PLANT GLYCOSIDES

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PLANT GLYCOSIDES
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Glycoside Definition

• A substance which on hydrolysis
• yields a reducing sugar
• one or more non-sugar substances
  (genin/aglycone)
• Normally aromatic in nature
• Known as the aromatic aglycone or genin portion

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Glycosides

• Glycoside Broad general term
• Embraces all the many various combinations of
  sugars aglycones
• e.g. Cardiac glycosides, flavonoid glycosides,
  phenolic glycosides etc.

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Glycoside Formation

• In nature Formed by the interaction of the
  nucleotide of a sugar group with the alcoholic or
  Phenolic group of a 2nd compound.
• This glycoside is called an O-glycoside
• Most numerous kind found in nature

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Other Glycoside Formation

• Other glycosides occur through
• sulphur links
• Called S-glycosides
• Nitrogen links
• Called N-glycosides
• Through Carbon links
• Called C-glycosides

NOTE Reactions for both the formation and
Hydrolysis of glycosides are reversible
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Glycosidal Reduction

• Glycosides themselves do not reduce Fehlings
  solution, But the simple sugars they produce on
  hydrolysis (aglycones) do (precipitate red
  cuprous oxide)

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Glycosidal Sugars

• Sugars found in glycosides may be
• Monosaccharides
• Glucose
• Rhamnose
• Fructose
• Deoxysugars (more rare)
• Cymarose
• E.g. those found in the cardiac glycosides

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Terms used to Describe Glycosides

• A Glycoside is a
• Glucoside
• Has glucose as the sugar component
• Pentoside
• Has a sugar such as arabinose
• Rhamnosides
• Contains rhamnose
• Rhanmoglucosides
• Contains both rhamnose and glucose

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Terms used for Aglycones

• Normally self-explanitory
• E.g. Phenol
• Anthroquinone
• Sterol glycoside

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Other Glycosidal Terms

• saponin (soap-like)
• Cyanogenic (producing hydrocyanic acid)
• Cardiac (having an action on the heart)
• Terms Are used to group glycosides together
  which have similar functions chemical structure.

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GLYCOSIDE STRUCTURE

• 2 types of genin are distinguished
• Based on the structure of the lactone ring
• 5-membered ring ? bufanolides or bufadienilolides
• E.g. scillarenin
• 6-membered ring ? cardinolides or cardiac active
  glycosides (medicinally more significant)

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Cardio-Active Glycosides

• A small group of plant glycosides act directly on
  the heart muscle.
• These include (but are not limited to cardiac
  glycosides or cardenolides)
• Cardenolides are steroidal glycosides ? exert a
  slowing and strengthening effect on the failing
  cardiac muscle.

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Cardenolide
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Cardiac Glycosides

• E.g. Digitalis purpurea (Purple Foxglove).
• Other uses of the plant (and glycoside) include
  being used as arrow poisonings.

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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

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Pharmacological Action of Cardiac Glycosides

• 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.
• It is thought to act in competition with K ions
  for specific receptor enzymes (ATPase) sites in
  the cell membranes of the heart muscle when there
  is an influx of Na ions.
• Effect is to increase the force of heart
  contraction
• Diuretic action relates to the improved
  circulatory effects.

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Digitalis puruperea (Scrophulariaceae)

• 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
• 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

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Digitalis purpurea Purple Foxglove

• Definition
• Digitalis consists of the dried leaves of
  Digitalis purpurea.
• It is required to contain at least 0.3 of total
  cardinolides calculated as digitoxin.

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Digitalis purpurea

• Parts Used
• Leaves
• Habitat Native to Western Europe. Although the
  plant is cultivated, wild plants are thought to
  be superior.
• Collection
• First or second-year leaves are permitted.
• After collection the leaves should be dried as
  soon as possible at a temperature of about 60ºC.
• Stored in airtight containers protected from
  light.
• Moisture content should be no more than 6.

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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.

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Microscopical Characteristics

• Stomata and hairs present on both surfaces (more
  on lower surface)
• No calcium oxalate
• Clothing hairs are uniseriate
• Glandular hairs

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Active Constituents

• glycosides
• purpurea glycoside A
• purpurea glycoside B
• (2 main actives in the fresh leaf)
• Glucogitaloxin
• At C-3 of the genin a linear chain of 3
  digitoxose sugar moieties terminated by glucose

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Active Constituents

• On drying enzyme degradation takes place ?
  loss of the terminal glucose. Produces
• Digitoxin
• Gitoxin
• Gitaloxin
• (main actives in dried leaves)
• Poor storage leads to further hydrolysis and
  complete loss of action

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Digitalis Active Constituents

• also contains anthraquinone glycosides
• Saponins
• Sopogenins
• Flavonoids

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Active Constituents

• Other glycosides (present in smaller quantities)
  include
• Digitalose
• Glucose
• Verdoxin (x3 more toxic than gitaloxin)

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Digitalis Active Constituents

• It is generally agreed that the first-year leaves
  collected in Jan-Feb (Southern Hemisphere) have
  the highest content of total glycosides. After
  that they decrease during the winter months.
  After that another peak is reached during the
  time of flowering, but not as high as the first
  one.

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Digitalis Medicinal Actions

• tonic effect on the diseased heart
• glycosides enable the heart to beat more
  strongly, slowly and regularly, without using or
  needing more O2.
• Stimulates urine production ? lessening the load
  on the heart.

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NB!

• Kellar-Keliani Test for digitoxise
• Pg 509/Pg146

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Digitalis purpurea

• Allied Drugs
• D. thaspi
• D. lutea
• D. ferruginia

• Adulterants
• Verbascum thapsus (mullein leaves)
• Symphytum officinalis (Comfrey)
• Primula vulgaris (Primrose)
• Inula helenium (elecampane)
• Urtica dioica (stinging nettle)

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Digitalis purpurea

• Cautions
• Potential for overdose
• Only under professional supervision
• Plant is subject to legal restrictions.

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Digitalis lanata Woolly Foxglove

• Todays main source of cardiac glycosides
• Self-study Pg 147-9

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Convalaria majalis (Liliaceae)

• Cardioactive properties
• Similar to Digitalis, but less cumulative
• Therefore sometimes preferred rather than
  Digitalis
• (tolerated better, fewer side effects)
• Therapeutic Action Heart stimulant

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Convallaria majalis lily of the valley

• Parts used
• Collected parts include
• aerial parts (when flowers begin to open)
• rhizomes roots

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Convallaria majalis Constituents

• Glycosides (highest in flowering period)
• Convallatoxin
• On hydrolysis give
• Strophanthidin
• (-) rhamnose
• minor cardinolides (40 glycosides)
• Convalloside (seed)
• Convallatoxol
• Saponins convallamaroside
• Flavonoids

• Convallatoxin
• Molecular Formula C29H42O10

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Convallaria Pharmacological Effects

• strengthens contraction of heart muscle
• lowers internal heart pressure
• increases cardiac efficiency
• venotonic

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Convallaria - Cautions

• very toxic
• only administered by professionals.
• may cause nausea, vomiting GIT symptoms if
  taken in large amounts
• Because Convallaria cardenolides are poorly
  absorbed in the stomach and intestines they are
  rarely deadly.

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Strophanthus kombe

• Part Used Dried seeds (ripe)
• Habitat East Africa.
• Greek strophos (a twisted cord or rope) anthos (a
  flower)

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Strophanthus kombe

• Constituents
• Strophanthoside
• strophanthin
• cymarin
• all based on genin - strophanthidin)
• Alkaloid Inoeine
• Fixed oil, resin
• mucilage

• Strophanthin Glycoside
• Molecular formula C29H44O12

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Strophanthus kombe

• Uses - similar to Digitalis
• Chronic cardiac weakness
• Diuretic action (thought to be more powerful than
  Digitalis)
• Can be administered IV
• Actions
• Similar to Digitalis
• POISONOUS

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Read

• Oleander Glycosides Pg 149

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Bufadienolides

• Less commonly distributed in nature than
  cardenolides
• Occur in some Liliaceae and Ranunculaceae
  Species. Also occur in toad venoms.
• Therapeutically there is not much value as the
  therapeutic index is low and production of side
  effects high.
• Squill, however has a time-honoured place as an
  expectorant
• Widely used in the treatment of cough.

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Bufadienolide
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Urginea maritima (Liliaceae)

• Definition Consists of the dried sliced bulbs
  of Urginea maritime, from which the membranous
  outer scales have been removed. It is
  commercially known as white squill.
• Description A perennial herb growing up to 1.5
  m from a large white (or red) bulb. It has a
  single flowering stem, a rosette of large basal
  leaves, and a dense spike of white flowers.

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Urginea maritima - Squill

• Parts used Bulbs
• Collection Preparation
• The bulbs are collected when the plant is
  finished flowering and has no aerial leaves.
• The dry outer scales are removed
• Bulbs cut transversely into thin slices
• Then dried in the sun or by stove heat.
• When 80 of the wt is lost, they are packed into
  bags/barrels.

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Urginea maritima - Squill

• History
• Squill appears in Egyptian Ebers papyrus (1500BC)
• In Greece it was used by Pythagoras Hippocrates
  in the 6th 5th centuries BC.

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Urginea maritima - Squill

• Microscopical Characteristics
• mucilage
• calcium oxalate
• small starch grains
• stomata are absent or rare (wide guard cells)
• Constituents
• Glycosides
• Scillaren A (most NB)
• Scillaren B

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Urginea maritima - Squill

• Actions Uses
• glycosides are poorly absorbed in GIT ? short
  action duration (not cumulative)
• In small doses mild gastric irritation causing
  a reflex secretion of bronchioles
• Reflex expectorant action
• Larger doses emetic
• Diuretic
• Cardiotonic

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Urginea maritima - Squill

• Cautions
• Only under professional supervision.
• Toxic in excessive doses
• Unofficial varieties
• Red Squill contains squilloriside very toxic
• Indian Squill Urginea indica