 Gen info
- Cerebra is a genus of evergreen shrubs or trees. The genus was first described by Carl Linnaeus is 1753 in his work Species Plantarum.
- As per Plants of the World Online, six species remain in the genus: Cerebra dumicola, C. floribunda, C. inflata, C. laeta, C. manghas, and C. odollam. (25)
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Cerebra odollam is a tree species in the family Apocynaceae, commonly known as the suicide tree or pong-pong. It bears a fruit known as othalanga that yields a poison used for suicide and trials by ordeal. (3)
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Cerbera is named after Ceberus, the three-headed dog of Greek mythology that guarded the gate to the Underworld.
Botany
• Cerbera odollam is a dicotyledonous angiosperm, a medium-sized tree up to about 12 meters high, with a round and bushy crown. The branches whorled around the trunk. Petioles are 2 to 5 centimeters long. Leaves are terminally crowded, with tapering bases, acuminate apices, and entire margins. Plant yields a milky white latex. Flowers are large, with a funnel-shaped corolla, five-lobed. Fruit, when green, resembles a small mango. It as a thick green fibrous husk enclosing an ovoid kernel which measures about 2 centimeters by 1.5 centimeters, with two cross-matching white fleshy halves. On exposure to air, the kernel turns violet to dark grey to brown or black.
Distribution
- Native to the Philippines.
- Also native to
Andaman Is., Bangladesh, Borneo, Cambodia, Caroline Is., Cook Is., India, Jawa, Malaya, Marianas, Myanmar, New Caledonia, Nicobar Is., Queensland, Samoa, Society Is., Sri Lanka, Sulawesi, Sumatera, Thailand, Tonga, Tubuai Is., Vanuatu, Vietnam.
- Grows preferentially in coastal salt swamps and marshes.
 Constituents
- Kernels yield cerberin, a digoxin-type cardenolide and cardiac glycoside toxin. (see below)
- Seed total extract yielded the vebioside, Deacetyl-tanghinin, nerifolin, tanghinin, and monoacetylneriifolin (N.G. Bisset). Another study of methanol extract of seed yielded a cardenolide glycoside, along with four known compounds, cerleaside A, 17 alpha-neriifolin, 17 beta-neriifolin and cerberin. (8)
- Study of carbon tetrachloride soluble fraction of a methanol extract of stem bark isolated three compounds i.e., one 14ß (H) steroid, which was established as triticusterol (1) and two benzoic acid derivatives, tentatively characterized as 2,6-dihydroxy-4-methoxy benzoic acid (2) and 2-hydroxy-4-methoxy-6-methyl benzoic acid (3).(see study below) (11)
- Study of air-dried leaves of Cerbera odollam and C. manghas yielded six minor monosides (L-thevetosides of oleagenin and of 8ß-hydroxy-17ß-abd 17α-digitosigenin. I-acofriosides of 17α- and 17α-digitoxigenin and of tanghinigenin), along with the major monosides, 17ß- and 17α-neriifolin and 17ß- and 17α-deacetyltanghinin. (13)
- Successive chromatographic separation and purification of crude methanolic extract and fractions yielded ß-amyrin, lupeol, ß-sitosterone, and triticusterol. (see study below) (15)
- Aqueous leaf extract yielded high content of phenols, tannins, flavonols, and alkaloids, whereas a methanolic extract exhibited higher content of anthocyanin and cardiac glycosides. (see study below) (16)
Properties
- Seeds are poisonous.
- Latex and leaves also reported as toxic.
- Strong cardiotoxic effects.
- Even the wood for a fire can produce a poisonous smoke.
- Studies have suggested anticancer, antinociceptive, antibacterial, antifungal, diuretic, cytotoxic, anti-termite, neuropharmacological, and antioxidant activities.
 Toxicity
- Seeds are used as poison; even one kernel can be fatal.
- Used for suicide and homicide.
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Kernels contain cerberin, a digoxin-type cardenolide and cardiac glycoside that blocks the calcium ion channels in the heart muscle, causing arrhythmias, most often fatally.
- Most common manifestation of poisoning is vomiting. Other common symptoms are burning sensation in the mouth, headache, irregular respiration. In severe cases, coma and deaths.
- Thrombocytopenia (low platelet count) is common.
- The most common electrocardiographic abnormality is sinus bradycardia (slowing of the heart rate), which may require temporary cardiac pacing besides other supportive measure, including atropine administration.
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In Madagascar, where the tree is also found, thousands of people died per year after consuming the seed in "trials by ordeal" believed to determine guilt of witchcraft or other crimes. (12)
- A team led by Yvan Gaillard of the Laboratory of Analytical Toxicology in La Voulte-sur Rhone, France, documented more than 500 cases of fatal Cerbera poisoning between 1989-1999 in south-west Indian state of Kerala.
- In Kerala, India, it is the cause of deaths in more than a half of plant poisoning deaths; one in 10 of all fatal poisonings are attributed to Cerbera.
- Difficulty in detecting cerberin in autopsies and the masking of its taste by strong spices make it a suitable agent of homicide and suicide in India. (3) (See Cerberine toxicity and management) (10)
Parts used
Wood, latex, leaves, seeds.
 Uses
Edibility
- In Bangladesh, a coastal region species is reported as not "too poisonous" and even the locals use the fleshy portion of the fruit as food. (8)
- Used traditionally as emetic, cathartic, in curing hydrophobia and rheumatism. (15)
Folkloric
- Wood used in paralysis. Latex used as emetic and purgative. (8)
Others
- Fruits are used in the manufacturing of bioinsecticides and deodorants. (3)
- Seeds are being studies as feedstock in the production of biodiesel. (3)
- Poison: In the Philippines, seeds used as fish poison. Elsewhere, seeds used as biopesticide, insect repellant, and rat poison.
- Oil: Seed contain a non-selective oil which produces a shining flame with a pleasant nut-like odor. The Burmese use it for lighting, as cosmetic, or mixed with other oils as insecticide or insect repellent. (8)
- Charcoal: Wood produces a fine charcoal that was used as gunpowder by the Thais. (8)
- Wood: Used for non-durable indoor applications.
Studies
• Fruit Extract as Antimicrobial Deodorant Ingredient / No Antimicrobial Effect: Study evaluated a methanolic extract of seed kernel against common skin bacteria viz., Staphylococcus epidermis, Micrococcus luteus, and Propionibacterium acnes. The kernel extract did not record significant antimicrobial effect when compared to Triclosan and Farnesol. Results suggest not viable deodorant benefit. (6)
• Fatality from Intentional Ingestion of C. odollam Seeds: Cerebrin is a cardiac glycoside concentrated in the plant's seeds, which causes disruption of cardiac electrical activity leading to fatal dysrhythmias. This report is a fatal case of intentional seed ingestion. The patient developed high-degree heart block and cardiac arrest despite supportive treatment and digoxin immune fab administration. (7)
• Cytotoxic / Anticancer / Leaves: Leaf extracts were evaluated for cytotoxic activity against two kinds of breast cancer cell lines (T47D and MCF7). Crude fraction were fractionated with butanol, water, and ethyl acetate. All fractions showed strong anticancer activity with lower inhibitory concentration value. (8)
• Quantitative Det3ermination of Cerberin in Seed Extract by HPTLC: Cerberin (2-O-Acetyl neriifolin) is the principal cardiac glycoside in the seeds of C. odollam. The seeds are used as suicidal or homicidal poison, and detection in body fluids is somewhat difficult. This study reports on a HPTLC (high performance thin layer chromatography) method to identify and quantify Cerberin present in the seeds of C. odollam and cerberin in rat serum. The method provided good resolution of Cerberin in ethylacetate/ethanol extract of seeds and rat serum. Method is rapid, simple, precise and may be employed for detection and quantification of cerberin in human serum, aspirates, and other body fluids. (9)
• Cerberin Toxicity / Management: The bioactive toxin of the plant is cerberin, a cardiac glycoside of the cardenolide class. It has a mechanism of action similar to digoxin; hence, toxicity presents like acute digoxin poisoning, with nausea, vomiting, hyperkalemia, thrombocytopenia, and ECG abnormalities. Exposure to high doses carries highest risk of mortality. Initial management includes supportive therapy, administration of atropine followed by temporary pacemaker insertion. Digoxin immune Fab is considered in severe cases, although efficacy is variable, and data limited to isolated reports. (10)
• Antioxidant / Stem Bark: Study of carbon tetrachloride soluble fraction of a methanol extract of stem bark isolated three compounds i.e., one 14ß (H) steroid, which was established as triticusterol (1) and two benzoic acid derivatives, tentatively characterized as 2,6-dihydroxy-4-methoxy benzoic acid (2) and 2-hydroxy-4-methoxy-6-methyl benzoic acid (3). The n-hexane, carbon tetrachloride, chloroform and aqueous soluble fractions of the methanol extract showed moderate to potent antioxidant activity. The chloroform showed strongest activity with IC50 of 21.0 µg/ml. (11
)
• Clinical Profile / Predictors of Mortality in Cerbera Poisoning: In the study, 102 patients were identified with C. odollam poisoning, with a mortality of 126.7%. ECG changes were common, with different types of heart block. Significantly higher mortality was associated with ingestion of more than two kernels, late presentation to the hospital, vomiting, bradycardia, hypotension, hyperkalemia, and more severe ECG changes. (14)
• Antioxidant / Antimicrobial / Leaves: A methanol extract of leaves exhibited high inhibitory concentrations (IC%) value in SO and NO radical scavenging assay, exhibiting antioxidant properties in five antioxidant models. A methanol extract showed some antibacterial activity against B. subtilis, S. aureus, S. typhi, and E. coli with inhibitory zones ranging from 2 mm to 3 mm, while the aqueous extract showed no activity. High anti fungal activity was shown against S. cerevisiae and C. albicans with ZOI ranging from 9 mm to 28 mm. (see constituents above) (16)
• Anticancer / 17ßH-Neriifolin / Leaves: The cytoxicity of the crude methanolic leaf extract and fractions of C. odollam was investigated against two breast cancer cell lines (T47D). two ovarian cancer cell lines (SKOV3 and CaOV3) and a normal (Vero) cell line. Bioassay guided isolation yielded 17ßH-neriifolin as a potential anticancer agent from the leaf. It showed potent anticancer activity with IC50 of 17, 21, 28, 32, and 24 nM against MCF7, T47D, SKOC3, CaOC3 and Vero cell lines, respectively. (17)
• Antibacterial / Cytotoxic / Neuropharmacological Activities / Seeds: Study evaluated a methanolic extract of seeds for antibacterial, cytotoxic, and neuropharmacological activities. The extract showed moderate antibacterial activity against Salmonella typhi, Streptococcus saprophyticus, and Streptococcus pyogenes. It exhibited high level of cytotoxicity against brine shrimp (LC50 3 µg/ml). The extract also potentiated pentobarbital induced sleeping time in mice, along with a significant (p<0.02) decrease in open field score and decrease in number of hole crossed (p<0.001) at dose of 25 mg/kg. (18)
• Antinociceptive / Diuretic / Antibacterial / Roots; Study evaluated a crude methanolic extract of roots for antinociceptive, antibacterial, and diuretic activities in animal models. At doses of 250 and 500 mg/kbw, the extract showed significant antinociceptive effect in acetic acid writhing in mice comparable to aspirin. The extract exhibited significant in vitro antibacterial activity against S. saprophyticus, S. sonnie, S. typhi. V. cholera, S. epidermis,, S. flexneri, and S. aureus with ZOIs in range of 10.76 to 16.34 mm. Diuretic activity was evidenced by electrolyte loss ration (Na+/K+ excretion ration of 1.38 and 1.45 at doses of 200 and 400 mg/kg, respectively, compared to standard of furosemide (1.37). (19)
• Toxicity and CNS Effects / Leaves: Immediate and delayed toxicity of C. odollam leaf extract was studied in mice. Under experimental conditions adopted, the leaves appeared to be relatively devoid of the marked toxicity found in seeds. At doses smaller than maximal dose lethal (14.5 g/kg i.p), the leaf extract decreased mice spontaneous motor activity significantly, increased reaction time to thermal stimulus, reduced the duration of PTZ-induced tonic seizures and mortality, and potentiated sodium pentobarbital-generated hypnotic effects. (20)
• Biodiesel Production from Sea Mango: A catalyst-free and environmentally friendly process was employed for the production of biodiesel from sea mango seed oil. The oil is non-edible and yielded several fatty acids viz., palmitic acid, trans-9-elaidic acid, oleic acid, linoleic acid, and linolelaidic acid. Results indicate the inedible seed is a suitable precursor for biodiesel production. (21)
• Environmentally Friendly Pesticide / Anti-Termite / Liquid Smoke for Pine Wood Preservation / Fruit: Study evaluated the possibility of using liquid smoke from waste of pyrolysis Cerbera odollam friuit
as an environmental friendly pesticide to prevent pine wood from subterranean termite Captotermes curvignathus attack. Results based on anti-termite test, pyrolysis temperature of 300ºC, 400ºC, and 500ºC caused termite deaths of 96.55, 07.56, and 100%, respectively. (22)
• Antinociceptive / Sedative / Bark: Study evaluated a crude methanolic extract of bark of C. odollam for possible antinociceptive and neuropharmacological activities in animal models. At doses of 250 and 500 mg/kbw, the extract showed significant antinociceptive effect in acetic acid induced writhing in mice comparable to aspirin (p<0.001). Extract significantly reduced time of onset of sleep (p<0.01) and significantly (p<0.001) potentiated pentobarbital induced sleeping time in mice at 400 mg/kbw and significantly decreased score in open field test at dose of 400 mg/kbw (p<0.05). Results suggest antinociceptive and neuropharmacological activities of the crude extract of bark. (23)
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