medicine to health, wellness, and health care; and promoting the safe and effective use of traditional medicines by regulating, researching, and integrating traditional medicine products, practitioners, and practice into health systems [14].

1.1.2 International Trend in the Usage of Complementary Medicines

Complementary medicines have maintained their popularity in all regions of the world. The global market for herbal medicines is significant and growing rapidly. In China, traditional herbal preparations account for approximately 40% of the total health care delivered [1]. In the United States, over 42% of the population have used complementary or alternative medicine at least once. Total out-of-pocket expenditure relating to alternative therapies in 1997 was conservatively estimated at $27.0 billion, which is comparable with the projected 1997 out-of-pocket expenditure for all US physician services [15]. In the United Kingdom, estimate of annual out-of-pocket expenditure on practitioner visits in 1998 was £450 million [16].

In Australia, it has been reported that in 2000, 52% of the population used at least one nonmedically prescribed complementary medicine [17]. The estimated expense on complementary medicines was nearly twice the patient expenditure on pharmaceutical medicines during 1992–1993 [17]. The expenditure on alternative therapies in 2000 was $AUD 2.3 billion [18]. In 2005, the annual out-of-pocket expenditure was estimated to be $AUD 4.13 billion [19]. More recent studies have indicated that complementary medicines are finding a growing preference amongst patients with chronic or serious diseases who are looking for natural options to assist in the ongoing management of these conditions. For instance, St. John’s wort preparations have low rates of side effects and good compliance, comparatively low cost, making it worthy of consideration in the management of mild-to-moderate depression [20]. An overview of complementary medicines use and regulation in Australia is available in the Australian government’s commissioned report, Complementary Medicines in the Australian Health System [21].

1.2 PRECLINICAL RESEARCH ON PHYTOTHERAPIES

1.2.1 Pharmacognosy and Quality Standardization of Phytotherapies

Pharmacognosy is the study of medicinal materials, mainly plants, using theory and methods of modern sciences such as botany, zoology, chemistry, pharmacology, and traditional medicines to study the origin, production, harvesting and processing, identification and evaluation, chemical components, physical and chemical properties, resource development, pharmacology, toxicology, and therapeutic application of herbal medicines to ensure the quality of herbal materials and to develop new herbal resources. Its main focus is on the study of authentication and quality control of herbs [22].

Plant descriptions are used in the identification of herbal materials. They are first classified by the plant parts of origin, such as roots and rhizomes, stems, leaves, flowers, fruits, or whole herbs. Then the macroscopic and microscopic descriptions are included in each monograph. Some microscopic features reflect the secondary metabolites, starch granules, resin ducts, and oil cells. The macroscopic features are still very useful for authentication; for example, the colors of herbs such as yellow coptis, brown rhubarb, and black valerian are related to their alkaloid, anthraquinone, and iridoid contents, respectively.

Pharmacognosy, particularly correct identification and high quality of the herb, is the foundation of safety, clinical efficacy, and research on phytotherapy. It is a subject most relevant to professionals in testing laboratories, herbal dispensing, and regulatory bodies. Pharmacognosy is the principal discipline employed in national and international pharmacopeia in the form of the following topics: species identification using plant taxonomy, macroscopic identification using morphology, microscopic identification using anatomy, and quality control with analytical methods. The WHO monographs are examples of such comprehensive monographs [13], while British Pharmacopoeia used as statutory standards in Europe and Australia focuses on chemical analysis for quality control [23].

Bioequivalence is a useful concept in the quality standardization of herbal medicines. European Guideline on the Investigation of Bioequivalence defined bioequivalence as same active substances and similar bioavailability that results in similar clinical effectiveness and safety [24]. To approve two products to be bioequivalent, the following studies need to be carried out: pharmaceutical equivalence (quality standardization), pharmacokinetic equivalence (same bioavailability and time-to-peak concentration), pharmacodynamic equivalence (in vivo and in vitro), and therapeutic equivalence (clinical study). For example, a study found that the bioavailability of ginkgolide A, ginkgolide B, and bilobalide of two different Ginkgo biloba commercial brands were clearly different and did not demonstrate bioequivalence of test and reference products. The slow in vitro dissolution of the test product resulted in a large decrease in bioavailability [25]. The bioequivalence concept implies the need for a comprehensive platform for evaluation of herbal products [22].

Kudzu root is an example of a herb requiring a comprehensive quality control platform. Kudzu is one of the most commonly used Chinese herbal medicines for the treatment of diabetes, cardiovascular disease, and many other conditions. It includes two closely related species, Pueraria lobata and Pueraria thomsonii, which are not well-differentiated in pharmacopoeias. Isoflavonone puerarin is currently used as a marker for quality control of the species [26]. Recent studies indicate that ultra-performance liquid chromatography combined with partial least square discriminant analysis (PLS-DA) was more effective than using puerarin alone in differentiating the two species [27]. HPTLC coupled with multivariate classification analyses has also been used effectively to differentiate the two species [28].

Similarly, multiple markers have been used in the quality control of propolis. High-performance liquid chromatography with UV detection has been used to simultaneously quantify the eight major bioactive phenolic compounds in Chinese propolis [29] and a rapid thin-layer chromatography combined with chemometric fingerprinting has also been used to distinguish Chinese propolis from poplar tree gum [30].

1.2.2 Pharmacological Studies and Identification of Bioactive Compounds

Herbal pharmacology is the study of the function and mechanism of action of herbal medicines in biological systems and the pharmacokinetics of herbal compounds with modern scientific methods to understand the underlying nature of the likely clinical application. Herbal medicines are unique in that they contain multiple components and can act on multiple pharmacologic targets. The major types of herbal pharmacology research are in vitro studies at the cellular or tissue level to uncover the mechanism of action of the herbal components at the molecular level, for example, cytotoxicity in cancer cell lines; whole animal models to test preclinical properties of herbal medicines and to determine the pharmacokinetic properties, for example, streptozotocin-induced diabetic rats and human clinical studies to confirm the efficacy and safety of the herbal medicines. For instance, preclinical and limited clinical evidence have shown pentacyclic triterpenoids including the oleanane, ursane, and lupane groups have multiple biological activities and may contribute to their use in traditional medicine for the treatment of diabetes and diabetic complications [31]. Increasing evidence also has shown common chemical components such as gallic acid, a common phenolic compound, playing some role in the potential health benefits of food and nutraceuticals [32, 33]. Quercetin is clinically used as a nutraceutical for cardiovascular disease [34], and berberine has been used for the management of diabetes [35].