Plant steroids.pptx

plant steriods

1. Plant Steroides 1

2. STEROIDS Steroids may be defined as: “Any of numerous naturally occurring or synthetic fat soluble organic compounds having as a basis 14 Carbon atoms arranged in four rings. They include sterols, bile acids, adrenal and sex hormones, certain natural drugs such as Digitalis compounds and precursors of certain vitamins .” “A steroid is any compound that contains a cyclopentanoperhydrophenanthrene nucleus.” 2

3. The diversity of biologic activities of steroids includes; Plant steroids: Plant steroids are natural products which influence the development and control of the reproductive tract in humans( estradiol , progesterone, testosterone) The molting of insects ( ecdysone ) The induction of sexual reproduction in aquatic fungi. 3

4. In additions, steroids contribute to a wide range of therapeutic applications, such as; Cardiotonics ( digitoxin ) Vitamin D precursors ( ergosterol ) Oral contraceptive agents (semisynthetic estrogens and progestins ) Anti-inflammatory agents (corticosteroids) Anabolic agents (androgens) 4

5. Plant Sterols : Sterols, also known as steroid alcohols, are a subgroup of the steroids Steroidal alcohols C 27 – C 29 are present in the lipid fraction of many tissues. These are solids therefore named as sterols. The most widely occurring sterol is cholesterol. It has been identified in algae, fungi, bacteria, ferns, animals and higher plants. 5

6. Different Plant Steroids: Cardiac Glycosides: Some steroids present in nature are characterized by highly specific and powerful actions that they exert on cardiac muscles. These steroids occur as glycosides with sugars attached at position 3 of steroid nucleus. For example: Gitoxigenin . Gitaloxigenin . Digitoxigenin . Digoxigenin . 6

7. Steroidal Aglycones or Genins : The steroidal aglycones or genins are of two types: Cardenolides : The more prevalent in nature are t he cardenolides which are C 23 steroids. For example Digitalis, strophanthus . Bufadienolides : The bufadenolides are C 24 homologs of Cardenolides . For example White squill and Red squill. 7

8. Bufadienolide . Cardenolide 8

9. Digitalis: Botanical origin: Digitalis purpurea Part used: dried leaves. Family: Scrophulariaceae Constituents: The drug contains a large number of steroidal glycosides ( neaely 30) of which the most important from medicinal point of view are Digitoxin , Gitoxin , Gitaloxin . Uses: Digitalis is used in the form of tablets or capsules to treat congestive heart failure, supraventricular tachycardia, atrial flutter and atrial fibrillation. 9

10. Digitalis lanata : Constituents : Nearly 70 glycosides have been detected from digitalis lanata . They conatain derivatives of five different aglycones three of which i.e digitoxigenin , gitoxigenin , and gitaloxigenin also occur in digitalis purpurea . The two other derivatives not found in digitalis purpurea are digoxin and Lanatoside C. 10

11. Oubain : Botanical Origin : Strophanthus gratus Part used: Dried ripe seeds . Family: Apocynaceae Constituents: It contains Oubain which is a glycoside of oubagenin and rhamnose . Uses: Most rapidly occurring cardiac glycoside used in the treatment of cardiac failure 11

12. Squill : Botanical origin: Urginea maritime Part used: Dried fleshy inner scales of bulb. Family: Liliaceae Constituents: Scillaren A , glucoscillaren A, Proscillaridin A, Rhamnose , Scillarenin Uses: Used as expectorant, diuretic, cardiotonic , rodenticide and emetic property 12

13. Steroidal saponins : Steroidal saponins are of great pharmaceutical importance because of their relationship to compounds such as sex hormones , cortisone, diuretic steroids, vitamin D and cardiac glycosides. Some are used as starting materials for the synthesis of these compounds . The glycosides which when shaken with water, produce persistent froth, are called saponin glycosides, Aglycone part of a saponin glycoside is called ‘ sapogenin ’ 13

14. Example: Ginseng Steroidal Alkaloids: Steroidal alkaloids arise by inclusion of a basic nitrogen at some point in the steroid molecule. Example: Veratrums : Steroidal alkaloidal glycosides: They are particularly abundant in the families solanaceae and liliaceae . Like saponins they have hemolytic properties. Examples are : Solanin ( potato; solanum tuberosum ). Tomatin ( tomato; lycopersicon esculentum ) Rubijervine . ( veratrum spp.) 14

15. Other steroids: Withanolides : This class of steroidal lactones involves an ergostane type framework in which C-22 and C-26 are appropriately oxidize to form a δ -lactone ring. In 1968, Israeli workers determined the structure of a constituent lactone ( withaferin A) of the plant Uses : Sedatives, hypnotics, antiseptics, antimitotic and antitumor agents 15

16. Botanical origin: Withania somnifera Family: Solnaceae Constituents: The constituents have been divided into 9 groups of which the withanolides are of wide therapeutic importance Since then many more compounds of this now large class, have been characterized. 9 groups; Withanolides , Withaphysalins , Physalins , Nicandrenones , Jaborols , Ixocarpalactones , Perulactones , Acnistins and Miscellaneous withasteroids 16

17. Ecdysones : Ecdysones or insect molting hormones are substances which stimulate the transformation of larvae into an adult. Ecdysone was first isolated from silk-worm pupae . Only a few such compounds have been isolated from arthropods, but in plants they occur in much greater variety and abundance Ecdysterone is also an example which has been isolated from both plant and insect sources . Whether a plant-insect relationship exists with regard to this substance and whether such compounds have a function in the plant, is at present not known 17

18. It is perhaps significant, however, that insects do not themselves biosynthesize steroids de novo and rely on plant materials for suitable precursors In the plant, cholesterol is a precursor of insect molting hormones, and in one morphological group of Helleborus they are formed together with bufadienolides and saponins Cucurbitacins : They occur in Cucurbitaceae , Euphorbiaceae and Cruciferae Family. These tetracyclic triterpenoids are of interest because of their cytotoxic and antitumour properties . Cucurbitacin may occur in the glucosidic form and are hydlolysed by the enzyme elaterase . 18

19. Cycloartanes : The ring closure of squalene 2,3-oxide yields cycloartenol as an intermediate in plant sterol biosynthesis. However, these phytosterols are also found in the free state in a wide range of plants. Medicinal examples include the neem and olive plants , Euphorbio spp., Hypericum , the woody nightshade and a number of members of the Cucurbitaceae 19

20. Steroid hormones: A steroid hormone is a steroid that acts as a hormone Sex hormones: Produced primarily in the gonads Mediate the growth, development, maintenance, and function of the reproductive tract and the accessory sex organs These hormones fall into three chemically and physiologically distinct categories; Estrogens and Progestins . These regulate the various functions of female reproductive tract. Androgens . S timulate the development of male reproductive organs 20

21. 2. Adrenocortical hormones: Produced by outer cortical portion of the adrenal glands Divided into two classes, depending on their biological activity; Mineralocorticoids . Principally affect the excretion of fluid and electrolytes, with a subsequent sodium retention Glucocorticoids. They regulate the metabolism of proteins and carbohydrates. At the present time, the principal source of steroid chemical nucleus used in drug industry is the plant kingdom. 21

22. Glucocorticoids, Affect intermediary metabolism Estrogens : Estradiol, Estriol , Estrone Progesterone : Progesterone Androgens : Testosterone , Dihydrotestosterone (DHT), Androstenedione Mineralocorticoids : Aldosterone, Deoxycorticosterone Glucocorticoids : Cortisone, Hydrocortisone 22

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24. Commercial production of steroids The steroid hormones and their semisynthetic analogues represent a multi-million-dollar annual business for the American drug industry In the past, the source of steroid hormones was from the gonads and adrenal glands of animals The amount of hormones present in these glands was extremely small; consequently, it was not practical to use the pure hormone in the therapy At the present time, the principal source of the steroid chemical nucleus used in the drug industry is the plant kingdom 24

25. These nucleuses are modified by chemical or biological methods to produce steroid hormones For example ; Diosgenin (a sapogenins ) Isolated from various species of Dioscorea → Progesterone Stigmasterol Isolated from Glycine max (Fam. Leguminosae ) → Hydrocortisone 25

26. Plant steroids used for the synthesis of steroid Hormones Diosgenin : It is a steroidal sapogenin used to prepare progesterone. Stigmasterol : It is converted chemically to progesterone which is then chemically converted to cortisone. Cortisone is dehydrogenated to form prednisolone . Desoxycorticosterone that is a mineralocorticoid is synthesized from stigmasterol . 26

27. Cholesterol: Cholesterol is used to prepare testosterone which is the true testis hormone. It is used to treat various reproductive dysfunctions in both males and females. 27

28. Bile Acids : Bile acids are steroid acids, found predominantly in the bile of mammals and other vertebrates The primary bile acids formed in the liver of man are; Cholic acid Chenodeoxycholic acid Generally, the bile acids do not exist in the free state, but are conjugated through a peptide bond to either glycine or taurine 28

29. Biosynthesis: The precursor of the bile acids is cholesterol, which is either present in the diet or synthesized in the liver cells during the course of fat metabolism The cholesterol is first converted to cholic acid and chenodeoxycholic acid in about equal quantities These acids in turn combine principally with glycine and to a lesser extent with taurine to form glyco - and tauroconjugated bile acids Bile salts are the sodium salts of the conjugated acids These salts are then secreted in the bile; therefore, they are referred to as bile acids/bile salts 29

30. About 94 % of the bile salts are reabsorbed into the blood from the small intestine (enterohepatic circulation) The liver cells synthesize about 6 grams of bile salts daily Deoxycholic acid and lithocholic acid are also found in substantial amounts in mammalian bile They are not formed in the liver They are produced in the intestinal tract by the action of microorganisms on; Cholic acid to form deoxycholic acid Chenodeoxycholic acid to form lithocholic acid Their presence in the bile is attributed to enterohepatic circulation 30

31. Functions of bile salts The bile and bile salts play three important roles in our body 1. Emulsifying or Detergent action Bile salts have a detergent action on the fat particles in the food This decreases the surface tension of the particles and allows agitation in the intestinal tract to break the fat globules into minute sizes 2. Excretion of waste products Bile serves as a means for excretion of several important waste products from the blood These include especially bilirubin and excesses of cholesterol 31

32. 3 . Micelles formation (help in the absorption) Bile salts help in the absorption of fatty acids, monoglycerides , cholesterol, and other lipids from the intestinal tract They do this by forming very small physical complexes with these lipids; the complexes are called micelles These micelles are semi-soluble in the chyme because of the electrical charges of the bile salts The intestinal lipids are “ferried” in this form to the intestinal mucosa, where they are then absorbed into the blood Without the presence of bile salts in the intestinal tract, up to 40 % of the ingested fats are lost into the feces, and the person often develops a metabolic deficit because of this nutrient loss 32

33. Ox bile extract Fresh ox bile is partially evaporated Mucous and albuminous matter is precipitated with alcohol, Filtered , washed and evaporated to dryness at a temperature not exceeding 80 °C It contains an amount of the sodium salts of glycocholic acid and taurocholic acid equivalent to not less than 45% of cholic acid It is used therapeutically as a choleretic (increase the volume of secretion of bile from the liver) The use of chenodeoxycholic acid to dissolve gallstones is a significant advance in drug therapy, But it is still in investigational stages 33

34. Therapeutic uses of Steroids : 1.Treatment of Heart Diseases: i. Improved Circulation: They increase the force of systolic contraction. Increased cardiac output causes decreased heart rate. The improved circulation tends to improve renal secretion which relieves the edema often associated with heart failure . ii. Congestive heart failure: Digitalis preparations, Lanatoside C, Gitalin and Digoxin are used for the treatment of congestive heart failure. Digoxin has a greater margin of safety than other drugs. Oubain is the most rapidly acting cardiac glycoside for the treatment of cardiac failure. 34

35. iii.Cardiotonic : Digitoxin is a cardiotonic that increases the tone of cardiac muscles and thus causes the heart to empty more effectively. Deslanoside is also a cardiotonic and is used to attain rapid initial dosing by parenteral administration . Strophanthus also acts as cardiotonic . iv.Cardiac Tachyarrhythmia: Digoxin is used for the treatment of Cardiac arrhythmias. v.Cardiac depression: veratrum viride (green hellebore) acts as cardiac depressant 35

36. vi.Hypercholestrolemia : Plant sterols lower the LDL cholesterol levels in hypercholestrolemic , diabetic and healthy human volunteers. They lower LDL levels without affecting HDL level. They exert hypercholestrolemic effects possibly by interfering with uptake of both dietry and biliary cholesterol from intestinal tract. They are now used as first line therapy as well as adjunctive therapy in patients on statin therapy. vii.Emetics : Red squill contains cardiac glycosides induces the vomiting reflex and reduces the life threatening aspects of toxic menifestations . 36

37. viii.Expectorants : Squill also acts as expectorant. ix. Sedative and Hypnotics: Withanolides act as sedatives and hypnotics. x.Antitumors : Some withanolides are cell differentiation inducers whereas others act as antimitotics . Cucurbitacins have cytotoxic and antitumor properties. 37

38. xi.Hypotensives : veratrum viride contains alkaloids that are responsible for their hypotensive activity. xii.Insecticides : veratrum spp and cevadilla seeds act as insecticides . xiii.Antiseptics : Withanolides act as antiseptics. xiv.Antiamoebics : Kurchi or Hollarhena bark is used for amoebic dysentery. 38

39. xv.Rheumatide Arthritis : Natural cortisones are used to treat rheumatide arthritis. Glucocorticoids are also used for the treatment of rheumatism. xvi.Electrolyte balance: Deoxycorticosterone synthesized from stigmasterol is used to restore a balance of sodium and potassium in body fluids and restore kidney function in cortical deficiency. 39

40. Other therapeutic applications of plant sterols : They are also used for: Treating gall stones. Boosting immune system. Treating common cold and flu. Treating asthma. Relieving menopausal symptoms. Helping with hair loss or baldness. Relieving enlarged prostate symptoms. 40