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Family Apocynaceae
Campanero
Cascabela thevetia (L.) Lippold

LUCKY NUT, YELLOW BELL
Huang hua jia zhu tao

Scientific names  Common names 
Cascabela peruviana (Pers.) Raf. Campanilla (Span., Tag.) 
Cascabela thevetia (L.) Lippold Campanero (Span., Tag.) 
Cerbera linearifolia Stokes Narciso amarillo(Span.) 
Cerbera peruviana Pers. Be-still tree (Engl.)
Cerbera thevetia Linn. Bush milk (Engl.)
Thevetia linearis Raf. Lucky nut (Engl.)
Thevetia linearis A. DC. Yellow bell (Engl.)
Thevetia nereifolia Juss. ex A.DC. Yellow oleander (Engl.)
Thevetia peruviana (Pers.) K Schum.  
Thevetia thevetia (L.) H.Karst.         [Invalid]  
In the Philippines, the "yellow flower" is source of great confusion, especially when it refers to "yellow bell" and "kampanilya." Kampanilya is a shared common between two species of plant: (1) Thevetia peruviana, campanilla, campanero and (2) Allamanda cathartica, campanilla, kampanero, goldfen trumpet.
"Yellow bell" is a shared common name by (1) Allamanda cathartica (2) Allamanda neriifolia, and (3) Tecoma stans.
Thevetia peruviana (Pers.) K.Schum. is a synonym of Cascabela thevetia (L.) Lippold The Plant List
Cascabela thevetia (L.) Lippold is an accepted name The Plant List

Other vernacular names
CHINESE: Huang hua jia zhu tao.
FRENCH: Oleandre jaune.
INDONESIA: Ginje, Ki hujan.
MALASIA: Tevetia peru.
THAILAND: Sae nawa, Ban buri, Ram phoei.
VIETNAM: Th[oo]ng thi[ee]n, Hu[yf]nh li[ee]n.

Botany
Campanero is an erect, branched, smooth shrub or small tree growing to a height of 2 to 5 meters, with a copious milky sap. Leaves are linear, glossy and green, 10 to 15 centimeters long, 7 to 10 centimeters wide, stalkless and shining. Calyx teeth are pointed, 7 to 9 millimeters long and green. Corolla is funnel- or bell-shapped, about 7 centimeters long, about 5 centimeters wide, and yellow. The fruit is a drupe, smooth, green, shining, somewhat hard, rounded and angled, 3 to 4 centimeters in diameter.

Distribution
- Widely scattered cultivation as an ornamental plant in Manila and larger towns in the Archipelago.
- Introduced.

- Native to South America.

- Now pantropic.

Parts utilized:
Leaves and bark.

Constituents
- Seeds yield a toxic compounds, mostly cardiac glycosides and their free aglycones such as thevetin, theveridoside, theveside, cerberine, peruvoside, perusitin, and digitoxigenin.
- Study showed that on hydrolysis the glucoside breaks up tino glucose and an amorphous product, thevetidine.
- Seeds yield a fixed oil containing triloein 63%, tripalmitin and stearin, 37%. Also yields equally high protein content of the defatted meal (30-37% protein).
- Thevetin has been classified with the digitaline group so activity on the heart muscle, blood pressure elevation, heart irregularities. It also causes increased intestinal peristalsis, increased salivation, and pupil contraction. Experiments have showed thevetin produces death by asphyxiation and cardiac paralysis. Applied to the skin, it produces convulsions of cerebral origin, and paralysis of spinal origin.
- Flowers yielded quercetin, kaempferol and quercetin-7-o-galactoside.
- Phytochemical evaluation showed the plant to be rich in active constituent, 1.e., a-amyrin acetate, lupeol acetate, a-amyrin, ß-amyrin, lupeol, and thevetigenin.
- Phytochemical screening of leaf extracts yielded bioactive compounds, viz. alkaloids, phenols, flavonoids, steroids, tannins, coumarins, and reducing sugars. (21)
- Fruits yielded alkaloids, steroids, flavonoids and tannins, with the absence of phenolics, saponins, and anthroquinone. (23)

Properties
- Bark is emetic, febrifuge, and antiperiodic.
- Leaves are cathartic.
- Seeds are purgative.
- Milky juice is poisonous and vesicant.

Uses
Folkloric
- In the Philippines, bark decoction, in regulated doses, used as an emetic and febrifuge, especially for intermittent fevers.
- The bitter bark is considered a powerful febrifuge, only grains equal a dose of cinchona. In excess, it is emetic and poisonous.
- Bark is antiperiodic in small doses.
- Leaves used as cathartic.
- In some countries, seeds are chewed for a drastic emetic effect.
- In Bengal and neighboring provinces, seeds also used as abortifacient.
- In Puerto Rico, seeds are used as drastic emetic.
- One kernel of seed produces acro-narcotic symptoms similar to aconite.
- Seeds are bitter and chewed for purgative effect.
- Milky juice considered highly poisonous and used as vesicant.
- Oil is used externally for skin ailments.

Others
- Poison: Used for poisoning fish. In India, highly poisonous seeds used for homicidal and suicidal purposes.

Studies
Antimicrobial: Study of an ethanol extract showed antimicrobial activity which may be attributed to various phytochemicals – flavanoids, phenolics, polyphenols, tannins, terpenoids, sesquiterpenes – effective antimicrobial substances against a wide range of microorganisms. (2) Study of hexane, chloroform, methanol, and ethyl acetate leaf extracts of Cascabela thevetia showed significant antimicrobial activity against tested human pathogens. Chloroform and methanol extracts showing highest activity. (see constituents above) (21)
Antimicrobial: Study showed the extract of T peruviana proved to be effective against E coli, Klebsiella pneumonia, P aeruginosa. It also showed moderate activity against S aureus, C albicans, Aspergillus niger, Mucor, Rhizopus and Penicillium species. (3)
Flavanone and Flavanol Glycosides / Reverse Transcriptase Inhibition: Flavanone and flavonol glycosides from the leaves of Thevetia peruviana and their HIV-1 reverse transcriptase and HIV-1 integrase inhibitory activities: Two new flavanone glucosides and a new flavonol glycoside were isolated from the leaves of T. peruviana and were investigated for their inhibitory effects against HIV-1 reverse transciptase and HIV-1 integrase.
Toxicity Studies / Processing: Study showed that raw Thevetia seed cake, even at a low 5% replacement of soybean meal in the diet, is very toxic and lethal to rabbits. Death may have occurred because of thevetins A and B (cardiac glycosides) and other multisystem effect of toxins. Tp seed cakes need adequate processing to remove toxic agents and anti-nutritive factors. Processing may allow it to be used as a protein supplement in rabbits and other livestock feeds.
Cardenolide Glycosides: Study isolated four cardenolide glycosides and four triterpenoid saponins. Cardenolide glycosides 1 and 2 showed significant reversal effect on TRAIL resistance in human gastric adenocarcinoma cells. (6)
Anti-Termite / Antimicrobial: Thevetia peruviana seed oil was used to make a surface coating with antifungal, antibacterial and anti-termite properties. Results showed T. peruviana-based oil paint was self-preserving against microbes and substantially protected wood from subterranean termites. (9)
High Protein Content / Toxicity Reduction / Seed: Tp seeds have a high oil content and equally high protein content. Seed detoxication is required before the seed can find application as a possible protein source. Previous studies have shown the oilseed protein content can be improved by alcoholic extraction of toxic components to leave a protein concentrate. Study results show the toxic cardiac glucosides of the seed meal can be significantly reduced while increasing the protein content of the residual meal, with a potential of serving as a protein source for animal feed formulations.
Biodiesel-Termite: Emulsified fuels have more priority in reducing nitrogen oide and smoke simultaneously than other fuels. Tp biodiesel emulsified with water in various ratios (5, 10, 15, and 20%) tested for engine performance and emission characteristics showed improvement in brake thermal efficiency with a drastic reduction in NO. The 15% water emulsified fuel showed the best results. (12)
Anti-Inflammatory: In an in vitro evaluation of fresh flowers, an isolated compound showed anti-inflammatory activity with a biphasic property.
Antidiarrheal / Cytotoxic: Study of ethanol-extracted leaves of yellow oleander tested against castor oil-induced diarrhea in a model of albino rats showed significant antidiarrheal activity. Study also showed Tp also possess moderate cytotoxic activity. Antimicrobial ability was poor. (13)
Antispermatogenic / Male Contraceptive: Study of Tp bark methanol extract in male rats showed a decline in spermatogenic elements, with reduction in sperm density and motility, with an 18% residual fertility. Results show an inhibition of spermatogenesis in rats, with a potential for developing a male contraceptive. (14)
Toxicological Studies / Stem Bark, Leaf and Seed Kernel: Comparative study evaluated the toxic effects of extracts of stem bark, leaf, and seed kernel of yellow oleander in albino rats. Rats injected with an aqueous kernel extract died faster than those with the aqueous leaf or stem bark extracts. (16)
Activated Carbon from TP Leaves and Seed Skin: Activated carbon was prepared from Thevetia peruviana leave (TPLC) and seed skin (TPSC) by chemical activation with phosphoric acid. Both TPLC and TPSC showed ability to remove methylene blue from aqueous system and TPSC showed better absorption capacity. Both showed comparable characteristic with commercial activated carbon. (17)
Piscicidal / Bark and Leaves: Sublethal doses of acetone leaf and bark extract caused significant alterations in total protein, free amino acids, DNA and RNA protease and acid and alkaline phosphatase activity in muscle, liver, and gonadal tissues of fish Catla catla in laboratory conditions. (18)
Biologic Activities / Immunomoduation / Cytotoxicity / Twigs: Study of twigs of Thevetia peruviana yielded 17 bioactive compounds. Biological assays on a hydroalcoholic extract demonstrated a broad spectrum of bioactivity such as a four-fold increase in ß-cell proliferation in immunomodulation experiments, strong cytotoxicity in pancreas, lung, prostate, breast, and colon cancer cells and anti-inflammatory activity. (22)
Antifertility / Fruit: Study evaluated the antifertility effect of aqueous, alcoholic, and petroleum ether extracts of Cascabella thevetia fruit in female albino rats. Results showed significant post coital antifertility activity, with reduced number of live fetuses, and increased resorption indes and post implantation losses, with prolonged estrous cycle and diestrus phase in experimental animals. (23)

Caution !
Toxicity Concerns

• All parts of the plant are poisonous, especially the kernels of the fruit.
• As an ornamental plant, accidental ingestion is common.
• Toxic effects of glycosides due to digitalis-like action on the heart and GI irritation (nausea, vomiting, diarrhea, cardiac arrhythmias and varying degrees of heart block.). Other clinical features are drowsiness, dilated pupils. Jaundice and renal failure have been observed. The usual cause of death is ventricular fibrillation.
• In SrI Lanka, the kernel of the seeds has been used in suicide attempts. It is one of the most common poisons used for self-harm in South Asia.
• Although the cardiac glycoside peruvoside has been used for cardiac insufficiency, the margin between therapeutic and toxic is too narrow for it to be a useful therapeutic agent.
• Some authors have suggested between four to seven seeds as the lethal dose. However, other studies have failed to find a simple relationship between number of seeds ingested and outcome. Also, the onset of side effects are variable, with a case reporting a delay of 3 days before the onset of second degree heart block. (8) (10)
• Study described clinico-pathological features. Clinical features included vomiting, diarrhea, drowsiness and dilated pupil, jaundice and renal failure, with varying degrees of heart block. Postmortem showed renal tubular necrosis with obliteration of the liver lumen, focal necrosis around the central vein, and patchy hemorrhages and dilatation of the central veins. (4)
Multi-Dose Activated Charcoal: An unblinded study reported that multiple-dose activated charcoal did not reduce mortality in patients with yellow oleander poisoning. This finding is at variance with the results of our large investigator-blinded study in which multiple-dose activated charcoal significantly reduced mortality. (19)

Availability
Ornamental cultivation.
Wildcrafted.

Godofredo U. Stuart Jr., M.D.

Last Update January 2016

Photos © Godofredo Stuart / StuartXchange
OTHER IMAGE SOURCE / Public Domain / File:Thevetia peruviana Blanco1.45-cropped.jpg / Flora de Filipinas / Franciso Manuel Blanco (OSA), 1880-1883 / Modifications by Carol Spears / Wikimedia Commons

Additional Sources and Suggested Readings
(1)
Thevetia peruviana / Poisonous Plants / IPCS INCHEM
(2)
IN VITRO ANTIMICROBIAL ACTIVITY OF ETHANOL EXTRACT OF THEVETIA PERUVIANA / Ravikumar Patil H. S, Makari, H. K., Gurumurthy H./ Electronic Journal of Environmental, Agricultural and Food Chemistry
(3)
Flavanone and flavonol glycosides from the leaves of Thevetia peruviana and their HIV-1 reverse transcriptase and HIV-1 integrase inhibitory activities / Tewtrakul Supinya et al / Chemical and pharmaceutical bulletin • 2002, vol. 50, no5, pp. 630-635

(4)
Clinico-pathological study of Thevetia peruviana (yellow oleander) poisoning / K K Samal et al / Journal of Wilderness Medicine: Vol. 3, No. 4, pp. 382–386.
(5)
Effect of Thevetia peruviana Seed Cake-Based Meal on the Growth, Hematology and Tissues of Rabbits / V O Taiwo et al / Tropical and Subtropical Agroecosistems 4 (2004):7-14
(6)
Cardenolide Glycosides of Thevetia peruviana and Triterpenoid Saponins of Sapindus emarginatus as TRAIL Resistance-Overcoming Compounds / Takashi Miyagawa et al / J. Nat. Prod., 2009, 72 (8), pp 1507–1511 DOI: 10.1021/np900202n
(7)
Antimicrobial Activity Of Thevetia Peruviana (Pers.) K. Schum. And Nerium Indicum Linn. / B U Reddy / The Internet Journal of Pharmacology. 2010 Volume 8 Number 2
(8)
Acute yellow oleander (Thevetia peruviana) poisoning: cardiac arrhythmias, electrolyte disturbances, and serum cardiac glycoside concentrations on presentation to hospital / M Eddleston, C A Ariaratnam et al / Heart 2000;83:301-306 doi:10.1136/heart.83.3.301
(9)
Anti-termite and antimicrobial properties of paint made from Thevetia peruviana (Pers.) Schum. oil extract / P G Kareru, J M Keriko et al / African Journal of Pharmacy and Pharmacology Vol. 4(2). pp. 087-089, February, 2010
(10)
Epidemic of self-poisoning with seeds of the yellow oleander tree (Thevetia peruviana) in northern Sri Lanka
/ M. Eddleston, C. A. Ariaratnam, W. P. Meyer, G. Perera, A. M. Kularatne, S. Attapatt4, M. H. R. Sheriff, D. A. Warrell / Tropical Medicine & International Health. Vol 4, No 4, pages 266–273, April 1999 / DOI: 10.1046/j.1365-3156.1999.00397.x
(11)
Extractability of Thevetia peruviana glycosides with alcohol mixture
/ Omolara O. Oluwaniyi and Samuel A. Ibiyemi / African Journal of Biotechnology Vol. 6 (18), pp. 2166-2170, 19 September 2007
(12)
THEVETIA PERUVIANA BIODIESEL EMULSION USED AS A FUEL IN A SINGLE CYLINDER DIESEL ENGINE REDUCES NOx AND SMOKE / Kannan T. K. et al / THERMAL SCIENCE, Year 2011, Vol. 15, No. 4, pp. 1185-1191 1185
(13)
Studies on the antidiarrhoeal, antimicrobial and cytotoxic activities of ethanol-extracted leaves of yellow oleander (Thevetia peruviana) / M.M. Hassan, A.K. Saha, S.A. Khan, A. Islam et al / Open Veterinary Journal, (2011), Vol. 1: 28-31
(14)
Phytochemical evaluation and antispermatogenic activity of Thevetia peruviana methanol extract in male albino rats / Gupta R, Kachhawa JB, Gupta RS, Sharma AK, Sharma MC, Dobhal MP. / Hum Fertil (Camb). 2011 Mar;14(1):53-9.
(15)
Thevetia peruviana / Vernacular names / GLOBinMED
(16)
Toxicological studies on stem bark, leaf and seed kernel of yellow oleander (Thevetia peruviana). / Oji O, Okafor QE. / Phytother Res. 2000 Mar;14(2):133-5.
(17)
Preparation of Activated Carbon from Thevetia Peruviana Leave and Seed Skin by Chemical Activation with Phosphoric Acid / Adedirin O*, Akanji FT, Orijajogun OJ,Aguzue OC, Adebisi F, David BM, Osuagwu I, Obigwa PA, Adebiyi, AB / Pharma Research Library
(18)
Piscicidal activity of leaf and bark extract of Thevetia peruviana plant and their biochemical stress response on fish metabolism / S.K. SINGH*, R.P. YADAV, A. SINGH / European Review for Medical and Pharmacological Sciences
(19)
Multiple-dose activated charcoal in yellow oleander poisoning / H Asita de Silva, Arunasalam Pathmeswaran, David G Lalloo, H Janaka de Silva, Jeffrey K Aronson / The Lancet, Volume 371, Issue 9631, Page 2171, 28 June 2008 / doi:10.1016/S0140-6736(08)60949-6
(20)
Cascabela thevetia (L.) Lippold / Synonyms / The Plant List
(21)
Phytochemical Extraction and Antimicrobial Efficacy of Crude Leaf Extract of Medicinal Plant Cascabela thevetia / KM. Sowjanya, K. Narendra, J. Swathi and A. Krishna Satya* / International Journal of Research in Pharmaceutical and Biomedical Sciences, Vol 4(2): Apr-Jun 2013
(22)
Chemical and pharmacological study of the twigs of Thevetia peruviana plant and its bio-activity profiles / Swati A. Save, Usha Padmanabhan, Sweta T. Kothari, Rama S. Lokhande, Abhay .S. Chowdhary / International Journal of Research in Engineering and Applied Sciences, IJREAS, VOLUME 5, ISSUE 6 (June, 2015) (ISSN 2249-3905)
(23)
Antifertility Effect of the Aqueous, Alcoholic and Petroleum Ether Extract of Cascabella thevetia (L.) Fruit in Female Albino Rats / Vandana Deshmukh, Varsha Zade* / International Journal of Pharmaceutical & Biological Archives 2014; 5(4): 60 - 66

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