Atropine: Nature’s Powerful Aid in Critical Care

What is atropine?

Atropine is a tropane alkaloid that naturally occurs in plants of the nightshade family (Solanaceae). Members of this family include deadly nightshade (Atropa belladonna), henbane (Hyoscyamus niger), Angel’s trumpet (Brugmansia spp.) and Jimson weed (Datura stramonium). Atropine acts as an anticholinergic agent, blocking the action of the neurotransmitter acetylcholine in the central and peripheral nervous system.

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The Toxic Properties of Oleander: Understanding the Dangers

The toxic properties of oleander

Is oleander toxic?

Nerium oleander, commonly referred to as ‘oleander‘, is a highly toxic plant native to the Mediterranean basin and Asia. The toxic properties are several cardiac glycosides collectively known as ‘cardenolides including oleandrin, neriine, digitoxigenin, and digitoxin. These toxins disrupt the sodium-potassium pump (Na+/K+ ATPase pump) in the cell membrane. The sodium-potassium pump maintains the proper balance of sodium and potassium ions inside and outside the cell, which is critical for many cellular processes, such as nerve impulse transmission, muscle contraction, and nutrient uptake.

Cardiac glycosides are present in all parts of the oleander tree, including leaves, flowers, stems, roots and seeds. The highest concentration is found in the seeds, followed by the leaves. Dry oleander remains toxic and livestock have been poisoned by drinking water with the fallen leaves. Inhalation of smoke from burning oleander is also toxic.

Oleander poisoning ranks equal to mushroom poisoning for children’s hospital admissions in Australia and as little as one leaf can be fatal to an adult.

What is oleander?

What is oleander?

Botanical nameNerium oleander
Common namesOleander, Common oleander, Rose bay, Soland, Rose laurel
FamilyApocynaceae
Plant typeShrub, Tree
Mature height2 – 6 metres (6.5 – 19.6 feet)
Bloom timeSpring to autumn
Flower colourWhite, red, pink, yellow, orange, cream, purple
Leaf colourGreen
ToxicityToxic to humans, dogs, cats, livestock
Toxic propertiesCardiac glycosides (oleandrin, neriine,
digitoxigenin, and digitoxin)

Oleander is an ornamental shrub or small tree native to the Mediterranean, found in warm climates across the globe that is popular for its fragrant, showy flowers that bloom from late spring to autumn. The plant has long, narrow, leathery leaves that are arranged in whorls, and its five-lobed flowers grow in pink, red, white, cream, orange and purple.

Oleander is a popular ornamental plant due to its showy and fragrant flowers that bloom from late spring to fall, and its ability to tolerate a range of soil types and climatic conditions. The plant has long, narrow, and leathery leaves that are arranged in whorls, and its flowers are typically pink, red, or white and five-lobed. Oleander is also known for its use in traditional medicine, where it has been used to treat various ailments such as asthma, bronchitis, and stomach disorders.

In addition to its ornamental value, oleander has been used in traditional medicine to treat heart conditions, skin irritations and respiratory problems.

It is important for home gardeners to be aware of the plants in their garden and the potential risks some pose. As a pet owner and gardener, oleander is not a plant I would choose to grow due to its high degree of toxicity.

Identification

What does oleander look like?

Leaves

The leaves are long, narrow, and lance-shaped (lanceolate), measuring between 10 – 15 cm long and 2.5 cm wide. Leaf colour is glossy green on the upper surface, with a smooth and leathery texture. The leaves are arranged in pairs or whorls along the branch.

Flowers

The trumpet-shaped flowers have a diameter of 3 – 6 cm and are borne in clusters at the end of the branches. Each flower has five loves that are often ruffled at the edges.

Oleander flowers are showy and trumpet-shaped, with a diameter of 1.5 to 3 inches. Each flower has five petal-like lobes that are often slightly ruffled at the edges. The flowers are borne in clusters at the end of branches and can range in color from white to various shades of pink and red, depending on the cultivar. The flowers typically bloom from late spring through the fall, with a peak bloom period in the summer. The plant also produces a slender, cylindrical seed pod that contains numerous small, feathery seeds.

Toxicity

The toxic properties are oleandrin, neriine, digitoxigenin, and digitoxin, collectively known as cardiac glycosides. Cardiac glycosides are a secondary metabolite that affects the function of the heart by inhibiting the activity of the Na+/K+ ATPase pump. The concentration of these toxins can vary depending on the age of the plant, time of year and environmental conditions. Of all the cardiac glycosides that occur in oleander, oleandrin is the most toxic.

Touching oleander is generally not harmful, however, always wash your hands thoroughly after handling any part of the plant.

Mechanism of action

Oleander contains cardiac glycosides, including oleandrin, which can interfere with the function of the Na+/K+ ATPase pump.

  • Inhibition of Na+/K+ ATPase pump: The primary mechanism of action for oleander toxicity is the inhibition of the sodium-potassium ATPase pump (Na+/K+ ATPase) in cell membranes, particularly in cardiac myocytes (muscle cell). This pump plays a crucial role in maintaining the balance of sodium and potassium ions across the cell membrane, which is essential for generating and propagating electrical impulses in the heart.
  • Disruption of the ion balance and electrical activity: Inhibition of the Na+/K+ ATPase pump causes sodium ions to accumulate in the fluid inside the cell (intracellular fluid), while potassium ions accumulate in the fluid outside the cell (extracellular fluid). This imbalance causes a depolarisation of the cell membrane (a change in the electrical potential across the cell membrane, resulting in a less negative or more positive potential difference between the inside and outside of the cell), which in turn, activates voltage-gated calcium channels, leading to an influx of calcium ions into the cells.
  • Increased intracellular calcium and force of contraction: The increase in intracellular calcium levels enhances the contractile force of the heart (positive inotropic effect) which can lead to excessive workload on the heart and increased oxygen demand, potentially causing arrhythmias, heart failure, or ischemia.

Disruption of the normal electrical activity within the heart due to the altered ion balance can lead to various types of arrhythmias (abnormal heart rhythms) and conduction abnormalities. These disturbances can range from relatively mild, such as premature ventricular contractions (PVCs), to potentially life-threatening, such as ventricular tachycardia or fibrillation.

Severe poisoning can lead to neurological disorders as the toxins affect the balance of neurotransmitters in the brain. Altered ion balance interferes with the generation and propagation of electrical signals in neurons, leading to impaired nerve impulse transmission.

In addition to the toxic effects on the heart, oleander can also cause a variety of extracardiac symptoms due to its action on smooth muscle cells of the gastrointestinal tract.

What is the purpose of cardiac glycosides?

Cardiac glycosides are secondary metabolites (metabolites not involved in the growth or reproduction of the plant) that are produced to protect the plant against herbivory from animals and insects. Other plants known for their cardiac glycosides include foxglove (Digitalis purpurea), lily of the valley (Convallaria majalis), hawthorn (Crataegus spp.), squill (Urginea maritime), Christmas rose (Hellebore spp.) and cascabela (Cascabela thevetia).

How does oleander poisoning occur?

Poisoning may be accidental, or deliberate (attempted murder or suicide). Children and pets are at greater risk due to their curious nature while adults may mistake oleander for a non-toxic species.

Herbal remedies from unknown sources, or using unknown ingredients is another potential risk factor. Always buy supplements and remedies from reputable sources and know what’s in the product.

Burning oleander plant material can release toxic fumes as cardiac glycosides aren’t destroyed by heat.

Poisoning can also occur if food or drink is contaminated with oleander plant parts, such as using oleander branches for skewers, mistakenly using oleander leaves as a food wrap, or brewing tea from the leaves or flowers.

What are the symptoms of oleander poisoning?

Ingesting or contact with any part of the plant can lead to a host of symptoms affecting the cardiovascular, gastrointestinal and neurological systems. The severity of the symptoms can vary depending on the amount of toxin ingested and the individual’s susceptibility, but prompt recognition and treatment are critical for managing the toxic effects and improving the chances of recovery. The following list details some of the most common symptoms associated with oleander poisoning:

Gastrointestinal:

  • Loss of appetite
  • Nausea (possibly with blood)
  • Vomiting
  • Diarrhea
  • Melena (dark, tarry stools caused by the presence of digested blood)
  • Abdominal pain

Cardiac:

  • Palpitations (irregular, rapid, or forceful heartbeats)
  • Bradycardia (slower than normal heartbeat)
  • Tachycardia (faster than normal heartbeat)
  • Arrhythmias (abnormal heart rhythms)
  • Chest pain
  • Dyspnea (shortness of breath)
  • Heart failure
  • Sudden cardiac arrest

Neurological:

  • Dizziness
  • Headache
  • Confusion
  • Disorientation
  • Altered mental status
  • Seizures
  • Coma (in extreme cases)

Dermal:

Dermal contact with oleander sap can cause skin irritation in some individuals. While dermal contact with oleander is generally less dangerous than ingestion or inhalation, it is still important to exercise caution when handling this plant. If you come into contact with oleander sap, wash the affected area thoroughly with soap and water to minimize irritation. If you develop a rash or severe skin reaction, consult a healthcare professional for appropriate treatment.

Use in medicine

Despite its toxic nature, the toxic compounds have potential medical uses.

  • Cardiac applications: Oleander extracts have been historically used in small, controlled doses to treat heart failure and certain arrhythmias. The cardiac glycosides in oleander, exert positive inotropic effects (increasing the force of the heart’s contractions) and negative chronotropic effects (decreasing the heart rate) by inhibiting the sodium-potassium ATPase pump in heart cells, which increases intracellular calcium levels.
  • Anticancer activity: Some compounds derived from oleander have been studied for their potential anticancer effects. One such compound is Anvirzel, a patented extract derived from oleander. Anvirzel has shown promising results in preclinical studies by inducing apoptosis (programmed cell death) in cancer cells. It is thought that the cardiac glycosides in Anvirzel may inhibit cancer cell growth by disrupting cellular metabolism and energy production. Clinical trials are ongoing to evaluate the safety and efficacy of Anvirzel for cancer treatment.

Treatment

There is no specific antidote to oleander toxicity. The goal of treatment is to decontaminate the GI tract to prevent further absorption and manage clinical signs.

  • Gastrointestinal decontamination: If the poisoning occurred through ingestion and the patient presents within one hour of exposure, healthcare providers can induce vomiting to decontaminate the GI tract, this will be followed up with administration of activated charcoal (a highly porous form of carbon with a large surface area and strong adsorptive properties, commonly used to bind to and remove toxins) to bind to any remaining toxins and reduce their absorption in the gastrointestinal tract.
  • Fluid therapy: Intravenous fluids can help maintain blood pressure and hydration, as well as support kidney function and assist in the elimination of toxins and correct electrolyte imbalances.
  • Antiarrhythmic medications: If the patient experiences life-threatening arrhythmias due to oleander toxicity, healthcare providers may administer antiarrhythmic medications to help stabilize the heart rhythm.
  • Digoxin-specific antibody fragments (Digibind or DigiFab): Healthcare providers may consider using digoxin-specific antibody fragments for severe toxicosis. This medication binds  to and neutralises cardiac glycosides, thereby reversing their toxic effects on the heart. Although these antibody fragments were initially developed for digoxin poisoning (cardiac glycoside medication derived from the foxglove plant), they have shown effectiveness in treating severe oleander poisoning as well.
  • Supportive care: Healthcare providers will continue to monitor and manage any symptoms or complications that arise from oleander poisoning, such as treating pain, nausea, or seizures, and providing respiratory support if necessary.

Safety

  • Keep out of reach of children and pets: Make sure oleander plants are planted or stored in areas inaccessible to children, pets, or livestock. Puppies are like toddlers, and they love to explore their world. Unlike toddlers, they have no hands and everything goes into their mouths. As the current owner of a puppy, I have regularly watched her proudly bring branches and sticks into the house to play with. Educate children about the potential dangers of the plant and instruct them not to touch or ingest any part of it.
  • Wear protective gear: Wear gloves, long sleeves, and eye protection when handling oleander.
  • Wash hands and tools: After handling oleander, thoroughly wash your hands and any tools used to avoid accidental ingestion or contact with the toxic compounds.
  • Avoid burning: Never burn oleander plant parts, as the smoke can release toxic compounds that may cause respiratory irritation or other harmful effects if inhaled.
  • Be cautious with plant debris: Dispose of oleander clippings and plant debris carefully. The toxins can remain potent even in dried or dead plant material.
  • Do not use for food preparation: Never use oleander plant parts or utensils that have come into contact with the plant for food preparation or consumption.
  • Seek immediate medical attention: If you or someone you know ingests any part of an oleander plant or experiences symptoms of oleander poisoning (such as vomiting, diarrhea, irregular heartbeat, dizziness, or seizures), seek immediate medical attention.

How long does oleander poisoning last?

The duration of oleander poisoning symptoms varies on the amount of toxin ingested, the individual’s sensitivity to the toxin, and the overall health of the person affected. In general, symptoms of oleander poisoning last anywhere from a few hours to several days.

Initial symptoms such as nausea, vomiting, and abdominal pain may resolve within hours, however, more severe symptoms like cardiac issues, and coma may persist for a longer period. In some cases, it can take several days for the affected individual to fully recover.

Prompt medical treatment is crucial for managing oleander poisoning, as it can help alleviate symptoms and prevent complications. In severe cases, if left untreated, oleander poisoning can be fatal. It is essential to seek immediate medical attention if oleander poisoning is suspected.

Conclusion

  • Oleander is a beautiful and hardy plant that contains a number of potent toxins known as cardiac glycosides.
  • All parts of the plant are toxic to humans and animals upon ingestion or inhalation.
  • Oleander poisoning can lead to a variety of symptoms, including gastrointestinal distress, cardiac arrhythmias, and even death in severe cases. While dermal contact with the plant may cause irritation in some individuals, the risk of toxicity is significantly lower than when ingested.
  • Despite its toxic nature, oleander has been used in traditional medicine and continues to be a favourite among gardeners for its vibrant flowers and hardy nature.

Nettle Stings: How and Why They Happen

Why do nettles sting so much?

What Are Nettles?     The Nettle Family     How Do Nettles Sting?     Chemical Components Of A Nettle Sting   The Purpose Behind Nettle Stings     Effective Remedies     Duration Of Symptoms     Why Don’t Nettles Sting When Eaten?     Nettle Uses

What Are Nettles?

Nettles, also known as stinging nettles, are herbaceous plants that have needle-like hairs on their leaves and stems. These hairs contain a mixture of chemicals that cause a stinging, burning sensation when they come into contact with the skin. This reaction, called urticaria, can result in symptoms such as itching, redness, and swelling.

The Nettle Family


Attribute

Details
Common NameCommon Nettle, Stinging Nettle
Scientific NameUrtica dioica
Native AreaEurope, Asia, North America, North Africa
Type of PlantHerbaceous perennial
FamilyUrticaceae
HeightTypically 3 to 7 feet (1 to 2 metres)
Leaf ShapeHeart-shaped, with a pointed tip
Flower ColourGreenish or brownish
Blooming SeasonSummer
HabitatThrives in rich soil, often in disturbed areas
like edges of fields, roadsides, and gardens
UsesTraditional medicine, culinary (cooked leaves), textile fibres

 

The nettle is a perennial herbaceous plant renowned for its unique defence mechanism – tiny, hair-like structures known as trichomes that cover its leaves and stems. These trichomes deliver a stinging sensation upon contact, releasing a blend of chemical irritants including histamine, acetylcholine, and serotonin.

Native to Europe, Asia, North America, and North Africa, the stinging nettle thrives in rich soil and disturbed areas. Despite its notorious sting, this plant is valued for its versatility; it has uses in herbal medicine, as a culinary ingredient when cooked (which neutralises the sting), and in the production of textiles.

Nettles were likely introduced to Australia by European settlers. Over time, it has spread across various regions, thriving in disturbed soils, which are common in areas of human activity. In Australia, nettles can be found in a range of habitats, including urban areas, gardens, near waterways, and in agricultural lands. They prefer moist, nutrient-rich soils and can often be found in shaded areas.

The name ‘nettle‘ is derived from the Anglo-Saxon word ‘netel‘, which means ‘to sting‘.

How Do Nettles Sting?

Mechanism of action of nettle stings

  • The underside of the leaf and entire stem of the stinging nettle is covered in fine hollow hairs (known as trichomes or spicules) approximately 1 mm long, with a base that is more flexible and a brittle tip. Nettles synthesise and store the neurotransmitters histamine, acetylcholine, serotonin and formic acid which are stored in the base of the trichomes.
  • The tip of the trichome is reinforced with silica, which makes it brittle and easily breakable upon contact. When something brushes against the nettle, the fragile silica tip breaks off, leaving a sharp point. Once the tip is broken, the trichome acts like a hypodermic needle. The pressure from contact forces the chemicals stored in the base of the trichome through the hollow tube and into whatever touched it, like injecting a substance through a needle causing contact urticaria.

Chemical Components Of A Nettle Sting

Inside these trichomes, the nettle produces a cocktail of chemicals. This mixture typically includes histamine, which causes itching and swelling; acetylcholine, which increases pain sensitivity; serotonin, which contributes to pain and discomfort; and formic acid, which can cause a burning sensation.

Acetylcholine

Acetylcholine is a neurotransmitter that activates nicotinic acetylcholine receptors (nAChRs). When acetylcholine interacts with nAChRs on sensory nerve endings in the skin, it triggers the release of histamine, which can hives and itching. Acetylcholine can also increase sensitivity to pain and inflammation in some cases, by activating nociceptors (pain receptors) and promoting the release of pro-inflammatory cytokines.

Histamine

Histamine is a neurotransmitter produced by several living organisms that is involved in several physiological processes. When histamine pierces the skin, it binds to H1 receptors on nerve endings, it activates a signalling pathway involving the protein phospholipase C (PLC). Inositol triphosphate (IP3) and diacylglycerol (DAG) are secondary messengers that are released, which cause an influx of calcium ions into the cells triggering the release of neuropeptides, such as substance P and calcitonin gene-related peptide (CGRP), which activate sensory nerve fibres, transmitting the sensation of itchiness to the brain. Histamine also causes vasodilation, increased blood flow and inflammation in the affected area, which further contributes to the sensation of itchiness.

Serotonin

Serotonin is a neurotransmitter that is involved in the transmission of signals in the nervous system, and it plays a role in inflammation and pain sensation. When released from the trichome, it binds to receptors on sensory nerve fibres, causing them to fire, which sends signals to the brain, that are interpreted as itching, pain and burning.

Formic acid

Formic acid is a small and highly reactive molecule found in the venom of many insects such as bees and ants, as well as one of the chemicals in the trichomes of stinging nettles.  It interacts with nociceptors (pain receptors) located in the skin, triggering the sensation of stinging and burning.

Formic acid also causes inflammation in the skin, leading to redness, swelling and itching.

The Purpose Behind Nettle Stings

Extreme close-ups of stinging nettle stem(Urtica dioica) showing the sting cells or trichome hairs. four times magnification

Plants have adapted several ways to protect themselves against herbivory. Thorns, spikes and prickles, toxins, tough, waxy or hairy leaves, strong odours, inducing the sensation of burning, rapid growth and mimicry. The purpose of the stinging sensation is to deter animals and insects from eating the nettle.

Nettles fall into the toxic category. Plant toxins act as a defence and can range from mild to deadly. While extremely uncomfortable, most cases of nettle exposure are unpleasant, but not serious. However, some people may experience a severe allergic reaction to nettle stings and experience swelling of the face and throat, difficulty breathing, rapid heartbeat and low blood pressure. One person I spoke to recently described being pushed into a crop of nettles as a teenager, experiencing widespread stings that required hospitalisation.

Personal Experience: What Does a Nettle Sting Feel Like?

I would describe the feeling as a sharp and burning sensation along with intense itching. As an active bushwalker and gardener living in Australia, I’m quite often bitten or scratched by various insects and plants. Still, nothing has stung as much as I experienced when I accidentally brushed past some nettles during a visit to England a few years ago. While the discomfort didn’t last for more than an hour or two, it was certainly unpleasant.

Effective Remedies

Dock leaves (Rumex spp.) are a common remedy for relieving symptoms associated with stinging nettles. The exact mechanism of action is unknown but may be due to the mucilage and tannins in the leaves that may help to neutralise the irritant compound from nettles. It is also possible that they offer a placebo effect.

  • Wash the affected area: Use soap and water to wash the affected area and remove any remaining stinging hairs. There are some suggestions that you should wait for ten minutes to allow the chemicals to dry, which will make removing them easier. However, others claim that they should be removed immediately to reduce skin irritation and remove any remaining trichomes.
  • Apply a cold compress: A cold compress can reduce swelling and relieve pain and itching.
  • Topical creams: Over-the-counter corticosteroids or antihistamines can reduce inflammation and relieve itching.
  • Apply a paste of baking soda and water: Mix baking soda with water to make a paste and apply it to the affected area. This can help neutralise the chemicals and relieve symptoms.
  • Take over-the-counter pain relievers such as ibuprofen or paracetamol to relieve discomfort.

Duration Of Symptoms 

Untreated, the symptoms last between 2 – 24 hours, however, treating the affected area can reduce the duration.

Debating the Venomous Nature of Nettles

The jury seems to be out as to whether nettles are venomous or not. Generally, venom is associated with animals such as snakes and spiders which inject their venomous toxin using specialised stingers or barbs. However, the nettle also injects its toxic substance, so is often classed as venomous.

Why Don’t Nettles Sting When Eaten?

When nettles are cooked the heat destroys the trichomes along with the chemicals they contain, making nettles to handle and eat. The heat from cooking causes the trichomes to burst and the chemicals are denatured and broken down. This process is known as hydrolysis. Soaking nettles in water before cooking can also remove some of the chemicals and reduce the stinging sensation.

Nettle Uses

It’s not all bad news when it comes to nettles, they have a long history of culinary and medicinal uses, which include:

  • Antihemorrhagic agent: Nettles have been used to control menstrual bleeding and nosebleeds.
  • Arthritis: The anti-inflammatory properties such as flavonoids, lectins, phenolic acids and triterpenoids may assist with pain and inflammation associated with arthritis. Fresh stinging nettles are applied to the joint in a process known as urtification.
  • Urinary tract infections: Nettles are believed to have diuretic properties which can assist in flushing out the urinary system and prevent urinary tract infections.
  • Skin conditions: The anti-inflammatory and astringent properties of nettles can be used to treat eczema, psoriasis and acne.
  • Allergies: Nettles contain antihistamine compounds which include quercetin, kaempferol and lectins that can help to reduce allergic reactions.
  • Benign prostatic hyperplasia (prostate enlargement): One study¹ involving 287 patients found that the phytosterols, lignans and polysaccharides in nettles were able to significantly reduce the International Prostate Symptom Score (IPSS) score, serum PSA and prostate size.

Nettles have been used as a food source for centuries and are a popular ingredient in many traditional dishes, particularly in Europe. Culinary uses of nettle include nettle soup, pesto, tea and smoothies. Nettles are a great source of A, B, C, and K, proteins, iron, calcium, magnesium, linoleic acid, linolenic acid, palmitic acid, stearic acid, oleic acid, amino acid and antioxidants.

The tough fibres in the stalks of nettles have been used for thousands of years to create strong and durable textiles, such as linen and cordage. Nettle fibre is durable and has a unique texture. In recent years there has been a growing interest in using nettles as a sustainable and eco-friendly alternative to traditional textiles.

Wear protective clothing when harvesting nettles, even when cut down, they can still sting.

References:

  1. Ghorbanibirgani A, Khalili A, Zamani L. The Efficacy of Stinging Nettle (Urtica Dioica) in Patients with Benign Prostatic Hyperplasia: A Randomized Double-Blind Study in 100 Patients. Iran Red Cres Med J. 2013;15(1):9-10. DOI:10.5812/ircmj.2386

Deadly Seeds: The Dangers of Abrin Poisoning

What is abrin?

What is abrin?

Abrin is a ribosome-inactivating protein (RIP) found in the seeds of the rosary pea (Abrus precatorius L.), family Fabaceae. The rosary pea is a herbaceous flowering plant in the legume family, native to Africa, Madagascar, India and Indo-China. The black and red beans have been used to make jewellery in some cultures. The seeds are often strung together to create necklaces and bracelets, and their small size and colourful appearance make them popular for decorative purposes.

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Unraveling Grayanotoxins: Nature’s Toxic Secret

What is grayanotoxin?

What are grayanotoxins?

Grayanotoxins are a type of neurotoxin found in several plants of the Ericaceae family, including rhododendrons, azaleas, and pieris. Grayanotoxins bind to sodium channels on excitable cell (neurons, skeletal, cardiac and smooth muscles) membranes. This causes an influx of sodium ions and depolarisation of the cell leading to prolonged and repetitive action potentials and an overstimulation of the affected cells.  These toxins can cause a range of symptoms when ingested, including gastrointestinal distress, dizziness, and even heart failure in severe cases. Grayanotoxins can also be found in honey made from the nectar of these plants, and consuming large amounts of such honey can lead to a condition known as “mad honey” poisoning. If you suspect that you or someone you know has ingested grayanotoxins, seek medical attention immediately.

Grayanotoxins bind to sodium channels on excitable cell (neurons, skeletal, cardiac and smooth muscles) membranes. This causes an influx of sodium ions and depolarisation of the cell leading to prolonged and repetitive action potentials and an overstimulation of the affected cells.

The action potential is an electrical signal that travels along the neuron that allows it to communicate with other neurons and muscles. At rest, the inside of a neuron has a negative charge and the outside has a positive charge which is maintained by channels in the cell membrane that allow certain ions such as potassium and sodium to move in and out of the cell. When a neuron receives a signal from another neuron or sensory receptor, channels in the cell membrane open, which allows positively charged ions like sodium to enter the cell causing it to become more positive, triggering the opening of additional channels, to allow even more positive ions to flow in.

The first recorded documentation of grayanotoxin poisoning was in 401 when Greek historian and soldier Xenophon documented the effects of mad honey poisoning on soldiers in his work “Anabasis,” describing how the honey caused disorientation, vomiting, and diarrhea.

Related: What are insoluble calcium oxalate crystals?

Sources of grayanotoxins

Grayanotoxins are found in plants belonging to the Ericaceae family, which includes Rhododendrons, Azaleas, and Mountain Laurels which are grown as ornamental plants in gardens around the world. All parts of the plants contain grayanotoxins including the nectar, pollen, flowers and leaves. Grayanotoxin is a secondary metabolite, which is an organic compound produced by plants not directly involved in the growth, development, or reproduction of the organism. Its purpose is to protect the plant against herbivores and pests.

Honey produced by bees that have fed on the nectar of grayanotoxin-containing plants is also a source of toxicity. Mad honey is a type of honey that contains high levels of grayanotoxin, which occurs after bees feed off the nectar of grayanotoxin-producing plants. Many cultures throughout history have used made honey for medicinal purposes to treat a number of medical conditions.

  • Traditional medicine: In some cultures, mad honey has been used for centuries to treat a variety of ailments, including gastrointestinal disorders, hypertension, inflammation, and respiratory infections.
  • Pain relief: Mad honey has been used as a natural painkiller in traditional medicine. It is believed that the grayanotoxins in the honey can act as a natural anesthetic.
  • Wound healing: Mad honey has been used topically to treat wounds. One study found the application of mad honey to diabetic rats enhanced wound healing. This finding potentially has important ramifications for diabetics, as wounds heal slower in diabetics compared to non-diabetics.
  • Anti-inflammatory effects: Some studies suggest that the grayanotoxins in mad honey may have anti-inflammatory effects, which could potentially be useful in treating conditions such as arthritis.

Mad honey
Mad honey

Consumption of mad honey can lead to ‘mad honey poisoning‘, which is the most common source of grayanotoxin poisoning in humans. Symptoms can range from mild to severe and include dizziness, weakness, vomiting, nausea, sweating and abdominal pain. Severe cases can lead to hypotension (low blood pressure) and cardiac arrhythmia (irregular heartbeat), seizures and potentially death from cardiac or respiratory failure. Pets (especially puppies and kittens), livestock and children are at increased risk of consuming toxic plants.

In Turkey and Nepal, mad honey is intentionally produced to use in traditional medicine as well as for its hallucinogenic effects. The Turkish referer to it as deli bal, which loosely translates to ‘crazy honey’ in English. Mad honey has been used as a traditional medicine by the Napalese to treat hypertension (high blood pressure), gastrointestinal disorders, and as an aphrodisiac.

Mad honey is legal in the United Kingdom and the United States but is illegal in South Korea, India, Mexico, Brazil, Canada and Australia.

Mechanism of action

Grayanotoxins can cause excessive and prolonged activation of voltage-gated sodium channels in cell membranes. This causes exaggerated depolarisation of the membrane potential. This can cause a number of physiological effects, such as altered nerve impulse transmission, muscle weakness, and cardiac arrhythmias. The toxic effects can vary depending on the type and concentration, the different tissues and the location and expression of the sodium channels. In the nervous system, grayanotoxin can lead to altered transmission of nerve impulses, leading to tingling, numbness and muscle weakness. Alterations to the heart rate and rhythm can occur in the cardiovascular system, which can be life-threatening.

Clinical signs of grayanotoxin poisoning

Symptoms develop within a few hours of ingestion and last up to 24 hours.

  • Tingling or burning sensation in the mouth and throat, which can lead to difficulty speaking or swallowing
  • Nausea
  • Vomiting
  • Abdominal pain
  • Dizziness
  • Sweating
  • Blurred vision
  • Weakness or paralysis
  • Hypotension
  • Cardiac arrhythmia
  • Hallucinations
  • Aspiration pneumonia due to inhaling vomit
  • Loss of consciousness
  • Death

Symptoms and their severity can vary depending on the dose and type of grayanotoxin. The dose-dependent effects of grayanotoxin are due to the toxin’s ability to interact with voltage-gated sodium channels in the body. At low concentrations, grayanotoxins may only bind to a few of these channels, leading to mild symptoms. However, as the dose increases, more channels are affected, leading to a greater depolarization of the cell membrane and a more severe response.

Factors that influence toxicity:
  • Dose: The toxicity of grayanotoxins is dose-dependent, meaning that higher doses can cause more severe symptoms. Even small amounts of grayanotoxins can be toxic if ingested over a long period of time.
  • Source: Different plants contain different types and levels of grayanotoxin. GTX-I, GTX-II, and GTX-III. GTX-I and GTX-III are the most potent.
  • Route of exposure: The route of exposure influences the toxic effects. For example, oral ingestion of grayanotoxin is more toxic than dermal (skin) contact, due to the protective nature of the skin which acts as a barrier.
  • Other factors: The season when the honey or plant was consumed, (spring honey has higher concentrations compared to other seasons), and the presence of other chemicals or toxins in the plant.

Diagnosis

A diagnosis of grayanotoxin toxicity in humans is based on a history of recent honey ingestion. Animals are more likely exposed via ingestion of plant matter, which can be difficult for a veterinarian to diagnose unless ingestion was witnessed. There is no test available to detect grayanotoxin in the blood.

  • Medical history: The physical will obtain a medical history that can help identify if the patient has had exposure to honey or plants containing grayanotoxin. No prior history of heart abnormalities, low blood pressure, nausea and neurological signs may increase the doctor’s index of suspicion.
  • Physical examination: A physical examination may reveal an abnormal heart rate, irregular heart rhythm, low blood pressure and neurological signs.
  • Electrocardiogram (ECG): A recording of the electrical activity of the heart. The ECG may reveal an irregular heart rhythm or a decreased heart rate.

Treatment

There is no specific antidote to grayanotoxin exposure. Treatment is aimed at preventing further absorption as well as supportive care. This may include:

  • Gastric decontamination: If ingestion was recent, the doctor or veterinarian will administer medication to induce vomiting, or perform gastric lavage (stomach pumping) to evacuate the stomach contents. This will be followed by activated charcoal to bind to any plant matter left behind.
  • Fluid therapy: Intravenous fluids to help flush any remaining toxins out of the body, and maintain hydration and electrolyte imbalances.
  • Saline infusion: A saline infusion increases blood volume which can help patients with mild hypotension and dizziness.
  • Atropine: An anticholinergic drug that blocks the action of acetylcholine, a chemical messenger responsible for muscular movement, heart rate and glandular secretion. In patients with bradycardia, atropine can increase the heart rate.
  • Gastroprotectants: Medications to protect the gastrointestinal tract from damage and irritation due to prolonged vomiting. These either reduce the production of gastric acid or form a protective barrier over the stomach lining.

During treatment, the doctor or veterinarian will conduct electrocardiographic monitoring.

Prognosis

The prognosis for grayanotoxin ingestion depends on several factors such as the amount of toxin ingested, overall health and how fast medical treatment was initiated. For human ingestion of mad honey, most cases will resolve in 24-48 hours with supportive care.

However, in rare cases, particularly when large amounts of the toxin are ingested or when medical treatment is delayed, the prognosis can be more severe, which highlights the importance of prompt medical treatment.

Prevention

Avoid consuming honey from unknown sources. Commercial honey is typically obtained from bees who have fed on the nectar of a variety of plants, versus mad honey from bees who have sourced nectar from grayanotoxin-producing plants such as Rhododendron species.

Most adults are unlikely to ingest grayanotoxin-containing plants. Children and pets are at increased risk due to their curious nature. Puppies in particular will chew on anything and don’t know the difference between a toxic and non-toxic plant. It is important to know which plants are safe to grow in the garden and which are toxic. If you do grow toxic plants, always supervise children and animals, or create barriers around the plants to prevent accidental ingestion.

Conclusion

  • Grayanotoxins are a group of closely related potent neurotoxins found in members of the Ericaceae family. Plants in this family include Rhododendrons, Azaleas, Pieris, Heather, Agarista and Kalmia.
  • The most common route of exposure in humans is the consumption of mad honey. This is a type of honey from bees who have fed from the nectar of plants that contain grayanotoxin. Pets and livestock can be affected if they consume any part of a plant that contains grayanotoxin.
  • Symptoms range from mild to severe and include nausea, vomiting, dizziness, ataxia, hypotension and bradycardia.
  • It is important to seek immediate medical care if you or your pets have consumed grayanotoxin.
  • Prevention includes avoiding honey from unknown sources. Keep pets and children away from toxic plants.

 

The Mystery of the Burn: Unraveling Why Chillies Are Hot

Why are chillies hot?

Why are chillies hot?

Chillies contain a compound called capsaicin, which stimulates pain receptors in the mouth and tongue, causing a sensation of heat and burning. This happens because capsaicin binds to a receptor called TRPV1, which normally responds to heat, and sends signals to the brain that interpret the sensation as pain or heat. Interestingly, some people enjoy the “heat” of chillies, while others find it unbearable. This is because capsaicin also triggers the release of endorphins, which can create a pleasurable sensation for some individuals.

What is capsaicin?

Chillies, also known as hot peppers, contain a compound called capsaicin which is responsible for the burning sensation that they produce. When capsaicin comes into contact with the mucous membranes of the mouth or skin, it binds to a receptor called TRPV1, which is responsible for detecting pain and temperature. This binding triggers a series of chemical reactions that send signals to the brain, resulting in a burning or stinging sensation. Normally, TRPV1 would respond to thermal heat which would illicit an immediate protective response. If a burning hot piece of metal touched any part of our body, we would immediately feel pain and respond by removing ourselves from or dropping the object to prevent further tissue damage.

The amount of capsaicin in a chilli varies depending on the variety and can range from mild to extremely hot. The level of heat in chillies is measured in Scoville units, with higher Scoville ratings indicating a greater concentration of capsaicin. Interestingly, capsaicin is also known to have several health benefits, including pain relief and reducing inflammation.

Chillies aren’t the only plants that activate TRPA1, additional exogenous compounds include mustard oil, horseradish, cinnamon and wasabi.

Capsaicin
Capsaicin chili pepper molecule. Used in food, drugs, pepper spray, etc. Skeletal formula.

Why do chillies produce capsaicin?

Why do chillies produce capsaicin?

Plants have evolved a number of mechanisms to protect themselves against herbivory. Thorns on roses and blackberries, stinging trichomes on nettles, toxic compounds (phytotoxins) such as alkaloids, glycoalkaloids, solanine, amphiphilic glycosides and cyanogenic glycosides.

Chillies produce capsaicin as a means of defence. When an animal or insect chews a chilli, its strong heat is a deterrent. Ordinarily, this wouldn’t make sense as the purpose of fruit (chillies are classed as fruit) is for it to be consumed, which then disperses the seeds elsewhere when they pass out of the body. However, when mammals with teeth chew the chilli pod, the seeds are damaged and unable to germinate. Interestingly, birds have a different heat receptor which doesn’t induce a response to capsaicin, therefore they can eat hot chillies without the unpleasant (or pleasant) sensation of heat. As birds have no teeth to grind (and damage) consumed seeds and have a wide range, the seeds are widely distributed as they pass out of the body intact.

Birds are immune to capsaicin

Scientists in Bolivia have come upon a second reason that chillies are hot. Capsaicin hinders the growth of the fungus Fusarium semitectum, which ordinarily would rot the fruit resulting in the death of the seeds within.

Where does the heat come from?

Capsaicin is synthesised in the placenta, the fleshy interior of the chilli pepper where the seeds are located. The placenta is the hottest part of the chilli and not the seeds. The capsaicin glands are located between the placenta and the seeds and are responsible for the production of capsaicin.

Capsaicin production is influenced by genetics as well as the maturity of the fruit. Some chillies produce more capsaicin than others, which is why some peppers are spicier than others. The amount of capsaicin is measured using the Scoville scale, which ranges from 0 (no heat) to over 2 million (extremely hot).

Chilli placenta

Scoville scale 

Scoville score

The Scoville scale is a measure of the spiciness of chilli peppers and other spicy foods. It was created by Wilbur Scoville in 1912 and is based on the concentration of capsaicin, the compound responsible for the heat in chilli peppers.

Scoville scales range from 0 (no heat) to over 2,000,000 (extremely hot). The scale is a measure of capsaicin concentration in Scoville heat units (SHU). For example, a bell pepper has a Scoville rating of 0, while a jalapeño pepper has a rating of 2,500 to 8,000 SHU. On the other end of the scale, a habanero pepper can have a rating of 100,000 to 350,000 SHU, and the world’s hottest pepper, the Carolina Reaper, has a rating of over 2 million SHU.

How the Scoville scale measures the heat of chillies

  • Scoville organoleptic test: The original test uses dried chillies dissolved in alcohol to extract the capsaicinoids and then diluted in sugar water. This solution is placed onto the tongue of trained testers and is repeatedly diluted until the tester can no longer detect the heat. The Scoville score is assigned based on the number of dilutions required to eliminate the heat, for example, it will take 2,500 to 8,000 dilutions for Jalapeño for the heat to be removed. This test is not entirely reliable due to the different levels of tolerance people have. For example, I can often not detect chilli in a meal while my adult children are unable to eat it because it is so hot.
  • High-performance liquid chromatography (HPLC): This advanced test uses a machine to measure the capsaicin in a dried and ground chilli combined with a solvent. The machine measures the levels of compounds in the sample, producing a graph known as a chromatogram.

Why can some people eat hot chillies?

Some people are able to build up a tolerance to the sensation of heat by gradually introducing hotter and hotter chillies. From personal experience, I was extremely sensitive to any foods with the smallest amount of chilli when I was younger, however, even as a child, my brother enjoyed hot food. I have learned to love hot chillies over time, and now grow some of the world’s hottest chillies in my garden. I will never be able to eat raw habanero the way my brother does.

The sensation we experience when we eat hot food releases feel-good hormones and natural painkillers known as endorphins. Endorphins are released during sex, after running (runner’s high), and in response to pain or stress. In the case of chillies, there is no real danger (in most cases), so we can enjoy the endorphin rush without the danger of a real burn.

How to reduce the burn from a hot chilli

Unfortunately, as capsaicin is hydrophobic (does not mix with water) drinking water is not an effective antidote to the heat from chilli. Milk contains casein, a hydrophobic protein that displaces capsaicin from the sensory receptors.

One test with 72 participants was conducted to test the effectiveness of different beverages in reducing the burn from spicy tomato sauce. The results found: the following in order of effectiveness: 

  • Whole milk
  • Kool-Aid
  • Skim milk
  • Beer
  • Cola
  • Water
  • Seltzer
  • Nothing

An unusual case was reported where a woman accidentally inserted a tampon contaminated with pepper spray. She presented to an emergency department in extreme pain. Doctors administered pain relief and removed the tampon. A lidocaine jelly was administered into the vagina using a speculum, followed by a tampon soaked in pasteurised milk. The woman reported a decrease in pain relief within several minutes.

Remember, a little goes a long way. It is always better to start with a small amount of chilli and add more if the heat isn’t strong enough. We find adding half a hot chilli to a curry gives a nice heat, but isn’t too hot. Adding chillies to raw food such as a salad intensifies the heat as it’s not being diluted in any sauce.

Does cooking chilli over a long period reduce the heat?

Cooking over a longer period doesn’t make the heat any less or more intense, however, as noted above, when adding chilli to a cooked meal that contains a sauce, the intensity tends to be less due to the distribution of capsaicin throughout the entire meal. If you are eating a meal with slivers of chilli, such as a cooked pizza, you are more likely to experience the heat from the chilli.

How to reduce the intensity of chilli in food

Look for chillies with a lower Scoville rating such as bishop’s crown, jalapeno, pepperoncini or banana pepper. You can reduce the heat from hotter chilli varieties by removing the placenta and seeds and using only the outer layers. Although noted below, chillies with a rating of 1 million SHU also have capsaicin present elsewhere, and not just the in placenta and seeds.

What is the hottest chilli in the world?

Carolina reaper, the world's hottest chilliSmokin Ed’s ‘Carolina Reaper’ was officially declared the world’s hottest chilli by Guinness World Records on 17th August 2017. The average Scoville heat unit of the Carolina Reaper is 1,641,183. In second place is the Trinidad Moruga Scorpion.

Super hot chillies are chillies with a SHU above 1 million. Unlike milder chillies where the greatest concentration of capsaicin is in the placenta and seeds, the super hot chillies have additional accessorial vesicles on the pericarp tissue.

Handling chilli safely

When handling hot chillies, always wear disposable gloves and glasses. Wash your hands thoroughly afterwards.

  • Use a knife and fork or food processor when handling chillies to minimize direct contact with your hands.
  • Wear disposable gloves to avoid getting the oils onto your skin.
  • Prepare in a well-ventilated area when working with chillies to avoid inhaling the fumes.
  • Keep a bowl of milk or yoghurt nearby when eating spicy foods to help neutralise the heat.
  • Avoid touching your eyes, nose or mouth when and after working with chillies.
  • Wash hands thoroughly after handling chillies.

If you accidentally rub your eyes after handling chilli, flush with sterile eye wash if you have some handy, or plain water. While water is less effective than other methods, it is better than nothing. Do not use milk to flush your eyes. Artificial tears may be used after the eyes have been flushed to relieve pain.

For external exposure, wash the area with shampoo or soap and water (water alone is ineffective). Oil products such as cooking oil or Vaseline will also reduce discomfort.

Poison Hemlock vs Queen Anne’s Lace: What is the Difference?

What is the difference between poison hemlock and Queen Anne's lace?

Poison hemlock (Conium maculatum) and Queen Anne’s lace (Daucus carota) are biennial plants with similar feather-like leaves and umbel flowers. However, while one is a popular garden plant, the other one is highly toxic. The similarity between the two poses a risk due to the high toxicity of poison hemlock which can easily be mistaken for Queen Anne’s lace.

Poison hemlock

Poison hemlock
Conium maculatum (poison hemlock), Dioscorides Garden, National Herb Garden accession number 64361H. Photo by John Winder, Flickr

Poison hemlock (Conium maculatum) is a biennial plant native to Europe and North Africa but has been introduced to many other parts of the world. It is known for its high toxicity, which can be fatal to both humans and animals. The entire plant, especially the seeds, contains coniine, which disrupts the functioning of the central nervous system. Ingestion of even a small amount can cause vomiting, paralysis, and, in severe cases, death. Historically, the plant has been used as a method of execution, including the famous death of the philosopher Socrates.

Coniine is an alkaloid that acts on the nicotinic acetylcholine receptors at the neuromuscular junction, blocking the transmission of nerve impulses to the muscles. This can lead to muscle paralysis and even death through respiratory failure. Its symptoms of poisoning are often characterised by a burning sensation in the mouth and throat, nausea, vomiting, and abdominal pain, followed by progressive paralysis of the skeletal muscles.

Poison hemlock (Conium maculatum) is different to water hemlock (Cicuta douglasii), which also has a similar appearance. While both plants are highly toxic, and should not be handled or ingested, water hemlock is considered more toxic, in fact, it is the most violently toxic plant that grows in North America.

Related: Water hemlock vs Queen Anne’s lace

Queen Anne’s lace

Queen Anne's lace
Queen Anne’s lace

Also known as wild carrot, Queen Anne’s Lace, is a flowering plant native to temperate regions of Europe and southwest Asia, but has naturalised in North America and Australia. This biennial plant can grow to about 1.5 metres (5 feet) tall and has a distinctive white or chocolate, lace-like flower head, or umbel, which closes up in a cup-like shape once the blooming is over. Interestingly, the flower cluster often contains a single dark purple floret in the centre, a feature considered unique to this species. The stems are hairy, solid, and grooved, and the leaves are finely divided and fern-like. The root is long, thin, and edible while young, with a flavour similar to cultivated carrots.

The sap of Queen Anne’s lace contains furocoumarins. If the sap gets onto the skin and the skin is then exposed to strong sunlight, a rash, blisters, and discolouration may occur, similar to a severe sunburn. This reaction is most commonly associated with handling the leaves and stems of the plant. While the roots and flowers have lower levels of these compounds, caution is still advised, especially for individuals with sensitive skin or known reactions to other plants in the Apiaceae family, such as parsnips or celery.

Difference between poison hemlock and Queen Anne’s lace


Characteristics

Poison
hemlock

Queen Anne’s lace
Scientific NameConium maculatumDaucus carota
FamilyApiaceae (Carrot family)Apiaceae (Carrot family)
OriginsEurope and North AfricaEurope and southwest Asia
Flower colourWhiteWhite, chocolate
Flower typeFlat-topped clustersSmall, white flowers in a flat-topped cluster (umbel), often with a single dark red flower in the centre
Bloom timeEarly to late springSummer to autumn (fall)
BractsAbsentBracts that resemble a bird’s nest,
are located where the flower stems meet the main stalk. They are divided into three or more finely divided, narrow segments, giving them a feathery or spiky appearance.
LeavesAlternate, serratedCompound, pinnate, with finely divided, fern-like leaves
StemChambered, purple blotchesHairy, solid, not mottled or striped
RootRuberousEdible when young, resembles a carrot
SeedsRidges and groovesOval and covered with tiny, fine bristles
SmellUnpleasant, mustyWhen crushed or bruised, the plant (especially the root) smells like a carrot
Height94-300 cm (3-10 feet)94-180 cm (3-6 feet)
HabitatDisturbed areas, moist soilPrefers drier habitats, often found in meadows, pastures, and along roadsides
ToxicityHigh toxicity (cicutoxin)Low toxicity if consumed (furocoumarins)

 Flowers

Poison hemlock vs Queen Anne's lace flowers
Poison hemlock (left), Queen Anne’s lace (right)

Leaves

Poison hemlock vs Queen Anne's lace leaves
Poison hemlock leaf (left), Queen Anne’s lace leaf (right)

Stem

Poison hemlock vs Queen Anne's lace stem
Poison hemlock stem (left), Queen Anne’s lace stem (right)

 

What are Insoluble Calcium Oxalate Crystals?

What are insoluble calcium oxalate crystals?

What are insoluble calcium oxalate crystals?

Insoluble calcium oxalate is a type of biomineral that is commonly found in plants and is made up of small, crystals of calcium and oxalate. These crystals are insoluble in water and other solvents and can accumulate in various tissues and organs of plants. Insoluble calcium oxalate (CaOx) crystals are the most abundant biomineral in plants¹ that can be found in the leaves, stems and roots of over 200 plant families.

The discovery of calcium oxalate crystals was made in the mid-17th century by Marcello Malpighi (1628-1694), an Italian physician, biologist, and anatomist. Dr Malpighi used the newly-invented microscope to examine the internal structure of plants and described them his work ‘Anatome Plantarum‘, which was published in 1675. In his book, he refers to calcium oxalate crystals as ‘sarmenta‘, which he observed in the stems, leaves and roots of a number of plant species.

Calcium oxalate crystals are found in five morphologies:

  • Raphides (needle-shaped crystals)
  • Druses (spherical aggregate of individual crystals)
  • Styloids (elongated crystals with ridged or pointed ends)
  • Prismatic (four or more sides similar in length and width)
  • Crystal sands (minute crystals in a single cell).

The focus of this article is raphides, which pose the greatest risk to humans and animals due to their shape which allows them to penetrate the tissues of the oropharynx and gastrointestinal tract. They can vary in size from micrometres to several millimetres and may be straight, clustered in groups, curved or spiral shaped or branched with multiple needle-like projections.

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Saponins: The Secret to Plant Defense

What are saponins?

Saponins are a class of natural compounds found in many plant species, that typically have a bitter taste. They are characterized by their amphiphilic nature, which means they have both hydrophilic and hydrophobic properties, due to the presence of a hydrophobic triterpene or steroidal sapogenin backbone and one or more hydrophilic sugar molecules attached to it. Saponins play a protective role in plants, serving as a natural defence mechanism against predators and pathogens.

Saponins
Saponins are a class of chemical compounds found in particular abundance in various plant species. More specifically, they are amphipathic glycosides

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