2. Why Oleandrin?
• Many everyday natural substances are toxic
– Some have been harnessed for medicine
• N. oleander is greatly known to be fatally toxic with
exposure to very low doses, BUT
– Has been used in folk medicine
– Under investigation for uses in Western Medicine
• Oleandrin is the main active compound in Nerium
oleander
3. Overview of Oleandrin
• Most potent of ~30 glycosides found in Oleander
• Most commonly known for its fatal cardiotoxicity
• Used in folk medicine for thousands of years
• Currently under investigation for uses in western
medicine
4. Where is Oleandrin found?
• In Nerium oleander plants
– In leaves, stems, flowers, and nectar
• Also found in Nerium oleander are
– Digitoxigenin, Neriin, and Oleondroside (cardiac
glycosides)
5. Nerium oleander
– Lance shaped leaves, summer flower
– Dogbane/Apocynaceae Family: many cardio toxic and
blood pressure effecting plants
– Native to Mediterranean,
Southeast Asia, and Africa
-Thrives in almost all warm climates
-Fast growing
-evergreen
-Commonly used In landscaping worldwide
- Also known as: Laurier
rose, rosebay, desert rose, and many
6. Oleander: known to be toxic
• Cardiotoxic: due to Cardiac glycosides like Oleandrin
• Toxic mostly to mammals
– Children and animals at higher risk for ingestion
– Highly toxic in low doses
• Single leaf can kill an adult human in hours
• Even honey from bees that take pollen and nectar from oleander contains
high amounts (relative to toxicity) of Oleandrin, and other toxins
• Symptoms of toxicity after ingestion or inhalation of smoke:
– Blurred vision - Tachyarrhythmia
– Vomiting/Diarrhea - Confusion
– Bradyarrhythmia - Death by heart attack
8. Oleandrin Action
• Is a Cardiac Glycoside (most potent in N. oleander)
• Inhibits the alpha-3 subunit of Na+/K+-ATPasepump
- Binds reversibly to the alpha-3 subunit causing
1) Intracellular sodium increase
2) Calcium ions increase in muscle cells of the
heart
3) Irregular muscle contraction
4) May have an effect of signaling pathways
5) May inhibit protein assembly
• Other effects:
– Cytochrome C release from mitochondria
– Apoptosis: activates caspases 6 and 8
10. 2) Calcium ions increase in muscle cells of the heart
• Na+ unable to move in against gradient
• Ca2+ unable to move out of cell via Na+/
Ca2+exchanger
•Increases intracellular Ca2+
• Calcium imbalance affects muscle contraction
• May have an effect of signaling pathways
• May inhibit protein assembly
11. Metabolism of Oleandrin
• Half life longer for ingested oleandrin than for intravenous
acquisition
• Oleandrin and metabolites travel throughout the body,
– Oleandrin rapidly accumulates in liver, brain, and kidneys
• Crosses the blood brain barrier
• Oleandrin converted to Oleandrinogen
– Happens in plasma of mice, but only in organs of humans
– Happens within 5-15 minutes of delivery
– Highest amounts of oleandrinogen found in liver, other (yet
unidentified) metabolites also found (only) in the liver
– To a lesser extent occurs in heart and kidney
• Excretion within 24 hours of delivery
– via mainly feces, and partially urine
12. Medical and Veterinary Importance
• Medical:
– Poisoning of people
• Via accidental ingestion (mostly children)
– Usually advised not to plant N. oleander near schools or playgrounds
• Via inhalation of smoke from fires burning N. oleander
• Veterinary:
– Quickly kills domestic animals and livestock after
accidental ingestion
13. Treatment for Ingestion
• Gastric Decontamination(ingestion): Charcoal
• Hydration via IV saline
• Electrolytes
• Antiemetics: to treat nausea
• Correction of Hyper or Hypokalemia
• Treatment of Arrhythmias
– Bradyarrhythmia correction:
• atropine or isoprenaline
– Tachyarrhymia correction:
• Usually poor prognosis
• Digoxin-specific antibody fragments
• Lidocaine
* Same treatments for Inhalation of smoke,
except charcoal
14. Oleander use in Folk Remedies
• Known for ~3500 years that ingestion is fatal, but external application shows
no toxic symptoms
• 15 century BC: oleander and licorice combo used to treat hangovers
• 8th Century AD: cancer treatment
• Other folk remedy uses originating from Mesopotamia: snakebite
treatment, external parasite remover, muscle
cramps, asthma, coma, menstrual pain, epilepsy, cancer, paralysis, skin
disease, cardiac problems (traditional
Chinese), insecticide, eczema, psoriasis, herpes, malaria, leprosy, used in
both ancient and more recent times for suicide
• Today: many websites detail how to make homeopathic cancer fighting
“oleander soup” at home (does that scare you too?)
15. Recent Folk Medicine use Gone Bad
• Topical aphrodisiac in New York
– 4 men died after exposure to an oleander based product
marketed as “topical aphrodisiac”
– Digoxin like compound was found in all 4, though none had
taken digoxin
– Later found that thedigoxin like substance in their blood was
oleandrin
*Take home message: even topical therapeutic applications
can have strong effects
16. Western Medical Developments
1. Cardiac failure and atrial fibrillation medicine
– Resembles digitalis (digoxin makes digitalis: a cardiac medicine)
1. Cancer treatment (Anvizrel)
– Not supported by FDA
1. Anti-aging Skin treatment (NeriumAD)
– Not supported by FDA
1. Neural protection from ischemic stroke being investigated
• For all medicinal developments, issues with narrow therapeutic range
• Many known and theoretical drug interactions
17. As a Cancer Treatment
• As a cancer treatment (Anvizrel)
• Anvizrel made by Nerium Biotechnology
– Same manufaturer as NeriumAD skincare
• Nerium Biotechnology Claims:
– Inhibits the Na+/K+ pump in cancer cells specifically, inhibiting
protien expression
• Because higher α3:α1 subunit ratio in cancer cells makes them more
susceptible to oleandrin
– Overexpression of the α3 subunit in tumor cells correlates with proliferation
– Blocks activation of NF-kβproliferation signal
– May cause apoptosis of cancer cells
• Did not pass FDA approval
– FDA claims Nerium Biotechnology posted misleading website
information on scientific proof of efficacy in clinical trial
http://www.neriumbiotech.com/cancer_research.htm
18. Protectant Against Ischemic Stroke
• Promising results
– Oleander has been shown to have neural protective
effects against electric shocks
– Oleander has been shown to have anticonvulsant effects
on rat models
19. Drug Interactions
• Usually cardiac in nature
• Interactions may arise from:
– Antibiotics
– Digoxin (and other cardiac medicines)
• Also herbal treatments derived from plants that contain cardiac
glycosides
– Cardiac glycoside toxicity
– Quinine
– Laxatives
– Corticosteroids
• Compounds Na+ retention
– Diuretics
– Calcium supplements
21. Conclusion
• Nerium oleander is highly toxic
– Mainly due to the cardiac glycoside Oleandrin
• Cardiac glycosides may be therapeutically useful
– Used in folk medicine
– May not be safe enough for use in western medicine
• Used currently in industry
– Gunpowder, rodent and insect poisons
22. For the Future
• Legal control of use for landscaping
– Agricultural areas: protect food supply and animals
– Near schools
• More research on adverse effects and specific
mechanisms of other toxins present in N. oleander
• More research on specific effects of interactions
with drugs, supplements, and herbal treatments
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