Cardioactive Glycosides

CARDIOACTIVE PLANTS

SUBMITTED TO: DR IRSHAD AHMAD

SB

Presented by: SAHARISH KHALIQ

• Heart disease and stroke are the principle

components of cardiovascular disease.

• Heart disease are the leading causes of

death ,often thought to primarily affect men

and older people .

• However cardiovascular disease also a major

killer of women and more than half of all

cardiovascular disease deaths each year occur

among women.

RISK FACTORS FOR CARDIOVASCULAR DISEASES

• High Blood Pressure

• High Blood Cholesterol

• Tobacco Use

• Physical inactivity

• Poor nutrition

• Obesity

• Diabetes

NATURAL PLANTS

1. Cardioactive glycosides

2. Atrichoke

3. Garlic

4. Ginkgo

5. Tea

GLYCOSIDES

A substance which on hydrolysis yields a

sugar part & non-sugar substances

(genin/aglycone) linked by glycosidic bond

e.g. Cardiac glycosides, flavonoid glycosides,

phenolic glycosides etc.

Pharmacologic activity is due to genin part.

Glycoside structure

2 types of genin are distinguished based on the

structure of the lactone ring.

1) Cardenolides or cardiac active glycosides 5-

membered ring medicinally more significant

2) Bufanolides or Bufadienolides 6-membere ring.

1)CARDIOACTIVE GLYCOSIDES

• A small group of plant glycosides act directly

on the heart muscle.

• Cardenolides are steroidal glycosides that

exert a slowing and strengthening effect on

the failing cardiac muscle.

PHARMACOLOGICAL ACTION OF CARDIAC GLYCOSIDES

• Effectiveness depends on both the aglycones and the sugar attachments.Medicinal action depends on the aglycone.

• But the sugars make the compound more soluble in increases the fixation of the glycoside to the heart muscle. The overall action of Digitalis glycosides is complicated by the number of different effects produced.

• The exact mode of action on the myocardial muscle still needs investigation.

MECHANISM OF ACTION OF CARDIAC GLYCOSIDES

• The mechanism whereby cardiac glycosides cause a positive inotropic effect and electrophysiologic changes is still not completely clear.

• Several mechanisms have been proposed, but the most widely accepted involves the ability of cardiac glycosides to inhibit the membrane bound Na+-K+-ATPase pump responsible for Na+-K+ exchange..

• The process of membrane depolarization / repolarization is

controlled by the movement of three cations, Na+, Ca+2, and

K+, in and out of the cell. At the resting stage, the

concentration of Na+ is high on the outside.

• On membrane depolarization sodium fluxes-in leading to

an immediate elevation of the action potential. Elevated

intracellular Na+ triggers the influx of free of Ca++ that

occurs more slowly. The higher intracellular [Ca++] results

in the efflux of K+.

• The re establishment of the action potential occurs later by the

reverse of the Na+-K+ exchange. The Na+ / K+ exchange requires

energy which is provided by an enzyme Na+-K+-ATPase. Cardiac

glycosides are proposed to inhibit this enzyme with a net result of

reduced sodium exchange with potassium that leaves increased

intracellular Na+.

• This results in increased intracellular [Ca++]. Elevated intracellular

calcium concentration triggers a series of intracellular biochemical

events that ultimately result in an increase in the force of the

myocardial contraction or a positive inotropic effect.

a)Digitalis purpurea:

• Botanical origin: . Digitalis purpurea (Purple Foxglove)• Family: (Scrophulariaceae)• Part used: Leaves It is required to contain at least 0.3% of total cardenolides calculated asDigitoxin.

Digitalis purpurea - Collection

• There is a general belief that the pharmacological activity of the leaves increase during the course of the day to reach a maximum in the early afternoon (when they should be harvested)

• This was supported by assays done in 1956 which showed a greater activity of the leaves at noon than 8am, irrespective of if the leaves where in the sun or shade.

• However, other work indicates that there is no glycosidal content variation of the leaves when measured at 3-hour intervals.

ACTIVE CONSTITUENTS• Glycosides

–purpurea glycoside A

–purpurea glycoside B (2 main constituents in

fresh leaf)

• Glucogitaloxin

On drying: enzyme degradation takes place

loss of the terminal glucose. Produces

Digitoxin,Gitoxin,Gitaloxin

Also contains anthraquinone glycosides,

Saponins, Flavonoids

Poor storage leads to further hydrolysis and

complete loss of action

b)Digitalis lanata – Woolly Foxglove

• It gets its name due to the texture of the leaves.

• Botanical origin: Digitalis lanata• Family: (Scrophulariaceae)• Part used: Leaves• Active constituents: Lanatoside A,B,C giving rise to digoxin,Digitoxin

USES:Digitalis lanata contains a powerful cardiac glycoside that may be used by patients with heart conditions

MEDICINAL USES:• Digoxin (Digitalin) is a drug that is extracted

from Digitalis lanata. It is used to treat some heart conditions such as atrial fibrillation.

• It slows atrioventricular conduction so that the heartbeat slows down and very slightly increases contraction power (positive inotropic effect).

• Because of the improved circulation in congestive heart failure caused by fast atrial fibrillation, the kidneys can function better, which stimulates the flow of urine, which lowers the volume of the blood and lessens the load on the heart.

c) CONVALARIA

Botanical origin: Convalaria majalis Family: LiliaceaePart Used: Leaf, flower Constituents: Cardio glycosides different types convallatoxin, convallatoxol, convallamarin, convallarin, and convallaric acid),saponins, flavonoids, asparagin.

Has similar but milder cardiac effects to Digitalis but without the toxic buildup. Exerts a positive inotropic and negative chronotropic action on the heart and is specific for congestive heart failure with edema. It is most indicated in bradycardic and/or arrhythmic forms of heart failure, although tachycardic hearts also respond to this herb. Mitral stenosis, mitral regurgitation are especially good indications for the use of this plan.

Convallatoxin

d)STROPHANTHUS

• Greek word strophos (a twisted cord or rope) anthos (a flower)

• Botanical origin: Strophanthus kombe • Family: Apocynaceae• Part used: Dried ripe seeds

Active Constituents:• Strophanthoside, strophanthin,

• Cymarin,Alkaloid,Fixed oil,

resin ,mucilage

• USES:The sole official use of

Strophanthus in medicine is for its

influence on the circulation,

especially in cases of chronic

heart weakness.

STROPHANTHIN

Bufadienolides:

• Less commonly distributed in nature than cardenolides

• Occur in some Liliaceae and Ranunculaceae Species.

• Therapeutically there is not much value as the therapeutic index is low and production of side effects high

• Squill, used as an expectorant• Widely used in the treatment of cough

a)SQUILL

• Botanical origin: Urginea maritima • Family: Liliaceae,known as white squill• Part used: dried sliced bulb • Constituents: Scillitoxin,• Scillipicrin • Scillin,• Calcium oxalate

USES:• Mainly used in cough treatment.• Cardiotonic• In the treatment of cardiac dropsy, Squill is

frequently combined with digitalis.

2) ARTICHOKE• Botanical origin: Cynara cardunculus OR Cynara scolymus

• Family: Asteraceae• Part used: flower buds before the flowers come into bloom.

• Constituent: Cynarine, apigenin and luteolin.

Mechanism of action:Aid in heart disease treatment that are induced by

high cholesterol level.It inhibit cholesterol synthesis.• In vitro studies on cultured hepatocytes, for

instance ,suggested that ALE inhibits the incorporation of 14C-labelled acetate into the nonsaponifiable lipid fraction and thus reduce cholesterol biosynthesis

CYNARINE

USES:• Used in cornory heart diseases.• digestive disorders• Like irritable bowel syndrome, • Crohn's disease

3) Garlic:• Botanical origin: Allium sativum

• Family: Lilliaceae

• Part used: Bulb

• Constituents: Allin,Allicin

• Sulphur compounds,volatile &

• some essential oils.

MECHANISM OF ACTION

• Garlic extract improves circulation and blood properties by preventing lipid peroxidation and hemolysis in oxidized erythrocytes .

• It favours vasoldilation by increasing the effect of nitric acid,vasodilator.Contribute arginine which act as a precursor for NO prep when acted by nitrous oxide synthase.

• It lessen the activity of ACE enzyme,favoring vasodilation,reducing blood pressure and heart associated diseases.

Uses:• It can be used in high blood pressure,

high cholesterol, coronary heart disease,heart attack, and “hardening of the arteries” (atherosclerosis).

• Garlic actually may be effective in slowing the development of atherosclerosis and seems to be able to modestly reduce blood pressure.

• Reduce high blood pressure and cholesterol• Prevention of certain cancers (stomach and

colon cancer)

4) GINKGO:

• Botanical origin: Ginkgo biloba• Family: Ginkgoaceae• Part used: Leaves• Constituents: Proantho-cyanidins, ginkgolic acid, ascorbic acid, carotenoids, many other flavonoids and TerpeneUses: Heart diseases

Uses: Heart diseases

CHLOROGENIC ACID

Mechanism of action:

• Acts by releasing vasodilators, specifically nitric oxide and PGI2, which allows increased blood flow throughout the circulatory system and therefore increase oxygen and nutrient delivery to the tissues.

• Allows increased microcirculation in the capillaries (i.e. better exchange on the cellular level)

5)TEA

• Botanical origin: Camellia sinensis• Famiy: Theaceae • Part used: Dried leaves • Constituents:Tea contains theanine, Proteins,Caffeine,vitamin C,Carbohydrates,Polysaccharides& lipids,flavonoids including catechin

Theanine:

Catechin:

CAFFEINE

MECHANISM OF ACTION

• In endothelial cells, it increases intracellular calcium stimulating the production of nitric oxide through the expression of the endothelial nitric oxide synthase enzyme. Nitric oxide is diffused to the vascular smooth muscle cell to produce vasodilation.

• In vascular smooth muscle cells its effect is predominantly a competitive inhibition of phosphodiesterase, producing an accumulation of cAMP and vasodilation.

• In addition, it blocks the adenosine receptors present in the vascular tissue to produce vasoconstriction.

Black and green tea:

• Depending on weather the tea harvests (leaves) undergo fermentation or not, respectively, makes tea to be black or green.

• The black tea is orange to dark-red in colour which sometimes gives scented infusion. It contains low level of Catechins (4.0 g/100g) and high level of Theaflavins (0.94 g/100g).

• The green tea, on the other hand, gives insipid beverage with yellowish colour and it contains highest level of Catechins (14.2 g/100g) and zero Theaflavins.

Uses:

• It is used as anti-oxidant.

• It reduces cholesterol and triglycerides.

• Inappropriate diets and smoking generates high levels of

reactive oxygen species, like peroxides in humans, which are

the basic cause of heart disease. Tea polyphenols have strong

scavenging properties for free oxygen radicals, thus lowering

the risk of heart ailment.

THANK YOU