Cascabela thevetia (L.) Lippold

Scientific Name

Cascabela thevetia (L.) Lippold

Synonyms

Cascabela peruviana (Pers.) Raf., Cerbera linearifolia Stokes, Cerbera peruviana Pers., Cerbera thevetia L., Thevetia linearis Raf., Thevetia neriifolia Juss. ex A.DC., Thevetia peruviana (Pers.) K.Schum., Thevetia thevetia (L.) H.Karst. [Invalid] [1]

Vernacular Name

MalaysiaTevetia peru [2]
EnglishYellow oleander, lucky nut tree [2], be-still tree, bestill nut, exile oil tree, exile tree lucky bean, lucky nut, milk bush, milk tree, thevetia, trumpet flower [3]
ChinaHuang hua jia zhu tao [4]
IndiaAshvaha, bija-mara, cempon, cemponmaram, cimaialari, cimaiyalari cuttavacikam, cuttavacikamaram, gohai takamaran, karavirah, kolka-phul, kolkaphul, manjaalari, marang kanaili, paccha ganneru, pacchaganmeru, pachaarai, pachchaganeru, pachcha-ganneru, pila kaner, pili-kaner, pivala-kanher, sangupoo, sherani, tankarali, tankaralimaram, thivati, tiruvacci, tiruvaccippu, tiruvatci, titivaram, titiravamaran, ucimiliraicceti [3]
IndonesiaGinje, ki hujan (Sundanese) [2][4], oleander (Javanese) [4]
ThailandSae nawa (Northern); ban buri (Bangkok); ram phoei (Central) [2]
PhilippinesCampanero, campanilla (Tagalog) [2]
VietnamTh[oo]ng thi[ee]n, hu[yf]nh li[ee]n [2]
AfricaMbagi (Swahili) [5]
FranceOléandre jaune [2]
South AmericaChilca (Honduras); Cavalonga (Puerto Rico); Caruache (Venezuela); Maichil, Bellaquillo (Peru) [5][6].

Geographical Distributions

Cascabela thevetia is native of Tropical America and West Indies. Today it is distributed widely as an ornamental plant. [7]

In its native habitat, C. thevetia is found in evergreen lowlands or riparian forests from 50-200 m altitude. [2]

Botanical Description

C. thevetia is a member of the Apocyanaceae family. It is a shrub or small tree which can reach up to 8m high. [5][8]

The branches are glabrous, with grey bark and white latex. [5][8]

The leaves are arranged in a spiral manner. They are simple, entire and almost sessile. The leaves are linear-lanceolate, 6-15cm x 0.5-1cm with decurrent base into the short petiole and long-acuminated apex. It is leathery with lateral veins obscure. [5][8]

The inflorescences are terminal and sometimes axillary cyme. The flowers are few with small liner bracts. They are bisexual, regular, 5-merous, faintly fragrant. The corolla tube and lobes are yellow to peach pink. The sepals are ovate, 1 cm long, acute and spreading. The corolla tube is trumpet-shaped. [5][8]

The fruits are in the shape of depressed-globose drupe 3-4 cm in diameter, yellowish-green when young and turning black upon maturing. Each fruit contains 2-4 seeds within a stony endocarp. [5][8]

The seeds are ovoid, 2 cm x 1.5 cm, flattened. [5][8]

Cultivation

No documentation.

Chemical Constituent

C. thevetia has been reported to contain 3-[2″”-sinapoylglucosyl](1 –> 4)[6″‘-sinapoylglucosyl](1 –> 2)galactoside, 5-α-adynerin, α-amyrin, α-amyrin acetate, bernesitol, β-sitosterol, cerebrin, cerebroside, digitoxigenin-α-L-oleandroside, eruvoside-e-monoactetate, gentiobiosyloleandrin, isolupenyl acetate, kaempferol, kaempferol 3-glucosyl(1 –> 4) [6″‘-sinapoylglucosyl] (1 –> 2) galactoside, kaneroside, linoleic acid, linolenic acid, lupeol acetate, lupedienyl acetate, neriifolin, neriperside, neriumoside, odoroside A-H, oleandrin, oleic acid, palmatic acid, perubosidic acid, peruvianoside I-III, peruvianursenyl acetate A, peruvianursenyl glucoside, peruvianursenyl acetate B, peruvianursenyl acetate C; peruvoside; plumericin; quercetin 3-glucosyl(1 –> 2)galactoside, quercetin 3-[6″‘-sinapoylglucosyl](1 –> 2)galactoside, ruvoside, stearic acid, thevebioside, thevefolin, thevelene, theveneriine, theveside, therviriside, thevitin A, and vertiaflavone. [5][9][10][11][12][13]

Plant Part Used

Barks, leaves, roots, seeds (whole plant). [4][5][9][10]

Traditional Use

C. thevetia was traditionally used as cardiotonic, diuretic, anti-inflammatory and anthelmintic. [4][5]

In Indonesia, the leaf is used in the treatment of cardiac failure associated with palpitations. The plant is recognized as a cardiotonic. [5] The bark or leaf decoction is a purgative and an emetic. In Ghana, they used the decoction of the leaves to purge out intestinal worms and to treat jaundice. [4][5] In India, the various parts of the plant are used in the treatment of skin problems. Charaka who is one of the founders of Ayurveda text recommended the use of the leaves of the white variety to treat obstinate and chronic skin diseases including leprosy. Sushruta who is the other pioneer also used the leaves to treat eczema, impetigo and other skin diseases. He also incorporates the plant in a paste for alopecia. The Indians also use seed oil for the same purpose. [4][5][9][10]

In Mali, the latex is applied to soften corns and calluses. [4][5][9][10]

The poison in the plant has been used for specific purposes. In Africa, the bark and seeds are used to poison rats. The seeds mashed with soap is used as insecticide. In Southern Africa and the Cameroon the seeds are used as an arrow or ordeal poison. [5]

The seeds, leaves and bark are also used to induce abortion in Africa. [5]

Preclinical Data

Pharmacology

Antispermatogenesis activity

The methanol extract of the stem bark of C. thevetia was found to inhibit spermatogenesis in male rats. When administered orally at the dose of 100 mg/rat/day to male rats, the following were observed:

  1.     Significant reduction in body weight and weight of reproductive organs
  2.     Significant fall in total protein and sialic acid content of testis, epididymides, seminal vesicle and ventral prostate
  3.     Fall in glycogen in testes and increased in cholesterol
  4.     Decline in spermatogenic elements i.e. preleptoteneand pachytene spermatocytes, secondary spermatocytes, round spermatids and mature Leydig cells.
  5.     Reduction in Leydig cell nuclear diameter, seminiferous tubular diameter and Sertoli area
  6.     Reduction in sperm density and motility. [14]

Emetic activity

Peruvoside, a glycoside obtained from C. thevetia was found to induce vomiting in cats. This action was inhibited by catecholamine depleting drugs (reserpine, tetrabenaxine or syrosingopine, chloropromazine hydrochloride, mepyramine maleate), phenoxybenzamine, and haloperidol. This indicates that catecholamines may play a role in the mechanism of vomiting induced by peruvoside. [15]

Cardiotonic activity

The frequent occurrences of poisoning by ingestion of seeds of C. thevetia provided researchers opportunities to study the cardiotonic effects of the cardiac glycosides present in the seeds. In one review of patients who ingested the seeds, it was found that palpitation occurs in 12% of cases; 46% showed varying types of arrhythmias including sinus bradycardia (49%); 39% showed ischaemic changes. All 14 fatal cases showed subendocardial and perivascular haemorrhage with focal myocardial oedema in the heart. Another observation showed that most symptomatic patients had conduction defects affecting the sinus node , the atrioventricular node or both with very few developing the atrial or ventricular tachyarrhythmias or ventricular ectopic beats seen in digoxin toxicity. These patients had higher mean serum cardiac glycoside and potassium levels, but not magnesium. Administration of C. thevetia to patients with congestive heart failure showed immediate and powerful positive inotropic and negative chronotropic effects. [16][17][18]

Toxicity

Most parts of the plant including the latex, are highly toxic; the seeds most highly so. The active principles are cardiac glucosides of the cardenolide type. The poison mainly affects the cardiovascular system causing various types of arrhythmias, and the gastrointestinal tract. Vomiting is a common symptom of poisoning in about 30% cases, ischaemic changes occur in about 40% and palpitations in about 10%. The most serious and immediate cause leading to death is a peripheral vascular failure. [5]

The cardiac glycosides of C. thevetia are triosides thevitin as the major component of the seeds in a mixture of cerebroside (thevetin B) and thevitin A in a 2:1 ratio or monosides neriifolin, cerebrin, peruvoside, ruvoside and perubosidic acid. [5]

Apart from the cardiac toxicity, animal studies showed that the plant also has marked neurotoxicity producing hind limb paralysis, rolling of the body on the long axis, circular flailing of the tail, muscular twitch, tetanic convulsions, tremors, collapse and death. [15][19][20]

Clinical Data

No documentation

Dosage

No documentation

Poisonous Management

Toxic parts

Whole plant including the latex. The seed kernel contains the highest concentration of the toxins. [5][8]

Toxin

At least 8 different cardiac glycosides of the cardenolide type.  The poison affects the cardiovascular system and the gastrointestinal tract. Thevetin is the bitter principle with potent cardiac action similar to digitalis and 1/8 the strength of ouabain. It also affects the smooth muscles of the intestinge, bladder, uterus and vascular walls. Other cardiac glycosides isolated from the plant include thevetoxin, neriifolin, peruvoside and ruvoside. They have similar effects as thevetin on the smooth muscles of the intestine, bladder, uterus and blood vessels and heart. [5][7][8]

Risk management

Serious effects of poisoning from ingestion of parts of this plant should be a deterrent for use of this plant in any landscape project. It has been reported that the fruits had been taken is suicidal attempts in certain society of the tropics. [5][7][8]

Poisonous clinical findings

Initial symptoms of ingestion of the seeds or leaves are dryness, numbness and burning in the mouth, and throat, followed by abdominal pain, vomiting, and diarrhoea. Subsequent to this, there is dilatation of the pupils, dizziness, slow and irregular heartbeat with high blood pressure. Death may ensue due to heart failure. There may be a delay of up to 24 hours for symptoms to appear. Lethal dose in children is 1 – 2 seeds while in adults more than 8 seeds can prove fatal. The sap can cause skin irritation with blistering. [5][7][8]

Management

Immediate treatment include gastric lavage and giving activated charcoal to the patient. The cardiac function should be frequently monitored through ECG and serum potassium level. Electrolyte monitoring and replacement may be needed. The use of atropine, lidocaine or even propranolol may be required based on levels of toxicity to the heart.  The use of anti-digoxin-specific Fab antibody fragments had been advocated, however, cost is a limiting factor for this form of therapy. [5][7][8]

Line drawing

107
Figure 1: The line drawing of C. thevetia [2]

References

  1. The Plant List. Ver1.1. Cascabela thevetia (L.) Lippold.[homepage on the Internet]. c2013 [updated 2012 Mar 23; cited 2016 May 20] Available from: http://www.theplantlist.org/tpl1.1/record/kew-34836
  2. van Valkenburg JLCH, Horsten SFAJ. Thevetia peruviana (Pers.) K. Schum. In: van Valkenburg JLCH, Bunyapraphatsara N, editors. Plant Resources of South-East Asia No. 12(2): Medicinal and poisonous plants 2. Leiden, Netherlands: Backhuys Publishers, 2001; p. 544-546.
  3. Quattrocchi U. CRC world dictionary of medicinal and poisonous plants: Common names, scientific names, eponyms, synonyms and etymology. Volume II C-D. Boca Raton, Florida: CRC Press, 2012; p. 136
  4. Dalimartha S. Atlas tumbuhan obat Indonesia Jilid 5. Jakarta: Pustaka Bunda, 2008; p. 38-40.
  5. Schmelzer GH, Gurib-Fakim A, editors. Plant Resources of Tropical Africa 11(1): Medicinal plants 1. Wageningen, Netherlands: PROTA Foundation/Backhuys Publishers/CTA, 2008; p. 606-608.
  6. Hanelt P, editor. Mansfeld’s encyclopedia of agricultural and horticultural crops. Berlin: Springer-Verlag, 2001; p. 1745.
  7. Burrows GE, Tyri RJ. Toxic plants of North America. Ames, Iowa: Iowa State Press, 2001; p. 106-107.
  8. Nellis DW. Poisonous plants and animals of Florida and the Caribbean. Sarasota, Florida: Pineapple Press, 1997; p. 146-147.
  9. Khare CP. Indian herbal remedies: Rational western therapy, ayurvedic, and other traditional usage, botany. Berlin: Springer, 2004; p. 328-330.
  10. Jangkaru Z. Tanaman obat pelanchar air seni. Jakarta: Penebar Swadaya, 2007; p. 44.
  11. Abe F, Iwase Y, Yamauchi T, Yahara S, Nohara T. Flavonol sinapoyl glycosides from leaves of Thevetia peruviana. Phytochemistry. 1995;40(2):577-581.
  12. Ali M, Ravinder E, Ramachandram R. New ursane-type triterpenic esters from the stem bark of Thevetia peruviana. Pharmazie, 2000;55(5):385-389.
  13. Tewtrakul S, Nakamura N, Hattori M, Fujiwara T, Supavita T. Flavanone and flavonol glycosides from the leaves of Thevetia peruviana and their HIV-1 reverse transcriptase and HIV-1 integrase inhibitory activities. Chem Pharm Bull (Tokyo). 2002;50(5):630-635.
  14. Gupta R, Kachhawa JB, Gupta RS, Sharma AK, Sharma MC, Dobhal MP. Phytochemical evaluation and antispermatogenic activity of Thevetia peruviana methanol extract in male albino rats. Hum Fertil (Camb). 2011;14(1):53-59.
  15. Gaitondé BB, Joglekar SN. Role of catecholamines in the central mechanism of emetic response induced by peruvoside and ouabain in cats. Br J Pharmacol. 1975;54(2):157-162.
  16. Bose TK, Basu RK, Biswas B, De JN, Majumdar BC, Datta S. Cardiovascular effects of yellow oleander ingestion. J Indian Med Assoc. 1999;97(10):407-410.
  17. Eddleston M, Ariaratnam CA, Sjöström L, et al. Acute yellow oleander (Thevetia peruviana) poisoning: Cardiac arrhythmias, electrolyte disturbances, and serum cardiac glycoside concentrations on presentation to hospital. Heart. 2000;83(3):301-306.
  18. Bhatia ML, Manchanda SC, Roy SB. Haemodynamic studies with peruvoside in human congestive heart failure. Br Med J. 1970;3(5725):740-743.
  19. Pahwa R, Chatterjee VC. The toxicity of yellow oleander (Thevetia neriifolia juss) seed kernels to rats. Vet Hum Toxicol. 1990;32(6):561-564.
  20. Oji O, Okafor QE. Toxicological studies on stem bark, leaf and seed kernel of yellow oleander (Thevetia peruviana). Phytother Res. 2000;14(2):133-135.
in this scope
Malaysian Herbal Monograph​
Medicinal Herbs & Plants Monographs​
Traditional Chinese Medicine Herbs (Professional Data)
Herbal Medicines Compendium (HMC) - U.S​