Saponin glycosides

General characters

1. Widely distributed in higher plants.

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

membranes).

3. Form colloidal solutions in H2O foam on shaking

due to: hydrophobic / hydrophilic asymmetry of the

molecule (large aglycone & small sugar moiety)

lowering of surface tension in aqueous solution.

4. Form insoluble complex with sterols.

Destroy RBCshaemolysis.

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

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.

– Sometimes -CH3 (side chain) -COOH, whichmay be esterified by a sugar.

Isolation

1. Plant material + water, alcohol or aqueous

alcohol + reflux.

2. Concentrate & precipitate crude saponin

mixture with:

– Ether or acetone.

– Lead acetate (acidic saponins), or basic lead

acetate (neutral saponins) followed by

decomposition with acid.

3. Individual glycosides are separated by

chromatography.

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

4. Hypoglycemic (saponins of Balanites aegyptiaca ,

Egyptian date-sugar)

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 ).

Quantitative Determination1.Gravimetric method

– Saponin glycosides + Ba(OH)2 precipitate [Saponin-Ba(OH)2complex]

– Filer, dry & weigh the precipitate original weight {W1}

– Ignite & weigh the residue {W2} (calculated as BaO)

– W1 - W2 = Saponin content

2.Determination of Foam Index

– The foam index is defined as:

“ The dilution of the drug, that gives a layer of foam of 1 cmheight, when an aqueous solution is shaken in a graduatedcylinder for 15 seconds after standing for 15 min.”

3.Determination of Fish Index

– Saponins are toxic to cold blooded animals.

– The fish index is defined as:

“The reciprocal of the saponin dilution that kills 60 % of theexperimental animals within 1 hour.”

4.Determination of Haemolytic Index

– The heamolytic index is defined as:

“The greatest dilution of saponin that produces completehaemolysis.”

Steroidal saponins-

Balanites saponins (Balanitins 1-4)Chemistry

Steroidal saponin glycosides.

Aglycone: yamogenin (furanostane

type).

Source

Fruits & bark of Balanitesaegyptiaca : Balanitins 1-4 &

balanitoside.

Uses

Hypoglycemic, anticancer &

molluscicidal

Balanites aegyptiaca

Fruits

Triterpenoidal Saponins -

Licorice saponins

Source

Rhizomes & roots of licorice: 2-6 % of Glycyrrhizin

Structure

Glycyrrhizic acid = Glycyrrhetic

acid -3 O- diglucuronide (2 molecules

of glucuronic acid)

Glycyrrhetic acid Glycyrrhetinic acid

Glycyrrhizic acid Glycyrrhizinic acid

HO

COOH

Glycyrrhetic acid(aglycone)

O

3

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

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 = licorice preparation with very low % of glycyrrhizin (< 1 %)used as antiulcer for hypertensive patients.

5. Used in laxative formulations to facilitate absorption ofanthraquinone glycosides due to surfactant properties ofsaponins.

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

Ginseng saponinsSource

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

Classification

Classified into 3 types:

1. Ginsenosides,

2. Panaxosides

3. Chikusetsusaponins.Aerial partsRoots

Ginseng saponinsGinsenosides

1. Major saponins of ginseng (0.7-3 % calculated asginsenosides).

2. Aglycones of most ginsenosides have a tetracyclicsteroidal structure. They are glycosides of:

20 (S)-protopanaxadiol: aglycone of ginsenosidesRb1, Rb2, Rc, & Rd. Rb1 is the major.

20(S)-protopanaxatriol: aglycone of ginsenosidesRe, Rf, Rg1, Rg2 & Rh1. Rg1 is the major.

3. Ginsenoside Ro is an exception, being a triglycoside ofthe pentacyclic triterpene (oleanolic acid).

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 uses1. Tonic, stimulant, diuretic & carminative.

2. Adaptogenic (antistress): enhances bodynonspecific resistance to external stress (physical,chemical or biological).

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

4. Improves immune function & metabolism.

5. Used in anemia, diabetes, insomnia, neurasthenia,gastritis & sexual impotence.

6. Contraindicated in case of hypertension & duringpregnancy.

Cyanogenic glycosides

Cyanogenetic glycosides

N.B. Cyanogenic = Cyanogenetic= Cyanophore

Introduction

O-glycosides hydrolysis HCN gas.

Present in over 3000 plant spp. (110 families).

In plants, cyanogenic glycosides & their hydrolytic

-glycosidase enzymes are present in different

cellular compartments.

Cyanogenesis: is a chemical defense mechanism

protecting plants against damaging organisms by

release of toxic HCN gas

Cyanogenic glycosides-Structure

-hydroxynitrile derivatives = cyanohydrins.

Fairly unstable, stabilized by -D-linked sugar

chains with -D-glucose as first sugar

attached to the aglycone.

R1 & R2 are often differentpairs of epimers.

C

R2sugar-O

R1

CN

General structure of cyanogenic glycosides

Cyanogenic glycosides vs. non-

cyanogenic nitriles

Non-cyanogenic nitriles :

1. Glucosides of - & -hydroxynitriles.

2. On hydrolysis: do not yield free HCN except under

specific conditions.

Examples: cyanolipids (esters of fatty acids with

- & -hydroxynitriles) & Simmondsin

OCH3

OCH3

OOH

NC H

O

HOHO

OH

HO

O (CH2)nCH3

O

HNC

Non-cyanogenic nitrile compounds

SimmondsinCyanolipid

Cyanogenic glycosides-Amygdalin

SourceKernels of peaches, apricots (Prunus

armeniaca) & bitter almond seeds(Prunus amygdalus var. amara)[Rosaceae] .

HydrolysisAmygdalin + emulsin enzyme (mixture of 3

enzymes:

Amygdalin hydrolase + prunasin hydrolase +

mandelonitrile lyase) benzaldehyde +HCN + 2 glucose.

UsesPreparation of benzaldehyde (volatile oil of

bitter

almond)

Peaches

C

O

CN

Glc-(1 - 6)-Glc

H

(gentiobiose)

Amygdalin

Amygdalin- hydrolysis

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)

Cyanogenic glycosides-Linamarin

Source

Seeds of Linum usitatissimum, (Linseed, Flaxseed,

Linaceae), Lotus arabicus & in lima beans.

Hydrolysis

Linamarin acetone cyanohydrin ( acetone + HCN) +

glucose

H3C

CH3

C

O

CN

Glc

Linamarin

Linseed

Glucosinolates

Glucosinolates-General characters

Common in Cruciferae (mustard family), Capparidaceae,

Resedaceae & Liliaceae.

Bound toxins like cyanogenetic glycosides.

Found in plants with specific hydrolytic enzymes

(thioglucosidases= myrosinases).

Characterized by presence of:

1. One S atom attached to glucose S-glycoside

2. Another S atom present as a sulfonated oxime group.

Aglycones: aliphatic or aromatic formed from amino acids.

Members of family Brassicaceae ( = Cruciferae) are rich in

glucosinolates:

1. Oilseeds e.g. rapeseed

2. Condiments e.g. mustard & horseradish

3. Vegetables e.g. broccoli, cabbage & turnips

Glucosinolates = Thioglycosides = Isothiocyanate glycosides

Pharmacological action & uses1. Play an important role as

feeding deterrent against

insects & mammals.

2. Anticarcinogenic.

3. Improve flavor of foods.

Rape Black mustard Horse radish Turnip

Broccoli

Cabbage

Glucosinolates - Sinigrin

Source

Seeds of Brassica nigra (black mustard) [Brassicaceae]

Properties

Sharp odor & biting taste.

Hydrolysis

Sinigrin + myrosinase enzyme allylisothiocyanate (volatile oil of mustard) + KHSO4 + glucose.

Uses

1. Internally: emetic.

2. Externally: local irritant, rubefacient & vesicant.

3. Commercially: condiment.

H2C CH

CH2

C

N-O-SO3K

S-Glc

S C N

H2

C

CH

CH2 KHSO4+ Glucose+

myrosinase

allylisothiocyanateSinigrin

Glucosinolates - Sinalbin

Source

Seeds of Brassica alba (white mustard), Brassicaceae.

Hydrolysis

Uses: Condiment

H2O

MyrosinaseSinalbin p-Hydroxybenzyl isothiocyanate + Sinapine acid sulfate + Glucose

Slightly volatile

& pungent

Non-glycosidic organo-sulfur drugs- Alliin

Source & decomposition

Bulb of Allium sativum (Fam. Liliaceae)

Food & traditional medicine since Pharaohs.

Intact cells of garlic contain Alliin (1.2 % in fresh garlic).

Alliin + crushing (allinase enzyme) Allicin (diallyl

thiosulfinate).

Allicin is responsible for the characteristic odor & flavor of

garlic.

Allicin + air + water diallyl disulfide + diallyl trisulfide +

polysulfides (All strong smelling).

Uses: Allicin is used as antibacterial, antihyperlipidemic; inhibits

platelet aggregation & enhances the blood fibrinolytic (anti-

thrombic) activity.

SH

O

NH2

COOH SS

O

Allinase+ H2O

Alliin Allicin