[Mid] Pharmacognosy (Glycosides Part 1)

Glycosides

• Compounds that yield one or more sugars upon hydrolysis

• sugars include:

  • β-D-glucose (most common)

  • rhamnose

  • digitoxose

  • glucoside

  • fructoside

Glycosidic bond

Bond through which sugar groups are attached in glycosides

Chemical definition of glycosides

Acetals where hydroxyl of sugar condenses with hydroxyl of non-sugar component

Secondary hydroxyl condenses within sugar molecule forming an oxide ring

Aglycone (Genin)

• Non-sugar component

• therapeutically active

• basis of classification

Glycone

• Sugar component

• yields sugar

• common denominator

• present in all glycosides

• inactive

Isomeric forms of glycosides

Alpha (α) form

Beta (β) form

Role of glycosides in plants

Regulatory (hormone-related processes)

Protective (bitter taste deters predators)

Sanitary (antimicrobial protection)

Characteristics of glycosides

• Crystalline or amorphous

• water and alcohol soluble

• insoluble in organic solvents

• hydrolyzed by water, enzymes, mineral acids

• optically active

Classification of glycosides

• Based on glycone

• Based on glycosidic linkage

• Based on aglycone

O-glycoside

• Phenolic (–OH) linkage

  • arbutin

  • salicin

N-glycoside

• Amino (NH) group linkage

  • purine

  • nucleoside

S-glycoside

• Thiol (-SH) linkage

  • sinigrin

C-glycoside

• Carbon linkage

  • flavones

  • anthraquinone

  • vitrixin

Biosynthesis of glycosides

Uridine triphosphate reacts with sugar-1-phosphate via uridyl transferase

Anthraquinone

• glycosides formed from anthraquinones, anthranols, anthrones and derivatives

• old name ”anthracene”

• contains THREE benzene rings

Anthraquinone

• Yellow to light-grey to grey-green crystalline powder

• melting point = 286°C

• boiling point = 379.8°C

• reduced derivatives more active than oxidized aglycones

• insoluble in water and alcohol

• soluble in nitrobenzene and aniline

286°C and 379.8°C

Anthraquinone Melting Point and Boiling Point

Borntrager's Test

(+) pink to red color for anthraquinone glycosides

Modified Borntrager's Test

test to identify C-type anthraquinone glycosides

Cascara sagrada

• Dried bark of Rhamnus purshiana (Rhamnaceae)

• sacred bark aged 1 year to reduce emodin glycosides

• very bitter

• MgO added to reduce cathartic effect

• dose 1 mL liquid extract

Cascara sagrada constituents

• O-glycosides

• C-glycosides

• Cascaroside A and B (optical isomers of barbaloid)

• Cascaroside C and D (optical isomers of chrysaloin)

Casanthranol

• Purified anthranol glycoside mixture from cascara

• ingredient in Lane's Pills

• cathartic

• restores natural tone of colon

Frangula (Buckthorn bark)

• Dried bark of Rhamnus frangula

• laxative

• ingredient in Movicol®

• substitute for cascara sagrada

Aloe

• Dried latex from leaves of

  • Curacao aloe: Aloe barbadensis, Aloe vera

  • Cape aloe: Aloe ferox, Aloe spicata

• cathartic

• ingredient in Compound Benzoin Tincture

• constituents:

  • aloin

  • barbaloin

aloin, barbaloin

constituents of Aloe

Aloe gel

• treatment of burns, abrasions, skin irritations

• moisturizing and emollient

Rhubarb

• Dried rhizomes and roots of Rheum officinale or Rheum palmatum (Polygonaceae)

• other sources Rheum emodi, Rheum webbianum

• active constituent: rhein anthrones

• cathartic

rhein anthrones

active constituent of rhubarb

**Senna leaf

• Dried leaflets of Cassia acutifolia (Alexandria senna) and Cassia angustifolia (Tinnevelly senna)

• graded blue-green (high) and yellowish (low)

• stimulant cathartic

• more potent than cascara

Cassia acutifolia (Alexandria senna)

uses broken leaves of senna

Cassia angustifolia (Tinnevelly senna)

uses whole leaves of senna

Sennoside A & B (major), Sennoside C & D (minor)

constituents of Senna

Chrysarobin

• mixture from Goa powder Andira araroba

• extracted by hot benzene

• keratolytic

• used for psoriasis, trichophytosis, chronic eczema

• very irritating

• replaced by anthralin

Chrysarobin constituents

• Chrysophenolanthrone (30-40%)

• Emodinanthrone-monomethyl ether (20%)

• Dehydro-emodinanthrone-monomethyl ether (30%)

Saponins

• Widely distributed in higher plants

• natural detergents

• foam on shaking

• bitter, acrid taste

• optically active

• soluble in water and alcohol

• insoluble in organic solvents

Physiological effects of saponin

• Sternutator

• mucous membrane irritant

• hemolytic

• toxic to cold-blooded animals

• used as FISH POISON

Sapogenin

Aglycone portion of saponin

Classification of saponins

• Steroidal

  • neutral

  • related to cardiac glycosides

  • cortisone precursor

• Triterpenoid (acidic)

Sarsaponins, Diosgenin

Steroidal saponins (the second is very important)

Sapotoxin

Triterpenoid saponin (poisonous)

Hemolysis Test for Saponin

• Drop of Blood + aq. saponin soln. = ruptured RBC

Foam Test for Saponin

1g drug + water = stable froth (60-120 secs.)

Glycyrrhiza (Licorice)

• Dried rhizome and roots of Glycyrrhiza glabra (Leguminosae)

• Glycyrrhiza (Greek) = “sweet root“

• Glycyrrhyza “Glabra“ = “smooth“

  • typica (Spanish licorice)

  • glandulifera (Russian licorice)

“Spanish Licorice“

Glycyrrhiza glabra var. typica

“Russian Licorice“

Glycyrrhiza glabra var. glandulifera

Glycyrrhizin

• major constituent of Glycyrrhiza

• a.k.a “glycyrrhizic acid”

• 50× sweeter than sugar

• hydrolysis (loss of sweet taste) → glycyrrhetic acid and two glucuronic acids

Effects of glycyrrhizin

• Causes sodium and fluid retention

• K depletion

• contraindicated in HTN and cardiac problems

Uses of Glycyrrhiza

• Demulcent

• expectorant

• flavoring agent

• foam enhancer in beer

• used in gums, chocolates, cigarettes

Glycyrrhetic acid

• Hydrolysis product of Glycyrrhiza

• anti-inflammatory

• used in peptic ulcer disease and Addison's disease

Pure Licorice Root (Glycyrrhiza) Extract

ingredient in aromatic Cascara sagrada fluid extract

Glycyrrhiza Fluid Extract

• pharmaceutic aid

• prepared by extracting coarsely ground Licorice root + warm water, and render alkaline by using NH₄OH, qs ad H₂O and Alcohol

Dioscorea (Yam)

• Dried rhizome of Dioscorea species

• Dioscorea spiculiflora (diosgenin abundant); Dioscorea floribunda (best steroid source)

• Constituents:

  • Diosgenin

  • Botogenin

Dioscorea spiculiflora

diosgenin abundant

Dioscorea floribunda

best steroid source

Diosgeni, Botogenin

Constituents of Dioscorea

Diosgenin

• Major constituent of Dioscorea

• produced by hydrolysis of diosin

Ginseng

• Dried roots of Panax ginseng and related species:

  • P. japonicus

  • P. pseudoginseng

  • P. quinquefolius

  • P. trigol

• Constituents:

  • ginsenosides

  • chikusetsusaponin

  • panaxoside

ginsenosides, chikusetsusaponin, panaxoside

Constituents of Ginseng

Uses of ginseng

• Adaptogen

• Carminative

• Demulcent

• Tonic

• Aphrodisiac

• CNS stimulant and inhibitor

Asparagus

• Dried tuberous roots of Asparagus racemosus

• Constituents:

  • shatavarin I-IV

• aglycone: sarsapogenin

Shatavarin I-IV

constituent of Asparagus

Sarsapogenin

aglycone of Asparagus

Uses of asparagus

• Antispasmodic

• aphrodisiac

• demulcent

• diuretic

• refrigerant

• galactagogue

Gotu kola

“Indian pennywort“; “Brahmi”

• Fresh or dried herb of Centella asiatica

• Constituents:

  • asiaticosides (most used)

  • brahmoside

  • brahminoside

  • thankuniside

  • isothankuniside

asiaticosides, brahmoside, brahminoside, thankuniside, isothankuniside

Constituents of Gotu kola

Uses of gotu kola

• Connective tissue development

• wound healing

• Tonic

• improves memory

• increases keratinization (stronger hair and skin)

Cyanophores

• Glycosides that yield:

  • hydrocyanic acid

  • benzaldehyde

  • sugars

• derivatives of mandelonitrile (α-benzaldehyde-cyanohydrin)

• group is represented by Emulsins

  • Amygdalin (Amydalase)

  • Prunasin (found in Prunus serotina)

D-mandelonitrile

aglycone of Cyanophore

L-mandelonitrile

collected from Sambunigrin from plant Sambicus nigra

Amygdalin (Amydalase)

• found in bitter almonds, apricots, cherries, peaches

• Amygdalin + H₂O —amygdalase → Mandelonitrile glucoside + Glucose

• Mandelonitrile glucoside + H₂O — prunase → Mandelonitrile & glucose → Benzaldehyde & Hydrocyanic acid

Sodium picrate test (Quignard test)

(+) Brick-red color for Cyanophore

Almond

• fixed oil from seeds of Prunus amygdalus

• varieties

  • dulcis

  • amara

• amygdalin 2.5-4.0%

• uses:

  • Emollient: almond oil

  • Ingredient in cosmetics

  • Flavoring agent

Wild cherry

• dried bark of Prunus serotina

• constituent:

  • prunasin

• flavored vehicle

• sedative

• expectorant

Apricot

• Pits of Prunus armeniaca

• contains amygdalin

• source of laetrile (Vit. B₁₇)

• releases hydrogen cyanide

Isothiocyanates

• Sulfur-containing compounds

• family Cruciferae

• generally irritant

• used externally

• Group is represented by:

  • Sinigrin

  • Sinalbin

  • Gluconapin (Rapeseed)

Black mustard

• Dried seeds of Brassica nigra

• fixed oil 30-35%

• sinigrin → allyl isothiocyanate

Myrosinase allyl

catalyzes hydrolysis of Sinigrin into Allyl Isothiocyanate (volatile mustard oil)

Uses of black mustard

• Local irritant

• emetic

• rubefacient

• vesicant (blistering of skin)

• condiment

White mustard

• dried seeds of Brassica alba

• fixed oil 20-25%

• sinalbin → acrinyl isothiocyanate (pungent-tasting oil)

Myrosinase acrinyl

catalyzes hydrolysis of Sinalbin into Acrinyl Isothiocyanate

Flavonol (Flavone)

• generally termed as “Flavonoids“

• Yellow pigments

• occur free in nature

• derivatives:

  • flavone

  • flavonol

  • flavonone

  • isoflavone

  • chalcones

Rutin and Hesperidin

• Vitamin P

• permeability factor

• used for capillary bleeding

Constituents of Flavonol

• Rutin + Hesperidin

• Quercitin

• Citrus Bioflavonoids

  • Hesperidin

  • Hesperitin

  • Diosmin

  • Naringen

Chemical tests for Flavonol

• Ammonia test (yellow spot on paper)

• Shinoda test (red colo)

• Vanillin HCl test (pink)

Ginkgo

• Dried leaves of Ginkgo biloba

• ginkgolides A, B, C, J, M

• constituents

  • kaempferol

  • quercetin

  • isorhamnetin

kaempferol, quercetin, isorhamnetin

constituents of ginkgo

Use of ginkgo

• Anti-asthma

• bronchodilator

Salicin

• From bark of Salix purpurea and Salix fragilis

• hydrolysis forms glucose and saligenin

• anti-rheumatic

• oxidized to SALICYLIC ACID

• action closely resembles salicylic acid

Populin

• “Benzoyl salicin”

• found in Salicaceae bark

• contains glucose and benzoyl group