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Transcript
Glycosides
• Sugar + non-sugar
• In the body they are broken down by enzymes or
acids into:
sugars= glycone/ water soluble
non sugar= aglycone/ active portion
• Aglycone may be an alcohol, sulfur or phenol
compound.
Classification of glycosides
• Based on the nature of the aglycone
• Aglycones can be:
phenols
quinones
terpenes
steroids
• Huge variety of medicinal activity from one
glycoside to the next.
How are they broken down?
• Pro-drugs: glycosides remain inactive until
they are hydrolized in the large intestines by
the help of specialized bacteria
• This leads to the release of the aglycone which
is the active constituent
• The body can absorb some aglycones better
than others depending on the herb
Glycosides and Plant Families
•
•
•
•
Brassicaceae- glucosinolates
Rosaceae- cyanogenic glycosides
Scrophulariaceae- phenylpropanoid glycosides
Asteraceae- phenylpropanoid, flavinoid
glycosides
• Polygonaceae- anthraquinones
Cyanogenic Glycosides
Wild Cherry
Cyanogenic glycosides
• Colorless plant constituent
– Hydrogen cyanide was first isolated from Prussian blue dye
• aglycone contains nitrogen
• BREAK DOWN:
• Cyanogenic glycoside hydrocyanic acid
(prussic acid)  cyanide
Cyanogenic Glycosides
•Cyanogenic glycosides are
found in pits and seeds of
apples, apricots, peaches,
plums and elderberries leaves
and stems.
•Their function in plants is not
really known but they are
suspected to be anti-feedants.
Cyanogenic glycosides
• Main cyanogenic glycosides
1. Amygdalin- found in bitter almonds and peach
kernels (Chinese herb)
- used in to make Marizpan flavoring in cooking.
2. Prunusin- found in wild cherry bark
3. Sambunigrin- from the leaves of the elder tree,
Sambucus nigra
• Other food plants that contain cyanogenic
glycosides include flaxseed and manioc.
– Manioc root must be boiled and the water discarded
in order to remove the toxins.
Cyanogenic glycocides-toxicology
• In large doses hydrogen cyanide (hydrocyanic acid)
inactivates respiratory enzymes, shuts down the CNS
and leads to death.
• However large doses of raw plant material are needed for toxicity
to occur.
• Our bodies can nuetralize cyanides and eliminate them
through the urine.
• Cyanogenic glycosides are broken down slowly and are easily
detoxified by the body in smaller doses.
• 500mg three times a day to produce a toxic effect, which is A
LOT!!– there are 4-9 mg hydrogen cyanide per bitter almond
– You would have to eat 150 bitter almonds a day for a toxic effect!!!
Cyanogenic Glycosides: Properties
• Sedative and expectorant to the respiratory tract.
• Wild Cherry Bark (prunus serotina) is a classic prunasin conataining
respiratory herb for dry irritable coughs.
• Apricot kernels in Chinese medicine are used for coughs and
asthma.
• Cooling
• Hydrocyanic acid cuts down heat at a cellular level.
• Ex- peach, apple and pear are all cooling fruits that contain
Cyanogens.
• Anti-cancer
• Amygdalin/Laetrile- has been researched as an anti-tumor remedy.
Cardiac Glycosides
Digitalis purpurea
• Cardiac glycosides have a long history of use in
herbalism
• The famous cardiac glycoside, digitoxin, was
isolated in 1785 by William Withering. He found
out about the use of foxglove by an elder lady
herbalist in his village using it for CHF (dropsy).
Of course she gets no credit!
• Digitoxin and other cardiac glycosides from plants
day play a large role in modern medicine.
Cardiac Glycosides
• Found in many medicinal plants such as
Digitalis purpurea and lilly of the valley
(Convallaria majalis)
• Direct action on the heart supporting its
strength and rate of contraction when it is
failing.
Cardiac Glycosides- Plant protection
Plants and animals create cardiac
glycosides as a strategy for
protection against being eaten by
other creatures. Some animals,
like monarch butterflies, have
evolved immunity to the toxins.
They consume plants like
milkweed (Asclepias syriaca) that
are high in cardiac glycosides and
store the toxins in their tissues.
This makes them poisonous to
other predators
• Used as arrow poisons by hunters
Cardiac Glycosides- chemistry
• Steroidal structure- 3 six carbon rings and one
five-carbon ring
• The sugar portion of the cardiac glycoside is
important in the absorbtion and distribution
in the body.
• The aglycone portion is important in binding
to Na/K pumps in the heart cells
Cardiac Glycosides
CONDITIONS: Used in arrhythmias and congestive heart
failure(dropsy)
•
In the past dropsy was the only sign of heart failure. Dropsy (CHF)
fluid accumulation in the lower limbs and abdomen due to the heart
not being strong enough to handle venous return.
ACTIONS:
1. increase the force and speed of contraction
•
Inhibit sodium potassium pump leading to a rise in intracellular
calcium which increases contraction of the heart.
2. Decrease heart rate
3. Slows conduction velocity in the pace maker- used for
arryhthmias
Cardiac glycosides
• Toxicity- Narrow therapeutic window. The
therapeutic dose is not much smaller than the
toxic dose.
– Too high of a dose can make the pace maker more
sensitive and lead to atrial fibrillation.
• Cardiac Glycosides are antagonistic to Potassium.
If person is low in K+ they will be more likely to
have digitalis intoxication.
– Taraxicum in combition helps to replenish K+
• Digitalis Intoxication- nausea, vomiting, diarrhea,
vision disturbances, headache, arrhythmias.
Cardiac Glycosides
• Cardiac remedies in other than drop doses
should be used with discretion.
• Digitalis lasts a long time in the body and its
effects are cumulative. Half life is over 6
days!
• Convallaria should be considered before
digitalis because it has a lower toxicity
Cardiac Glycosides
•
•
•
•
•
•
•
Plants containing cardiac glycosides include:
Digitalis purpurea- Used for CHF and edema
Apocyanum cannabinum (Dogbane)
Strophanthus hispidus (Kombe Seed)
Adonis vernalis (False Hellibore)
Urginea Maritima (Squill)
Convallaria margalis (Lily of the Valley)
Isothiocyanate glycosides
Isothiocyanate glycosides
(Glucosinolates)
• Found in the Brassicaceae (Mustard) Family.
• Sulpher link between the glycone and the
aglycone.
• Sulpher is what gives the brassicas their pungent
quality. ( Horseradish clears the sinuses, mustard oil
opens the lungs)
• In plants they are used as protection against
microbes that disrupt their cell walls.
Isothiocyanate Glycosides
• Therapeutic Actions:
• Culinary- black and brown mustard seeds used in
cooking are high in nutrients, stimulate digestion.
• Rubefacients- mustard seed oils act as irritants
when applied topically, causing local vasodilation
• Mustard poultices over the lungs break up congestion.
• Decongestant for the sinus and bronchial
conditions (horseradish, onion and garlic).
• Large doses may have an emetics effect.
Isothiocyanates- goiterogens
• When consumed in excess they inhibit
pumping of iodine into the thyroid follicles.
This leads to goiter formation especially in
those who are iodine deficient.
• pertains more to people who are very iodine deficient
like in parts of Asia or central Africa.
• Isothiocyanate botanicals are low enough not
to cause a problem.
Isothiocyanate glycosides- Antitumor
• Glucobrassicin is widely distributed amongst
the Brassicaceae family
• Glucobrassicin produces indoles when broken
down.
• Indole-3-carbinol and diindoylmethane (DIM)
• Indoles are known for their ability to induce
tumor inhibiting enzymes. Thus are protective
against cancer.
• Indoles do not break down under heat.
Isothyocyanate Glycosides
• Toxicology: External use
of should not be
sustained for longer than
two weeks because of
irritating effects.
• mustard seed oils should
never be used internally
or externally because it
toxic to the skin and
mucus membranes.
Saponins
Wild Yam (Dioscorrea spp.)
Saponins- Definition
• Saponins are glycosides with foaming
characteristics.
• Saponin- comes from “sapo” in Latin which
means soap.
– Historically soap was made from the soapwart
plant.
• In plants they are anti-feedants and protect
plants against microbes and fungi
Saponins- synthesis
• Synthesized from acetyl CoA via the mevalonic
pathway (similar to cholesterol in animals)
– Major economic importance: saponins are used to
synthesize pharmaceutical steroids (corticosteroids,
estrogens, progesterone and progestins)
– Agave, fenugreek and wild yam root are examples of
plants used for their steroidal properties in the
laboratory.
– Human body doesn’t possess the gut flora to
interconvert plant steroids to human steroids.
Saponins- classification
• Consist of polycyclic aglycones attached to
one or more sugar side chains.
• Two subcategories of saponins
– Triterpenoid: pentacyclic structure
– Steroidal saponins (phytosterols): tetracyclic
structure
Licorice is a
Pentacyclic
triterpenoid
Saponins= Suds
• The foaming ability of saponins is caused by
the combination of a hydrophobic (fat soluble)
aglycone along with the the sugar which is
hydrophilic (water loving).
• Allows lipids to dissolve in water
• Emulsification in foods that allow water and fat to mix.
• They have a detergent effect on the skin and
the mucus membranes.
Saponins
Wound healing herbs contain saponins such
as calendula.
Saponins- Actions
• Saponins are bitter or acrid in taste
• If injected intravenously they cause hemolysis.
Use only orally!
– Destroy the membranes of red blood cells.
• Lower cholesterol:
– Because they are structurally similar to cholesterol
they interfere with cholesterol absorption
– Increase cholesterol excretion into the bile which then
gets excreted through the feces.
– Ex. Trigonella foenum-graecum (fenugreek)
Saponins- Actions
• Medicinally they have many uses:
– anti-inflammatory: Licorice, wild yam
– anti-viral: licorice, ashwaganda
– Digestive: licorice,
– Expectorant: lobelia, squill
– Adaptogenic: licorice, gensing,ashwaganda
Saponins- reflex expectorants
• Acrid and flavor of saponins make them reflex
expectorants
• Reflex expectorants irritate the upper digestive tract
causing emesis. This irritation also causes a reflex
action via the vagus nerve to promote expectoration.
• Historically herbalists have used emesis to
clear the lungs in chronic bronchitis
Saponins- reflex expectorants
•
•
•
•
•
•
Lobelia inflata
Cephaelis ipecacuanha (Ipecac)
Urginea maritima (Squill)
Verbasum thapsus (Mullein flowers)
Viola spp (Violet flowers)
Glycyrrhiza glabra (licorice)
Steroidal Saponins
• Dioscorea villosa (Mexican
wild yam) root
– Diosgenin: saponin
aglycone
– NOT PROGESTROGENIC in
the body. Complex chemical
reactions in the laboratory
make it progestrogenic.
Naturally it is antispasmodic
and anti-inflammatory.
– Human body cannot
convert diosgenin into
hormones.
Steroidal Saponins
• Panax gensing (Asian) and
P.quinquefoium (American
gensing):
– Gensenosides:
immunomodulating, antistress, anti-dementia
– Saponins foam and
enhance absorption of
other plant constituents.
• Withania somnifra
(Ashwaganda) root
– Withanolides: calming and
immunomodulating
Panax gensing
Triterpenoid Saponins
• Glycyrrhiza glabra (Licorice)
• Glycyrrhizin- reduces toxicity
of other saponins
– anti-inflammatory, antiviral,
immunomodulating,
hepatoprotective, anti-ulcer
– Used as a synergizer in herbal
formulas rendering other
ingredients more bioavailabe
• Bupleurum falcatum
– Hepatoprotective, antiviral,
immunostimulating
Saponins in medicine making
• Saponins are poorly bioavailable in the human
body. Other plant constituents present in the
plant aid in assimilation of saponins.
• Saponin rich plants influence absorption of other
plant constituents:
• Help lipophilic constituents of plants be absorbed
• Saponins in high doses can cause gastric
irritation. Better if they are taken with food.
• Mostly soluble in dilute ethanol (30%), water and
lipids
Alkaloids
Alkaloids
• Have had a major impact on humanity
• Examples are caffeine, morphine, ephedrine,
atropine, cocaine and many more…
Alkaloids
• Most potent of all plant constituents
• alkaloids are seen in pharmaceuticals such as
codeine, morphine, atropine, pseudoepinephrine
and vincristine.
• High doses will cause vomiting, diarrhea,
immediate central nervous system symptoms and
death.
• Important for the herbalists to be careful with
herbs that have a high alkaloid content.
– Many herbs that contain alkaloids such as berberis
and California poppy are low toxicity.
Alkaloids in the plants
• Why do plants have alkaloids? We don’t know,
there are just theories…
• Unclear
• alkaloids are a way for plants to excrete excess
nitrogen, like mammals excrete nitrogen though urea in
the urine
• Alkaloids serve as defenses from predations
• Alkaloids are a way for the plant to store nitrogen which
is hard element to come by.
Alkaloids in plants
• Alkaloids are common in
plants: 10-15% of all plants
have some kind of alkaloid
• May be found in roots,
leaves, bark, fruit or seeds.
• Over 40 different alkaloids
can be present in one
plant, like Vinca major.
Vinca Major
Alkaloids- chemistry
• The word alkaloid is derived from vegetable
alkali, which refers to their
nature due
to the presence of nitrogen
• Alkaloids are best classified according to their
biosynthetic origen.
• Most are synthesized by the plant from amino acids
• Psuedoalkaloids- derived from terpenes
Alkaloids-chemistry
• General characteristics 
• alkaline
• Contain a nitrogen
• Part of a heterocyclic ring system
Berberine
Alkaloids- Properties
• Most are white in color when extracted, except
berberine alkaloids which are yellow
• Bitter in taste
• Soluble in alcohol
• Tinctures (45% ethanol) are very effective at extracting
alkaloids
• Acetracts extract alkaloids well, such as apple cider vinegar.
• Less soluble in water
• This may be a good way to deliver medicine if there is a
potential for giving too high of a dose of alkaloids.
Alkaloids- Properties
• Irreversibly precipitated by tannins.
• Alkaloid containing medicines should not be tinctured
with tannins, unless you wish to counteract the
alkaloid.
• If you want to mix a tincture that has both alkaloids and
tannins use 10% glycerine to the tincture.
• Black tea (Camelia sinensis), cranesbill
(Geranium maculatum) or witch hazel
(Hamamelis virginiana) are the three
remedies for alkaloid poisoning
Alkaloids- Actions
•
•
•
•
•
•
•
Analgesics/narcotics- morphine
Mydriatics- atropine
Hypertensives- ephedrine
Hypotensives- reserpine
Stimulants- caffeine, strychnine
Antimicrobials- berberine
Anti-cancer- vinblastine
Alkaloids
• Many different groups of alkaloids exist
• The most common groups that we will be
covering in this class are:
– Tropane Alkaloids- Belladonna, Henbane ect
– Isoquinoline- California poppy, berberis
– Pyridine- Tobacco, Lobelia
– Pyrrolizidine- Comfrey, Western Coltsfoot
– Indole- Peyote, Iboga
– Purine- Cacoa, Caffeine
Tropane Alkaloids
• Synthesized from amino acids ornithine or
proline.
• Mostly Solanaceae family
•
•
•
•
•
Atropa belladona – Deadly nightshade
Datura stramonium- Thornapple
Hyoscymus niger- henbane
Mandragora officianialis- mandrake
Erythroxylum coca - Bolivian coca
Tropane Alkaloids
• Anticholenergics (inhibit parasympathetic
nervous system)
• Smooth muscle relaxants
– Atropine: dilates pupils, anti-emetic, decreases
salivation
– Hyoscamine: bronchial and intestinal
antispasmotic, hallucinagenic
– Cocaine: Anesthetic (novacaine), narcotic
Isoquinoline Alkaloids
• Synthesized from amino acid tyrosine
• Alkaloid Berberine- Hydrastis canadensis and
Mahonia root
•
•
•
•
Bitter digestive stimulant
GI tonic
Anti-microbial
Immune stimulant
Hydrastis canadensis
Isoquinoline alkaloids
• Papaver somnifera (opium poppy): papaverine,
morphine, codeine
• Analgesic, antitussive, seditave narcotic
• Corydalis spp : corydalin
• Analgesic
• Ipecac root: emetine
• Emetic in high dose, reflex expectorant in low dose,
anthelmintic
• Sanguinaria candensis (Bloodroot):sanguinarine
• Antimicrobial, antineoplastic
Isoquinoline alkaloids
Sanguinaria canadensis
Isoquinoline Alkaloids
Papaver somnifera
Pyridine alkaloids
• Derived from the B vitamin nicotinin acid
• Nitrogen atoms in six-membered benzene
rings
Pyridine Alkaloids- Actions
• Lobeline (lobelia inflata leaf):
• expectorant, smasmolytic, nicotic agonist
• Nicotine (Nicotiniana tabacum leaf):
• Nicotinic agonist, addictive
• Trigonelline (fenugreek seed):
• hypolipidemic (lowers blood cholestrol)
• Piperine (Piper longum fruit):
• Increases gut permeability, hepatoprotective, used in
combination with other herbs to increase efficacy
Pyrrolizidine alkaloids
• Synthesized from ornithine in plants
• Ingested by butterflies to protect them from
invadors
• Asteraceae and Boranginaceae families
contain PA- ex) comfrey, echinacea and arnica
• Herbal medicine containing PA are
contraversial and have been banned from use
in Australia.
Pyrrolizidine Alkaloids
• Hepatotoxic in large doses
• PA can cause hepatic venous occlusive
disease if large doses are ingested
– When metabolized in liver they cause DNA damage to liver cells which then
fibrose around the venules of the liver. Jaundice and liver failure ensue.
– PA don’t affect everyone equally. Some people may not have
sufficient levels of liver enzymes to metabolize PA.
– Intake of over 3 gm/day of PA can cause liver damage within
three months.
Pyrrolizidine Alkaloids
• Symphytum off. (Comfrey) has PA
• Mucilagenous, anti-inflammatory, heals ulcers
internally and externally.
• Has been condemned as toxic by many.
• Few cases of injury have been reported and of those
cases people who were poisoned ate the root which is
much higher in PA than the leaves.
• Glycyrrhizin (saponin from licorice) has been
found to protect the liver from PA
Pyrrolizidine Alkaloids
• Other plants that
contain PA:
– Tussilago farfara (Eastern
coltsfoot)
– Sencio spp (Life root)
– Borago officianlis ( Borage)
Tussilago farfara
Pyrrolizidine Alkaloids
Senecio spp. (Liferoot or
Ragweed)
Indole Alkaloids
• Large number of medicinal alkaloids are found
in this group
• Derived from tryptophan or tryptamine in
plants.
• Contain 2 nitrogens and often involve multiple
rings.
• Form the basis of several hallucinogenic and
pharmaceutical drugs.
Indole Alkaloids
• Apocynacea family- Rauwolfia, Vinca,
Catharanthus, Iboga
• Fungus family- psylocybin mushroom and
ergotimine
Indole Alkaloids- Reserpine
• Reserpine found in Rauwolfia serpentina has
been used in Aryuvedic medicine as a
hyptotensive, seditave and tranquilizer.
• Reserpine temporarily inhibits noradreniline and
depletes the amino acids in the central nervous system.
• Hypotensive effects have a slow onset and their
duration is long.
• Use cautiously depression and severe hypotension are
indications of overdose.
Indole Alkaloids
• Cantharanthus roseus (Madigascar Periwinkle)
• Contain vinblastine and vincristine- antineoplastic used in
chemotherapy for childhood luekemia and non-Hodgkin’s
lymphoma
• Vinca minor, major (Common Periwinkle)
• Vincamine- anti-hemorrhagic and astringent. Does not
contain the anti-cancer alkaloids that cantharanus has.
• Claviceps purpurea (Ergot)
•
•
•
•
Ergotamine- fungus grows on rye.
Migraine relief
St.Anthony’s Fire- epileptic convulsions and spasms.
LSD is derived from ergot. Similar compounds found in
Ipomoea spp. (Morning Glory)
Other Indole Alkaloids
• Pausinystalia yohimbe ( Yohimbe)
• Yohimbine- Aphrodesiac and nerve tonic
• Gelsimium sempervirens (Yellow jasmine)
• Gelsemine- heart tonic, nerve seditave, toxic.
• Strycnhos nux vomica (Nux Vomica)
• Strychnine- powerful CNS stimulant in low doses. Toxic
• Banisteriopsis caapi ( Ayahuasca)
• Harmine- entheogenic
Indole Alkaloids
Banisteriopsis caapi
Purine Alkaloids
• Caffeine, theobromine (chocolate),
theophylline (from cacao and tea)
• Methyl xanthines- Derived from the purine
nucleotides adenine and guanine with
attached methyl groups.
• Mild stimulants and bronchodilators
• Theophylline is a drug used for respiratory distress and
asthma.
Purine Alkaloids
Cacao Tree
Purine Alkaloids
• Increase the rate of cardiac contraction
• Increase alertness and induce digestive enzyme
activity in the GI
• They act by stimulating the Central nervous
system and prolonging the life of hormones, such
as adrenaline.
Bitters
Why are bitters important?
• Increase the appetite:
– Have been used in aperitifs or to induce appetite
in convalescence
• Increase digestive secretions
– Low enzymes or stomach acid aid in depressed
digestive ability and leads to proteins from food
penetrating into the wall of the gut.
– Increases stomach and pancreatic enzyme
secretions and aid the body in breaking down
food.
Bitters
– Protect gut tissue: Increase the tone of the lower
esophageal sphincter
» Prevent reflux or heart burn, hiatal hernia or esophageal
irritation.
– Promote bile flow: reduces toxic load on liver by
flushing out toxic accumililations by increasing
bile.
– Increases bicarbonate from gallbladder and thins
bile
» Gallstone and gallbladder disease
Bitters
• Indicated for symptoms of poor digestions
– Belching, loss of appetite, constipation, bloating
and nausea after eating.
• Controversy weather bitters are safe to use
with people who have ulcers because too
much acid could aggravate the ulcer
• Bitters increase secretions of bicarbonate from the
pancreas which protect the stomach from acid.
Some plants containing bitters
•
•
•
•
•
•
•
•
•
•
•
Achillea millefolia (Yarrow)
Artemesia spp. (Wormwood, mugwort..)
Arctium lappa (Burdock)
Tanacetum (Feverfew)
Taraxicum ( Dandilion)
Gentiana lutea (Gentian)
Centaurium minus (Centaury)
Berberis spp (Oregon Grape)
Hammamelis spp (Witch Hazel)
Humuls lupus (hops)
Tussilago farfara ( Coltsfoot)
Acids
• Weak acids constitute a main part of all plant
material
• Acids we will cover
– Unsaturated fatty acids
– Formic Acid
– Oxalic Acid
– Citric Acid
• Other acids that occur in plants are
– Acetic, succinic, benzoic and tartaric
Unsaturated Fatty Acids
• Found universally in plants and less so in
animals.
• Linolenic and arachadonic acids- found in
seeds and reproductive tissues of the plants
• Linolenic acids- found in the green tissues of
plants
• PUFAs (Polyunsaturated fatty acids) are vitally
necessary in the diet = ESSENTIAL FATTY ACIDS
Essential Fatty Acids
Why are they so important?
• Build and repair cell membranes
• Form raw material for prostaglandin
production in the body
• Prostaglandins are important in smooth muscle
contractions, inflammatory mediators, and raise blood
pressure
• Example of PUFA- Evening Primrose
(Oenothera biennis) has gamma linolenic acid
Evening Primrose
Used as an anti-inflammatory
conditions like rhuematoid
arthritis, PMS and eczema
Formic Acid
• The smallest organic acid and the most
corrosive to the skin….just like fire ants!
• Used in counterirritants and vesicants
• Found in red ants
• Formic Acid is the sting in stinging nettles
• Oxidizes and is inactive after being exposed to
heat.
• Cook your nettles to eat them!!
Oxalic Acid
• Forms insoluble salts with minerals such as
calcium.
• Found in foods such as spinach, beets and parsley
• Found in the dock and rhubarb families.
• Oxalic acid bound to iron and calcium is what makes Yellow
Dock so highly nutritious.
• Care needs to be taken to not consume too many
oxalate rich foods if there is a history of oxalate
kidney stones.
Citric Acid
• Found widely in fruits and berries, especially
citrus fruits
• Cleansing in the body
1. Alkalinizing effect:
–
–
citrus breaks down into bicarbonate once in the stomach
Alkalinizing effect in mouth provides the environment
inhospitable to bacteria
2. Increases bile flow from the liver
–
Explains use of lemon for gallbladder cleanses
Thank you