Herbal medicine
Herbal medicine..................................................................................................... 1
Lecture 1................................................................................................................ 4
What is pharmacognosy, what are natural products?..........................................4
Plant derived drugs: pure chemical entities, examples (to be recognised).........4
Plant derived drugs: herbal medicines................................................................4
What are supply problems and how can these be solved....................................4
Steps in medicinal plant discovery......................................................................4
Plant organs as botanical drugs..........................................................................4
Binomial nomenclature of plant names...............................................................5
Hierarchical classification system of Plant Kingdom............................................5
Synonyms, homonyms........................................................................................ 5
Chemotaxonomy (taxonomy and (chemo)systmetatics).....................................5
Global classification of the plant kingdom...........................................................5
What are secondary metabolites, examples?......................................................5
Ethnopharmacology and drug development.......................................................5
Convention of Rio................................................................................................ 6
General aspects and characteristics of oriental traditional medicine..................6
Traditional medicinal systems in non- western countries....................................6
Global description of CAM, anthroposophy, aromatherapy.................................8
Homeopathy characteristics................................................................................ 9
Phytotherapy definition, characteristics............................................................10
International ‘bodies’ involved: WHO, ESCOP, EMA...........................................10
Lecture 2.............................................................................................................. 11
Production and product quality.........................................................................11
Quality in relation to HMPs: GACP, CLP, GMP; international guidelines, quality
Parameters........................................................................................................ 11
Wildcrafted plants versus cultivated.................................................................11
Quality control, where in process......................................................................11
Role of Ph. Eur................................................................................................... 12
DNA-based methods.......................................................................................... 12
What are extracts, how are they prepared (standardised, non-standardised)...13
Drug (herb)-extract ratio, drug-solvent ratio.....................................................13
Maceration, percolation..................................................................................... 14
Influence of extraction fluid on extract..............................................................14
, Adulteration and contamination........................................................................14
Counterfeit products.......................................................................................... 15
Phyto-equivalence............................................................................................. 15
Lecture 3->slide 6+7............................................................................................ 16
Lecture 4.............................................................................................................. 17
General aspects of toxicity of plants and plant constituents.............................17
Risks of use of herbals....................................................................................... 17
Safety related to quality aspects.......................................................................18
Composition of product in relation to safety......................................................18
Types of adverse effects.................................................................................... 18
Determinants of adverse effects.......................................................................19
Pharmacovigilance of herbals, signals, causality...............................................19
Herbal Preparations Decree to protect consumer..............................................20
Pyrrolizidine alkaloids........................................................................................ 21
Aristolochic acids............................................................................................... 21
(Mechanism of toxicity) of various secondary metabolite groups......................22
Herb-drug interactions: mechanism, clinical relevance.....................................23
Pharmacokinetic and pharmacodynamic interactions.......................................23
Role of the pharmacist...................................................................................... 24
Lecture 5.............................................................................................................. 25
Pharmacology and clinical efficacy....................................................................25
HMPs: antagonism and synergism.....................................................................25
Polyvalent action of HMPs................................................................................. 25
Effect of extract versus effect of isolated compound........................................25
Possibilities and limitations with HMP in health care.........................................26
Levels of evidence of efficacy, limitations.........................................................26
Cases studies, observational studies, interventional studies............................27
Examples of proved effective, plausible effective and traditional HM...............27
Herbal medicine list.............................................................................................. 29
Central nervous system..................................................................................... 29
St. John’s wort, gingko, cannabis...................................................................29
Circulatory tract disorders................................................................................. 32
Hawthorn, gingko, horse chestnut, garlic, red rice yeast...............................32
Digestive tract................................................................................................... 34
Artichoke, turmeric, ginger, liquorice, milk thistle, laxatives (bulk formers and
anthranoids)................................................................................................... 34
Respiratory tract................................................................................................... 40
, Ivy, liquorice, other plants in groups (e.g. diaphoretics, cough).....................40
Skin................................................................................................................... 43
Arnica, marigold, chamomile, St. John’s wort oil, aloe, tea tree oil, centella. .43
Urinary and genital tract................................................................................... 46
Bearberry, cranberry, saw palmetto, chasterberry, black cohosh,
phytoestrogens.............................................................................................. 46
Pain and inflammation....................................................................................... 50
Peppermint oil, feverfew, willow bark, devil’s claw........................................50
Immune system................................................................................................. 53
Adaptogenic, immunostimulant, ginseng, taiga, umckaloabo and mistloee,
mushrooms.................................................................................................... 53
Pharmacovigilance for herbal and traditional medicines......................................56
Definitions......................................................................................................... 56
Why is causality assessment difficult for herbal medicines?.............................56
First example 1.................................................................................................. 57
Why is pharmacovigilance important?..............................................................58
Case study examples........................................................................................ 60
Safety example 1.............................................................................................. 60
Safety example 2.............................................................................................. 61
Third example................................................................................................... 61
Safety example 4.............................................................................................. 62
Example 5: nice up of tea.................................................................................. 62
,Lecture 1
What is pharmacognosy, what are natural products?
=is the science of biogenic or nature-derived pharmaceuticals and poisons (natural products)
- Plants, bacteria, fungi, animals
- Healthcare, therapeutics-oriented
- Pharmaceutical biology
Plant derived drugs: pure chemical entities, examples (to be recognised)
› Pure chemical entities (active pharmaceutical ingredients (API), licensed drugs)
- Isolated natural products (morphine, digoxin, quinine, vincristine, atropine, paclitaxel, galantamine)
- Semi-synthetic derivatives of natural products (etoposide, arteether, topotecan)
- Synthetics based on natural product template (atropine, morphine, cocaine and tubocurarine)
1. Etoposide:
- rhizome of podophyllum peltatum L.mayapple.
- Use: lung, testicular and lymphoid cancer
2. Arteether :
- from annual wormwood.
- Use: resistant forms of malaria
3. Topotecan :
- from happy tree.
- Use: metalized ovarian cancer, lung cancer
Plant derived drugs: herbal medicines
› Botanical drugs (from specific medicinal plant parts)
§ ‘Herbal medicines’
- Herbal substances (raw materials)
- Herbal preparations (e.g., extracts)
- Herbal medicinal products (HMPs, phytomedicines)
What are supply problems and how can these be solved
Supply problems:
1. Environmental (climate related, political situation)
2. Plant related (slow growth, cultivation problems)
3. Isolation and purification (low concentration, many closely
related structures)
Solutions:
- Other plant sources (chemosystematics: related plant species
often contain similar constituents)
- Selection (high-producing plants, plants with a different metabolic pattern)
- Use of more abundant precursors (from plants) (semi-synthetic derivatisation, enzymatic
derivatisation)
- Biotechnology (plant cell and tissue cultures, heterologous expression systems)
- Organic synthesis
Steps in medicinal plant discovery
› Increased recognition of plants as source of potential drug leads
› Starting point: ethnobotanical use (ethnopharmacology)
› From basis preclinical research to clinical trials
Plant organs as botanical drugs
› Derived from a plant and transformed into a drug by drying certain plant parts, or sometimes the whole plant
› Obtained from a plant, but no longer retains the structure of the plant or its organs
§ Essential oil, gum, resin, balm
› Isolated pure natural products are not botanical drugs
› Aerial parts or herb (herba)
› Leaf (folia)
› Flower (flos)
› Fruit (fructus)
, › Bark (cortex)
› Root (radix)
› Rhizome (rhizoma)
› Bulb (bulbus)
› Seed (semen
Binomial nomenclature of plant names
› Species name is binomial
§ Papaver somniferum L. (opium poppy)
› Genus name plus (specific) epithet (italic) with authority (abbreviated, not italic)
Hierarchical classification system of Plant Kingdom
- Species: somniferum (sleep-producing)
- Genus: Papaver- contains group of species
- Family: Papaveraceae- group of genera
- Order: Papaverales
- Class: Magnoliatae
- Division (=phylum): Spermatophyta (seed-bearing plants)
- Kingdom: Plantae (plants; other kingdoms: animals, fungi)
Synonyms, homonyms
Synonyms: one plant, many names (many languages)
Homonyms: same name for different plant species-> false
Chemotaxonomy (taxonomy and (chemo)systmetatics)
=science of naming organisms and correct integration into existing system of nomenclature
- (based on taxa, hierarchic system, from small to big, relationship (morphology, chemistry)
Chemosystematics: closely related plants contain similar constituents
- Related species within one genus
- Related genera within one family
- Genetic background
Global classification of the plant kingdom
1. Green algae
2. Bryophytes
3. Pteridophytes
4. Conifers
5. dicots
What are secondary metabolites, examples?
- Not essential to the functioning of plant
- Ecological role, protection against microbes
Examples:
- Isoprenoids
- Phenolic compounds
- Essential oils
- Glycosides
- Alkaloids
- Carbohydrates
- Fats
Ethnopharmacology and drug development
Ethnobotany, ethnopharmacology
› Traditional medicine used for novel drug development
- Many commonly used drugs are developed by studying indigenous remedies
- Local knowledge (e.g., traditional healers; oral and written) scientifically developed
› Ethnobotany: study of relationships between humans and plants in all its complexity
- Observations and study of the use a society makes of plants, including beliefs and cultural practices
- Medicinal use, food, poison, building material, fertilisers, colouring agents, ornamentals
- Ethnobotanists live with the endogenous people
Herbal medicine..................................................................................................... 1
Lecture 1................................................................................................................ 4
What is pharmacognosy, what are natural products?..........................................4
Plant derived drugs: pure chemical entities, examples (to be recognised).........4
Plant derived drugs: herbal medicines................................................................4
What are supply problems and how can these be solved....................................4
Steps in medicinal plant discovery......................................................................4
Plant organs as botanical drugs..........................................................................4
Binomial nomenclature of plant names...............................................................5
Hierarchical classification system of Plant Kingdom............................................5
Synonyms, homonyms........................................................................................ 5
Chemotaxonomy (taxonomy and (chemo)systmetatics).....................................5
Global classification of the plant kingdom...........................................................5
What are secondary metabolites, examples?......................................................5
Ethnopharmacology and drug development.......................................................5
Convention of Rio................................................................................................ 6
General aspects and characteristics of oriental traditional medicine..................6
Traditional medicinal systems in non- western countries....................................6
Global description of CAM, anthroposophy, aromatherapy.................................8
Homeopathy characteristics................................................................................ 9
Phytotherapy definition, characteristics............................................................10
International ‘bodies’ involved: WHO, ESCOP, EMA...........................................10
Lecture 2.............................................................................................................. 11
Production and product quality.........................................................................11
Quality in relation to HMPs: GACP, CLP, GMP; international guidelines, quality
Parameters........................................................................................................ 11
Wildcrafted plants versus cultivated.................................................................11
Quality control, where in process......................................................................11
Role of Ph. Eur................................................................................................... 12
DNA-based methods.......................................................................................... 12
What are extracts, how are they prepared (standardised, non-standardised)...13
Drug (herb)-extract ratio, drug-solvent ratio.....................................................13
Maceration, percolation..................................................................................... 14
Influence of extraction fluid on extract..............................................................14
, Adulteration and contamination........................................................................14
Counterfeit products.......................................................................................... 15
Phyto-equivalence............................................................................................. 15
Lecture 3->slide 6+7............................................................................................ 16
Lecture 4.............................................................................................................. 17
General aspects of toxicity of plants and plant constituents.............................17
Risks of use of herbals....................................................................................... 17
Safety related to quality aspects.......................................................................18
Composition of product in relation to safety......................................................18
Types of adverse effects.................................................................................... 18
Determinants of adverse effects.......................................................................19
Pharmacovigilance of herbals, signals, causality...............................................19
Herbal Preparations Decree to protect consumer..............................................20
Pyrrolizidine alkaloids........................................................................................ 21
Aristolochic acids............................................................................................... 21
(Mechanism of toxicity) of various secondary metabolite groups......................22
Herb-drug interactions: mechanism, clinical relevance.....................................23
Pharmacokinetic and pharmacodynamic interactions.......................................23
Role of the pharmacist...................................................................................... 24
Lecture 5.............................................................................................................. 25
Pharmacology and clinical efficacy....................................................................25
HMPs: antagonism and synergism.....................................................................25
Polyvalent action of HMPs................................................................................. 25
Effect of extract versus effect of isolated compound........................................25
Possibilities and limitations with HMP in health care.........................................26
Levels of evidence of efficacy, limitations.........................................................26
Cases studies, observational studies, interventional studies............................27
Examples of proved effective, plausible effective and traditional HM...............27
Herbal medicine list.............................................................................................. 29
Central nervous system..................................................................................... 29
St. John’s wort, gingko, cannabis...................................................................29
Circulatory tract disorders................................................................................. 32
Hawthorn, gingko, horse chestnut, garlic, red rice yeast...............................32
Digestive tract................................................................................................... 34
Artichoke, turmeric, ginger, liquorice, milk thistle, laxatives (bulk formers and
anthranoids)................................................................................................... 34
Respiratory tract................................................................................................... 40
, Ivy, liquorice, other plants in groups (e.g. diaphoretics, cough).....................40
Skin................................................................................................................... 43
Arnica, marigold, chamomile, St. John’s wort oil, aloe, tea tree oil, centella. .43
Urinary and genital tract................................................................................... 46
Bearberry, cranberry, saw palmetto, chasterberry, black cohosh,
phytoestrogens.............................................................................................. 46
Pain and inflammation....................................................................................... 50
Peppermint oil, feverfew, willow bark, devil’s claw........................................50
Immune system................................................................................................. 53
Adaptogenic, immunostimulant, ginseng, taiga, umckaloabo and mistloee,
mushrooms.................................................................................................... 53
Pharmacovigilance for herbal and traditional medicines......................................56
Definitions......................................................................................................... 56
Why is causality assessment difficult for herbal medicines?.............................56
First example 1.................................................................................................. 57
Why is pharmacovigilance important?..............................................................58
Case study examples........................................................................................ 60
Safety example 1.............................................................................................. 60
Safety example 2.............................................................................................. 61
Third example................................................................................................... 61
Safety example 4.............................................................................................. 62
Example 5: nice up of tea.................................................................................. 62
,Lecture 1
What is pharmacognosy, what are natural products?
=is the science of biogenic or nature-derived pharmaceuticals and poisons (natural products)
- Plants, bacteria, fungi, animals
- Healthcare, therapeutics-oriented
- Pharmaceutical biology
Plant derived drugs: pure chemical entities, examples (to be recognised)
› Pure chemical entities (active pharmaceutical ingredients (API), licensed drugs)
- Isolated natural products (morphine, digoxin, quinine, vincristine, atropine, paclitaxel, galantamine)
- Semi-synthetic derivatives of natural products (etoposide, arteether, topotecan)
- Synthetics based on natural product template (atropine, morphine, cocaine and tubocurarine)
1. Etoposide:
- rhizome of podophyllum peltatum L.mayapple.
- Use: lung, testicular and lymphoid cancer
2. Arteether :
- from annual wormwood.
- Use: resistant forms of malaria
3. Topotecan :
- from happy tree.
- Use: metalized ovarian cancer, lung cancer
Plant derived drugs: herbal medicines
› Botanical drugs (from specific medicinal plant parts)
§ ‘Herbal medicines’
- Herbal substances (raw materials)
- Herbal preparations (e.g., extracts)
- Herbal medicinal products (HMPs, phytomedicines)
What are supply problems and how can these be solved
Supply problems:
1. Environmental (climate related, political situation)
2. Plant related (slow growth, cultivation problems)
3. Isolation and purification (low concentration, many closely
related structures)
Solutions:
- Other plant sources (chemosystematics: related plant species
often contain similar constituents)
- Selection (high-producing plants, plants with a different metabolic pattern)
- Use of more abundant precursors (from plants) (semi-synthetic derivatisation, enzymatic
derivatisation)
- Biotechnology (plant cell and tissue cultures, heterologous expression systems)
- Organic synthesis
Steps in medicinal plant discovery
› Increased recognition of plants as source of potential drug leads
› Starting point: ethnobotanical use (ethnopharmacology)
› From basis preclinical research to clinical trials
Plant organs as botanical drugs
› Derived from a plant and transformed into a drug by drying certain plant parts, or sometimes the whole plant
› Obtained from a plant, but no longer retains the structure of the plant or its organs
§ Essential oil, gum, resin, balm
› Isolated pure natural products are not botanical drugs
› Aerial parts or herb (herba)
› Leaf (folia)
› Flower (flos)
› Fruit (fructus)
, › Bark (cortex)
› Root (radix)
› Rhizome (rhizoma)
› Bulb (bulbus)
› Seed (semen
Binomial nomenclature of plant names
› Species name is binomial
§ Papaver somniferum L. (opium poppy)
› Genus name plus (specific) epithet (italic) with authority (abbreviated, not italic)
Hierarchical classification system of Plant Kingdom
- Species: somniferum (sleep-producing)
- Genus: Papaver- contains group of species
- Family: Papaveraceae- group of genera
- Order: Papaverales
- Class: Magnoliatae
- Division (=phylum): Spermatophyta (seed-bearing plants)
- Kingdom: Plantae (plants; other kingdoms: animals, fungi)
Synonyms, homonyms
Synonyms: one plant, many names (many languages)
Homonyms: same name for different plant species-> false
Chemotaxonomy (taxonomy and (chemo)systmetatics)
=science of naming organisms and correct integration into existing system of nomenclature
- (based on taxa, hierarchic system, from small to big, relationship (morphology, chemistry)
Chemosystematics: closely related plants contain similar constituents
- Related species within one genus
- Related genera within one family
- Genetic background
Global classification of the plant kingdom
1. Green algae
2. Bryophytes
3. Pteridophytes
4. Conifers
5. dicots
What are secondary metabolites, examples?
- Not essential to the functioning of plant
- Ecological role, protection against microbes
Examples:
- Isoprenoids
- Phenolic compounds
- Essential oils
- Glycosides
- Alkaloids
- Carbohydrates
- Fats
Ethnopharmacology and drug development
Ethnobotany, ethnopharmacology
› Traditional medicine used for novel drug development
- Many commonly used drugs are developed by studying indigenous remedies
- Local knowledge (e.g., traditional healers; oral and written) scientifically developed
› Ethnobotany: study of relationships between humans and plants in all its complexity
- Observations and study of the use a society makes of plants, including beliefs and cultural practices
- Medicinal use, food, poison, building material, fertilisers, colouring agents, ornamentals
- Ethnobotanists live with the endogenous people
