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|Nerium oleander in flower|
|Nerium oleander in flower|
Nerium oleander ( / /) is an evergreen shrub or small tree in the dogbane family Apocynaceae, toxic in all its parts. It is the only species currently classified in the genus Nerium. It is most commonly known as oleander, from its superficial resemblance to the unrelated olive Olea,[Note 1] but has many other names.[Note 2] It is so widely cultivated that no precise region of origin has been identified, though southwest Asia has been suggested. The ancient city of Volubilis in Morocco took its name from the old Latin name for the flower. Oleander is one of the most poisonous of commonly grown garden plants.
Oleander grows to 2–6 m (6.6–20 ft) tall, with erect stems that splay outward as they mature; first-year stems have a glaucous bloom, while mature stems have a grayish bark. The leaves are in pairs or whorls of three, thick and leathery, dark-green, narrow lanceolate, 5–21 cm (2.0–8.3 in) long and 1–3.5 cm (0.39–1.4 in) broad, and with an entire margin. The flowers grow in clusters at the end of each branch; they are white, pink to red,[Note 3] 2.5–5 cm (0.98–2.0 in) diameter, with a deeply 5-lobed fringed corolla round the central corolla tube. They are often, but not always, sweet-scented.[Note 4] The fruit is a long narrow capsule 5–23 cm (2.0–9.1 in) long, which splits open at maturity to release numerous downy seeds.
N. oleander is native or naturalized to a broad area from Mauritania, Morocco, and Portugal eastward through the Mediterranean region and the Sahara (where it is only found sporadically), to the Arabian peninsula, southern Asia, and as far East as Yunnan in southern parts of China. It typically occurs around dry stream beds. Nerium oleander is planted in many subtopical and tropical areas of the world. On the East Coast of the US, it can be planted as far north as Virginia Beach, Virginia, while in Southern California and Texas it is naturalized as a median strip planting.
Theophrastus in his Enquiries into Plants of ca. 300 BCE described among plants that affect the mind a shrub he called onotheras, which modern editors render oleander; "the root of onotheras [oleander] administered in wine," he alleges, "makes the temper gentler and more cheerful."
"The plant has a leaf like that of the almond, but smaller, and the flower is red like a rose. The plant itself (which loves hilly country) forms a large bush; the root is red and large, and, if this is dried, it gives off a fragrance like wine."
In another mention, of "wild bay" (Daphne agria), Theophrastus appears to intend the same shrub.
Oleander grows well in warm subtropical regions, where it is extensively used as an ornamental plant in landscapes, in parks, and along roadsides. It is drought-tolerant and will tolerate occasional light frost down to −10 °C (14 °F). It is commonly used in landscaping freeway medians in California, Texas and other mild-winter states in the Continental United States because it is upright in habit and easily maintained. Its toxicity renders it deer-resistant. It is tolerant of poor soils and drought. Oleander can also be grown in cooler climates in greenhouses and conservatories, or as indoor plants that can be kept outside in the summer. Oleander flowers are showy and fragrant and are grown for these reasons. Over 400 cultivars have been named, with several additional flower colours not found in wild plants having been selected, including red, purple, pink, and orange; white and a variety of pinks are the most common. Many cultivars also have double flowers. Young plants grow best in spaces where they do not have to compete with other plants for nutrients.
Nerium oleander has historically been considered a poisonous plant based on a number of its compounds that may exhibit toxicity, especially to animals, when consumed in high amounts. Among these compounds are oleandrin and oleandrigenin, known as cardiac glycosides, which are known to have a narrow therapeutic index and can be toxic when ingested.
Toxicity studies of animals administered oleander extract concluded that the rodent and avian species were observed to be relatively insensitive to oleander cardiac glycosides. Other mammals, however, such as dogs and humans, are relatively sensitive to the effects of cardiac glycosides and the clinical manifestations of "glycoside intoxication".
However, despite the common "poisonous" designation of this plant, very few toxic events in humans have been reported. According to the Toxic Exposure Surveillance System (TESS) in 2002 there were 847 human exposures to oleander reported to poison centers in the United States. Despite this exposure level, from 1985 through 2005, only three deaths were reported. One cited death was apparently due to the ingestion of oleander leaves by a diabetic man. His blood indicated a total blood concentration of cardiac glycosides of approximately 20 μg/L which is well above the reported fatal level. Another study reported on the death of a woman who self-administered "an undefined oleander extract" both orally and rectally and her oleandrin tissue levels were 10 to 39 μg/g which were in the high range of reported levels at autopsy. And, finally, one study reported the death of a woman who ingested oleander 'tea'. Few other details were provided.
In contrast to consumption of these undefined oleander derived materials, there is no toxicity or deaths reported from topical administration or contact with Nerium oleander or specific products derived from them. In reviewing oleander toxicity Lanford and Boor concluded that, except for children who might be at greater risk, "the human mortality associated with oleander ingestion is generally very low, even in cases of moderate intentional consumption (suicide attempts)."
The safety of parenterally and topically administered Nerium oleander extract and its glycoside constituents, intended for therapeutic application, has been studied in animals and humans. These studies all indicate that administration of Nerium oleander extracts as either a parenteral or topical preparation is safe when doses anticipated for commercial products are applied. Toxicity studies that have been conducted in dogs and rodents administered oleander extracts by intramuscular (IM) injection indicated that on an equivalent weight basis, doses of an oleander extract with glycosides 10-times in excess of those likely to be administered therapeutically to humans are still safe and without any "severe toxicity observed". These pre-clinical studies, which also include oral dosing of oleandrin, were conducted in preparation for an investigational drug submission to the U.S. Food and Drug Administration to allow for administration of the oleander extract to patients with cancer.
A study in which a proprietary, concentrated extract of Nerium oleander (containing oleandrin and other cardiac glycosides) was administered orally to humans for the first time was recently concluded. A concentrated oleander extract (PBI-05204) was formulated for oral consumption was given to 46 cancer patients where doses explored included those from 0.2 mg to 10.2 mg extract/day. These doses were administered daily in cycles consisting of 21 out of every 28 days. The researchers concluded that PBI-05204 was "well tolerated up to the 10.2 mg extract/day dosage" with few significant side effects and with evidence of tumor response.
There does not appear to be any toxicity associated with exposure of a Nerium oleander extract to the skin. Both animal and human studies suggest that dermal application of Nerium oleander extract is safe. In four human studies in which a Nerium oleander extract was applied to the skin of people with different dermal conditions, sensitive mass spectrometry based blood analyses were not able to detect the presence of cardiac glycosides such as oleandrin, indicating that these compounds are not readily absorbed through the skin.
Historically, Nerium oleander has been reported in ancient texts and folklore for more than 1500 years. Used traditionally by herbalists as a folk remedy for a wide variety of maladies and conditions, including dermatitis, abscesses, eczema, psoriasis, sores, warts, corns, ringworm, scabies, herpes, skin cancer, asthma, dysmenorrheal, epilepsy, malaria, abortifacients, emetics, heart tonics, and tumors. It has been used extensively for medicinal purposes in Mediterranean and Central and Southern Asian countries, although these applications also have their basis in folk medicine and efficacy has not been documented by clinical research. Macerated leaves of oleander have been applied topically for treatment of dermatitis, loss of hair, superficial tumors and syphilis. A decoction of oleander leaves has been used for the treatment of gingivitis and as a nose drop for children.
The cardiac glycosides, are known to increase cardiac contractility and have been traditionally used for treatment of congestive heart failure in China. In correct dosages, they are also used as anti-arrhythmic agents to control atrial fibrillation. Additionally, recent research has determined that small quantities of these glycosides are responsible for stimulating effects on the immune system in cancer patients.
Despite their potential for what could be serious side-effects, application of Nerium oleander cardiac glycosides applied intramuscularly (IM) and orally to combat cancers is now being investigated. The National Cancer Institute has defined oleandrin, one of the principal glycosides in Nerium oleander as "A lipid soluble cardiac glycoside with potential antineoplastic activity."
After evaluating all safety and toxicity data, the U.S. Food and Drug Administration determined that a defined Nerium oleander extract is safe enough to be administered to humans by mouth, and a defined Nerium oleander extract is now being used to treat cancer patients under an FDA-approved Investigational New Drug application. At this time the Nerium oleander extract has been administered to over 100 people by injection or mouth at total IM doses of from 0.5 mL to 2.25 mL and oral doses of 0.6 to 10.2 mg/day, for treatment of cancer, with no substantial negative side effects.
With regard to dermal application, three industry-sponsored human studies in which 1 to 2 mL of Nerium oleander extract containing the cardiac glycosides were applied topically on a twice daily basis to 85 subjects with different skin conditions, including sunburn, acne, cold sores and age spots, for up to 30 days. Improvement in some of the conditions was noted, and safety was confirmed by the lack of adverse dermal reactions and by the lack of detectable glycosides in blood samples taken periodically during this 30-day period.
Reactions to ingestion of this plant can include both gastrointestinal and cardiac effects. The gastrointestinal effects can consist of nausea and vomiting, excess salivation, abdominal pain, diarrhea that may or may not contain blood, and especially in horses, colic. Cardiac reactions consist of irregular heart rate, sometimes characterized by a racing heart at first that then slows to below normal further along in the reaction. The heart may also beat erratically with no sign of a specific rhythm. Extremities may become pale and cold due to poor or irregular circulation. Reactions to poisonings from this plant can also affect the central nervous system. These symptoms can include drowsiness, tremors or shaking of the muscles, seizures, collapse, and even coma that can lead to death.
Poisoning and reactions to oleander plants are evident quickly, requiring immediate medical care in suspected or known poisonings of both humans and animals. Induced vomiting and gastric lavage are protective measures to reduce absorption of the toxic compounds. Charcoal may also be administered to help absorb any remaining toxins. Further medical attention may be required and will depend on the severity of the poisoning and symptoms. Temporary cardiac pacing will be required in many cases (usually for a few days) till the toxin is excreted.
Digoxin Immune Fab is the best way to cure an oleander poisoning if inducing vomiting has no or minimal success, although it is usually used only for life-threatening conditions due to side-effects.
Drying of plant materials does not eliminate the toxins. It is also hazardous for animals such as sheep, horses, cattle and other grazing animals, with as little as 100 g being enough to kill an adult horse. Plant clippings are especially dangerous to horses, as they are sweet. In July 2009, several horses were poisoned in this manner from the leaves of the plant. Symptoms of a poisoned horse include severe diarrhea and abnormal heartbeat. There is a wide range of toxins and secondary compounds within oleander, and care should be taken around this plant due to its toxic nature. Different names for oleander are used around the world in different locations, so, when encountering a plant with this appearance, regardless of the name used for it, one should exercise great care and caution to avoid ingestion of any part of the plant, including its sap and dried leaves or twigs. The dried or fresh branches should not be used for spearing food, for preparing a cooking fire, or as a food skewer. Many of the oleander relatives, such as the Desert Rose (Adenium obesum) found in East Africa, have similar leaves and flowers and are equally toxic.
Some invertebrates are known to be unaffected by oleander toxins, and feed on the plants. Caterpillars of the Oleander or Polka-Dot Wasp Moth (Syntomeida epilais) feed specifically on oleanders and survive by eating only the pulp surrounding the leaf-veins, avoiding the fibers. Larvae of the Common Crow Butterfly (Euploea core) also feed on oleanders. The Common Crow larvae retain or modify toxins, making them unpalatable to would-be predators such as birds, but not to other invertebrates such as spiders and wasps.
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