2. Glycosides are compounds that yield one or more sugars upon
hydrolysis. The more frequently occurring sugar is β-D-glucose
although rhamnose, digitoxose, cymarose, and other sugars are found
as components of glycosides. if the sugar formed is glucose, the
substance may be called as a glucoside.
Chemically the glycosides are acetals in which the hydroxyl of sugar
is condensed with a hydroxyl group of the non-sugar component and
the secondary hydroxyl is condensed within the sugar molecule itself
to form an oxide ring. More simply they may be considered as sugar
ethers. The nonsugar component is known as the aglycone and the
sugar component is known as glycone. Both ∞ and β glycoside are
possible. Only beta forms are found in the plants
3.
4. From the biological point of view, glycosides play an important
role in the life of the plant involving its regulatory, protective,
and sanitary functions. Some of the most valuable cardiac
specifics are glycosides from Digitalis, Strophanthus, Squill,
Apocynum. Laxative drugs such as Senna, Aloe, Rhubarb,
Cascara sagrada and Frangula contain anthraquinone
glycosides. Sinigrin, a glycoside from Black Mustard, yields
allyl isothiocyanate, a powerful local irritant. Many of the
glycosides, such as strophanthin, salicin and digitoxin have been
isolated, purified and used in this form as medicinals.
5. PROPERTIES OF GLYCOSIDES
• Colorless, solid, amorphous, nonvolatile (flavonoid- yellow,
anthraquinone-red or orange.
•Give positive reaction with Molisch's and Fehling's solution test
(after hydrolysis).
•They are water soluble compounds, insoluble in organic solvents
•Most of them have bitter taste
(except: populin, glycyrrhizin,).
•Odorless except saponin (glycyrrhizin).
6. ISOLATION OF GLYCOSIDES
Stas-Otto Method
• Drug containing glycoside is finely powdered is extracted by continuous
hot percolation using soxhlet apparatus with alcohol as solvent.
• Various enzymes are deactivated due to heating.
• Thermolabile glycosides are extracted below 45 ◦C
• Extract then treated with lead acetate to precipitate tannins and thus
eliminate non-glycosidal impurities. Excess lead acetate is precipitated
as lead sulphide by passing hydrogen sulphide gas through solution.
• Extract is filtered, concentrated to get crude glycosides.
• From crude extract, the glycosides are obtained in pure form by making
use of processes like fractional solubility, fractional crystallization and
chromatographic techniques such as preparative thin layer and column
chromatography.
• Characterization of isolated purified compounds is done by IR, UV,
visible, NMR and mass spectrometry and elemental analysis.
7. CLASSIFICATION OF GLYCOSIDES
Classification of glycosides on the basis of the linkage between
glycone and aglycone part
•O-glycosides : in these glycosides the sugar part is linked with
alcoholic or phenolic hydroxyl or carboxyl group.
•S-glycosides : in these glycosides the sugar attached to a Sulfur
atom of aglycone such as in sinigrin.
•N-glycosides : in these glycosides the sugar linked with Nitrogen
atom of (-NH2,-NH-) amino group of aglycone like in nucleosides
DNA,RNA
C-glycosides : in these glycosides the sugar linked (condensed)
directly to Carbon atom of aglycone like in aloin.
8. On the basis of the chemical nature of aglycone the glycosides are
classified as follows:
9. CARDIOACTIVE GLYCOSIDES
The members of this group are characterized by their highly specific action
on cardiac muscle, increasing tone, excitability, and contractility. The
aglycones of these glycosides are sometimes designated as the cardiac
genins.
The cardioactive glycosides contain a polysaccharide chain, a steroid
portion and a lactone ring.
10. Action of Cardiac Glycosides
• In medicinal doses, cardiac glycosides increase the
contractions of heart and the force of the heart beat .
• Increases cardiac output.
• Improved circulation, decreases edema, and increases
kidney output.
• Most effective for congestive heart failure.
• Toxic doses cause arrhythmias or even cardiac arrest –
fine line between medicinal and toxic.
11. What is important for activity of Cardioactive Glycosides :-
1) The presence of hydroxyl group in C14 position makes the glycoside
very active and gives rapid action in the body, but if we change it to (H+)
group the drug will be inactive or less active.
2) The presence of Alpha & Beta unsaturated lactone ring increases the
activity of Cardioactive glycoside but if we make it saturated the
Cardioactive glycoside will lose its activity.
3) The sugar part increases absorption and distribution of Cardioactive
glycoside in the body
S.P : Glucose, Rhamnose, Cymarose, Digitoxose.
12. DIGITALIS OR FOXGLOVE (SCROPHULARIACEAE)
DIGITALIS
Digitalis consists of the dried leaves of Digitalis purpurea. It is
required to contain at least 0.3% of total cardinolides calculated as
digitoxin.
Digitalis is from the Latin word digitatus, meaning a finger, and it
refers to the finger-shaped corolla, purpurea is a Latin word and
refers to the purple colour of the flower.
•Description: A perennial herb growing up to 1.5m with a single
erect stem, broad lance-shaped leaves and bell-shaped, purple-pink
or white flowers in long spikes.
13.
14. •History: The poisonous nature of the leaves are well
known, and the drug was recommended for use since 1542.
•Discovered by William Withering, an 18th century country
doctor (cardiac effect)
•His work led to the production of a life-saving medicine
15. Active Constituents
The drug contains a large number of glycosides of which the most
important from a medicinal viewpoint are
Digitoxin
Gitoxin
Gitaloxin
16. Nearly 30 other glycosides have been reported in the drug. The major
ones include:
•glycosides
purpurea glycoside A
purpurea glycoside B
Glucogitaloxin
DIGITALIS – MEDICINAL ACTIONS
1. Powdered Digitalis is a cardiotonic
2. It enables the heart to beat more strongly, slowly and regularly,
without using or needing more O2.
3. Stimulates urine production lessening the load on the heart.
18. STROPHANTHUS
Strophanthus is the dried ripe seeds of S. kombe, S. hispidus and S.
gratus, Family Apocyanaceae, deprived of their awns.
Strophanthus is from Greek meaning "a turn or twist" and a
"Flower" and refers to the twisted lobes of the corolla, hispidus
means "hairy" referring to the hairy character of the plant , kombe is
the native African name for the seed.
Basically 2 varieties on basis of color and shape of seed
1) Green variety: S. kombe bcz seed color is green and shape of
seed is lanceolated (vase like).
2) Brown variety: S. hispidus because seed color is brown and
shape is spindle like.
19.
20. The 30 species of Strophanthus native to Africa are perennial woody climbers. The fruits are
gathered when ripe. The seeds are green, lanceolate and flattened. The testa is covered with
closely appressed hairs directed towards the apex giving a silky appearance to the seed.
Active Constituents
S. Kombe seeds contain 8 to 10% cardiac glycosides known as k-strophanthin, which is a
mixture of three glycosides, cimarin, k-strophanthin-β and k-strophanthoside, which differs only
through attached sugars and have same aglycone strophanthidin.
Strophanthidin
21. All these three on hydrolysis yields
Cymarin → strophanthidin + cymarose
K-strophanthin- β → strophanthidin + cymarose+ β-glucose
K-strophanthoside → strophanthidin + cymarose β-glucose +
ᾲ-glucose
It also contains other constituents e-g kombic acid present only
in S. kombe and nitrogenous base ( trigonelline found in both)
G-strophanthin (Ouabain) cardiac glycoside in S. gratus.
It’s a pure crystalline substance and is used as a standard for
biological assay of other cardiac glycosides. Activity is double
than k-strophanthin. Ouabain on hydrolysis gives ouabagenin.
22. USES OF STROPHANTHUS
It is used as a cardio tonic similar to digitalis but is more
potent.
It is used intravenously in emergency/not absorbed
orally.
Used in congestive heart failure.
Diuretic (in case of congestive heart failure only) and
increases blood pressure.
Used as arrow poison by tribals.
Unlike digitalis it has no cumulative property and
particularly no side-effects.
24. Squill or Squill bulb consists of the cut dried, fleshy inner scales of
the bulb of white variety of Urginea maritima, family Liliaceae.
Scilla is from the Greek word Skilla meaning to split and refers to
the separating scales.
P.U: dried inner scale of bulb
Description:
•Perennial herbaceous plant with white flowers .
•The bulb scales have slight odor and bitter taste .
•Origin
Mediterranean Sea regions
25. •Red Squill contain :
1-Scillaren A,B
2-Scillirosid and scillirubroside (glucosides) which used to
kill rodents.
(cause convulsion+Respiratory failure then death)
White Squill:
glycosides (cardiac group) Scillaren A&B
CHEMICAL CONSTITUENTS & USES:
•In the nature present White & Red Squill
•Both of them contain Cardiac Glycoside.
26. Scilla contains cardiac glycosides, scillaren A and B and enzyme
scillarenase.
Scillaren A is crystalline and responsible for the activity of
drug. Glucoscillaren A, glycoside of scillaren A and glucose are
present in small quantity.
Scillaren B is amorphous and its exact chemical structure is not
known.
27. White Squill bulbs used as:
1-Cardiotonic(CHF, Arrhythmia)
2-Diuretic
3-Expectorant (in small doses)
4-Emetic
5-absorbed approximately 25% in human beings so can be
administered orally
28. ANTHRAQUINONE GLYCOSIDES
A number of glycosides related to anthracene are present in such
drugs as Cascara Sagrada, Frangula, Aloe, Rhubarb, Indian
Rhubarb, Senna and Colchicum. These glycosides on hydrolysis
yield aglycones which are di, tri or tetrahydroxy
anthraquinones or modifications of these compounds.
Chemical Properties
Anthraquinone derivatives: orange-red compounds
Soluble in hot water/dilute alcohol.
Identified via Borntrager’s test
Powdered drug – macerated with ether
Filter
29. ANTHRANOLS AND ANTHRONES
•Reduced anthraquinone derivatives
•Occur either freely (aglycones) or as glycosides.
•Anthrone: Parent structure (pale yellow, non-soluble in alkali, non-fluorescent)
•Anthronol: brown-yellow, soluble in alkali, strongly fluorescent
Anthronol derivatives (e.g. in Aloe – have similar properties – fluorescence used for
identification
MOA
Anthraquinones possess laxative action bcz of their irritative action on large intestine. Its
basically due to the stimulation of smooth muscles of large intestine through which
peristalsis occurs resulting in quick passage of (evacuation) of intestinal contents.
Similarly mucus secretion is stimulated and water absorption is hindered resulting in soft
stools.
30. Function of Aglycon
These compounds are stimulant and have purgative actions and exert their actions by
increasing the tone of muscles of large intestine thus helping in the treatment of
constipation.
Function of glycon
Glycon or sugar part facilitate the aglycon to transport and absorption of aglycon to the
site of action.
31. SENNA - LEGUMINOSAE
Consists of the dried leaflets of Cassia senna (Alexandrian senna), or
Cassia angustifolia (Tinnevelly senna).
P.U: Dried leaflets
•Indigenous to Africa (tropical
regions)
•Used since 9th – 10th century
•Introduced into medicine by Arab
physicians (used both the leaves and
pods)
•Exported by Alexandria – name of
the Sudanese drug.
32. COLLECTION
•Collected in September
•Whole branches bearing leaves are dried in the sun.
•Pods and large stalks are separated with sieves.
•Leaves are graded (whole leaves, whole leaves and half-leave mix,
siftings).
•Whole leaves – sold to public
33. SENNA - CONSTITUENTS
•2 active glycosides: Sennoside A
Sennoside B
Both hydrolyse: 2 molecules glucose + aglycones:
Sennidin A and Sennidin B.
•Sennoside C & Sennoside D
•Rhein
•Aloe-emodin
•Palmidin A (Rhubarb)
•Kaempferol (yellow flavanol)
• + glucoside (kaempferin)
•Mucilage
•Calcium oxalates
•Resin
34. USES:
Senna is a used as a purgative (stimulate the muscular part of large intestine especially colon.
SENNA FRUIT
Senna pods are the dried, ripe fruits of Cassia senna and Cassia angustifolia, which are
commercially known as Alexandrian and Tinnevelly senna pods respectively. Both
have separate monographs.
COLLECTION
•Pods are collected with the leaves and dried in a similar fashion. After separation of the leaves,
the pods are hand-picked into various qualities, the finer being sold (commercially), while the
finer pieces are used to make galenicals.
35. Constituents
•Active constituents – found in the pericarp
•Similar to those actives of the leaves
Sennoside A
Sennidin
Senna - Uses
•Laxatives (habitual constipation or occasional use).
•Lacks astringent after-effect (Rhubarb)
•Medicinal Actions
•Vermifuge, diuretic, febrifuge
•Other uses: laxative candy (bitter taste).
Also used to treat flatulence, gout, fever.
•Topically: poultice prepared with vinegar to treat pimples.
36. CASCARA BARK- RHAMNACEAE
Definition: Official Cascara sagrada is the dried bark of Rhamnus
purshianus. Bark is collected from wild trees. P.U: Dried bark
Cinnamon bark
Cascara bark
37. Rhamnus purhsianus - Cascara
Rhamnos – Greek, branch, shiny shrub. Purshiana after Pursh,
botanist 1st described herb in 1814.
•Other Common Names
Bearwood, bitterbark, buckthorn, coffeeberry, mountain cranberry,
persiana, sacred bark
Cascara – Collection & Preparation
•Collected form mid-April to end of August, when it separates readily
from the rest of the trunk.
•Longitudinal incisions are made 10cm apart and the bark removed.
38. •Tree usually upon felling and the branch bark separated.
Bark is then dried in the shade with the cork facing upwards. This is
referred to as ‘natural’ cascara. Commercial supplies are comminuted to
give small, even fragments called ‘processed’, or ‘compact’ cascara
39. Cascara Bark - Storage
•During preparation and storage the bark should be protected from rain
and damp (partial extraction of constituents may occur or bark may
become mouldy).
•Should be stored for at least 1 year before use (although no longer a BP
requirement).
Bark appears to increase in medicinal value up unto its 4 years old
(stored bark)
Fresh cascara bark contains anthranol derivatives which have griping and
emetic properties. By storing for one year, anthranol derivatives are
oxidized to anthraquinone derivatives, loses its irritant properties.
40. Cascara Bark – Constituents 1
•4 main glycosides – Called Cascarosides
Cascaroside A
Cascaroside B
Cascaroside C
Cascaroside D
•Cascara Bark – Constituents 2
• 2 aloins: Barbaloin and chrysaloin (cascarosides A & B are derived from
barbaloin while cascaroside C & D from chrysaloin).
C – Glycosides (80-90%),
Breakdown products of Cascarosides A-D
Barbaloin (derived from aloe-emodin)
Chrysaloin (derived from chrysopanol anthrone)
Primary glycosides are more active than aloins which
are more active than free anthraquinones.
42. Cascara Bark – Constituents 4
•Dianthrones
Those from
Emodin
Aloe-emodin
Chrysophanol
Hetrodianthrones
Palmidin A, B and C (Rhubarb)
Cascara Bark – Constituents 5
•Emodin
•Aloe-emodin
•Chrysophanol (in the free state)
43. Cascara Bark - Uses
•Purgative
•Popular bitter tonic
•Normally used as a tablet (elixir cascara-bitter taste of
lactone is removed by alkali like magnesium carbonate).
•Also used on animals (used in vetinary medicine)
44. RHUBARB - POLYGONACEAE
Rhubarb/Chinese Rhubarb is the rhizome of Rheum palmatum. Other
species and hybrids of Rheum, except R. rhaponticum, may also be
included. Rheum emodi
P.U: dried roots and rhizome
45. Chinese Rhubarb - History
•Chinese Rhubarb has a long history.
•Mentioned in a herbal of 2700BC.
•Formed an important article of commerce on the Chinese trade routes to
Europe.
•Still used medicinally today.
46. Collection & Preparation
•Rhizomes are grown at high altitudes (+3000m).
•Collected in Autumn or spring (6-10yrs old)
•Cork is removed, cut.
•Artificially dried.
•Packed in tin-lined wooden cases.
•Inferior quality herbs are packed in bags
47. Constituents
•Anthraquinones without a carboxyl group – chrysophanol,
emodin, aloe-emodin & physcion.
2. Anthraquinones with a carboxyl group (rhein and its glycoside:
glucorhein).
• Anthrones and dianthrones of chrysophanol, emodin, aloe-
emodin or physcoin.
4. Dianthrone glucosides of rhein (Sennosides A and B).
5. Hetrodianthrones derived from 2 different anthrone molecules:
Palmidin A and Palmidin B
The greater purgative property of rhubarb may be attributed to the
greater percentage of both free and combined anthraquinones.
48. Uses
•Bitter stomachic
•Diarrhoea (low doses) – contains tannins
•Purgative (high doses) – followed by an astringent effect.
•Suitable only for occasional use, not for chronic constipation.
Rhapontic Rhubarb: Rheum rhaponticum
in addition to anthracene derivatives it contains rhaponticin, having estrogenic property.
49. ALOE - LILIACEAE
• Aloes are the solid residue obtained by evaporating the liquid which
drains from the transversely cut leaves of various Aloe species.
The juice is usually concentrated by boiling and solidifies on cooling.
Aloe is dried juice collected by incision from the bases of leaves of various species of Aloe.
50. •Official varieties are the Cape Aloes from SA and Kenya
(Aloe ferox), and the Curacao Aloes from West Indies
(Aloe barbadensis). (Aloe vera).
•P.U: dried juice obtained from the leaves
51. Preparation of Aloes
Aloes are prepared from the wild plants of Aloe ferox.
Leaves are cut transversely near the base.
200 leaves arranged around a shallow hole in the ground (lined with
canvas or goatskin).
Cut ends overlap & drain into the canvas.
After 6hrs all the juice is collected, its taste is bitter.
Transferred to a drum.
Boiled for 4hrs on an open fire.
Poured into tins while hot solidifies.
52. Characteristics
•Dark brown or Green-brown
•Glassy masses
•Thin fragments have a deep olive colour
•Semi-transparent.
•Powder: green-yellow
•Rub 2 pieces of drug together – powder is found on the surfaces.
•Characteristic sour odour (rhubarb/apple-tart odour).
•Taste: nauseous and bitter.
54. Uses
•Aloe and aloin are strong purgatives and in higher doses may act as
abortifacient.
• if used alone, aloe causes griping and usually combined with
carminatives and antispasmodics like belladonna and hyoscymus.
•Ointment of aloe gel is used in sun burns, thermal burns, radiation
burns, abrasions and skin irritation and prevents ulceration and
malignancy.
•Used in sun screen lotions, cosmetic preparations as an emollient.
55. Aloe vera Products
•These are derived from the mucilage gel – parenchyma cells
•Should not be confused with aloes (juice of pericycle – juice used for
laxative effect).
•Cosmetic industry - Used as suntan lotions, tonics and food
additives.
•Mucilage = polysaccharide of glucomannans and pectin
56. COCHINEAL
•Cochineal is the dried female insect, Dactylopius coccus, containing
eggs and larvae.
Insects are indigenous to Central America, commercial supplies are
derived from Peru
Carmine dye, a natural, red coloring agent derived from the cochineal insect.
Extracting carmine powder from the insects involves boiling the insects in water,
followed by filtration, precipitation, and washing and drying the final product.
57. •Eggs are protected during the rainy season are ‘sown’ on cacti – on
which it is intended to breed.
•Both male and females arise. After a time, fecundation occurs. Females
attach themselves to the cacti and the males die out.
•Females swell to x2 their original size due to developing larvae &
develop red colouring matter.
•Larvae mature after 14days and escape from the now dead body of the
parent.
•Only a small portion develop into males.
•For next 2 weeks, males fly and young females crawl on the plant.
•Life cycle = 6 weeks.
•3-5 generations may be produced in 1 season.
58. Collection
•Insects are brushed from plants with small brooms and killed (some left
to provide for subsequent crops).
•First crop killed contains the most colouring matter.
•Insects are killed by plunging them in boiling water, stove heat or
exposure to fumes by burning sulphur or charcoal.
•If heat is used – insects change to purple – black – called ‘black grain’.
•Fume killed – turn purple-grey called ‘silver grain’.
•Small immature insects and larvae which can be separated by sieves are
sold as ‘granilla’ or siftings.
59. Characteristics
Oval in shape
Half cm in length
Examined microscopically after removing the colouring
matter (ammonia solution).
Each insect contains 60 – 450 eggs and larvae
61. USES
•Anthraquinones take about 10hours to produce an effect (take
overnight)
•Should not be used for more than 10 days.
•Should not be used by children, pregnant and lactating women.
•Cause griping pain.
•Anthraquinones = phenolic glycosides, used as an irritating laxative
