Medicinal Plants, Natural Products and

Phytotherapy: Introduction
(2 h 4 slots)

Michael Heinrich
Centre for Pharmacognosy
and Phytotherapy
UCL School of Pharmacy,
29 - 39 Brunswick Sq.,
London, WC1N 1AX, UK

Waterhouse Pharmacy, Southgate

London
 Availability of complementary medicines for
retail sale in pharmacies in England (1998)
?
Why is it important

99% sell at least one type of

complementary medicine,
including vitamins/minerals
92% sell at least one type of
complementary medicine,
excluding vitamins and minerals

IPSOS /Mori 2009, Barnes J, Abbot NC.

Waterhouse Pharmacy, Southgate London Pharm J 1999;263:R37,R43
 UK: Herbal Medicines. Who Cares?
Online Survey 2018 (UK):

about herbal medicines.

Survey responses were
categorised and analysed
using Qualtrics
408 participants (numbers
varied across questions)
Herbal medicines are
people use natural products
→ seems to be natural

→ seems to have less side effects

→ considered to be effective

popular, particularly amongst we

with
are supposed
situations :
to help

the 36 to 55 year old age

these

↳ Sleep
↳
anxiety
↳ Stress
booster

group.
↳ immune system
↳ Survey highlight what people
do → patients care alot about

products .

Used herbal medicines for

minor-self-limiting conditions. Why are respondents
Herbal medicines are attracted to herbal remedies?
3 (N=307).
Lazarou and Heinrich 2019 Phytother. Res.
UK: Herbal Medicines. Who Cares?
Online Survey 2018 (UK):

about herbal medicines.

Survey responses were
categorised and analysed
using Qualtrics
408 participants (numbers
varied across questions) § Patient care

Herbal medicines are

a lot

popular, particularly amongst

the 36 to 55 year old age
group.
Used herbal medicines for
minor-self-limiting conditions.
Herbal medicines are Use herbal remedies for groups of
health conditions (N=324) -
4
multiple answers possible
UK: Herbal Medicines. Who Cares?

are
↳ patients in this survey
very clear about herbal medicine
→ herbal medicines have Place
for minor conditions

"" ""
""

(
herbal medicines
help but
may maybe
not .

"In general, herbal remedies are "In general, herbal remedies

effective
5 for minor health are effective for major health
conditions" (N=144) conditions" (N=144)
UK: Herbal Medicines. Who Cares?
Main plants →
used for

inflammatory
used in healthcare conditions

&
for
topically
some conditions
and also

internally

&

gastrointestinal
problems

6
Lazarou & Heinrich 2019 Phytother. Res.
How do you know if a herbal product is of good or bad
quality (N=304)
of product
most p¥ttient doriot know how to assess the
quality .

Response No. selecting % of

this answer Participants
64 21.1
I trust the supplier 30 9.9
I see if it works 49 16.1
Packaging 5 1.6
Smell, colour and taste 23 7.6
THR 10 3.3
Research 27 8.9
Using suppliers that use good manufacturing 7 2.3
practice (GMP)
Brand reputation 31 10.2
Reviews/ word of mouth 37 12.2
7
1
How do you know if a herbal product is of good or bad
quality (N=304)

Response No. selecting % of

this answer Participants
64 21.1

Informal interviews30showed9.9 that

I trust the supplier
I see if it works 49 16.1
Packaging
people were unaware 5
of how
1.6
poor
Smell, colour the quality of some
and taste 23 products
7.6
THR are on the market,10which could 3.3
Research 27 8.9
perhaps be why THR
Using suppliers that use good manufacturing 7
was2.3 so
practice (GMP)
lowly valued.
Brand reputation 31 10.2
Reviews/ word of mouth 37 12.2
8
1
Telling healthcare professionals?
Do people tell their doctor of pharmacists about using
traditional remedies? (British Indian)
Of the total research population, 106 participants who took
prescribed medication were asked if they told their doctor or
pharmacists about the concurrent use of traditional remedies.
90 ↳ If people are on diverse
medications

80 ↳ would
that
medicine
Patient

they
.
are
tell

taking
pharmacist
herbal

very few patients tell would

70
↳
Number of participants

tell doctor and even few of

their pharmacists
that
taking herbal
they are

meds .

60
50
Yes
40
No
30
Not applicable
20
Bhamra et al
10 2019.
0 Phytotherapy
Doctor Pharmacist Research
Community pharmacists need to be aware of the methods
for quality control and standardisation, the differences in
quality, and, of course, should promote high quality
products which very often also have many clinical studies
to back up the therapeutic claim(s)
Pharmaceutical analysis is a core skill of pharmacists and
particular attention needs to be paid to
phytopharmaceutical quality
All pharmacists need to be aware of the use of herbal
reported in our recent survey that they had used CAM in
the last 12 months. This usage then needs to be assessed
and not just disregarded as quackery or ignored because it
is natural.
Further reading: Heinrich, M., J. Barnes, J. Prieto-Garcia,
S. Gibbons and E.M. Williamson (2018) Fundamentals of
Pharmacognosy and Phytotherapy. 3rd ed. London.
Churchill Livingston (Elsevier) Edinburgh. (Chapter 10; or
chapter 9 in the 2nd ed.)
 Pharmacognosy study
produced
as
of

plants ,
medicines

from
animals
natural

,
or crude

resources

microbes .
drugs
such

Derived from pharmakon gignosco,

(Greek)
The science of biogenic or nature-derived pharmaceuticals and
poisons
Focuses on all medicinal plants, including those yielding
- complex mixtures, which are used in the form of crude
herbs or extracts [(rational) phytotherapy] → if it has evidence based

- pure compounds such as morphine, and

- foods having an additional health benefits (health food /
nutraceuticals). commonly
disease
→
prevention of
.
used not to treat a disease but

→
mostly plant
derived
Natural products
Natural products = small molecular weight organic compounds of natural
origin [plants, microbes (fungi and bacteria), marine organisms and more
exotic sources such as frog skins and insects] inthe molecular weight
range of 100 2000 Daltons (Da).They isolate the products . we look from the product has come from
,
as well as

the process

In the context of pharmacognosy, natural products are looked at y

regarding their biological origin, extraction [or (semi-)synthetic

production], pharmacology, clinical use and role in drug discovery
Important
↳ Natural products are

how processed How we get

the pure compound and how we do structure identification of
look at them from the perspective of fwhere they come from
, they are
,
↳
these
compounds .
Regulatory
framework
Herbal Medicines traditional
use OTC medicines
Registered traditional herbal medicines THMP
(Traditional Herbal Medical Product Directive)
This regulatory framework has been in place for over 15
years and regulates the uses (claims), quality and safety of
herbal medical products sold as OTC medicines
Any manufactured herbal medicine placed on the market
under Section 12 (2) of the Medicines Act since 30 April
2004 need to comply with the requirements of the scheme.
It is relevant for any product which
Symbol given by
- Makes a medical claim (treatment or
prevention of an illness) (or) } MHRA

- Is sold in a form which implies that it is used

medicinally (and) µ
e. g ↳ common
↳ GI
cold
Problems

- Can only be used for minor self-limiting

↳ milder form of
depression called
low mood .

diseases and generally as an OTC product

&
logo
Herbal Medicines traditional
use OTC medicines
Registered traditional herbal medicines THMP
(Traditional Herbal Medical Product Directive)
This regulatory framework has been in place for well over
ten years and regulates the uses (claims), quality and
safety of herbal medical products sold as OTC medicines
Any manufactured herbal medicine placed on the market
under Section 12 (2) of the Medicines Act since 30 April
2004 need to comply with the requirements of the scheme.
It is relevant for any product which
- Makes a medical claim (treatment or
prevention of an illness) (or)
- Is sold in a form which implies that it is used
medicinally (and)
- Can only be used for minor self-limiting
diseases and generally as an OTC product
Herbal Medicines traditional
use OTC medicines
Registered traditional herbal medicines THMP
(Traditional Herbal Medical Product Directive)
Key requirements
- The products are approved by the MHRA and fully
regulated
- The use is based on 30 years of traditional use (of which
15 have to be within the European Union)
- Mostly OTC products (an on the general sales list GSL)
- Produced under GMP (Good Manufacturing
Practice)
- For minor self-limiting diseases only
- Only for products which are considered to be
(very) safe
- A full Patient Information Leaflet (PIL)
approved by the MHRA must be included
-
Herbal Medicines traditional
use OTC medicines
Registered traditional herbal medicines THMP
(Traditional Herbal Medical Product Directive)
Key requirements (continued) what you should take e.g
how
many tablet

- Defined recommended dose and usage

→

- The pharmaceutical producer must conduct weekly

*

updates esp. with regards to safety (database searches)

- The therapeutic use must be plausiblee.g
respiratory
at problems
problems

if it is in Braille

- The product name is included in Braille on the box p

then it's

Product
a THR

- The MHRA regularly monitors the product y

↳ *

under
must be

Pharma
completely
co
violence

- They are medicines and as such YOU, If

any
so
concerns
they win raise it with producer

as a pharmacist, will have the professional

responsibility (as with all other medicines)
- You can recommend and sell these products
and need to give preference to THR
products vs. unregulated ones
- Most products now carry the THR logo
Main therapeutic uses of THR products
based on an EU-wide assessment
Most common products have been registered under the
THR to treat cough / cold, mental stress / mood disorders
and gastrointestinal complaints
from data what
This is
basically derived
relating to

products on the market .

Peschel 2014
 framework:
herbal medicines (1968)
Product Licences of Right (PLRs) granted to all existing
products when Medicines Act came into force (1968)
At PLR review, traditional herbal medicines used for minor, self-limiting
conditions were permitted to draw on bibliographic evidence of efficacy
and safety rather than carry out controlled tests and trials product
licence (PL number); now generally moved under the THR scheme
Section 12 of Medicines Act 1968 provides two crucial
exemptions from licensing for herbal medicines:
-
Patient get

medication treatment ]
might for the
herbal e Chinese / European herbalist → give meds to patient prepared on the premises treatment at home

(2) herbs only subjected to simple processing, sold under

common/botanical name, no written uses

without direct medical claims (> 5000?)

Only regulated herbal medicines are required to comply with
regulatory provisions on quality and pharmacovigilance only so

and 7
with THR logo win actually require to comply with regulatory provisions
Other elements of the regulatory framework
European Pharmacopoeia with > 240 monographs on herbal drugs
EU directive 65/65/EEC (now 2001/83) - medicinal product
(definition):
"Any substance or combination of substances presented for
treating or preventing disease in human beings or animals".
"Any substance or combination of substances which may be
administered to human beings or animals with a view to
making a diagnosis or to restoring, correcting or modifying
physiological functions in human beings or animals is likewise
considered a medicinal product".
i.e. medicinal by presentation OR function
applies to herbal products just the same as to other products

greater flexibility on use of bibliographic data to demonstrate

safety and efficacy
but interpretations varied between member states; not widely
applicable to wide range of unregulated herbal products
Medicines registered under the
THR (Traditional Use Directive)
those which are
↳ medicines

medicine derived from

Traditional
normally registered
Plants

under traditional use

directive for THR

↳ The evidence which is

use
derived from traditional
use
substituting tie
efficacy
based on
clinical studies

↳ traditional use implies

evidence for commeri.cat
product with a similar
chemical composition

having been on the

market in europe for

at least 30 years .

Quality Safety
Quality and safety of licensed
herbal medicines must show
Clinical
evidence for
efficacy

Quality Safety
 Herbal Medical
products and pure
natural products (used
as medicines)
 Herbal medicines are chemically rich
complex mixtures

contains whole range

of natural product ,
p individual compounds

Aspirin tablets wort

contain:
Aspirin
herb contain:
Hyperforin, adhyperforin, hypericin,
/
pseudohypericin, isohypericin, protohypericin,
protopseudohypericin, kaempferol, quercetin,
luteolin, hyperoside, isoquercitrin, quercitrin,
rutin, biapigenin, amentoflavone, catechins,
tannins, other phenols etc etc
(excipients) (excipients)
 Pure Natural Products
vs. Herbal Preparations

Chemically defined Herbal preparations /

biogenic drugs phytomedicines
One or very few active A complex mixture of active
substances derived from and inactive compounds
natural sources generally derived from plants
----
Definition of actives and
preferably standardisation actives
linked
↳
quality control
moynot be to the

linked
✓ & ↳
may be to
something you
can detect easily
They
.

↳ it is important to know which compound make an Important contribution

p
Medicinal products Are legally considered to be activity
to

THRS

medicinal products 9and/or

health food supplements
and

Generally licensed May be registered or licensed

 Production and quality are
linked intrinsically
Plants and fungi yield both

- pure natural products

like morphine → Produced
quantities
in large

- herbal medical products

(registered) and food
supplements
control of this herbal substance
↳ In Both cases quality
is very Important
 From plant to patient:
Pure compounds as medicines
The botanical starting material:
The living plant

Botanical Drugs

A multi-step
Extraction / Isolation / process resulting
Purification / Formulation in chemically
defined medicines
↳ If
at pure compound like morphine
looking a

need to understand the botanical

↳ Then you
materials that live in plant
starting
↳ How it grows
botanical drug

Use by patients
↳ need to understand

it
how is processed potentially
isolated ,
purified and then
formulated

into a medicine

herbal medicine
is similar but main difference
↳ the process

is in third step

↳ living plant , quality assurance ,

have botanical drugs
have extractions formulation i n to
and then
compounds called Phytochemicals
mixture of
.
 From plant to patient:
Herbal medicines
The botanical starting material:
The living plant

Botanical Drugs
Often a
simple formulation /
(Extraction) Formulation
generally resulting in
into Phytomedicines
chemically complex
products
Use by patients
 Extract (Definition)
European Pharmacopoeia (2002, chapter 01/2002-
765): an extract is a concentrated preparation of
liquid (fluid extract or tinctures) or intermediate
(semi-liquid) or solid (dry extract) consistency
normally produced from dried botanical or
zoological material by a technique involving the use
of adequate solvents for obtaining a mixture of
compounds.
For some preparations, the material to be extracted
may undergo a preliminary treatment prior to
extraction (e.g. de-fatting, inactivation of enzymes
or most commonly simply grinding).
See Fundamentals of Pharmacognosy and Phytotherapy
 Hypericum perforatum regulated
products vs. unregulated products
Hypericum perforatum (
Reference SJW%

products regulated (THR) products have

a consistent composition (but may vary in
Standard*

Sample 1

strengths) based on a TLC comparison

5
2
3
4

6
7
Two examples of
unregulated products
(often from the internet)
show a tremendous
variability and
adulteration including the
use of food dyes to trick
quality control schemes
Regulated products (1 7)
* - pure compounds as a reference
% - reference US Pharmacopoeia
 page explanation
previous

Akin and
z;⇐÷÷÷•
consistent chemical profile

n
Ginkgo biloba unregulated supplements
HPTLC-based analysis
Globally used as a herbal
medical product (licensed /
registered) or supplement.
Large unregulated market
(internet)
Mainly produced in China,
Southern America and parts of
Europe

Note the enormous

differences in the

with rutin
https://www.bbc.co.uk/programmes/articles/4hX30rMYkMv9YjMTH38MY6/do-herbal-supplements-contain-what-
31
they-say-on-the-label
 Most
↳ supplements are
unregulated
it decline
↳ is used for cognitive in the
elderly
it is also used for some other specific
↳
syndromes
The 35 looks all but
↳ Samples the same
they are

different

↳
Unregulated herbal medicine products cannot be dispensed by pharmacies because we have concerns about the
quality and
safety

↳ it is a TLC which helps to first separated than visualised individual compounds found in the specific

plant .
Ginkgo biloba unregulated supplements
HPTLC-based analysis
Globally used as a herbal
Often
medical product or
supplement. Intentional
Large unregulated market
(internet)
Mainly produced in China,
Southern America and parts of
Europe

Unregulated herbal medical

Note the enormous
differences in the
products cannot be dispensed
by pharmacists with rutin
https://www.bbc.co.uk/programmes/articles/4hX30rMYkMv9YjMTH38MY6/do-herbal-supplements-contain-what-
32
they-say-on-the-label
 Herbal
Medical
Products
(HMPs)
 ↳ Comes from

speific plant \
↳ You would proceed called

Botanical Drugs
essential oil extraction

Botanical drug, defined as

dried parts of entire plants,
plant organs, or parts of
plant organs for use as fused for

medicines, aromatics, → tooth

ache

tooth

2
→

spices or excipients decay

used in the production of pharmaceuticals or Clove

in
useful
is
very helpful
dentistry →

antiseptic

Isolated products directly obtained from plants which no

longer have an organ structure, such as essential and fatty
oils, balsams etc.
Botanical drugs also are the basis for the isolation of pure
natural products the production of herbal medicines (e,g
herbal teas and for the production of extracts used for
phytomedicines Picture from Wichtl et al 2004
 A wide range of herbal medicinal products is
available to patients
for bruises
fused
and other external
applications

→ regulated
Wide range of preparations
available:
Crude herbs often sold by
herbalists / in TCM shops
Extracts (today the main range)
Formulations / dosage forms
Solid dosage forms: tablets,
capsules
Semisolid: creams, ointments
Liquid dosage forms: tinctures
etc
Combination preparations:
several herbs (multiherb);
herb-vitamin/mineral products
] → unregulated
Image from European Herbal Practitioners → not controlled at standard above product
some as

Association website → it
these
is
legal
prescription
to sell

given
this
by TCM
but it
practitioner
is quite important to know whether takes
 A wide range of herbal medicinal products is
available to patients
Wide range of preparations
Fully available:
Crude herbs often sold by
registered herbalists / in TCM shops
medicines Extracts (today the main range)
Formulations / dosage forms
Solid dosage forms: tablets,
capsules
Semisolid: creams, ointments
Liquid dosage forms: tinctures
etc
Unlicensed Combination preparations:
several herbs (multiherb);
herb-vitamin/mineral products

Image from European Herbal Practitioners

Association website
Some top-selling herbal medical products (HMPs)

Echinacea (Echinacea angustifolia) Hypericum perforatum

Valerian (valeriana officinalis)

Some top-selling herbal medical products (HMPs)

Echinacea (Echinacea angustifolia)

↳ used in of cold mild form of
Hypericum perforatum
management common ,
↳ mild
,
moderate form of depression or low mood
few •

←
Induce sleep

help people
who are

restless

inflammatory Back pain

p
Valerian (valeriana officinalis)
Some top-selling herbal medical products (HMPs)

A large number of fully

regulated (THR and some
licensed) products are
available and can be
Echinacea (Echinacea angustifolia) Hypericum perforatum
dispensed with great
confidence.

Valerian (valeriana officinalis)

 Traditional herbal medicines registered under the THMPD
(examples): Single ingredient products some examples
Common Botanical name Registered Products
name
Agnus castus Vitex agnus-castus L. Premherb Tablets
fruit ↳ common used in
premenstrual syndrome

Arnica Arnica montana L. Atrogel Arnica Gel

flowerheads ↳ topically Put on unbroken skin to treat inflammatory skin
conditions

Black Cohosh Cimicifuga racemosa (L.) Menoherb Tablets

root / rhizome Nutt.
↳ menopausal

symptoms -

Harpagophytum
Chronic
root procumbens D.C. and/or H. tablets
↳ pain
condition zeyheri L. Decne. Flexiherb Tablets
specially
inflammatory
conditions Based on Linda Anderson, MHRA
 Plant Derived Pharmaceuticals: General
Features 1
Derived from herb (aerial parts), leaves, fruits, seeds,
roots/rhizome (or other underground organs), bark or
other parts of a (higher) plant

material, they may be sold as such or as an extract

Most of these products are on the GSL (General Sales
List), some are P only (Pharmacy only) or POM
(Prescription only medicines), see above
Herbal medicines (and the botanical drugs the are
derived from) are generally made up of complex
mixtures of natural products, some of these are the
active compounds, others are considered to be of little
of no pharmacological relevance (This is an essential
difference to other pharmaceuticals).
 what are the unique pharmaceutical features

need to define where within the plant

↳ you
it comes from

↳ need to be clear what plant part it is

↳ it can be aerial part of the leaves

materials
↳ Then important to know whether it is fresh or
dry plant

complex mixture of natural products of

↳ herbal medicine are made of

individual compounds
are active compounds
→ some

→ others are little or no

pharmacological relevance

↳ NOT
selling pure compounds ars costs are too
high .
 Plant Derived Pharmaceuticals:
General Features 2
In the context of pharmacy a botanical drug is a
Product derived from a plant and transformed into a
drug by drying certain plant parts or sometimes the
whole plant or
Product obtained from plants, which no longer retains
the structure of the plant or its organs but which
contains a complex mixture of biogenic compounds
(e.g. fatty and essential oils, gums, resins, balms)
Isolated, pure natural products like the numerous
nature-derived pharmaceuticals used in pharmacy are
thus not a botanical drug, but a chemically defined
drug derived from nature.
See Fundamentals of Pharmacognosy and Phytotherapy Chapters 10 and 11
 From plants to medicines
Botanical name and family Living plant
Plant parts used in pharmacy
(botanical drug) Drying
Botany ↳
is it
it
a THR
ash
or

or
not

not
µ is a

Legal category (UK)

↳

Botanical drug
Monographs (e.g. Eur.
Pharmacopoeia)
Phytotherapeutic (and other) Processing
uses (incl. extraction)
Chemistry
the active
so what are

product in it
natural

benefit

Pharmacology and
p
Herbal medical product /
toxicological risk phytomedicine
 Herbal Drug

(Often Drying, Grinding),

Drying and Processing Extraction:
Herbal Drug Preparation

Formulation Formulation

Chemical

type
ont
2 of extracts
pharmacological

Herbal
^

drug material then extracted

nine
is

Medical extracts a re more effective in

treating specific conditions

Product
 What do we need to know about a
phytomedicine
Botanical origin (species and family)
Plant part which provides the drug
Type of product used as a phytomedicine with a specific
health claim:
- Ground plant material, Lower pharmaceutical quality
- Uncharacterised extract,
- Standardised extract,
- Processed (special) extract Higher pharmaceutical quality
Active constituents
(if known) g
e-

what
need
active
to know
compound
if plants
actually is
has a certain active compounds .
it is useful to know

Pharmacological effects and clinical effectiveness, side

effects and interactions with other (botanical) drugs
 From plant to patient:
Herbal medicines Pure natural p morphine
(phytomedicines) products as medicines
The botanical starting material: The botanical starting material:
The living plant The living plant

Botanical Drugs Botanical Drugs

-

! *
extraction of

"" " " " " (Extraction) Formulation morphine is Extraction / Isolation /
extracted
results in

into Phytomedicines as
Purification / Formulation
a mixture a
mixture
of
compounds
and then

! *
this
purified
than is

formulated Uncontrolled sale and dispensed

Dispensing
into under

or Dispensing very carefully

a

Phyto medicine defined

↳ sad in an
uncontrolled was
conditions

or
↳ dei rented based on your ow n

ass e me n t of the Patient

Use by patients Use by patients

The pharmaceutical process is often similar for both groups, and the main
differences are in the chemical complexity of the final products and until
recently in the uncontrolled status of many (but not all) herbal medicines
?⃝
 Herbal Medical
Products
Some
examples
Or:
What do you
need to know
about these
products
Extractor for herbal medical products, you put the plant material in and the solvent
and

W. Ransom, Hitchin, UK
you boil it and then the solvent with extract
is removed and dried and further processed
A herbal drug needs to be defined
precisely, as have to be the
medicines derived from it
- Plant species
- Plant part used }
}
- Extraction
- Processing A medical product*
-

* - or a supplement
 Extract (Definition)
European Pharmacopoeia (2002, chapter 01/2002-
765): an extract is a concentrated preparation of
liquid (fluid extract or tinctures) or intermediate
(semi-liquid) or solid (dry extract) consistency
normally produced from dried botanical or
zoological material by a technique involving the use
of adequate solvents for obtaining a mixture of
compounds.
For some preparations, the material to be extracted
may undergo a preliminary treatment prior to
extraction (e.g. de-fatting, inactivation of enzymes
or most commonly simply grinding).
See Fundamentals of Pharmacognosy and Phytotherapy
 Quality assessment of extracts
Extracts are often characterized by the drug:solvent
ratio (DSR), which gives the relationship of the amount
of drug extracted to the volume of solvent (e.g. 1:10)* -
most commonly used
The drug-extract ratio (DER), on the other hand, gives
information on the amount of extract obtained from a
botanical drug: 4 : 1 (maceration, 70% ethanol). In this
case 4 units (e.g. kg) of a drug yield 1 unit of dried
extract. This DER is often given as a range (e.g. 3 5)
and always in whole numbers.
An extract prepared from (dried) drug material using
defined solvent systems is processed into a variety of
pharmaceutical products (e.g. tablets for crude
extracts). DER
amount
=
give
OF
info

extract
e-
about
g.
the HABEAS
obtained

*-
↳
extracted
from botanical
a
drug
e-
9 4 :| 4 units of drug
→
with 1 unit of

botanical drug
An example of a medicinal drug: Cloves 1
Botanical name: Syzygium aromaticum (L.)
Merr. et L. M. Perry
Family: Myrtaceae (Myrtle family)
Plant parts used in pharmacy: the unripe flower
buds, also clove oil is used
Botany: derived from an evergreen tree native

Indonesia), but now widely cultivated, the

flower buds are particularly rich in essential oil
An example of a medicinal drug: Cloves 2
side effects
dermatitis Inflammation
↳ Contact -

The flowering parts of the The botanical drug:

plant Syzygium Cloves
aromaticum - Cloves Tree
An example of a medicinal drug: Cloves 3
Chemistry: The most important compound is eugenol
(C10H12O2) a simple phenylpropane-derivative.
Pharmacology: Eugenol - Effective antiseptic and
bactericidal compound
Toxicological Risk: Clove oil is stated to be a membrane
irritant, to cause contact dermatitis and others, the drug

not be taken in doses greatly exceeding those used in

food. In Jan 2008 some concerns have been raised about
the toxicological risk of high doses of clove oil in babies
(based on a case of a 15 months old boy who developed
hepatitis after the oil was used (in a high concentration) the dose
administering

for teething problems.

was not the oil but ppl it got
problem
wrong so they used
inappropriately
high dose .
 Turmeric (Curcumae domesticae rhizoma) 1
↳ +used for
travel sickness

Turmeric is the subject of much current

research but detailed clinical evidence is
lacking so far.
The plant and the drug: Curcuma domestica Val.
(syn. C. longa L.) (Zingiberaceae)
Rhizomes dark yellow powder with a characteristic
taste and odour.
Spice and colouring agent
A related species - Javanese turmeric (Curcuma
xanthorrhiza Roxb., Curcumae xanthorrhizae rhizoma
Ph. Eur.), mostly used for dyspepsia and other
gastrointestinal problems.
 Turmeric (Curcumae domesticae rhizoma) 2
of constituent
Constituents active groups
µ
Curcuminoids; the mixture known as curcumin, consisting of
several phenolic diarylheptanoids, including curcumin,
monodemethoxycurcumin and bisdemethoxycurcumin
CH3O OCH 3

HO CH CH CO CH C CH CH OH

OH

←
An essential oil (about 3-5%), containing about 60%
it is

extracted
not
sesquiterpene ketones (turmerones), including arturmerone,
but

used in
instead alpha-atlantone, zingberene; with borneol, alpha-phellandrene,
this
mixture
eugenol and others
Polysaccharides such as glycans, the ukonans A-
Turmeric (Curcumae domesticae rhizoma) 3
Pharmacological effects and clinical efficacy
Extract (turmeric): not registered product it is used food supplement
→
a but one
repeatedly

- Protects against stomach ulcers in rats

- Antispasmodic effect
- Hypoglycaemic (in vivo in animals)
- hypocholesterolaemic effects (both in animal and
human clinical studies
- Immunostimulant activity, due to the polysaccharide
fraction,
- anti-asthmatic effects have been noted, together with
anti-mutagenic and anticarcinogenic effects.
- Antibacterial and antiprotozoal in vitro
Example of an issue often encountered in natural
product pharmacology: strong effects but on multiple
targets
Toxicology: Turmeric is well tolerated (spice).
Cf. Fundamentals of Pharmacognosy and Phytotherapy
 traditional uses are excitability , mild -

moderately
p depression .

Hypericum perforatum L.)

24.6.
Traditional uses
- Nervous afflictions: excitability,
menopausal neurosis, hysteria,
nervousness, anxiety, depression,
and as a nerve tonic
Physiological nerve disorders: sciatica, neuralgia, spinal
injuries
- External use: oily preparations for wounds, bruises,
swellings, shingles
Clinically well-validated uses: Symptomatic relief of mild to moderately
severe depression (low mood), topically for wound healing
- see workshop -
 An example of a phytomedicine:
Harpagophyti radix -
↳ used pain
The plant and the drug
for back

Derived from Harpagophytum procumbens DC

(Pedaliaceae)-
Fairly recently developed into a successful and
relatively well-characterised medicine which is
monographed in the Ph. Eur.
Botanical drug: The secondary storage roots currently only
collected in the savannahs of southern Africa (South Africa
and Namibia, mainly the Kalahari desert), while still fresh,
cut into small pieces and dried.
Obtained from the wild (gathered), but attempts are
underway to cultivate it.
Traditional uses (Africa) -

bladder problems.
 desert plants
p grows very
slowly
rainfall
→ depends on

so hard to 0 btai

Plant part used medicinally: Rootstock

(Foto W. Caesar, Stuttgart, DE)
See Fundamentals of Pharmacognosy and Phytotherapy p. 152 and 263-4,
 An example of a phytomedicine:
Harpagophyti radix -
Harpagophytum zeyerhi, another species BP
common in southern Africa - considered and
to be an adequate substitute. It contains
similar natural products as H. procumbens. EP
Historical uses (Europe), a tea (made from a dose of
about 1.5g/day of the powdered drug) for the
treatment of dyspeptic disorders such as indigestion
and lack of appetite ( bitter glycosides).
Most pharmacological and clinical
research has, however, been conducted
using standardised extracts for the
treatment of rheumatic conditions and
lower back pain as well as other
degenerative conditions of the
musco-skeletal system (see below).
 An example of a phytomedicine:
Harpagophyti radix -

Relevant Natural Products HO OH

Bitter iridoids, harpagide HO OH
O
and harpagoside, with O O
O
H
8-O-p-coumaroylharpagide, HO H
OGlc
OGlc

procumbide -O-p-coumaroyl- Harpagide Harpagoside

procumbide and procumboside. OH

(active substances)

Phenylethyl-glycosides like HO
O
verbascoside and isoacteoside. O
O
CH2OH
O
OH
O
Especially the iridoids are HO
O OH
HO
currently considered to be of am ,

HO
analytically • pharmacologically
i not
OH µ
pharmacological importance
active
they have become

Verbascoside (a marker substance)

marker substances
to assess the
quality
although research continues. Simple terpenoids
have mono
→ composed of
terpenoids = TO 10
5) 10,1520 carbons
Carbons + a
Here

glycoside
you

According to the Eur. Ph. the drug must contain 1.2%

harpagide and harpagoside, expressed as harpagoside.
Analysis is by HPLC.
Production and
Quality
Note Plants a re produced on a controlled agricultural conditions .

used medicine
most widely to
be controlled some extent

Production of botanical drugs

So impact o n quality can
.

Most important medicinal plants are today produced

under controlled agricultural conditions
Differences in quality may be due to:
- Temperature and annual course of temperature
- Rainfall (if it is not possible to irrigate the fields)
- Soil characteristics and quality
- Day length and sun characteristics
-
These require detailed studies for each species to
be cultivated.
Often the production is based on the principles of
GMP (Good Manufacturing Practice) and or ISO-
certification, in this case GAP (Good Agricultural
Practice) and the subsequent processing steps
(drying, cutting, grinding, storage, packaging,
transport etc., which are covered by GMP).
 European Pharmacopoeia:
Regulations for Botanical Drugs
Title (English name, Latin name used in international
trade)
Definition of the drug (plant part to be used; whether
it is fresh, dried, cut or powdered, and possibly also
specifying constituents typical for the drug, with
minimal amounts required)
Characters - Organoleptic or other properties of the
drug (smell, colour, other similar characteristics, and
rarely, taste (not usually included in the European
Pharmacopoeia for reasons of safety)
↳ trying to find good quality products
 European Pharmacopoeia:
Regulations for Botanical Drugs
Identification (macroscopic and microscopic
description, and in some cases TLC- characteristics)
Tests for purity (providing data on maximum amounts
of foreign matter, i.e. non-acceptable substances, loss
on drying, ash)
Required level of biologically active or lead
compounds
Storage (general information about required forms of
storage) cannot store a botanical drug in human environment as it will
get
moulded

See Fundamentals of Pharmacognosy and Phytotherapy Chapter 10,

 Quality of botanical drugs
Numerous specific requirements exist for
assuring appropriate quality of botanical
drugs and extracts:
- Botanical identity (Species and drug)
- Purity [max. level of other (botanical)
material]
what level
allowed
of other
botanical material is

- Moisture levels (bot. drug only)

- Pesticides (maximum)
- Microbial contaminants (maximum)
- .... (many things might go wrong)
 Microbiological Contamination
The maximum number of micro-organisms allowed is
regulated in the European Pharmacopoeia (for details
see Eur. Phar. 2002 -chapter 2.6.12):
up to 105 aerobic micro-organisms per g or ml,
including
- up to 103 yeast and fungi per g or ml and
- up to 103 enterobacteria per g or ml
no detectable Escherichia coli [in 1 g or ml]
no detectable Salmonella sp. [in 10g or ml] (Franz
1999).
(see Fundamentals of Pharmacognosy and Phytotherapy)
contamination is important
↳ why microbiological
material
→ because we start with living plant
of microorganism
→ that means there will be host for range
→ we will define Max amount of yeast and
fungi
→ we define intra bacteria
avoid C- coli and crucial ones which may
lead
→ salmonella species of are
we
try to both them
-

to health detect
Microbiological Contamination
Specific requirements for storage and transportation
of the drug have to be met
In many cases this is now controlled via GAP
(Good Agricultural Practise) and GMP (Good
Manufacturing Practise) standards storage , Processing
practise
agriculture
Good ,
have whole series

I must be complied with .

so
with
Of standards which must be complied Ethan

Similar requirement relates to microbial

labelled as GMP practise
,
.
This

in cooperates
importantly ways
to prevent spores and other
microorganisms from
entering

contamination of botanical drugs. Each natural the material .

material naturally harbours a large number of

spores and other micro-organisms.

See Fundamentals of Pharmacognosy and Phytotherapy

 Conclusion:
In order to advise patients
you need to understand
the chemical composition /
quality and production of
a herbal medical product
(and this is all based on the
herbal regulations)
 Third edition
2018

2015 (1st ed.)