Medicinal plants - Lecture (20)
We will start our discussion with Ginkgo biloba (G.biloba)
We have two major class of secondary metabolites: 1. flavonoids
(already discussed in chapter of falvonoid such as Rutin Quercetin )
2. terpenoids are again subdivide into diterpenoid and
sesquterpeneoid . In both classes we have (lactones) so diterpenoid
lactones and sesqueterpenoid lactones
Its structure is complex polycyclic, different numbers of the rings
and poly substituted.
O
O
OH
O
R2
O
O
R3
O
R1
O
Ginkgolide A
Ginkgolide B
Ginkgolide C
Ginkgolide J
Ginkgolide M
R1
OH
OH
R2
H
OH
R3
H
H
OH
OH
OH
OH
H
H
OH
OH
OH
The characteristic for the diterpenoid is the lactone ring and for
sesqueterpenoid is also lacton ring. The both (diterpenoid and
sesqueterpenoid) have biological activity from lacton ring that’s mean the
lacton ring responsible about biological activity of terpenoid.
The Ginkgo is one of the exception class not use purified secondary
metabolite but standardized crude extract : the standardized crude extract
contains 24% flavonoid and 6% terpenes, so they have the synergistic
activity some how of flavonoid and terpenoid for observing the biological
activity of the substances.
There is another requirement for this ginkgo, because we are using
crude drug while crude drug even go further standardization then there is
different other secondary metabolites and one of them is Gingolic acid
(alkyl derivative).
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GINGOLIC ACID:
R
COOH
13
OH
Gingolic acid(s)
R =
15:1 ( 8 )
R =
C 13-17 (0-1 double bond)
It's a free partial phenolic compound with very short R chain (13 –
17 carbons). It is very irritant substances and it cause dermatitis as well
as to at certain degree it is not very highly mutagenic. It has certain
mutagenicity so there for any preparation contains this gingolic acid or
phenolic derivative must to be nearly free (contain less than 5 P.P.M of this
Gingolic acid phenolic derivative, so standardization is required to
determine concentration of this toxic compound), because it is responsible
for irritant and mutagenicity to acertain degree.
MEDICAL VALUE OF GINKGO
In fact it is used to early management of the senile people specially
elderly people in order to improve cerebrovascular circulation and
peripheral circulation, it will improve the mental and physical performance
of senile and elderly people and these substance has potent and selective
activity against PAF(platelet activating factor). That means it has protective
effect or immuno-protective effect.
By experiment we found the Gingolide and Ginkgo extract has anti
inflammatory activity and improvement in cerebral circulation. - It is (not
drug) plant which is used in treatment of dementia (Alzheimer’s
symptoms) What is the difference between dementia and senile people ????
Both treated by G.biloba but the senile (age dependent) is impairment of
cerebral circulation because of old age but the cause of dementia is
impairment of transmission of neurotransmitter so it is a disease
(pathological case).
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What are the common symptoms of elderly people??
Note: these symptoms treated by G.biloba and its extract. These symptoms
resulted from impairment in cerebral circulation.
There are 12 major symptoms common in elderly people :
1. Difficulty in concentration
2. Difficulty in short term memory (definitely seen when you talk to
your grandparents, they will not remember what just before a while
but they could remember what happened in long 80 year ago, so
there is a decrease in the short term memory and improvement in
long term memory, so senile talking about childhood in very late age)
3. Absent in mindness
4. Confusion
5. Lack of energy and apathy
6. Tiredness
7. Decreased physical performance
8. Depressive mood
9. Anxiety
10.
Dizziness
11.
Frequent headache is the common
12.
Tinnitus sound in ear
 These symptoms are not considered a pathological condition
because they are signs of getting old or senile.
 Different sign of senility is not exam topic but it is a general
information or knowledge when we are talking about senile people
Note: the term elderly people become delayed, i.e. in the past a person
with 50 years was consider elderly but now a person with 60 or more
considered elderly and might develop senility.
G.biloba improves senile condition but it should be considered in
relation to the rest of drugs that taken by the elderly person (it is
contraindicated in different condition specially patients taking antiepileptic drugs and asthmatic patient, people taking hypo or hypertensive
drugs and spatially anticoagulant drug)
But a HTN is a common disease for elderly people, so if you want
sharing the anti-hypertensive drugs with G.biloba must to be under
supervision of the physician.
We have in Jordan tea packs of the G.biloba and most of the studies
indicate that the common drug in tea packs are not very beneficial so the
rest study indicate it should be standardized and should be available in
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the form of herbal tea mixture containing among other plant barks also
G.biloba.
Until now we talking about terpenoid and diterpenoid substances with
medicinal value but we have also toxic diterpens and these found in many
ornamental plants and it is specially precursor of allergy (dermatitis)
dermatism problem observe in gardeners.
Note: ornamental plants from family Euphorbiaceae and Thymelaceae.
The Euphorbiaceae is very widly distributed in Jordan and the milky juice
extracted from euphorbiacea will form dermatitis if it was handled without
gloves.
The phorbol ester (which is toxic diterpenes extract from euphorbiaceae
and thymelaceae) classified as carcinogenic compounds (promoter of
tumor formation).
The other class of the toxic diterpenes is Andomedotoxin
(gryanotoxin 1) from family Ericaceae, they are again irritant to the mucus
membranes and they cause vomiting diarrhea dizziness and GIT
disturbances if taken internally.
 If bees used Ericaceae plants for making honey, then we will obtain
toxic honey!
Note: Ericaceae is considered as an ornamental plant.
OH
H3C
OH
OR
HO
OH
CH3
H3C
CH3
OH
O
OH
Phorbol
OH
CH3
Andromedotoxin
(Gryanotoxin I) R=COCH3
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So from diterpens will be proceed to very small chapter of
sesterterpens
Sesterterpens are characterized by 25 carbon skeleton and have
been isolated from different fungi and marine organism from sponges.
Regarding biological activity we have active constituents from this
compound which consist of five isoprene until this substance its name give
to the H-C chain of gerenyl pyrophosphate (10 carbon) and pyrocilpyro
phosphate (15 carbon ) giving gyranyl pyrocil pyro phosphate (25 carbon).
What you will suggest name of this compound gyrynl – pyricyl pp??
Sesterterpen is the aliphatic chain of these secondary metabolites
and it is taken nowadays from marine organisms as a source of anticancer
and anti viral agents.
This interest will also increase in the sesterterpenoid compounds
because this substance can be found in the different marine and more
interest in the marine organism in the case of increase number of
sesterterpenoid (ophiobalanes) that isolated from this organism in next
days.
Keep always in mind that the compound which posses a cyclic
lacton (cyclic ester) will possess a biological activity of this compound so
many sesterterpenes isolated based on lacton ring and again expected
these substances will have biological activity mention already: antiviral,
antibacterial , antiphlogestic and antinematodal activities.
From the sesterterpen I will continue to the largest class of terpenoid
which is the triterpenes.
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Why do we consider the triterpens as the largest class of
terpenoid???
Because the triterpene are the bio-compounds of steroidal substances and
we cant consider any living organism without possessing steroidal
substances in the form of triterpenes. Then we have suggestions consider
the steroidal substances as primary or secondary metabolites, "their
importance is definitely primary"
sitosterol is the most common plant sterol, and we can find it in any
plant, and is structurally similar to cholesterol in mammals.
TRITERPENES: the largest class of terpenoids, obtained by acetate
mevalonate pathway, there are many types and the first type in our
discussion is SQUALENE C30H50: it's obtained by tail to tail
condensation, and we will not discuss how to synthesize it in details.
The basic structure is acyclic compound, in fact it’s a symmetric
acyclic compound, it's a trans 30 carbona terpenoid compound, it's a
spatial example how to occur in an open straight chain, the first time
isolated from the shark, later from rat liver and yeast.
Note: the name of squalene comes from where it's first isolated (Squalus
spp.)
SYNTHESIS OF SQUALENE: it consists of two FPP by tail to tail
condensation
FPP
+
FPP = symmetric acyclic squalene
15C
15C
30C
No double bonds between 15 and 15prime
SYNTHESIS OF DITERPENS: it consists of two GPP by tail to tail
condensation
GGPP
+
GGPP = tetraterpenes
20C
20C
40C
There is double bond between 20 and 20prime
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 So the difference between squalene and diterpenes is the double
bond
The squalene can occur in different conformations such as: chair-chair or
chair-boat or alternate chair-boat chair-boat condensation
It is obtained either from steroidal substances (in the chapter of
steroid we have again subgroup) or classical triterpenoid substances so
the parent compound depending on the folding of the squalene.
 Classical triterpenes usually either tetracyclic or pentacyclic
compounds.
Note: we have differences when we talk about steroidal substance for
mammalian or animal (lanosterol) or plant origin (cycloartenol)
H
H
Squalene
HO
2
O
HO
3
Squalene oxide
Cycloartenol
Plants
Lanosterol
Animals & Fungi
What are the steroidal substances????
This group contains cardiac glycosides, saponins, bile acids, steroidal
alkaloid and vit D
When we talk about steroids we talk about headlines of different
compounds with steroidal origin regardless of the number of carbons.
- Cholesterol with 27C and others with 19C Steroidal precursor
with different number of carbons.
Note: Steroidal substances with 19 C and other with 17C are much
nearer to diterpenoid but they originate from modifications of the side
chain of the backbone of squlene, so same origin regardless of the number
of carbons.
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Regarding triterpenes there is two type of cyclization 1.concerted: it is
continues one ring followed by the second, third and forth
2. arrested: no continuation of cyclization there is only one
ring formed then it will stop (this is mean arrested)
We have in nature triterpenoid substances which are containing a
product of the arrested cyclization and they are containing only one ring
structure contain one end and we can start with both end (one side end
and terminal end) also consider from arrested cyclization. But in the
majority of cases we have what called concerted cyclization then we will
obtain tetracyclic or pentacyclic triterpenoids.
CLASSICAL TRITERPENES
In the nature we have commonly pentacyclic triterpens but there is
one of the expectancies which is Dammarane, it is most common but from
tetracyclic triterpens.
Note: in Dammarane and other tetracyclic products you will see the ring
junction (cis or trans).
But the majority of terpenes are pentacyclic (the rings are termed as A,
B,C,D, and in the penta cyclic there is an E ring). In fact in the majority of
the triterpen ring A,B,C,D are always six member ring while we have the
option of ring E either a 5 or 6 , when E is a 5 membered ring then it is a
pentacyclic triterpens which is called lupeol. But if ring E was 6 membered
then it's called amyrin type. We have beta amyrin type, methyl group is in
different position and it can be converted to alpha amyrin type by
migration of the methyl group.
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Note: alpha alphabetically is before but in nature the first compound
isolated is beta amyrin which can be converted to alpha by migration of
the methyl group.
E
17
C
A
E
D
C
B
A
E
17
D
C
B
A
D
17
B
HO
HO
Alpha- Amyrin
HO
Beta-Amyrin
Lupeol
So lupeol, alpha and beta amyrin are pentacyclic triterpenes
defferent in 5 or 6 membered ring E, but the Dammarane is tetracyclic
triterpen, these are so called classical triterpens.
In the chapter of classical triterpens we will go in the first
compounds saponins.
SAPONINS:
Keep in mind that saponins occur in nature as classical triterpens
or steroidal, so it has both classes and it's a very big class of secondary
metabolite widely distributed in the plants.
CHARECTERISTICS OF SAPONINS;
1. the major characteristic of this substance that they are foaming
when they are shaken in H2O, so it is consider as one of the major
characteristics considered for the identification. If you take a certain
amount of saponins and shake it in 25 ml for example volumetric
flask, then we measure the amount of foam which is remaining for
the next 24 hours for the determination or quantification of
saponins. Because of this property it is used in the preparation of
different alcoholic and non-alcoholic beverages, of course there are
certain lignin widly use in the preparation of beverage
2. it occurs in the form of glycosides in nature and this glycoside of
saponin (saponin glycosides) are known as mono – desmoside
Note: if we are talking about triterpens or steroidal substances have
nearly a constant OH at position 3, that’s because there is an oxide ring is
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during biosynthesis loop converted to an OH group, this hydroxyl group
used in glycosidic linkage if there is only one sugar then it's called monodesmoside but if there is two sugars then we will use other OH on carbon
number 3 so it is will called bis-desmoside.
GLUCOURONIC ACID: Derivative of monosaccharide that we have carbon
number 6 oxidized to carboxyl group, so there is different possibility as
single, di or tri or up to 10 saccharide when isolated from the nature
3. there is different sites on saponins that are liable for introduction of
an oxygen
note : the majority of the steroidal substances originate from 30 carbon
(squalene), then by losing 3 methyl groups we will obtain cholesterol,
so the parent compound of steroid and triterpens is 30 carbon (squalene)
so in the triterpens we keep the number of carbons but in steroidal
substances there is modification of the number of carbon so when we have
27, 28, 29 carbon steroids it depends on if we are talking about the
steroidal substance of animal as human cholesterol (27) or mycosteroid in
fungi (28) or phytosteroid in plant (29)
29
19
O
12
11
1
2
A
3
4
25
10
C
5
6
14
8
B
HO
24
9
13
E
18
26
20
17
D
O
30
21
22
28
16
O
15
27
7
O
23
O
4. the saponin glycosides are safe with human and mammalian but
toxic for plant and toxic to insect and fish, if this fish is taken orally
then it is safe but will make damage to oral cavity and if taken
internally will be toxic and will lead hemolysis of RBCs and lead to
skin damage
5. can precipitate by any metal
6. surfactant property so widely used in pharmaceutical industry
7. there are different saponins contain plant where used in the mask of
the Arrow poison.

Good Luck
Done by : Azhar Atoom
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