Transcript Pharmacognosy_Topic_1_What_is_Pharmacognosy

PHARMACOGNOSY
AND
HERBAL PHARMACY
WHAT IS PHARMACOGNOSY?
Pharmacognosy is the science of naturally occurring
substances with medicinal actions. It includes the
simultaneous study from various disciplines:
Botany
Chemistry
Biochemistry
Physiology
Pharmacology
AN INTERESTING TIMELINE FOR THE ISOLATION
OF CONSTITUENTS
1806  Morphine
Extracted from Papaver somniferum (opium poppy). An alkaloid
that was found to be a very strong analgesic. The invention of
the hypodermic syringe in 1850 by the French doctor CharlesGabriel Pravaz enabled the rapid popularization and spread of
the new drug. By the 1870’s many doctors, chemists, nurses
and members of France’s elite upper class were addicted as it
was hailed as a wonder drug and universal panacea. At the
time little was known about the toxic affects and addictive
nature of morphine.
1817  Strychnine
Extracted from Strychnos nux-vomica. An extremely toxic alkaloid.
1820  Quinine
Isolated from Cinchona bark and found to be antimalarial.
1820  Caffeine
From Coffea arabica spp. Another alkaloid.
1828  Nicotine
From Nicotiana tabacum spp. Very poisonous alkaloid. 10
times as toxic as DDT to the CNS.
1829  Salicin
A phenolic glycoside isolated from Salix alba by Leroux
1833  Atropine
Isolated from Atropa belladonna amongst others. Was used
extensively in orthodox medicine as an anticholinergic to
decrease gastric function.
1860  Salicylic acid
Isolated from Salix alba but found to be far too corrosive to the
stomach and couldn’t be used.
1868  Digitalis Glycosides
Cardiac glycosides from Digitalis purpurea. Used
widely for congestive heart failure in orthodox
medicine.
1899  Acetysalicylic acid
Produced under the name of Aspirin. Still corrosive
but much better tolerated and more potent.
TERMINOLOGY
Pharmacognosy
Pharma  from the Greek word PHARMAKON = drug
Gignosco from the Greek = acquire knowledge
Cognito from the Latin = to know
Therefore, pharmacognosy is the knowledge of drugs. It
is the science of naturally occurring substances with
medicinal actions.
Pharmacology  the study of what drugs do in the body,
that is, their medicinal effects
Pharmacokinetics
 The quantitative
analysis of the
Absorption  how and where the substance enters
the body
(Braun & Cohen 2005 pp.28-35)
Distribution  where the substance goes when it is
absorbed
Metabolism  breakdown or detoxification of a drug
Excretion  removal of a substance or its
breakdown products from the body
of a medicine.
Pharmacodynamics
(Braun & Cohen 2005 p.33)

an interaction that results when one substance
alters the sensitivity or responsiveness of tissues to
another.
This type of interaction results in
synergistic or antagonistic drug effects.
additive,
In simplified form  this is how drugs elicit a
physiological effect.
Physicochemical interactions
 an
interaction that occurs when two interacting
substances come into physical contact and
chemically interact. This type of interaction can occur
during the manufacture or administration of
medicines and result in the inactivation of one or both
medicines.
(Braun
&
Cohen
2005
pp.34-35)
Adverse reaction
 a harmful or seriously
unpleasant effect caused by a medicine at doses
intended for prophylaxis, diagnosis or therapeutic
effect. When two medicines interact in a way that
produces an unwanted effect, this is also referred to
as an adverse reaction.
(Braun & Cohen 2005 pp.28-35)
Factors that may be responsible for adverse
reactions  Discuss why each of these is a risk
factor.
oHigh risk medicines
oSerious disease
oOlder patients
oSelf-medicators
oMultiple healthcare professionals
Active constituents  can be classified by either
Chemical composition e.g. cyanogenic glycosides. To
have an effect, a drug must exert some type of
chemical influence on one or more constituents of a
cell in order to have a physiological effect. Most exert
their effect by binding to particular proteins, with the
4 types of regulatory proteins being:
oEnzymes
oCarrier molecules
oIon channels
oReceptors
o
Their actions  Some drugs, particularly of
herbs, have more of a physical effect that a
chemical effect e.g. mucilages act by coating the
surface with a slimy substance which soothes
and protects the surface in which they come into
contact.
Pharmacological action  how herbs work. The two
main types of pharmacological actions are:
Agonists
oFacilitate a biological action by binding to the
particular protein and eliciting the effect of an
endogenous substance
Antagonists
oBlock a biological action by binding reversibly to the
binding site and therefore competing with the
endogenous substance – competitive inhibitors. If
they bind irreversibly, they are known as noncompetitive inhibitors as they are inactivating the
protein permanently.
There are many herbal substances which act to
balance a physiological action e.g. phytoestrogens
act as agonists at low levels of oestrogen and as
antagonists at high levels of oestrogen. This is
because phytoestrogens bind to oestrogen receptors
in the body and elicit some activity, but less than
that elicited by endogenous oestrogen. Therefore, if
there is too much oestrogen around, the
phytoestrogen takes up the receptor sites and
reduces the effect exerted by the oestrogen.
However, if there is not much oestrogen around, the
phytoestrogen
activates
otherwise
unused
receptors.
Therapeutic Index (TI)  the ratio between the average
minimum effective dose of a drug and the average
minimum tolerated dose.
This provides a crude measure of the safety of any
drug used
The higher the therapeutic index the safer the drug and
the less likelihood of toxicity problems or accidental
overdose.
Herbal remedies typically have a very high therapeutic
index, with a few very notable exceptions such as
digitalis. Digitalis has a TI of 1.5, soluble aspirin has a
TI of 10 but herbs often have a TI as high as 100.
The main limitation of the therapeutic index is that it
is based on animal toxicity data, which cannot
always be applied to human, and doesn’t take into
account individual variability.
Uniform scheduling of Drugs and Poisons (SUSDP)
Primary metabolites 
These are mainly the products of photosynthesis,
which provides the food that enables the plant to
live, grow and reproduce.
These are the substances necessary for the primary
functions of life and keep the plant healthy and alive
and include proteins, fats, sugars, organic acids etc.
They are involved in the assimilation of food,
digestion and respiration.
Secondary metabolites 
Not as universal in the plant kingdom, these are
usually unique to a plant or group of plant
Very diverse and thought to be a secondary function
for the plant such as protection.
Originally these were believed to be a by-product of
metabolic processes.
Now it is known that they have evolved to improve
the chances of the species’ survival.
This is based on the fact that specific enzymes have
been discovered which seem to be used in the
production of secondary metabolites
Most of our medicinal herbs are used because of
their secondary metabolites  it is the secondary
metabolites which provide the pharmacological
activity.
The purpose of these secondary metabolites is varied
and sometimes present in extremely minute
concentrations. They exert physiological or
pharmacological effects on man and are
responsible for the strong flavours and odours of
some species, for example:
Bitter tastes to repel grazing animals
Alkaloids and other compounds to poison predators
Bright colours to attract birds and insects for
pollination
Antimicrobial substances to resist bacterial / fungal
or viral attack
Compounds which prevent other plants from
growing nearby e.g. apricot trees secrete a
substance from their roots to prevent other apricots
growing too close – to prevent overcrowding
Waxes to provide waterproofing
The esters of ripe fruit and some flowers attract
birds and animals so that the seeds will be
dispersed
The ‘pink flush’ of lettuces. When growth and
photosynthesis is active in the young seedlings, high
concentrations of sugars build up increasing the
osmotic pressure of the cell sap to dangerously high
levels. If allowed to proceed, the cells would explode. At
this point, certain enzymes are activated which divert
the metabolism to break down these sugars into
aromatic compounds with low osmotic pressures called
flavonoids, which happen to be red. A pink colour
therefore develops in the leaves. After some time, when
the plant has grown
and can accommodate more sugar, the
red substances are removed by
reconversion into useful sugars so that
the pink hue gradually disappears.
Based on the principle ‘structure dictates function’,
being able to recognise structure goes a long way to
being able to make an educated guess as to what
function the compound performs. Many secondary
metabolites originate from a similar compound,
which is transformed at the last minute by an
alternative pathway, e.g. Shikimic acid is the starting
point for phenol-based compounds. (Aldred, EM, 2009,
‘Pharmacology: A handbook for Complementary Healthcare Professionals’, Churchill Livingston)
Phenol – a benzene with an alcohol group (OH)
Crude drugs  refers to the fresh or dried plant or
plant part e.g. fresh or dried leaves, fresh or dried
root
Galenical preparation  the whole of the crude drug
is used in the preparation. The active constituents
are not isolated:
For example: A tincture of licorice is produced by
extracting the powdered root with water and
ethanol. Anything soluble in water and ethanol will
be extracted. This includes many molecules. If the
main active is extracted e.g. glycyrrhizin, the
preparation is not a galenical preparation. This is
the main difference between allopathic pharmacy
and herbal medicine.
Modern pharmacologists argue that the use of crude
herbs is unpredictable, impure, has dosage variations
and cannot be precisely measured.
IMPORTANCE OF PHARMACOGNOSY
Credibility  if we understand why herbs act the way
they do, we can communicate more effectively as to
how and why individual herbs work.
When a particular herbs is unavailable, with knowing
what it contains, we can make informed choices
about alternatives.
If we want to use Hydrastis canadensis for internal
parasites and it is unavailable, it can be substituted
with Berberis vulgaris or Mahonia aquifolium as they
both contain berberine which has a broad range of
antimicrobial activity.
By understanding which components have the most
pharmacological activity, better choices can be made
about how to extract the herb. For example 
Whether to use more or less alcohol – if the main
constituents are alkaloids, more alcohol is needed; if
they are mucilages, more water is needed.
By understanding how a herb acts, informed choices
can be made about appropriate herbs to use with
conventional drugs.
Despite the fact that studying active constituents can
give a better understanding of the herbs, never
forget that it does not substitute for a holistic
approach based on years of empirical evidence.
Approximately a quarter of prescription drugs contain
at least one chemical that was originally isolated
and extracted from plants. (Aldred, EM, 2009, ‘Pharmacology: A handbook
for Complementary Healthcare Professionals’, Churchill Livingston)
CHEMICAL VARIATIONS WITHIN A SPECIES
Even within a particular species there is huge variation
of the component chemicals.
Tea tree oil is a good example:
Some is high in the chemical terpinen-4-ol  gives tea
tree its antifungal activity
Terpinen-4-ol
Some is high in cineole  irritating to the mucous
membranes
Cineole (or Eucalyptol)
But none are high in both
The Australian standard for tea tree oil requires that all
tea-tree oil contain less than 15% cineole and more than
30% terpinen 4-ol. A good quality contains 2 – 5%
cineole and 40 – 47% terpinen 4-ol.
Variation of plant components within a species
occurs with most species, and is dependent on a
number of different factors:
1. Heredity:
 Within a species, there is a lot of domestic
diversity.
 This variation causes differences in the
chemistry of the plant.
 Populations within a species with a consistent
chemical difference are known as chemical
races.
 Normally chemical races are geographically
separated and have evolved separately.
 Examples are:
o Achillea millefolium has a number or
substances of which at least one is a distinct
chemical race with a high level of
chamazulene
in
its
essential
oil.
chamazulene
Chamazulene has an intensely blue colour.
o Acorus calamus (sweet flag) is scheduled.
Different populations of sweet flag contain
different chemicals. Some contain B-asarone
which is considered to be a carcinogenic, but
it is only found in certain chemical races of
the plant.
Claviceps purpurea (Ergot) is a fungus that attacks rye and
grow on the rye kernel. It was a serious problem in the past
in that it contains ergot alkaloids which are hallucinogenic,
similar to LSD, and can cause gangrene by their
vasoconstriction action. Two of the ergot alkaloids are used
widely in allopathic medicine:
oErgotamine is a vasoconstrictor used in the treatment of
migraine
oErgometrine is oxytocic and sometimes is used post
partum to reduce the risk of haemorrhage by making the
uterus contract quickly
It has been possible to separate the chemical races to
produce almost entirely the alkaloid required  that is
ergoramine and ergometrine can be produced by
different chemical races.
2. ONTOGENY  that is the stage of development,
which often equates with age. Plants contain different
qualitative and quantitative properties at different
stages of development e.g. unripe fruit and ripe fruit
tastes different.
 In Mentha x piperita menthol is the main
constituent. Mentha is a constituent which gives
an unpleasant smell to inferior peppermint. Young
peppermint plants have high menthofuran content
and so it is better to harvest the mature plant

Symphytum officinale is known to contain
pyrrolizidine alkaloids. A small leaf contains
about the same amount of PA’s as a large leaf.
Consequently, the concentration of PA’s in a
small leaf is much greater than in a large leaf.
3. ENVIRONMENT: that is, the effects of soil,
pollutants, water, altitude, latitude, competition
from other plants and animals
 Climate: Plants produce more oils if they have a
lot of sun. Mentha x piperita should be grown in
areas which have very long summer days. In
Australia, peppermint is grown in Tasmania for
that reason. Thyme, sage, lavender and dill all
produce more oil in full sunlight.
 Soil: Conditions affect the chemistry as many of
the constituents required are derived from the
soil. Alkaloids will yield higher if grown in
nitrogen rich soils.
 Pollutants: Many plants take up pollutants such
as lead. Sunflowers take up cadmium and the
seeds of sunflowers grown in high cadmium soils
are quite dangerous.
 Altitude and latitude: latitude affects the amount
of sunshine – equatorial regions have smaller
variations in day length, therefore those further
from the equator have longer summer days and
shorter winter days – hence Tasmania is used for
growing many of the herbs used for essential oil
production. Altitude also affects essential oil
content e.g. Artemisia absinthium grown at
sea
level
produces
more
essential
oil than if grown in the mountains.
TOXICITY
The benefit of such a long history of herbal medicine, is
that it has brought to light the adverse effects.
This is not the same as quality issues (for example: the
method of extraction has resulted in a toxic
substance) – that is a separate issue.
Pyrrolizidine alkaloids
Some of these are toxic, when they are unsaturated at the
1,2 position (remember: unsaturated means a double bond!)
There is evidence to suggest that these are hepatotoxic, and
thus damaging to the liver. However if the herb goes
through a good heating process, it may reduce the
number of toxic chemicals present. Comfrey (Symphytum
spp.) is a good example.
Wormwood
This is an example of a herb containing a potentially toxic
monoterpene (Thujone), which is also hallucinogenic and
famously present in absinthe. Extremely high levels of
thujone has been shown to be fatal in mice postconvulsion, the median lethal dose being approx
45mg/kg.
Höld KM, Sirisoma NS, Ikeda T, Narahashi T & Casida JE (2000). Alpha-thujone (the active component of absinthe): gammaaminobutyric acid type A receptor modulation and metabolic detoxification. Proc. Natl. Acad. Sci. U.S.A. 97 (8): 3826–31.
doi:10.1073/pnas.070042397
Pokeweed
This contains agglutinins called ‘pokeweed mitogens’. A
mitogen is any chemical substance that causes a cell to
start mitosis (division). When taken as a fresh herb it can
cause gastric upset, but the mitogens are usually
denatured
with
heat.
Pokeweed
is
generally
recommended in small doses only.
Gingko
Gingkgolic acid is phenolic (contains phenol). They are
related to similar chemicals in poison ivy. Gingkgolic acid
is found in much higher quantities in the fruit rather than
the leaf segment. It only very rarely causes allergic
reaction, but it is possible. It is recommended to not use
one’s own preparation of Gingko, but rather use a
commercially produced product that has had the
dangerous chemicals removed; or thoroughly research a
good extraction method.