Saponin glycosides

General characters Widely distributed in higher plants. Bitter, acrid taste & sternutatory (irritant to mucous membranes). 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. Form insoluble complex with sterols. Destroy RBCs haemolysis. Toxic to cold- blood animals (fishes & frogs). Toxic by i.v. injection & harmless by oral route.

Chemical characters O-glycosides  hydrolysis  aglycone (sapogenin) + sugar moiety. Aglycone: triterpenoidal (C-30) [mainly in Dicotyledons] steroidal (C-27) [mainly in Monocotyledons] Sugar moiety: Often contain uronic acids or acyl residues. Usually glycosylation is at C-3. Sometimes -CH3 (side chain)  -COOH, which may be esterified by a sugar.

Isolation Plant material + water, alcohol or aqueous alcohol + reflux. Concentrate & precipitate crude saponin mixture with: Ether or acetone. Lead acetate (acidic saponins), or basic lead acetate (neutral saponins) followed by decomposition with acid. Individual glycosides are separated by chromatography.

Economical & Medicinal importance Economical uses Cleaning industrial equipment & fine fabrics. Powerful emulsifier. Steroidal sapogenins used in semisynthesis of cortisone & sex hormones. Medicinal uses Expectorant Immunostimulant Control of schistosomiasis snails Hypoglycemic (saponins of Balanites aegyptiaca , Egyptian date-sugar)

Tests for identification 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 ).

Quantitative Determination Gravimetric method Saponin glycosides + Ba(OH)2  precipitate [Saponin-Ba(OH)2 complex] Filer, dry & weigh the precipitate  original weight {W1} Ignite & weigh the residue {W2} (calculated as BaO) W1 - W2 = Saponin content Determination of Foam Index The foam index is defined as: “ The dilution of the drug, that gives a layer of foam of 1 cm height, when an aqueous solution is shaken in a graduated cylinder for 15 seconds after standing for 15 min.” 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 the experimental animals within 1 hour.” Determination of Haemolytic Index The heamolytic index is defined as: “The greatest dilution of saponin that produces complete haemolysis.”

Steroidal saponins- Balanites saponins (Balanitins 1-4) Chemistry Steroidal saponin glycosides. Aglycone: yamogenin (furanostane type). Source Fruits & bark of Balanites aegyptiaca : Balanitins 1-4 & balanitoside. Uses Hypoglycemic, anticancer & molluscicidal Balanites aegyptiaca Fruits

Triterpenoidal Saponins - Licorice saponins Source Rhizomes & roots of licorice: 2-6 % of Glycyrrhizin Glycyrrhizin = mixture of K+ & Ca++ salts of Glycyrrhizic acid Glycyrrhizic acid  Glycyrrhizinic acid Structure Glycyrrhizic acid = Glycyrrhetic acid -3 O- diglucuronide (2 molecules of glucuronic acid) Glycyrrhetic acid  Glycyrrhetinic acid

Major non-saponin constituents of Licorice Flavonoid glycosides: major liquiritin (flavanone). Coumarins: herniarin & umbelliferone. Others: asparagine, dihydrostigmasterol, glucose, mannitol & starch.

Licorice - Uses Expectorant & demulcent by stimulation of tracheal mucous secretion due to glycyrrhizin. Antiinflamatory & adrenocorticotropic activity due to steroidal-like activity of glycyrrhizin &/or glycyrrhetic acid. 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 = licorice preparation with very low % of glycyrrhizin (< 1 %) used as antiulcer for hypertensive patients. Used in laxative formulations to facilitate absorption of anthraquinone glycosides due to surfactant properties of saponins. Used as sweetener (glycyrrhizin 50 times > sweet than sucrose) & as flavoring agent to mask the bitter taste of some drugs as aloe, quinine & others.

Ginseng saponins 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 Classification Classified into 3 types: Ginsenosides, Panaxosides Chikusetsusaponins. Roots Aerial parts

Ginseng saponins Ginsenosides Major saponins of ginseng (0.7-3 % calculated as ginsenosides). Aglycones of most ginsenosides have a tetracyclic steroidal structure. They are glycosides of: 20 (S)-protopanaxadiol: aglycone of ginsenosides Rb1, Rb2, Rc, & Rd. Rb1 is the major. 20(S)-protopanaxatriol: aglycone of ginsenosides Re, Rf, Rg1, Rg2 & Rh1. Rg1 is the major. Ginsenoside Ro is an exception, being a triglycoside of the pentacyclic triterpene (oleanolic acid).

Ginsenosides

Ginseng -Therapeutic uses Tonic, stimulant, diuretic & carminative. Adaptogenic (antistress): enhances body nonspecific resistance to external stress (physical, chemical or biological). Improves physical & mental performance e.g. learning, memory & physical capabilities. Improves immune function & metabolism. Used in anemia, diabetes, insomnia, neurasthenia, gastritis & sexual impotence. Contraindicated in case of hypertension & during pregnancy.

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 different pairs of epimers.

Cyanogenic glycosides vs. non-cyanogenic nitriles Glucosides of - & -hydroxynitriles. On hydrolysis: do not yield free HCN except under specific conditions. Examples: cyanolipids (esters of fatty acids with b- & -hydroxynitriles) & Simmondsin

Cyanogenic glycosides-Amygdalin Source Kernels of peaches, apricots (Prunus armeniaca) & bitter almond seeds (Prunus amygdalus var. amara) [Rosaceae] . Hydrolysis Amygdalin + emulsin enzyme (mixture of 3 enzymes: Amygdalin hydrolase + prunasin hydrolase + mandelonitrile lyase)  benzaldehyde + HCN + 2 glucose. Uses Preparation of benzaldehyde (volatile oil of bitter almond) Peaches

Amygdalin- hydrolysis

Cyanogenic glycosides-Linamarin Linseed Source Seeds of Linum usitatissimum, (Linseed, Flaxseed, Linaceae), Lotus arabicus & in lima beans. Hydrolysis Linamarin  acetone cyanohydrin ( acetone + HCN) + glucose

Glucosinolates

Glucosinolates-General characters Glucosinolates = Thioglycosides = Isothiocyanate glycosides 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: One S atom attached to glucose  S-glycoside 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: Oilseeds e.g. rapeseed Condiments e.g. mustard & horseradish Vegetables e.g. broccoli, cabbage & turnips

Pharmacological action & uses Broccoli Rape Black mustard Horse radish Cabbage Turnip Pharmacological action & uses Play an important role as feeding deterrent against insects & mammals. Anticarcinogenic. Improve flavor of foods.

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 Internally: emetic. Externally: local irritant, rubefacient & vesicant. Commercially: condiment.

Glucosinolates - Sinalbin Source Seeds of Brassica alba (white mustard), Brassicaceae. Hydrolysis Uses: Condiment

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.