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 RBCs blood 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 (sapogenin) + sugar moiety.
aglycone

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.

21 20 18 12 11 19 1 2 A 3 4 5 6 10 9 B C 8 7 17 13 D 14 E 16 15 22

27 26

29 19

30 20 17

25

21 22

23

24 11 25 1 2 10 3 4 5 6 9 8

12

18 13

14 15 7

16

Steroidal saponin aglycone

Triterpenoidal saponin aglycone

Economical & Medicinal Importance

Economical uses 1. Cleaning industrial equipment & fine fabrics. 2. Powerful emulsifier. 3. Steroidal sapogenins used cortisone & sex hormones. in semisynthesis of

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. 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 ).

2.

Licorice Root (RADIX GLYCYRRHIZAE) -

Botanical origin: The dried peeled or unpeeled roots and stolons of Glycyrrhiza glabra L. and its varieties (Family Leguminosae = Fabaceae). Geographical Source: Licorice is native 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 faint characteristic odor and a very sweetish taste,. Powdered licorice is characterised by: Numerous fragments of fibres accompanied by crystal 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, with no 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 triterpenoid saponin Glycyrrhizin Glycyrrhizin = mixture of K+ & Ca++ salts of Glycyrrhizic acid
COOH O

Glycyrrhizic acid = Glycoside of Glycyrrhetic acid

HO

Glycyrrhetic acid (aglycone)

2-Major non-saponin constituents of Licorice

Flavonoid glycosides: major liquiritin (flavanone). Coumarins: herniarin & umbelliferone. Others: asparagine, dihydrostigmasterol, glucose,
mannitol & starch.

Licorice - Uses
1. 2. Expectorant & demulcent by stimulation of tracheal mucous secretion due to glycyrrhizin. Antiinflamatory & adrenocorticotropic activity due to steroidallike activity of glycyrrhizin &/or glycyrrhetic acid.

3.
4.

Antihepatotoxic, antibacterial, antirheumatic, antitumour & antiviral.

Used in treatment of gastric & duodenal ulcers by increasing the rate of healing of gastric mucosa mainly due to liquiritin. DGL = (Deglycyrrhizinated extract) licorice preparation with very low % of glycyrrhizin (< 1 %) used as antiulcer for hypertensive patients. Used in laxative formulations. Used as sweetener (glycyrrhizin 50 times > sweet than sucrose) & as flavoring agent to mask the bitter taste of some drugs as aloe, quinine & others.

5. 6.

Contraindications
The drug is contraindicated in hypertension, hypokalaemia, or insufficiency, and during pregnancy. patients with chronic renal

The drug should not be taken concurrently with corticosteroid treatment.

Side effects
Aldosterone-like effects: sodium and water retention, potassium depletion, hypertension.

Ginseng Root
Source Roots of Panax quinquefolius (American ginseng) & P. ginseng (Asian ginseng), Araliaceae. Contains a complex mixture of triterpenoidal saponins with a tetracyclic ( steroids) or pentacyclic structure (in its cork). Classification Classified into 2 types: 1. Ginsenosides, 2. Panaxosides ( differ from ginsenosides in the sugar moiety).
Roots Aerial parts

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
HO R2O CH3 HO R2 O CH3

R1O

HO O R1

20(S)-Protopanaxadiols
Ginsenoside Rb1 Rb2 Rc Rd R1 R2 -glc (6-1)glc -glc (6-1)arab -glc (2-1)arab -glc

20(S)-Protopanaxatriols
Ginsenoside Re Rf Rg1 Rg2 R1 R2 -glc -H -glc -H

-glc (2-1)glc -glc (2-1)glc -glc (2-1)glc -glc (2-1)glc

-glc (2-1)rha -glc (2-1)glc -glc -glc (2-1)rha

Ginseng -Therapeutic uses

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

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. Contraindicated in case of hypertension & during pregnancy.

6.

Preparation
Ginseng is often processed in two forms: -White ginseng (peeled). -Red ginseng (unpeeled). There are many types and grades of ginseng and ginseng extracts depending on the source, age; and parts of the root used, and the methods of preparation

FENUGREEK SEED
Dried ripe seeds of Trigonella Foenum-graecum Leguminosae).

(Fam.

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 palisadelike 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 4hydroxy isoleucine which has an insulin- stimulating activity .

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 in the 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.

Uses
Horse-chestnut demonstrates anti-edema and antiinflammatory 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. Horse-chestnut has been used for the treatment of varicose veins, haemorrhoids, diarrhea, fever and enlargement of the prostate gland. 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.

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 a three-carbon chain = diphenyl propane derivatives]. *** Flavonoids give yellow color with alkali as well as with aluminium chloride.

Flavonoids-Chemistry
3' 2' 4' 1 O

B
7

1'

B
6'

5'

H2 C
6

A
5 Ring A 4

Ring B

C H2

CH2

Pyran ring

Diphenyl propane skeleton C6-C3-C6

Flavonoid 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 spherocrystals (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.

OMe Rh1-6Glc-O Rutinose OH O

7

OH

Diosmetin Diosmin

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 monogyna Jaq. ( = C. oxycantha L.), Family: Rosaceae.

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 ).

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.

Ginkgo Leaf
Ginkgo leaf consists of the dried leaf of Ginkgo biloba (Ginkgoaceae). Major chemical constituents 1- The major constituents are flavonoids of which mono-, di-, and triglycosides and coumaric acid esters that are based on the flavonols kaempferol and quercetin dominate. 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)

Echinacea
Echinaceae consists of the fresh or dried roots or whole herb of Echinacea angustifolia or, E.purpurea or E. pallida (Asteraceae). Active constituents 1- Volatile oil. 2- More than 20 alkamides, mostly isobutylamides 3-Caffeic acid ester derivatives present include echinacoside, cynarin, and chicoric acid. 4-Polysaccharides Medicinal uses: 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

Drugs containing Cyanogenic (Cyanogenetic or Cyanophore) glycosides

Cyanogenic glycosides ( Cyanogenetic or Cyanophore glycosides)

CN sugar-O C R1

R2

General structure of cyanogenic glycosides

-hydroxynitrile derivatives = cyanohydrins. Fairly unstable, stabilized by -D-linked sugar chains with -D-glucose as first sugar attached to the aglycone. O-glycosides hydrolysis HCN gas. Examples (Linseed & Bitter almond seed)

Linseed

Names: Linseed, Flax Seed Origin: Linseed is the dried ripe seeds of Linum

usitatissimum

Family: Linaceae.

 30 to 40% of fixed oil. The oil is rich in unsaturated fatty acids : oleic acid (39%), linoleic acid (15%) and a-linolenic acid (3060%). 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 seeds are free from starch.

Constituents

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 and hypertension. They offer protection against angina and thrombosis as they reduce the blood 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?

H 3C

CN C CH3

Chemical tests

O Glc

Test for Cyanogenic glycosides: Linamarin

(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.

Bitter almond seeds

Source
Kernels of bitter almond seeds (Prunus amygdalus var. amara) , [Rosaceae] .

Constituent:
The kernel contains mainly Cyanogenic glycoside named as Amygdalin Peaches

Hydrolysis
Amygdalin + emulsin enzyme 2 glucose. benzaldehyde +HCN +

Uses
Preparation of benzaldehyde (volatile oil of bitter almond) which is used as sedative and flavoring agent.

Kernels of apricots

Amygdalin-hydrolysis

CN C O

Glc-(1 - 6)-Glc (gentiobiose) Amygdalin

CN C + Glucose

CN C Amygdalin hydrolyase

H O Glc

Bitter almond
Glc-(1 - 6)-Glc
(Gentiobiose)

Amygdalin

Prunasin
Prunasin hydrolyase

CHO

H Mandelonitrile lyase HO

CN C + Glucose

HCN +

Benzaldehyde (Volatile oil of bitter almond)

Mandelonitrile

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.