Nerium oleander L.

Last updated: 03 Mar 2017

Scientific Name

Nerium oleander L.

Synonyms

Nerion oleandrum St.-Lag., Nerium carneum Dum.Cours., Nerium flavescens Spin, Nerium floridum Salisb., Nerium grandiflorum Desf., Nerium indicum Mill., Nerium indicum subsp. kotschyi (Boiss.) Rech.f., Nerium indicum var. laucanthum Makino, Nerium indicum f. leucanthum (Makino) Okuyama, Nerium indicum var. lutescens Makino, Nerium indicum var. plenum Makino, Nerium japonicum Gentil, Nerium kotschyi Boiss., Nerium latifolium Mill., Nerium lauriforme Lam., Nerium letuem Nois. ex Steud. [Invalid], Nerium mascatense A.DC., Nerium odoratissimum Wender., Nerium odoratum Lam., Nerium odorum Aiton, Nerium oleander var. indicum (Mill.) O.Deg. & Greenwell, Nerium oleander subsp. kurdicum Rech.f., Neium splendens Paxton, Nerium thyrsiflorum Paxton, Nerium verecundum Salisb., Oleander indica (Mill.) Medik., Oleander vulgaris Medik. [1]

Vernacular Name

Malaysia Bunga anis, bunga jepun, pedendang [2]
English Ceylon rose, common oleander, dog-bane, double oleander, laurier rose, pink bay-tree, rosa laurel, rose bay, rose of Ceylon, rosebay, scented oleander, South Se rose, sweet-scented oleander [2], oleander, rose-bay [3]
India Asvamarakah (asva horse; marakh, killer), ashvamaraka (ashva, horse; maraca, killer), kamili ba, kaner, kanher, karavi-marm, karavira, karvir, lal kaner, rajbaka [2]
Pakistan Jor [2]
Indonesia Bungan kenyeri (Bali) [2]
Philippines Adelfa, baladre, ginataan [2]
Vietnam Cay truc dao, truc dao, truoc dao [2]
Japan Kyô-chiku-tô, chochikutô [2]
Saudi Arabia Haban, khadhraya, ward el-homar [2], defla [3]
South Africa Oleander, rose of Ceylon, Selonsroos [2]
France Laurier rose [2][3]
Italy Oleandro [2]
Ecuador Laurel, laurel-rosa [2]
Mexico Flor de rosa, laurel, mbaj rosa [2]
Nicaragua Narciso [2]
Peru Adelfa laurel, laurel de campo, naranjillo, oleander [2].

Geographical Distributions

Nerium oleander is originated from Morocco, Algeria, Tunisia, and Libya. It also is widely distributed at Mediterranean, south-western Asia and North Africa. [3]

Botanical Description

N. oleander is a member of the Apocynaceae family. It is a perennial shrub which can grow up to 4 m tall. [3]

It has erect stem with profuse branching. [3]

The leaves forms whorls of three, each measuring 10 cm long, evergreen, leathery, simple, entire, lanceolate lengthwise, pointed with median veins which is prominent underneath and a number of secondary veins. [3]

The flowers are strongly aromatic which grows in terminal corymbs. The calyx is shorter than the corolla. There are 5 multifid scales opposing the lobes. The stamens are enclosed and inserted in the middle of the corolla. [3]

The fruits are cylindrical and composed of two fused, linear follicles. [3]

There are many seeds in each fruit, each with a red-haired pappus. [3]

Cultivation

No documentation.

Chemical Constituent

N. oleander leaves was found to contain cardenolides (e.g. oleandrine, uzarigenine, and adynergenine), triterpenoids, resin, tannins, glucose, paraffin, ursolic acid, vitamin C, and essential oil. The seeds contain glucosides (e.g. oleandrine, odorosides, and adigoside). The bark also contains glucosides (e.g. rosaginoside, nerioside, and corteneroside). While the roots were found to contain steroids. [3]

N. oleander leaves was found to contain coumaryloxy triterpenes (e.g. neriucoumaric and isoneriucoumaric acid) [4], labdane diterpene (e.g. oleanderoic); triterpene (e.g. oleanderen) [5], triterpene (e.g. kanerocin); ursolic acid; oleanolic acid [6], triterpenes (e.g.  α-neriursate and ß-neriursate) [7], pentacyclic triterpene, oleanderocioic acid; flavonoidal glycosides (e.g. quercetin-5-O-[α-l-rhamnopyranosyl-(1 → 6)]-β-d-glucopyranoside and kaempferol-5-O-[α-l-rhamnopyranosyl-(1 → 6)-β-d-glucopyranoside, and a cardenolide, oleandigoside) [8].

The root of N. oleander was found to contain cardenolides (e.g.  3β-hydroxy-5α-carda-14(15), 20(22)-dienolide (β-anhydroepidigitoxigenin), 3β-O-(D-digitalosyl)-21-hydroxy-5β-carda-8,14,16 , 20(22)-tetraenolide (neriumogenin-A-3β-D-digitaloside) (2), proceragenin, and neridienone A). [9]

The stems and twigs of N. oleander were found to contain cardenolide monoglycosides (e.g. cardenolides N-1, N-2, N-3, and N-4. [10]

Water extract of N. oleander leaves was found to contain polysaccharides (e.g. galacturonic acid, rhamnose, arabinose and galactose). [11]

Methanol extract of N. oleander leaves was found to contain cardenolide, neridiginoside, nerizoside, neritaloside, and odoroside-H. [12]

Methyl ester extract of N. oleander leaves was found to contain triterpenoid compounds (e.g. 3β,20α-dihydroxyurs-21-en-28-oic acid, 3β,12α-dihydroxyoleanan-28,13β-olide, (20S,24S)-epoxydammarane-3β,25-diol, 3β-hydroxy-12-ursen-28-oic acid, 3β,27-dihydroxy-12-ursen-28-oic acid, 3β,13β-dihydroxyurs-11-en-28-oic acid, 3β-hydroxyurs-12-en-28-aldehyde, 28-norurs-12-en-3β-ol, urs-12-en-3β-ol, urs-12-ene-3β,28-diol, 3β-hydroxy-12-oleanen-28-oic acid, 3β,27-dihydroxy-12-oleanen-28-oic acid, 3β-hydroxy-20(29)-lupen-28-oic acid, 20(29)-lupene-3β,28-diol, and (20S,24R)-epoxydammarane-3β,25-diol. [13]

Ethyl acetate extract of N. oleander leaves was found to contain taraxasterane-type triterpenes (20β,28-epoxy-28α-methoxytaraxasteran-3β-ol and 20β,28-epoxytaraxaster-21-en-3β-ol), together with ursane-type triterpenes (e.g. 28-nor-urs-12-ene-3β,17beta-diol and 3β-hydroxyurs-12-en-28-aldehyde). [14]

Methanol extract of N. oleander stems and twigs were found to contain cardenolide monoglycosides (e.g. cardenolides B-1, and B-2). [15]

N. oleander was found to contain pregnanes (e.g. 21-hydroxypregna-4,6-diene-3,12,20-trione, 20R-hydroxypregna-4,6-diene-3,12-dione, and 16β,17beta-epoxy-12β-hydroxypregna-4,6-diene-3,20-dione), neridienone A, and neridienone B [16], cardenolide diglycoside [17].

Plant Part Used

Roots and leaves. [3]

Traditional Use

In North Africa, N. oleander had been used in the treatment of many conditions including gangrene, eczema, headache and colds, toothache, scabies, lice and alopecia and non-bleeding skin lesions. [3]

N. oleander is used to treat various skin problems for both Africans and Indian. For parasitic infestations like scabies and lice the macerated leaves are applied over the lesion. The crushed leaves are allied over non bleeding skin lesion like bruises, burns and tumours. Scaly skin and leprotic ulcers the oil from the root is applied locally. For ringworm, the paste made from the roots and leaves are recommended. For gangrene, the leaves of N. oleander are pounded with honey and apply it as a poultice. [18]

In ophthalmia with copious lachrymation the Indian makes use of the fresh juice of the leaves. For earache, ear infection with pus discharging the crushed root heated in gingerly oil is dropped into the ear while still bearably warm. [18]

The roots of the N. oleander as a fumigant are used to treat common colds. In India the Santhal tribe makes use of the plant to treat asthma, bronchitis and pulmonary tuberculosis. [3][18]

Dioscorides and Pliny recommend the use of oleander poison in combination with wine and rue as an antidote for snakebite. In India the juice expressed from the leaves is applied over the venomous bites including those of scorpions. The leaves are considered emmenagogue and are used to induce abortion and to treat menorrhagia. [3][18]

Preclinical Data

Pharmacology

Hepatoprotective activity

The methanol extract of the flower of N. oleander exhibited potent antioxidant activity and hepatoprotective activity against CCl4 induced hepatotoxicity in rats. This is evidenced by the normalization of the serum enzymatic level and also in histopathological findings. [19]

Antidiabetic activity

N. oleander extracts improved insulin and glucose level in streptozotocin induced diabetic rats. However, this effect is not as good as glimepiride [20]. On the other hand the N. oleander distillate showed an ability to reduce fasting blood glucose, HbA1c, insulin resistance, total cholesterol, low density lipoprotein, atherogenic index, triglyceride-HDl ratio, and insulin and leptin levels. It also improved beta cell function and HDL concentration. At the same time the distillate enhanced mRNA expression of PPAR (peroxisome proliferator-activated-receptor) - α, ß, and γ in adipose tissue and the PPAR-alpha-gamma in liver [21].

Hypolipidaemic activity

The ethanol extract of N. oleander flowers has been reported to exhibit hypolipidaemic activity. In high-fat diet fed Sprague Dawley rats the extract was found to significantly lower the increased body weight gain, lipid and lipoprotein levels with concomitant increase in HDL in plasma and heart. The activities of lipolytic enzymes were also upheld by the extract. [22]

CNS depressant activity

The CNS depressant activity of the leaves of N. oleander was studies using the methanol extract and bioassay directed fractionation. Two purified fractions (B-1 and B-3) showed reduction in locomotor activity, roat rod performance and potentiation of hexabarbital sleeping time. Both showed protection against convulsion induced by picrotoxin and bicuculline. [23]

Three cardenolides isolated from methanolic extract of N. oleander leaves showed CNS depressant activities. They are 3 β-O-(D-2-O-methyldigitalosyl)-14 β-hydroxy-5 β-carda-16,20(22)-dienolide; 3 β-O-(D-digitalosyl)-14 β-hydroxy-16 β-acetoxy-5 β-card-20(22)-enolide; and 3 β-O-(D-digitalosyl)-14 β-hydroxy-5 β-card-20(22)-enolide. [24]

Neuroprotective activity

Cardiac glycoside oleandrin isolated from supercritical CO(2) extract of N. oleander was demonstrated a neuroprotective activity in brain slice-based stroke models, in vitro and in vivo. Results showed a potent anticancer activity and are currently in phase I clinical trial as a treatment for patients with solid tumours. [25]

Cardiogenic activity

The crude ethanol extract of N. oleander dried leaves was found to exhibit cardiogenic activity by increase the force of contraction, heart rate and cardiac flow in isolated guinea pig heart. [26]

The fresh leaf extract of N. oleander showed changes in adult rat cardiomyocytes and cultured neonatal cardiomyocytes comparable to verapamil and ouabain. These changes include (1) increased intracellular calcium levels in a dose dependent manner; (2) reduced calcium transient heights and eventual cessation of beating; and (3) increased sparking intensity led to subsequent beating and eventual calcium overload. [27]

Oleandrine isolated from hydroethanolic extract of N. oleander flowers was reported to inhibit ryanodine receptor calcium release channels, calcium uptake via Na+, K+ - ATPase inhibition and/or dysfunction of sarcolemmal calcium release channels. [28]

Antimicrobial activity

Several extracts of dried leaves of N. oleander containing alkaloid, terpenoids, cardiac glycosides, saponins, tannins and carbohydrates, showed antibacterial activities against Staphylococcus aureus, Pseudomonas aeruginosa and Salmonella typhimurium. [29]

Oleandrin isolated from the aqueous extract of N. oleander was found to significantly reduce the expression of the envelope protein gp120, the sole determinant of virus activity, of HIV. [30]

Cytotoxic activity

Oleandrin is a cardiac glycoside that is present in aqueous extract of the leaves of N. oleander and is the active component of a proprietary drug Anvirzel. This compound was found to have anticancer activities. It blocked TNF-induced activation of NF-ΚB in a concentration and time-dependent manner [31]. This effect seems to be species specific [32]. Amongst the human cancers that were found to be inhibited by Anvirzel and oleandrin include human prostatic cancer PC3 and DU145 [33], human pancreatic cancer [34], and human melanoma BRO [35].

Oleandrin (trans-3,4',5-trihydroxystilbene), a polyphenolic cardiac glycoside derived from the leaves of N. oleander was found to blocked ceramide-induced NF-ΚB activation. Oleandrin-mediated suppression of NF-ΚB was not restricted to human epithelial cells; it was also observed in human lymphoid, insect, and murine macrophage cells. [36]

Oleandrin, derived from the leaves of N. oleander, has been shown to possess antitumour activity. Topical application of oleandrin (2 mg per mouse) 30 min before TPA (3.2 nmol per mouse) application onto the skin afforded significant inhibition, in a time-dependent manner, against TPA-mediated increase in cutaneous edema and hyperplasia, epidermal ornithine decarboxylase (ODC) activity and ODC and cyclooxgenase-2 (COX-2) protein expression. [37]

Cardenolide isolated from the cold aqueous extract of N. oleander leaves was found to exhibit anticancer in human tumour cell lines. The results indicate that the cytotoxic effects are induced by the inhibition of the plasma membrane bound Na(+)/K(+)-ATPase. [38]

Pharmacokinetic activity

Pharmacokinetic studies of [3H]oleandrin, a cytotoxic component of N. oleander, were conducted in mice after either an i.v. dose (40 µg/kg) or a p.o. dose (80 µg/kg). Results obtained show an oral bioavailability of approximately 30%. [39]

Toxicity

No documentation.

Clinical Data

Clinical findings

Precautions

Anticancer activity

Anvirzel is an aqueous extract of N. oleander has been utilized to treat patients with advanced malignancies. The current study reports a phase 1 trial to determine the maximum tolerated dose (MTD) and safety of Anvirzel in patients with advanced, refractory solid tumours. Patients were randomized to receive this agent by intramuscular injection at doses of 0.1, 0.2, 0.4 mL/m2/day with subsequent patients receiving 0.8 or 1.2 mL/m2/day sequentially. Most patients developed mild injection site pain (78%). Other toxicities included fatigue, nausea, and dyspnea. [40]

Side effects

No documentation.

Pregnancy/Breast Feeding

Preparations containing N. oleander should not be taken by pregnant and lactating women. This plant had been used to induce abortion. [18]

Age limitation

Being considered a toxic plant, preparations containing N. oleander should not be given to children for whatever purpose. [18]

Adverse reaction

Unsupervised intake of herbal preparation containing N. oleander leaves had resulted in victims developing digitalis-like intoxication symptoms. [41]

Interaction & Depletion

Interaction with drug

The presence of cardiac glycosides in the substance of the plant presents a potential interaction of summative effects when taken with digitalis. There had been reports of death in patients on digoxin ingesting herbal tea containing N. oleander. It has been proven that the plant can potentiate the effects of barbiturates. Its antidiabetic activity can potentiate hypoglycaemia in patients on anti-diabetic therapy. [20][21][23][24][25][26]

Interaction with other Herbs

No documentation.

Case Report

From 1985 to 2012 there had been 13 case reports of poisoning due to ingestion of N. oleander leaves either accidentally or intentionally. The plant is classified as highly poisonous with the toxic component being its content of cardiac glycosides [42]. There have been reports of death from consumption of the plant parts either in fresh form or processed form. Of these 3 cases were reported fatal [43][44][45]. There was even a case report of a couple developing symptoms and signs of toxicity by consuming escargot stew. Analysis of the snail showed significant levels of cardiac glycosides derived from N. oleander namely oleandrin [46]. The non-fatal cases usually presented with gastrointestinal symptoms which were nausea, vomiting and diarrhoea [47][48][49]. Detectable cardiac symptoms included bradycardia, tachycardia, first and second degree of atrioventricular nodal block and digitalis-like toxicity changes in ECG (e.g. ST-T wave changes) [41][50][51][52][53][54][55][56]. 

Dosage

No documentation.

Poisonous Management

Toxic parts

Whole plant especially the leaves and flowers. [57][58]

Toxin

The plant contains several cardiac glycosides which are the toxic principles present. This cardiac glycoside includes neriin (nerioside), oleandrin (oleandroside), folinerin, rosagenin, conevin, pseudocuranine, rutin and cortenerin. The total glycoside of each plant makes up as much as 0.5% of the weight of the plant at various seasons of the year. The red-flowered from seem to have more glycosides than the white variety. [3][58]

All parts of the plant contain the toxic glycosides. Even smoke from burning wood and honey extracted from flowers are poisonous. There have been reports of poisoning even by drinking water from wells where the leaves and flowers had fallen into. A baby was reportedly died following consumption of milk from a cow that had consumed oleander leaves. [3][58]

Risk management

No documentation.

Poisonous clinical findings

The cardiac glycosides produce symptoms almost similar to digitalis poisoning. These include bradycardia, dysarrhythmias, abdominal cramps with vomiting and diarrhoea, dizziness, persistent headache, fatigue, drowsiness and dilated pupils, loss of visual acuity with blurred or aberrant colour vision. In more severe cases, convulsions, respiratory failure, coma and death are a possibility. A red flush around the mouth has been reported in cases of intoxication and fatalities. [57][58]

Local symptoms include rashes in sensitive people. [58]

Management

Gastric lavage to remove as much of the plant material as possible immediately. This is followed by providing slurry of activated charcoal. [58]

Rapid acting cathartic should be given in order to remove any plant materials that had escaped into the small intestines. [58]

Monitoring of serum potassium and cardiac function by electrocardiogram in all cases as a way of monitoring the effects of nerin and oleandrin in circulation. [58]

Treatment similar to that of digitalis poisoning. The old method of using atropine and propranolol is still equally effective where digoxin-specific Fab antibody fragments are not available. [58]

Line drawing

No documentation.

References

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