Drugs Containing Saponin

glycosides

General Characters of Saponins

1. Widely distributed in higher plants.

2. Bitter, acrid taste & sternutatory (irritant to mucous

membranes).

3. Form colloidal solutions in H2O foam on shaking

lower of surface tension in aqueous solution.

4. Destroy RBCsblood haemolysis.

5. Toxic to cold- blood animals (fishes & frogs).

6. Toxic by i.v. injection & harmless by oral

route.

Chemical Characters

1. O-glycosides hydrolysis aglycone(sapogenin) + sugar moiety.

2. Aglycone:

triterpenoidal (C-30) [mainly in Dicotyledons]

steroidal (C-27) [mainly in Monocotyledons]

3. Sugar moiety:

Often contain uronic acids or acyl residues.

Usually glycosylation is at C-3.

OO

A B

C D

1

2

3

4

56

7

89

10

11

12

13

1425

21

22

19

15

16

1718

20

1

2

3

45

6

7

89

10

11

12

13

1415

16

17

18

19

2021

22

23 24

25

26

27

E

Steroidal saponin aglycone Triterpenoidal saponin aglycone

3029

Economical & Medicinal Importance

Economical uses

1. Cleaning industrial equipment & fine fabrics.

2. Powerful emulsifier.

3. Steroidal sapogenins used in semisynthesis of

cortisone & sex hormones.

Medicinal uses

1. Expectorant

2. Immunostimulant

3. Control of schistosomiasis snails (molluscicides)

4. Hypoglycemic.

Tests for Identification

1. Froth test:

1 ml of aqueous solution of saponin or plant

extract + shake persistent & voluminous

froth.

2. Haemolysis test:

Suspension of RBCs in normal saline + equal

volume of plant extract in normal saline +

shake gently clear red solution indicating

heamolysis of RBCs (compared with blank ).

Licorice Root

(RADIX GLYCYRRHIZAE)

- Botanical origin: The dried peeled or

unpeeled roots and stolons of

Glycyrrhiza glabra L. and itsvarieties (Family Leguminosae =

Fabaceae).

Geographical Source: Licorice isnative to the Mideterranean region,

as Spain, Italy, England, France,

Germany, U.S.A. ,Russia and Egypt.

Licorice Powder

Powdered licorice, is light yellow, having a faintcharacteristic odor and a very sweetish taste,.

Powdered licorice is characterised by:

Numerous fragments of fibres accompanied bycrystal sheath.

Dark yellow fragments of borded-pitted vessels . Prismatic crystals of calcium oxalate. Numerous starch granules, free or in parenchyma

cells, mostly simple, oval, round or fusiform, withno striations but occasionally showing hilum

Cork may be present

Licorice

Active Constituents of Licorice

1- Saponins

Rhizomes & roots of licorice contains 2-6 % of the triterpenoidsaponin Glycyrrhizin

Glycyrrhizic acid = Glycoside of

Glycyrrhetic acid

HO

COOH

Glycyrrhetic acid(aglycone)

O

3

Glycyrrhizin = mixture of K+ & Ca++ salts of Glycyrrhizic acid

2-Major non-saponin constituents of

Licorice

Flavonoid glycosides: major liquiritin (flavanone).

Coumarins: herniarin & umbelliferone.

Others: asparagine, dihydrostigmasterol, glucose,

mannitol & starch.

Licorice - Uses1. Expectorant & demulcent by stimulation of tracheal mucous

secretion due to glycyrrhizin.

2. Antiinflamatory & adrenocorticotropic activity due to steroidal-like activity of glycyrrhizin &/or glycyrrhetic acid.

3. Antihepatotoxic, antibacterial, antirheumatic, antitumour &antiviral.

4. Used in treatment of gastric & duodenal ulcers by increasing therate of healing of gastric mucosa mainly due to liquiritin.

DGL = (Deglycyrrhizinated extract) licorice preparation with verylow % of glycyrrhizin (< 1 %) used as antiulcer for hypertensivepatients.

5. Used in laxative formulations.

6. Used as sweetener (glycyrrhizin 50 times > sweet than sucrose)& as flavoring agent to mask the bitter taste of some drugs asaloe, quinine & others.

ContraindicationsThe drug is contraindicated in patients with

hypertension, hypokalaemia, or chronic renal

insufficiency, and during pregnancy.

The drug should not be taken concurrently with

corticosteroid treatment.

Aldosterone-like effects: sodium and water retention,

potassium depletion, hypertension.

Side effects

Ginseng RootSource

Roots of Panax quinquefolius (Americanginseng) & P. ginseng (Asian ginseng),Araliaceae.

Contains a complex mixture of triterpenoidalsaponins with a tetracyclic ( steroids) orpentacyclic structure (in its cork).

Classification

Classified into 2 types:

1. Ginsenosides,

2. Panaxosides ( differ

from ginsenosides

in the sugar moiety).

Aerial partsRoots

Ginseng saponins

Ginsenosides:

1.Major saponins of ginseng (0.7-3 %

calculated as ginsenosides).

2.Aglycones of most ginsenosides have a

tetracyclic steroidal structure.

Ginsenosides

HOR2O

HO

CH3

O R1

HOR2O

R1O

CH3

20(S)-Protopanaxadiols 20(S)-Protopanaxatriols

Ginsenoside R1 R2

Rb1 -glc (2-1)glc -glc (6-1)glcRb2 -glc (2-1)glc -glc (6-1)arabRc -glc (2-1)glc -glc (2-1)arabRd -glc (2-1)glc -glc

Ginsenoside R1 R2

Re -glc (2-1)rha -glc Rf -glc (2-1)glc -HRg1 -glc -glc Rg2 -glc (2-1)rha -H

Ginseng -Therapeutic uses

1- Adaptogenic (antistress): enhances body nonspecific resistanceto external stress (physical, chemical or biological).

2- Improves physical & mental performance e.g. learning, memory& physical capabilities.

Tonic, stimulant, diuretic & carminative.

Improves immune function & metabolism.

Used in anemia, Hepatoprotective (ginsenosides), diabetes(saponins and polysaccharides), insomnia, gastritis, Antitumor(polyacetylenes and polysaccharides) & sexual impotence.

6. Contraindicated in case of hypertension & during pregnancy.

Preparation

Ginseng is often processed in two forms:

-White ginseng (peeled).

-Red ginseng (unpeeled).

There are many types and grades ofginseng and ginseng extractsdepending on the source, age; andparts of the root used, and themethods of preparation

FENUGREEK SEED

Dried ripe seeds of Trigonella Foenum-graecum (Fam. Leguminosae).

Powdered Fenugreek is characterized by its yellow color,

and its characteristic odor and mucilaginous bitter taste.

Microscopically, it is characterized by:

Fragments of the testa showing the palisade-

like cells and the basket-like cells of the

hypodermal layer.

Fragments of mucilaginous endosperm cells.

Fragments of the cotyledons with

parenchymatous cells containing fixed oil and

aleurone grains.

Starch granules are small and very few.

Fenugreek powder

Cuticle (c), epidermis (ep.) and

hypodermis(h.) of

the testa in sectional

view.

Epidermis of the testa in surface

view.

Hypodermis of the testa in surface view

Active Constituents: Neutral mucilage (28%) It gives blue color With

methylene blue, (neutral mucilage).

Proteins and amino acids. Protein (23-25%)containing high quantities of lysine and tryptophan.Free amino acids, and a non essential amino acid 4-hydroxy isoleucine which has an insulin- stimulatingactivity .

Biotin, choline, essential oil, folic acid, inositol, iron, and

lecithin.

Fixed oil (6%).

Saponins (diosgenin, gitogenin and tigogenin).

Two alkaloids (trigonelline and choline).

Vitamins (A, B1, B2, B3, B6, B12, and D).

Uses

As lactagogue, demulcent and emollient.

Laxative.

For nutritive purposes.

Source of diasogenin, a basic compound inthe semi-synthesis of steroid drugs such as

cortisone and sex hormones.

Antidiabetic, cholesterol-lowering, anti-ulcer and

anti-cancer.

Horse chestnut Seed

(Semen Hippocastani)

Names :Aesculus kernel

Origin :Horse chestnut is the dried and fresh kernel of

Aesculus hippocostanum L. Family Hippocastamaceae.

Constituents

-Saponin referred to as escin (which is a complex mixture

of over 30 individual pentacyclic triterpene diester

glycosides) is regarded as the main active constituent; and -escin are the major glycosides. -Flavones, caumarins and tannins are also present.

Horse-chestnut demonstrates anti-edema and anti-

inflammatory effects due to saponin content. Escin

stimulates the release of corticosteroids necessary for

the anti-inflammatory activity. Antioxidant,

hypoglycemic and cyto-toxic activities were also

reported and attributed to the saponin content of the

extract.

Uses

The flavonoids of the horse-chestnut leaves normalize

the pathologically increased permeability of blood

vessels and reduce the fragility of vessel walls, whereas

their coumarins content, being a vitamin K antagonist,

inhibits prothrombin production.

Horse-chestnut has been used for the treatment of

varicose veins, haemorrhoids, diarrhea, fever and

enlargement of the prostate gland.

DRUGS CONTAINING

FLAVONOID GLYCOSIDES

Flavonoids Chemistry

Variety of structural forms

Free aglycones or glycosides

Skeleton contains 15 carbon atoms:

C6-C3-C6 [2 phenyl rings linked by athree-carbon chain = diphenyl propanederivatives].

*** Flavonoids give yellow color withalkali as well as with aluminiumchloride.

Flavonoids-Chemistry

O

A

B

Ring A

Ring B

Pyran ring

O1

2

3

45

6

7

8 1'

2'

3'

4'

5'

6'

CH2

CH2

H2CA

B

Diphenyl propane skeleton

C6-C3-C6Flavonoid skeleton

Buchu Leaves

Origin of The Pant:

Buchu is the dired leaves of Barosma betulina

Family Rutaceae. Known as short buchu,

round buchu or diosma.

Origin of the name:

Buchu is a Zulu name of the drug. Barosma

refers to the heavy odor of the leaves.

Buchu Leaves

Constituents:

1. Crystalline rhamnoglycoside diosmin

(flavone glycoside),found as sphero-

crystals (in the epidermal cells) and

hesperidin.

2. Volatile oil which is contained in the

oil glands cotains up to 30%

diosphenol.

3. Mucilage which is deposited on the

inner walls of the epidermal cells.

OOOH

OH

OMe

Rh1-6Glc-O

Rutinose

Diosmetin

Diosmin

7

Uses:

1- Disinfectant to urinary tract, excreted

by the kidney rendering the urine

antiseptic due to diosphenol.

2- Diuretic and Diaphoretic due to

diosphenol.

3-Diosmin is used to treat peripheral

vascular disorders (capillary fragility)

just like varicose veins and piles

(hemorrhoids).

Crataegus Fruits

(Fructus Crataegi, Hawthorn)

Names: Hawthorn berry, Crataegus fruits, Fructus

oxycanthae

Origin: Hawthorn berry consists of the dried fruits of Crataegus monogynaJaq. ( = C. oxycantha L.), Family: Rosaceae.

Uses and Actions:

It has been claimed that preparations of hawthorn berry

have been applied to the treatment of :

Early forms of cardiac insufficiency and angina pectoris.Nervous heart complications.Heart and circulatory disturbances.Hypotension, and atherosclerosis.

Constituents:

1- Oligomeric procyanidins (1-3%).

2- Flavonoids (1-2%) named: Hyperoside, vitexin 2-rhamnoside

and rutin.

3- Amines ( some with cardiotonic action).

4-Catechins and epicatechins.

5- Phenol-carboxylic acids (especially chlorogenic acid ).

Ginkgo Leaf

Ginkgo leaf consists of the dried leaf of Ginkgo biloba (Ginkgoaceae).

1- The major constituents are flavonoids of which mono-, di-, and tri-

glycosides and coumaric acid esters that are based on the flavonols

kaempferol and quercetin dominate.

Major chemical constituents

2- Diterpene lactones ginkgolides A, B, C, J, and M and the

sesquiterpene lactone bilobalide

Medicinal uses

Extracts have been used for symptomatic treatment of mild to moderate

cerebrovascular insufficiency (memory deficit, disturbance in concentration,

depressive emotional condition, dizziness, and headache)

1- Volatile oil.

2- More than 20 alkamides, mostly isobutylamides

3-Caffeic acid ester derivatives present include echinacoside,

cynarin, and chicoric acid.

4-Polysaccharides

Active constituents

Preparations of Echinaceae are administered orally in supportive

therapy for colds and infections of the respiratory and urinary tract.

Beneficial effects in the treatment of these infections are generally

thought to be brought about by stimulation of the immune response

Medicinal uses:

Echinacea

Echinaceae consists of the fresh or dried roots

or whole herb of Echinacea angustifolia or, E.purpurea or E. pallida (Asteraceae).

Drugs containing Cyanogenic

(Cyanogenetic or Cyanophore)

glycosides

Cyanogenic glycosides

( Cyanogenetic or Cyanophore glycosides)

-hydroxynitrile derivatives = cyanohydrins.

Fairly unstable, stabilized by -D-linked sugar chains with -D-glucose as firstsugar attached to the aglycone.

O-glycosides hydrolysis HCN gas.

Examples (Linseed & Bitter almond seed)

C

R2sugar-O

R1CN

General structure of cyanogenic glycosides

Names: Linseed,Flax Seed

Origin: Linseed isthe dried ripe

seeds of LinumusitatissimumFamily: Linaceae.

Linseed

Constituents 30 to 40% of fixed oil. The oil is rich in

unsaturated fatty acids : oleic acid (39%),

linoleic acid (15%) and a-linolenic acid (30-

60%).

Linoleic acid ( Omega-6- fatty acid), and

linolenic acid (Omega-3 fatty acids) are

essential fatty acids.

25% of protein.

3-6% of mucilage

Small amount of a cyanogenic glycoside(linamarin).

Unripe seeds contain starch but the ripe seedsare free from starch.

Uses and actions In folk medicine, decoction as demulcent in

acute or chronic gastritis.

Omega-3 fatty acids are anti-inflammatory.Thus, used in rheumatoid arthritis and

psoriasis. They cause a significant reduction

of very low density lipoprotein (VLDL), and

low density lipoprotein (LDL). They may be

used to reduce the blood pressure,especially in hypercholesterolaemia andhypertension. They offer protection againstangina and thrombosis as they reduce theblood viscosity.

Cake is used in poultices for boils and carbuncles.

As a laxative in habitual constipation, due to its mucilage. (crushed seeds). The laxative

action is due to increase in the volume of the

intestinal bowel contents and stimulation of

peristalsis (bulk laxative).

Linseed is used as antitussive due to its cyanogenic glycoside content.

Toxicity:

Linseed is advisable with plenty of fluids otherwise it may cause flatulence.

Liberation of HCN.

Whats the economic and commercial importance of linseed

plant and seeds?

Chemical tests

Test for Cyanogenic glycosides: (Guignards paper test):

Crushed seeds in test tube moistened

with water covered with a piece of

cork having a sodium picrate paper

(yellow color), leave in a warm place

for 30 min., HCN will be evolved

converting the yellow colored paper to

brick red color.

H3C

CH3

C

O

CN

Glc

Linamarin

Bitter almond seeds

SourceKernels of bitter almond seeds (Prunus amygdalus var.

amara) , [Rosaceae] .

Constituent:The kernel contains mainly Cyanogenic glycoside named

as Amygdalin

HydrolysisAmygdalin + emulsin enzyme benzaldehyde +HCN +

2 glucose.

UsesPreparation of benzaldehyde (volatile oil of bitter

almond) which is used as sedative and

flavoring agent.

Peaches

Kernels of apricots

Amygdalin-hydrolysis CO

CN

Glc-(1 - 6)-Glc

H

(gentiobiose)

Amygdalin

CO

CN

Glc-(1 - 6)-Glc

CO

CN

Glc

C

HO

CNCHO

HCN

+ Glucose

Mandelonitrile

PrunasinAmygdalin

Benzaldehyde

hydrolyase

Prunasin hydrolyase

Mandelonitrile lyase

H

H H

(Gentiobiose)

Amygdalin

+ Glucose+

(Volatile oil of bitter almond)

Bitter almond

Drugs containing Glycosinolates

(containing sulphor and

nitrogen)

Drugs containing glycosinolates

Black mustard seeds (Brassica nigra, containing sinigrin glycoside).

White mustard seeds ( Brassica alba,containing sinalbin glycoside).

The two drugs are mentioned under drugs containing volatile oils as sinigrin glycoside

on hydrolysis gives the volatile oil

allylisothiocyanate.