ALDEHYDE GLYCOSIDES

Vanilla

B.O. Vanilla panifolia (Mexican or Bourbon Vanilla)

Vanilla tahitensis (Tahiti vanilla)

Family Orchidaceae.

P.O. Vanilla beans (carefully cured fully grown but unripe fruits).

Production and Commerce: -

The plants are perennial climbing epiphytes which arise from soil roots by means of a fleshy dark green sucklent stem that reaches it self to the trunk and branches of trees by means of aerial rootlets.

The plant is indigenous to Eastern Mexico and cultivated in tropical countries like Mauritius, Sri Lanka, Indonesia, Java and Thailand, where temperature does not fall below 18 C and where humidity is great. Plant is usually propagated by means of cuttings and after 2-3 years reaches the flowering stage and continues to produce fruit for 30-40 years.

The fruits are collected as they are ripened to a yellow colour, 6-10 months after pollination and are cured by dipping them in warm water and repeatedly sweating them between woolen blankets in the sun during the day and packing them in wool covered boxes at night. This requires about two months during which the fruit loses 70-80 % of their original weight and takes on the characteristic colour and odour of the commercial drug. The fruits are then graded, tied into bundles of about 50-75 and sealed in tin container for shipment.

Characteristics: -

Vanilla pods are 15-25 cm in length, 8-10cm in diameter and somewhat flattened.

The surface is longitudinally wrinkled dark brown to violet black in colour and frequently covered with needle like crystals of vanillin. The odour and taste is characteristically aromatic.

Constituents: -

Before curing, green vanilla contain two glycosides

Glucovanillin (vaniloside)

Glucovanillic alcohol

During curing these two compounds are acted upon by an oxidizing and a hydrolyzing enzyme, which occur through out the plant. Glucovanillin upon hydrolysis yield glucose and vanillin where as glucovanillic alcohol yield on hydrolysis glucose and vanillic alcohol.

Vanillic alcohol by oxidation converted into vanillic aldehyde (vanillin).

Vanillin: -

Vanillin consists of fine white or light yellow crystals having aromatic odour and taste. It is slightly soluble in water and glycerin but freely soluble in alcohol chloroform and ether.

Uses: -

It is mainly used as flavouring agent. Vanilla pods are widely used in confectionery and perfumery.

MISCELLANEOUS ISOPRENOIDS

Gentian

B.O. Gentiana lutea

P.U. Dried rhizomes and roots

Family Gentianaceae.

Habitat: -

Plants are perennial herb, 2-3 m in height., these are indigenous to mountains of central and Southern Europe and Turkey. Commercial supply comes cheaply from France and Spain.

Collection: -

Rhizomes and roots are cut from 4-5 years old plants in autumns.

Drying: -

For drying there are two methods

a) Gentian is quickly dried in sun and this quickly dried drug contain bitter principle gentiopicrin or gentiopicroside or gentiomarin. The colour of exude drug is yellowish brown or yellowish orange.

b) In second method of drying the drug is dried slowly firstly in open air and then in shades. During this slow drying process, the drug is allowed to ferment. As a result of fermentation, the drug loses its most of bitter principle and possesses aromatic qualities which are desirable in certain alcoholic beverages or drinks. Slowly dried drug is used as a flavouring agent in preparation of alcoholic drinks. The colour of slow dried drug is reddish brown.

c) The fracture in both the cases is short and even when dry and tough and flexible when most.

Constituents: -

Gentiopicrin is the principle constituent of the quickly dried drug. It also contains gentioside in traces the drug also contain alkaloids, gentianine and gentialutine, pectin, fixed oil, tannin and sugar.

The drug is rich in sugar, which during fermentation is converted to glucose and fructose. If fermentation is allowed to proceed too far the hexose sugars are converted into alcohol and carbondioxide.

Uses: -

Drug, which is dried quickly, is used as bitter tonic in anorexia and dyspepsia.

Quassia

B.O. Picrasma excelsa

Quassia amara.

Family: - Simaroubaceae.

P.U. Dried wood.

Picrasma excelsa is a tall tree of 25m height. It is indigenous to west Indies and commercially known as Jamaica Quassia.

Quassia amara is small spreading shrub about 2-3m in height. It is found in Brazil, Venezuela and Guineas. It is commercially known as Surinam Quassia.

Collection: -

The drug which is wood is collected in the form of chips and small cubes. The wood is dried in oven to prevent the growth of mold (fungi, bacteria).

Fracture is short and even. It is odourless and the taste is bitter.

Constituents: -

The drug contains terpenoid bitter principle Quassin accompanied by smaller amounts of Isoquassin (picrasmin) and Neoquassin. Quassin is a molecular complex of Isoquassin and Neoquassin.

Uses: -

Quassia is used as a bitter tonic

As an insecticide

As an enema for expulsion of threadworms.

CYANOGENIC GLYCOSIDES

(Cyanophore or cyanogenetic glycosides)

These glycosides upon hydrolysis yield HCN. They mostly present in plants of family Rosaceae, Euphorbiaceae, Leguminosae.

Most commonly occurring glycoside is amygdalin from bitter Almonds.

Test: -

HCN evolves over a period of 30min. This changes the colour of paper from yellow to Brick red due to conversion of sod-picroate to sod-isopurpurate. Hydrolysis will be more rapid if we add few drops of H₂SO₄.

Wild Cherry

B.O. Prunus seotina

Family Rosaceae

P.U. Dried (stem) bark

Habitat: -

Plants are indigenous to Eastern United States and Canada. Plants are tall attaining a height of 30m.

Collection: -

The bark is collected in autumn, at which time it is most active carefully dried in sun and kept in airtight container. The colour of bark is short and granular and the colour of fractured surface is reddish Grey. The drug is almost odourless but after moistening with water it evolves a strong odour of bitter almonds i.e. odour of benzaldehyde. Taste of drug is astringent, bitter resembling to that of bitter almonds.

Constituents: -

Active constituents are prunacin, which is formed by partial hydrolysis amygdalin. It is accompanied by enzyme prunase, benzoic acid, trimethyl gallic acid and traces of volatile oil.

Uses: -

Wild cherry possesses tonic, sedative and expectorant properties. It is also used as flavouring agent.

Lactone Glycosides

Cantharide (Animal source). Beatles

Z.O. Cantharis vesicatoria

Family Meloidae

P.U. Dried insects

These are found on certain shrubs or trees of the families caprifoliaceae and oleaceae. These plants are found in central and southern Europe.

Collection: -

These insects are collected in June and July particularly in morning when they are inactive or sluggish plants are shaken with sticks and insects are collected on cloths spreading on the ground. The insects are killed by exposing them to the fumes of carbon disulphide, acetic acid, chloroform or ammonia. Finally the dried insects are stored in airtight containers and few drops of carbon tetrachloride or chloroform are added as a preservative.

Constituents: -

Contheridine 0.1-0.6% is the active constituent, other constituents are fat 12%, fixed oil, uric acid, formic acid and acetic acid.

Uses: -

Counter-irritant

Vesicant.

Rubifacient.

Now a day it is less commonly used.

ANTHRAQUINONE GLYCOSIDES

Anthraquinone glycosides upon hydrolysis yield aglycone, which are di, tri or tetra hydroxy anthraquinone or derivative of these compounds. The free anthraquinone aglycone exhibits little therapeutic activity.

The sugar residue facilitates translocation and absorption of aglycone at the site of action. These compounds are stimulant, cathartic or purgation and they exert their action by increasing the tone of smooth muscle in the wall of large intestine.

Chemical Tests: -

There are two chemical tests for anthraquinone glycosides.

(i) When alkali is added to the powdered drug or to the section of drug red colour produced serve to locate the anthraquinone derivative in the tissue e.g. in the case of carcara bark, when treated with alkali the medullary rays assume red colour.

(ii) Borntrager Test: -

Powdered drug is mixed with ether, which is filtered, and to the filtrate add caustic soda and aqueous ammonia. Red, pink or violet colour produced indicates the presence of anthraquinone glycoside.

Aloe

B.O. Aloe ferox

Aloe barbadensis

Aloe perryi

P.U. Dried juice of leaves

Family Liliaceae.

Habitat: -

These are about 150 species of Aloe.

Most of them are indigenous to Africa and naturalized in Europe. Specie indigenous to Pakistan is Aloe spinosissima.

Habit: -

Plants are herb, shrub or trees. Out of above three Aloe ferox is 7 meter, in height. These plants are xerophytic (characteristic of desert plant). Leaves are pink, fleshy. Strongly cuticularized with prickly margin.

Collection and Drying: -

Leaves are cut from 9-10 months old plant in March and April. They are placed in V-shaped trough is placed on an inclined so that the juice from the leaves may be led into a vessel. This juice is then evaporated to a sufficient degree and then is placed in a metal container and allowed to harden. The odour of drug is characteristic and taste is bitter.

Constituents: -

Aloe contains a no. of anthraquinone glycosides. The principal of which Barbaloin. It is Aloe emodin anthrone c-10 glycoside. So it is an example c-glycoside.

Uses: -

Purgative

Cathartic

Fresh mucilaginous juice of the leaves is used for the treatment of skin burns, skin abrasion and other skin irritations.

Used in compound Benzoin tinctures.

Chemical Tests: -

(i) When 2 ml of Nitric acid is added to 5ml. 1% aq solution of Aloe it gives pale brown colour.

(ii) When few crystals of sod. nitrite along with a little acetic acid is added to 5ml 1% soln. of aloe. It gives brown colouration due to isobarbaloin.

Cascara

B.O. Rhamnus purshiana, Cascara sagrada

Family Rhamnaceae

P.U. Dried bark

Habitat: -

These plants are indigenous to the coast of North America. Commercial supply comes from Washington, California and Oregon. Systematic cultivation is carried in Canada and U.S.A.

Collection: -

Bark is collected from mid April to the end of August. Cut into small pieces and dried in shade to retain colour. Its fracture is short and glandular in outer layers and somewhat fibrous in phloem region. Odour of bark is slight and characteristic. Taste is bitter.

Constituents: -

Primary glycosides i.e. cascaroside A and B and cascaroside C and D. These primary glycosides are more effective.

Cascaroside A and B are related to Barbaloin while cascaroside C and D are related to chrysoloin.

Plants also contain two Aloins.

(i) Barbaloin.

(ii) Chrysoloin.

Chrysophanol, Aloe emodine and emodine in free state are least effective.

Uses Of Cascara: -

Purgative

Cathartic

Veterinary work.

The primary glycosides are more active then aloins while the free anthraquinone have little purgative property. The cascarosides have a sweet and more pleasant taste than the aloins and it is evaluated that aloins and cascarosides should be extracted separately.

Rhubarb

B.O. Rheum emodi

Rheum webbianum (Indian Rhubarb)

Rheum palmatum

Rheum officinale.

Family Ploygonaceae

P.U. Dried rhizome and roots.

Collection: -

Plants are perennial herbs. Underground portion consists of strong vertical rhizomes and roots are collected from 6-9 years old plants and dried artificially or in the sun. the drug has a frim texture, non-shrunken appearance, dried yellow surface, aromatic odour.

Taste is bitter and is astringent.

Constituents: -

Principal constituent is related to Rhein anthrone.

Drug also contain astringent principal i.e. rheotannic acid, gellic acid, glucogallin and other constituents like emodin, aloe-emodin, chrysophonol in free state and their glycosides but in trace amount.

Uses: -

Cathartic, purgative

In addition to this secondary astringent action in indigestion. Due to astringent action this drug is not commonly used.

Chemical Test: -

A little powder is shaken with 10ml of ferric chloride solution mixed with 5ml of hydrochloric acid and heated on a water bath for 10min. after filtration and cooling filtrate is extracted with 10ml of carbon tetrachloride. The organic layer is separated, washed with 5 ml of water and shaken with 5ml of solution of ammonia. Official rhubarb gives a rose pink to cherry red colour.

Senna

B.O. Cassia acutifolia,

Cassia angustifolia.

Family Leguminosae

P.U. Dried leaflets.

Habit: -

Senna plants are shrub, almost 2-meter in height. The leaves are compound and paripinnate.

Collection: -

Senna is collected mainly in September. The branches bearing leaves and pods are collected by cutting the tops of plants about 15cm above the ground.

The stems and fruits (pods) are separated from leaflets by means of seives. This step is separation. Then garbling takes place. Then tossed in shallow trays. The leaflets being lighter remains on the top of the tray while sand particles settle down. Blue green leaflets are best leaves. The branches bearing leaves and pods are dried in the sun.

Constituents: -

Principal constituents are sennoside A, B, C and D.

Uses: -

Senna is an effective purgative for either habitual constipation or occasional use. It lacks astringent after effect of rhubarb.

Saponins

Plant materials containing Saponins have long been used as detergents. For example in Europe root of Saponaria officinalis and in South America the bark of Quilage saponaria.

Diagnostic Characteristics Of Saponins: -

(i) They form colloidal solution with water, which foams upon shaking.

(ii) They have bitter taste and the drugs containing them are usually sternutatory or irritant to mucous membrane.

(iii) They destroy RBCs by haemolysis

(iv) They are toxic especially to cold-blooded animals.

(v) Saponins are extracted from plants by hot water or alcohol and after concentration of extract they are precipitated by ether.

On the basis of chemical nature of aglycone they are classified into two groups.

(i) Steroidol saponins (Tetracyclic triterpenoids)

(ii) Pentacyclic triterpenoids.

Steroidal saponins are of great interest and importance owing to their relation ship with compound like vit. D, cortisone, cardioactive glycosides and sex hormones. They are used as starting material for the synthesis of these compounds. Some species of digitalis and strophanthus contain both cardiac as well as saponin glycosides.

Pentacyclic triterpenoids saponins are abundant in many dicotyledonous families.

Basic Nucleus of Saponins

Glycyrrhiza

B.O. Glycyrrhiza glabra (variety lypica)

Family Leguminosae

P.U. Dried rhizome and roots.

Habit: -

Plants are perennial herbs about 1m in height with imperipinnate compound leaves.

There are three varieties;

(i) Typica

This is commercially known as saponish liquorice. It is cultivated in Spain, Italy, France, Germany, England, U.S.A.

(ii) Glandulifera

This is commercially known as Russian liquorice. It is cultivated in southern and central parts of Russia.

(iii) Violacea

(Due to colour of flower which is violet) It is commercially known as Persian liquorice. It is cultivated in Iran and Iraq.

Characteristics: -

Fracture is short in bark and splintry in wood. Odour is slight but characteristic. Taste is sweet.

Collection: -

Rhizomes and roots are collected from 3-4 years old plants and are air dried. Drying process takes 4-6 months.

In Spain and Turkey a considerable amount of crop is extracted with water. The liquid being purified and evaporated and resulting extract is molded into sticks or other forms.

Constituents: -

The chief constituent is glycyrrhizic acid or glycyrrhizin. It is 150 times as sweet as sugar. Upon hydrolysis yield a glycone, glycyrrhotinic acid or glycyrrhetic acid and two-glucoronic acid. Other constituents are flavonoid, glycoside liquiritin and isoliquiritin. Drug also contains glucose, mannitol and 20% starch.

Uses: -

Liquorice possesses demulcent, laxative and expectorant properties.

Many laxatives contain anthraquinone glycosides and liquorice because liquorice potentiates anthraquinone drugs by sensitizing the intestine.

Glycyrrhiza is also used as Flavouring agent and frequently applied to mask the bitter taste of a drug i.e. Aloe, quinine and Amm. Chloride. Commercially liquorice is added to chew gum, chocolate, candy cigarette.

Currently Glycyrrhiza and sarsaparilla roots both are used in the treatment of peptic ulcer.

Ginseng

(Chinese or oriental ginseng)

B.O. Panax ginseng

P.U. Dried root

Family Araliaceae.

Panax is Greek word (pan-axos means all healing)

Habitat: -

These plants are indigenous to East Asia and cultivated in Korea, China Japan and Russia.

Collection: -

Plants are harvested in summer or autumn, when they are 6-7 years old. The roots are dried in sun after removal of outer layers to produce white ginseng. The red ginseng is obtained by first staining the root in large pressure vessels when they are dried artificially in the over and finally they are sun dried.

Characteristics: -

Fracture is short odour is slightly aromatic. Taste is sweetish, aromatic and mucilaginous and some times slightly bitter.

Constituents: -

Active constituents are complex mixture of saponin which are termed ginsenosides and these are designated as R, Ra, Rb and Rb2 according to Rf values. This is termed by Japanese scientist. Russian scientist gives the name. Panaxosides A, B, C etc. upon hydrolysis Panaxosides yield panaxadiol, panaxatriol and oleanolic acid. First two compounds appear to be artefact (Not naturally occur but appear upon hydrolysis). In addition to these, ginseng also contain sterols, volatile oils, vitamins (B₁.B₂,B₁₂) amino acids, sugars (glucose, fructose, mannitol and sucrose).

Uses: -

Ginseng possesses diuretic, carminative, tonic and stimulant properties. It reportedly reduces blood sugar conc. and acts favourably on metabolism i.e. C.N.S and endocrine secretions. In Chinese and orient medicines, it is employed in treatment of anemia, insomnia, diabetes and gastritis.

Cardioactive or Cardiotonic or Cardiac Glycosides

These glycosides are used therapeutically to strengthen the weakened heart. These thus allow the heart to function more efficiently. These compounds have the ability to increase the force of systolic contraction and shortening the period of systole thus giving the heart more time to rest between contractions.

The therapeutic efficiency of cardiac glycoside depends both upon the chemical nature of aglycone and the type and no. of sugar to which it is attached. The aglycones have steroidal skeleton, which is closely related to Vit-D, bile acid, or sex hormones. The sugar part renders the comp. More soluble and increases the power of fixation of glycoside to heart muscle. Two types of aglycones can be distinguished depending upon whether there is 5-membered or 6-membered lactone is attached

Cardenolide: -

Present in digitalis and strophanthus.

Bufadienolide: -

It is present in white squill.

R = C₆H₁₁O₅ (Cardenolide & Bufadienolide)

R = H in Cardenolide it is Digitoxigenin

Digitalis: -

B.O. :- Digitalis purpurea

Digitalis lanata

FAMILY :- Scrophulariaceae

P.U. :- Dried Leaves

Habitat:-

The plants are biennial or perennial herbs. Digitalis purpurea is indigenous to central and south-eastern Europe. Cultivated in Holland, Germany, France, Australia and U.S.A.

Digitalis lanata is also indigenous to central and south-eastern Europe and cultivated in Holland, U.S.A and Aqua Dor.

Collection & Drying: -

Leaves are collected in June from 2^nd year of growth of plant before opening of flower. Immediately dried artificially at 60⁰C. Dried leaves should not contain more than 5% of moisture.

Digitalis purpurea leaves Digitalis lanata leaves

Ovate or oblong Sessile without petiole

Petiole winged Oblong lanceolate

Dentate margin Linear lanceolate

10 cm Straight margin, entire margin

Upto 40 cm 4 cm – 35 cm

Digitalis Glycosides:-

There are four types of glycosides.

Digitoxigenin

Gitoxigenin

Gitaloxigenin

Digoxigenin

First three types are present in D. purpurea and D. lanata, while the last group of glycosides (Digoxigenin) is present only in D. lanata.

Derivatives of Digitoxigenin

Digitalis purpurea Digitalis lanata

Digitoxin Acetyl Digitoxin

The sugar chain contains This contains three molecules of

3 molecules of digitoxose. digitoxose and one acetyl group.

Purpurea Glycoside A Lanotosie A

This comp. Contains This glycoside contains 3 digitoxose

3 molecules of digitoxose units, one acetyl group,

and one mol. of glucose one glucose molecule.

Digitoxin: -

Digitoxin is a chief constituent of D. purpurea. 1 mg of digitoxin is therapeutically equivalent 1 g of digitalis leaves. It is completely absorbed through G.I.T. Therefore in equivalent or I.V. doses produce essentially same therapeutic effects and the drug has similar onset of action by either route.

Onset of action after I.V. injection is ½ to 2 hours with maximum effect occurring at 8 – 9 hours later. Following oral administration onset occur at 2 – 4 hours with maximum effect occurring at 12 – 24 hours.

The chief disadvantage of Digitoxin is its slow onset of action and prolonged half life, when compared with digoxin which is the active constituent of D. lanata. These constituents (Acetyl Digitoxin lanatoside A) are properly absorbed from G.I.T, so are rarely used.

Derivatives of Gitoxigenin: -

Digitalis purpurea Digitalis lanata

Gitoxin Lanatoside B

This glycoside contains three

digitoxose units, one acetyl group

and one glucose molecule.

Glucogitoxin or Purpurea glycoside B

This contains 3 digitoxose and

one glucose molecule.

Derivatives of Gitaloxigenin: -

Digitalis purpurea Digitalis lanata

Gitaloxin Lanatoside E

This glycoside contains three

digitoxose, one acetyl

and one glucose.

Derivatives of Digoxigenin

All these derivatives are found in D. lanata

1. Digoxin (3-Diqitoxose)

2. Acetyl digoxin (3-diqitoxose+1-Acetyl)

3. lanatoside C (3-diqitoxose+1acetyl+1-glucase)

4. Deslanoside (3-digitoxose+1-glucose)

Digoxin

Digoxin is chief constituent of D. lanata. It is the drug of choice in the treatment of congestive heart failure for following reasons.

1. Rapid onset of Action: -

Onset of action occurs in 5-30min. Following the I.V injection with somewhat longer when drug is administered orally. Maximum, effect occurring at 2-4 hours, depending upon the route through which drug is administered. Drug is completely eliminated with 2-6 days. The biologic half-life of digoxin is 18 hours.

2. It has relatively short duration of action, which minimize the chance of digitalis intoxication.

3. It can be administered orally as well as IV and I. M.

Deslanoside

Deslanoside is a derivative of lanatoside c and is given in left side heart failure. Onset of action occurs at 10-30min. With maximum effect occurring at 2-5 hours.

All digitalis glycosides possess same qualitative effect on heart, peripheral vascular system, C.N.S and GIT. But they vary in potency, rate of absorption, onset of action and rate of elimination.

In sufficient doses they produce nausea and vomiting b/c of their direct effect on CNS. Other toxic effects, which occur slowly, include drowsiness, marked confusion particularly in old age patients’ visual disturbances and disturbances of cardiac rhythm i.e. premature ventricular contraction.

Gitalin

Gitalin is a mixture of

(i) Gitoxin 13-14%

(ii) Gitaloxin 13-14%

(iii) Digitoxin 14-20%

Adulterants Of digitalis

It has three adulterants available in literature.

Verbascum Leaves (Mullein leaves)

These can easily be distinguished from the standard drug by the presence of numerous branched veins.

Leaves of Salvia Spp:-

These can be easily distinguished from shape. The cordate shape and long petiole while digitalis purpurea had rounded shape.

Leaves of Digitalis Thapsi: -

(i) These do not contain glandular trichome D. purpurea contain glandular and non-glandular trichome.

(ii) Colour of D. thapsi leaves is dark yellowish green while that of standard drug is grayish green.

(iii) Prisms of Ca-oxalate are present in D. thapsi while absent in case of standard drug.

Strophanthus

B.O. Strophanthus kombe

Strophanthus hispidus.

Family Apocynaceae

P.U. Dried ripened seeds.

Habitat

Strophanthus kombe is indigenous to forests of eastern Africa and yield a commercial variety of seeds known as green strophanthus. Strophanthus hispidus is indigenous to the forest of West Africa and yield a commercial variety of seeds known as brown seeds strophanthus.

Collection and Drying

The fruits are collected in Tune and July when they are fully ripened. Epicarp and mesocarp are removed and seeds are dried in endocarp.

Green Strophanthus is considered to be the best since it contains high conc. of strophanthus.

The seeds of St. kombe are lanceolated while that of St. hispidus is spindle shaped.

Constituents: -

The endosperm of seeds contains in addition to aleurone grains, strophanthin, fixed oil 30%.

Other constituents are two nitrogenous base trigonelline and choline. The seeds also contain resin and mucilages. Seeds have a spike odour, very bitter taste. The active constituent Strophanthin is soluble in water and dil. Alcohol. It is insoluble in chloroform ether and benzene.

Uses

Cardiotonic

Diuretic

Structure: -

Histochemical test: -

Section of seeds + drops of 67% H₂SO₄ the cells of endosperm containing strophanthine will resume green colour i.e. in the case of St. kombe and St. hispidus.

White Squill

It consists of white flesh inner scales of the bulb of white variety of Urginea maritima.

Family Liliaceae

Habitat These are found in France, Greece, Spain, Algeria, and Morocco.

Collection and Drying: -

The bulbs are collected late in August the outer membranous scales are removed. The inner fleshly scales are cut into small pieces and dried artificially, or in sun. the drug has slight odour and bitter taste.

Constituents: -

Squill contains a principal glycoside Scillaren that on hydrolysis yields aglycone; scillarenin and sugars.

Structure: -

Uses: -

Cardioactive

Diuretic

Expectorant

Emetic