[3.2] GLYCOSIDES (FROM MEVALONATE PATHWAY)

Cardiac Glycosides

• Have specific action on the cardiac tissues; they increase force of systolic contraction

• Inhibit Na+/K+ ATPase, thereby increasing the Ca⁺² inside the heart muscles (positive inotropic effect)

• cardenolide

• bufadienolide

Cardiac Glycosides

• aglycones

CPPP (cyclopentanoperhydrophenanthrene)

Cardiac Glycosides

• has a sterol nucleus

Cardenolide

• Five-member unsaturated lactone

• Usually found in plants

• More common in nature

Bufadienolide / Bufanolide

• Six-member unsaturated lactone 

• Usually found in animals

• or plants, scillaren (from squill)

• digitalis

• convallaria

• apocynum

• adonis

• cactus grandiflorus

• black hellebore

• strophanthus

• squill

• red squill

• rose bay

• yellow oleander

examples of cardiac glycosides

DIGITALIS

narrow therapeutic index

Digitoxin

very lipopholic, longer half-life (168 to 192 hours) 

Digoxin:

more polar, shorter half-life (30 to 40 hours), excreted via kidneys (Lanoxin)

foxglove

Digitalis purpurea

• other name

• Digitoxin

• Gitoxin

• gitaloxin

Digitalis purpurea

• constituent

Grecian foxglove

Digitalis lanata

• other name

• Digoxin

• Deslanoside (desacetyllanatoside)

Digitalis lanata

• constituent

LILY OF THE VALLEY ROOT

CONVALLARIA

• other name

rhizome and root of Convallaria majalis

CONVALLARIA / LILY OF THE VALLEY ROOT

• source

Convallotoxin

CONVALLARIA / LILY OF THE VALLEY ROOT

• constituent

• black indian hemp

• dogbane

• canadian hemp

APOCYNUM

• other name

rhizome and root of Apocynum canabinum

APOCYNUM /  BLACK INDIAN HEMP / DOGBANE / CANADIAN HEMP

• source

Cymarin

APOCYNUM /  BLACK INDIAN HEMP / DOGBANE / CANADIAN HEMP

• constituent

pheasant’s eye

ADONIS

• other name

Adonis vernalis

ADONIS / PHEASANT’S EYE

• source

• Adonitoxin

• Cymarin 

• K-strophantin

ADONIS / PHEASANT’S EYE

• constituent

night blooming cereus

CACTUS GRANDIFLORUS

• other name

Stem of Selenicereus grandiflorus

CACTUS GRANDIFLORUS / NIGHT BLOOMING CEREUS

• source

CHRISTMAS ROSE

BLACK HELLEBORE

• other name

Rhizome and root of Helleborus niger

BLACK HELLEBORE/ CHRISTMAS ROSE

• source

hellebrin

BLACK HELLEBORE/ CHRISTMAS ROSE

• constituent

cardiac stimulant

BLACK HELLEBORE/ CHRISTMAS ROSE

• use

cardiac depressant

green hellebore

Dried ripe seed of Strophanthus kombe 

STROPHANTHUS

• source

• K-Strophanthin 

STROPHANTHUS

• constituent

Preparation of arrow poisons (Africans)

STROPHANTHUS

• use

has oubain (“G-strophanthin”)

Strophanthus gratus:

bulb of the white variety of Urginea maritima

SQUILL / SQUILL BULB

• source

• Scillaren A

SQUILL / SQUILL BULB

• constituent

• Expectorant

• Emetic

• Cardiotonic

• Diuretic

SQUILL / SQUILL BULB

• use

red variety of Urginea maritima

RED SQUILL

• description

Rat poison since they lack the vomiting reflex

RED SQUILL

• use

OLEANDER

ROSE BAY

• other name

Nerium oleander

ROSE BAY/ OLEANDER

• source

apocynaceae

ROSE BAY/ OLEANDER

• family

oleandrin

ROSE BAY/ OLEANDER

• constituent

Oleandrin & Digitalinum verum- causes many cases of poisoning worldwide (some fatal, resulting from suicide)

ROSE BAY/ OLEANDER

• notes

Thevetia peruviana

YELLOW OLEANDER

• source

apocynaceae

YELLOW OLEANDER

• family

thevetin

YELLOW OLEANDER

• constituents

mild myocardial insufficiency

YELLOW OLEANDER

• use

• keller kiliani

• liebermann burhdard

• salkowski

• kedde

Cardiac glycosides identification tests

• presence of deoxy sugar

KELLER KILIANI TEST

• test for

Blue or violet coloration

KELLER KILIANI TEST

• positive result

unsaturated sterol group

LIEBERMANN BURCHARD TEST

• test for

(+) green, Blue

LIEBERMANN BURCHARD TEST

• Conc. sulfuric and acetic anhydride:

pale yellow

LIEBERMANN BURCHARD TEST

• if saturated sterol

sterol

SALKOWSKI’S  TEST

• test for

conc. sulfuric acid

SALKOWSKI’S  TEST

• reagent

 red or violet

SALKOWSKI’S  TEST

• positive result

unsaturated lactone

KEDDE’S TEST

• test for

0.025% digitoxin in methanol

KEDDE’S TEST

• std

 Blue to  violet coloration

KEDDE’S TEST

• positive result

Saponins

• One of the most toxic plant principles (poisonous: “Sapotoxins”) 

• Irritating to the mucus membranes (sternutatory- violent sneezing); toxic to cold-blooded animals (fish poisons)

• Must be administered as IV in humans (can hemolyze RBC)

• Used orally as tonic (improve GIT motility) tea

sapogenin

Saponins

• aglycone

precursors in preparation of steroids

Saponins

• use

• natural/ steroidal

• acid/ triterpenoid

2 TYPES OF SAPONINS

• Derivative of steroids

• Tetracyclic

• Present in monoco

Neutral / Steroidal

• Derivative of triterpenoid

• Pentacyclic

• Present in dicots

Acid / Triterpenoid

• froth test

• liebermann burchard test

• hemolysis test

• capillary tube test

• fehling’s

• in aq solutions

Saponins identification tests

• Foam (honeycomb froth) upon shaking with water

• foam/ lather formation

FROTH TEST

honeycomb froth persisting for 10 minutes above 2cm

FROTH TEST

• positive result

 add aqueous Na₂CO₃ to neutralize the free acids 

FROTH TEST

• if froth is unstable

• Destroy RBC 

• Use blood agar plate

HEMOLYSIS TEST

Gugo solution

HEMOLYSIS TEST

• standard

forms a hemolytical yellow (white ring), zone of hemolysis

HEMOLYSIS TEST

• positive result

Measures fluidity of extract; (+) saponins tend to ↓ surface tension

CAPILLARY TUBE TEST

Formation of a brick red ppt of Cu₂O

FEHLING’S (saponins)

Forms a froth

IN AQUEOUS SOLUTIONS (saponins)

• dioscorea

• sarsaparilla

• ginseng

Steroidal Type of saponins

Dioscorea floribunda (Mexican yam)

Dioscorea spiculiflora- contains diosgenin (glucocorticoid precursor)

DIOSCOREA / YAM

• source

• Botogenin

• Diosgenin

DIOSCOREA / YAM

• constituent

Major precursors of glucocorticoids

DIOSCOREA / YAM

• use

dried root of Smilax aristolochiaefolia

 SARSAPARILLA ROOT

• source

Liliaceae

 SARSAPARILLA ROOT

• family

• Smilagenin

• Sarsasapogenin 

• Parillin

 SARSAPARILLA ROOT

• constituent

Treatment of syphilis, rheumatism, skin diseases, psoriasis, eczema

 SARSAPARILLA ROOT

• use

• Panax ginseng 

• Panax quinquefolium (USA)

GINSENG

• source

aralicaceae

GINSENG

• family

• panaxosides

• ginsenosides

• chikusetsusaponins

GINSENG

• constituents

• Aphrodisiac & adaptogen (resistance to stress) 

• Treatment of anemia, diabetes, gastritis, sexual impotence

GINSENG

• use

• glycyrrhiza

• centella asiatica

• quillaja bark

• gugo

Triterpenoidal Type of saponins

Licorice root

GLYCYRRHIZA

• other name

• Dried roots / stolons of: 

  • Glycyrrhiza glabra (Spanish) 

  • var. glandulifera  (Russian)

  • var. β-violacea (Persian)

GLYCYRRHIZA / LICORICE ROOT

• source

• Glycyrrhyzin (50x sweet as sugar) 

• Genin portion: glycyrrhetic acid

GLYCYRRHIZA / LICORICE ROOT

• constituent

• Expectorant

• flavoring agent 

• mask taste of bitter drugs (paralyze taste buds), increases the foaminess of beer

GLYCYRRHIZA / LICORICE ROOT

• uses

• Anti-inflammatory 

• For peptic ulcer disease

• For addison’s disease

Glycyrrhetic acid

• use

• causes fluid/Na+ retention, K+ depletion

Caution in hypertensive patients

• glycyrrhizin

Dried aerial parts (Apiaceae)

CENTELLA ASIATICA

• source

apiaceae

CENTELLA ASIATICA

• family

• Asiaticoside

• Centelloside

CENTELLA ASIATICA

• constituent

• Diuretic

• Antirheumatic

• Vasodilator

CENTELLA ASIATICA

• use

• Dried inner bark of Quillaja saponaria

 QUILLAJA BARK / SOAP BARK

rosaceae

 QUILLAJA BARK / SOAP BARK

• family