2. Contents
• Introduction
• Plant Toxins
• General Mechanism
• Classification of Plant Toxins
• Mechanism of Action of Plant Toxins
• Sources and toxicological effects of
various plant toxins
• References
3. Introduction
• Herbal medicines are widely used in therapeutics and believed to be safe
having no side effects.
• Phytoconstituents include primary and secondary plant metabolites which
are responsible for the positive or negative health effects exhibited by the
plant.
• Poisonous plants have the potential to cause severe toxicities, injury or
even death in man and animals after accidental consumption, inhalation,
dermal or ocular exposure.
• The concentration of toxin in the plant determines the severity of toxicosis,
which is dependent on certain factors including plant part, age/stage of the
plant, sunlight and soil type where the plant has grown in.
• Phytotoxins have great diversity in their composition, occurrence, mode of
action and lethal effects.
• Toxins play an important role in the field of pharmacology especially in
forensic medicine and clinical toxicology, veterinary medicine,
agrochemicals and their application as vaccines to inactivate toxoids.
4. As far as
safety is
concerned,
plants can be
classified into
three
categories:
Firstly, the plants with toxic principles at therapeutic doses which are to be used
only with the advice of qualified clinician. E.g., plants like Digitalis spp., Areca
catechu, Atropa belladonna, etc.
Next class includes plants with potential pharmacological properties which are
safer under appropriate circumstances.
Lastly, the plants which are known to be potentially toxic like Lantana camara,
Strychnos nuxvomica and others.
Toxic plants
have a
worldwide
distribution
and are further
categorized
into 2 classes:
One type represents plants having toxic principle and known to cause poisoning.
Other group include apparently non-toxic plants which are poisonous only under
certain conditions.
5. Plant toxins
Special poisonous substances that are produced in small quantity by
plants.
The important
phytotoxins
include:
Cyanogenic glycosides (Linamarine, Amyglidin)
Cardiac glycosides (Digitalis, Nerin)
Alkaloids (Strychnine, Atropine, Nicotine)
Toxalbumins (Ricin, Abrin), Triterpenes (Lantadene)
Saponins, Resins, Tannins, etc.
Phytotoxins in the animal or human body, act through various specific
mechanisms involving receptors, transporters, enzymes and even genetic
material at specific cells and tissues to produce toxic effects.
6. The general mechanisms of plant poisoning include :
Teratogenicity
Ribosomal inactivation
Cytotoxicity
Neurotoxicity
Cardiotoxicity
Hepatotoxicity
Nephrotoxicity
Thyrotoxicosis
Photosensitization
Protease inhibition
Haemagglutination
Vitamin antagonism
Metal chelation
7. Classification of Plant Toxins
Classified based on their structural and chemical properties.
a. Alkaloids
• Compounds containing nitrogen in heterocyclic ring, basic in nature and
derived from amino acid.
• Most compounds exhibit strong physiological activity.
• e.g., Colchicines, Nicotine, Aconitine, Cocaine.
Some common toxins from this class include:
• Indole alkaloids: e.g., Harmine (active on CNS).
• Pyrrolizidine: Causes Veno-occlusive disease of the liver.
• Tropanes: Atropine, Scopolamine, Hyoscyamine active on ANS.
• Glycoalkaloid: Glycoalkaloids consist of a steroidal alkaloid coupled to one or
more monosaccharides. All members of the botanical family Solanaceae produce
glycoalkaloid toxins. In potatoes, the major glycoalkaloids are α-solanine and α-
Chaconine. Its level is increased in greened potatoes or blighted potatoes, and
can reach very high levels in the sprouts.
8. b) Glycosides
• These substances are consisting of a non-sugar moiety i.e., aglycone
to which one or more sugar chains is bound.
• Cyanogenic glycosides release prussic acid. The cyanide ions (CN-
) attach to the mitochondrial cytochrome oxidase and in this way
blocks electron transport.
• The clinical symptoms of acute cyanide intoxication can include rapid
respiration, drop in blood pressure, rapid pulse, dizziness, headache,
stomach pains, vomiting, diarrhea, mental confusion, stupor, cyanosis
with twitching and convulsions followed by terminal coma.
• Cardiac glycosides such as digitoxin from foxglove. Digoxin inhibits
the enzyme Na-K-ATPase. Vomiting, confusion, changes in color
perception and in particular, cardiac arrhythmias are dominant
symptoms.
• Goitrogenic glycosides: Too much ingestion and simultaneous iodine
deficiency may lead to thyroid disorders.
9. c) Tannins
• These substances have the capability to precipitate proteins. They make the skin tough by deception of the
proteins in the skin.
d) Proteins
• A number of protein toxins produced by plants enter eukaryotic cells and inhibit protein synthesis
enzymatically.
• Examples of poisonous proteins include Ricin {Ricinus communis, Fam. Euphorbiaceae (Castor plant)} &
Abrin {Abrus precatorius, Fam, Legumes (Rosary pea)}.
10. e) Oxalic acid and oxalates
• These substances may be present in trichomes or in raphides (needle-like structures).
• Ingested oxalate will be absorbed. Oxalate in blood binds calcium to form the insoluble
calcium oxalate. Severe hypocalcemia with tetany can occur.
f) Anti-vitamins
• Some substances work against the vitamins, e.g., thiaminases in horsetails {Equisetum, Fam.
Equisetaceae} and bracken {Pteridium aquilinum, Fam. Polypodiaceae} cause breakdown of
thiamine and anti-vitamin K such as coumarins.
11. g) Photosensitising and contact-
sensitising substances
• St. John’s wort with hypericin (an
Anthraquinone derivative) and
hogweed causes photo allergy.
• Poison ivy is known in North
America. Many of the active
substances are phenols,
furanocoumarins or derivatives of
these, which causes allergy to
sunlight.
12. h) Volatile oils
• Volatile oils are liquid substances formed in special oil cells, glands, hairs, or channels.
• They are all soluble in alcohol.
• At certain concentrations, some are irritant (forming blisters) and emetic & Some volatile oils are
nephrotoxic.
i) Lectins
• Lectins (phytohaemagglutinins) are proteins or glycoproteins of non-immune origin which have multiple
highly specific carbohydrate binding sites.
• Widespread in the plant kingdom including grain products.
• Lectins are particularly concentrated in legume seeds and have been shown to cause gastroenteritis,
nausea, and diarrhea in men.
j) Saponins
• Saponins are water-soluble plant constituents, which can form soapy foam even at low concentrations.
• They are glycosides with a non-sugar aglycone portion which is termed a sapogenin.
• Cardenolides have a bitter taste and influence NA+/K+ activated ATPases in human heart, they may slow
or strengthen the heart rate.
13. MECHANISM OF ACTION OF PLANT TOXIN
a) Neurotoxins
b) Inhibitors of cellular respiration
c) Cytotoxins
d) Toxins of skin and mucosal tissues
a) Neurotoxins
• The neuroactive alkaloids can function either as agonists which excite a neuroreceptor or as
antagonists which would block a certain neuroreceptor.
• Receptors on neuron cells are another major target for many of alkaloids, which structurally
resemble the endogenous neurotransmitters such as glutamate, acetylcholine, dopamine,
noradrenalin, and adrenaline.
• Some alkaloids inhibit the enzymes that break down neurotransmitters, such as cholinesterase
and monoamine oxidase. Neurotoxins also have an effect on significant ion channels of neuronal
cells, such as Na+ , K+ and Ca2+ channels, whichever by activating or inactivating them
eternally.
• These activities stop neuronal signal transduction and block the activity of the CNS.
• Datura stramonium, Conium maculatum (hemlock), Coriaria myrtifolia (redoul), Ricinus
communis, Gloriosa superba, Catharanthus roseus.
14. b) Inhibitors of cellular respiration
• Cellular respiration, which occur in mitochondria and produces ATP, is another susceptible
target, in view of the fact that ATP is essential for all cellular and organ functions.
• Many plant toxins can attack this target with HCN, which binds to iron ions of the terminal
cytochrome oxidase in the mitochondrial respiratory chain.
• HCN does not occur in a free form, but is stored as Cyanogenic glucoside in plant cell
vacuoles. When plants are injured, the content of the vacuoles gets into contact with
enzymes, such as β-glucosidase and Nitrilase due to ruptured cellular matrix.
• These enzymes hydrolyze and Cyanogenic glucoside releases extremely toxic HCN.
• The Diterpene atractyloside {(toxic glycoside) obtained from Callilepis laureola} is a potent
inhibitor of the mitochondrial ADP/ATP transporter and thus inhibits the ATP supply of a cell.
15. c) Cytotoxins
• Many Phyto-constituents are regarded as cytotoxins as they obstruct important cellular functions.
• Bio membrane are prime target of such compounds which are involved in the import and export of
metabolites and ions in cells.
• Membrane fluidity and integrity can be severely disturbed by both steroidal and triterpenoids
saponins.
• Saponins are usually stored as inactive bidesmosidic saponins in plant vacuoles; on injury and
destruction, they are transformed into the active monodesmosidic saponins, which are amphiphilic
with detergent activities.
• Several enzymes, proteins, DNA/RNA and related processes are other important targets of such
compounds.
• A number of strong plant toxins inhibit ribosomal protein biosynthesis, such as the Alkaloid
emetine, Amanitins, and the Lectins. These toxins can attach to cells by their B-chain, the
haptomer, whereas the A-chain is taken up by endocytosis into the cytosol, where it blocks protein
biosynthesis. The elements of the cytoskeleton, especially microtubules and actin filaments, are
also vulnerable targets in animal cells.
• Abdominal pain, hair loss, disruption of menstrual cycle, fetal loss and birth defects.
16. • A number of plant toxins are known as microtubule poisons, such as Colchicine,
Podophyllotoxin, Vinblastine, Chelidonine, Noscapine, Cucurbitacins and Taxol.
• These poisons are known to block cell division, vesicle transport and microtubules.
• Several secondary compounds can covalently bind to proteins, such as aldehydes,
epoxides, secondary compounds with exocyclic methylene groups, with SH groups or
reactive double or triple bonds.
• These protein modifications influence the three- dimensional structure of proteins and
can inhibit their function.
• Therefore, many poisons with such properties have neurotoxic and cytotoxic properties
or are irritants to skin and mucosal tissue.
17. d) Toxins of skin and mucosal tissues
• Skin and mucosal tissues are also affected by several toxins. Diterpene, which resemble the
endogenous signal compounds diacylglycerol (DAG), an activator of the key enzyme protein
kinase.
• These diterpenes are classified as phorbol esters and they stimulate protein kinase. When they
come in contact of skin, mucosal tissues or eye they cause severe painful inflammation, with
ulcers and blister formation.
• Furanocoumarins can penetrate the skin and intercalate dermal cells. When the skin is exposed
to sun light, the Furanocoumarins alkylate DNA, which kills the cells and induces strong blister
formation and necrosis.
• Many species of the Ranunculaceae accumulate the glycoside ranunculin in the vacuole. It
splits into the active protoanemonin, which can alkylate proteins and DNA, which causes skin
and mucosal irritation, followed by a severe inflammation. The proteases or other noxious
proteins of plants further worsen the condition by their damaging activity.