Cardioactive Glycosides

1. CARDIOACTIVE PLANTS SUBMITTED TO: DR IRSHAD AHMAD SB Presented by: SAHARISH KHALIQ

2. 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.

3. RISK FACTORS FOR CARDIOVASCULAR DISEASES High Blood Pressure High Blood Cholesterol Tobacco Use Physical inactivity Poor nutrition Obesity Diabetes

4. NATURAL PLANTS C ardioactive glycosides Atrichoke Garlic Ginkgo Tea

5. 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.

6. Glycoside structure 2 types of genin are distinguished based on the structure of the lactone ring. 1) C ardenolides or cardiac active glycosides 5-membered ring medicinally more significant 2 ) B ufanolides or Bufadienolides 6-membere ring.

7. 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.

8. 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.

9. 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..

10. 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 + .

11. 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.

12. 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 as Digitoxin.

13. 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 .

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

15. ACTIVE CONSTITUENTS G lycosides purpurea glycoside A purpurea glycoside B (2 main constituents in fresh leaf) Glucogitaloxin

16. 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

17. 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

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

19. 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.

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

21. 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

22. d)STROPHANTHUS Greek word strophos ( a twisted cord or rope) anthos (a flower ) Botanical origin : Strophanthus kombe Family : Apocynaceae Part used: Dried ripe seeds

23. 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

24. 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

25. a)SQUILL Botanical origin : Urginea maritima Family: Liliaceae , known as white squill Part used: dried sliced bulb Constituents: Scillitoxin, Scillipicrin Scillin, Calcium oxalate

26. USES: Mainly used in cough treatment. Cardiotonic In the treatment of cardiac dropsy, Squill is frequently combined with digitalis.

27. 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.

28. 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

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

30. 3 ) Garlic: Botanical origin : Allium sativum Family: Lilliaceae Part used: Bulb Constituents: Allin,Allicin Sulphur compounds,volatile & some essential oils.

31. 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.

32. 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)

33. 4) GINKGO: Botanical origin: Ginkgo biloba Family: Ginkgoaceae Part used: Leaves Constituents: Proantho - cyanidins, ginkgolic acid, ascorbic acid, carotenoids, many other flavonoids and Terpene Uses: Heart diseases

34. Uses: Heart diseases CHLOROGENIC ACID

35. 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)

36. 5)TEA Botanical origin: Camellia sinensis Famiy: Theaceae Part used: D ried leaves Constituents:Tea contains theanine, Proteins,Caffeine, vitamin C,Carbohydrates, Polysaccharides& lipids, flavonoids including catechin

37. Theanine :

38. Catechin : CAFFEINE

39. 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.

40. 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.

41. 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.

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