Cerbera manghas L.

Last updated: 13 July 2016

Scientific Name

Cerbera manghas L.

Synonyms

Cerbera linnaei Montrouz., Cerbera tanghin Hook., Cerbera venenifera (Poir.) Steud., Elcana seminuda Blanco, Odollamia manghas (L.) Raf., Odollamia moluca Raf., Tabernaemontana obtusifolia Poir., Tanghinia manghas (L.) G.Don, Tanghinia veneneflua G.Don, Tanghinia venenifera Poir. [1]

Vernacular Name

Malaysia Bentan, bintaru (Peninsular) [2]
English Sea-mango [2], tanghin, ordeal plant [3]
China Hai mang guo, niu xin qie zi [4]
India Caat aralia, cande, chattankaya, garna, garaunda, garji, hindaramba, kalachedi, kattarali, kodalma, kottuma, monde, sukanu, utalam [4]
Indonesia Bintaro (Java); bintan (Manado); mangga brabu (Moluccas) [2]
Thailand Teenpet lek (Central); teenpet sai (Peninsular); rak khao (Southeastern) [2]
Myanmar Kalwa salat [2]
Philippines Baraibai (Tagalog) [2]
Japan Mi-fukura-gi, okinawa-kyô,-chiku-tô [4]
France Tanghin [3].

Geographical Distributions

Cerbera manghas is originated from the Seychelles towards Indo-China, Taiwan, Thailand, throughout the Malesian area to North-Eastern Australia and Melanesia. [2]

Botanical Description

C. manghas is a member of the Apocynaceae family.It is a shrub or tree that can reach up to measure 25 m tall and its bole is measure up to 70 cm in diametre. [2]

The leaves are narrowly obovate to elliptical in shape, with a size of measuring  5-31 cm x 1-7(-8) cm, measure (1.7-)2.4-7 of length-width ratio, wedge-shaped base, acuminate apex, apiculate or rounded and with 15-40 pairs of secondary veins. [2]

The inflorescence is a few- to many-flowered, measure up to 30 cm long and usually only one flower opens at a time. The sepals are very variable in shape and size, measure 1.2-12 of length-width ratio while the petal tube is narrowly infundibuliform, measuring 17-55 mm long and with 5 lanate scales just below the mouth. The petal lobes are measure 15-50 mm long, usually white in colour, but locally tinged pink or yellow at the base. The stamens are inserted just beneath the mouth and covered by the lanate scales. [2]

The fruit consists of 2 mericarps, ellipsoid in shape, with a size of measuring 5-12 cm x 3-7 cm x 3-5.5 cm and purplish-red or pale green in colour. [2]

Cultivation

Cerbera species are generally associated with water and occur along rivers or streams, in swamp forest and behind mangroves, but may also be found in shrubby savanna or in secondary forest edges. [2]

Chemical Constituent

C. manghas  has been reported to contain (-)-14-hydroxy-3β-(3-O-methyl-6-deoxy-α-L-glucopyranosyl)-11α,12α-epoxy 5β,14β,17βH)-card-20(22)-enolide, (-)-14-hydroxy-3β-(3-O-methyl-6-deoxy-α-L-rhamnosyl)-11α12α-epoxy-(5β,14β,17βH)-card-20 (22)-enolide, (-)-17β-neriifolin, 7,8-dehydrocerberin, 1,3-bis(m-carboxylphenyl)-propan-2-one, 2'-O-acetyl-cerleaside A, 2’-O-acetyl thevetin B, 2-(m-carboxylphenyl)-3-(m-carboxylbenzyl) succinic acid, 17β-neriifolin, 17α-cerdollaside, 17α-deacetyltanghinin, 17α-digitoxigenin β-D-gluco-3-ulosyl-(1→4)-α-L-thevetoside, 17α-digitoxigenin β-D-apiosyl-(1→6)-β-D-glucosyl-(1→4)-α-L-thevetosided, 17α-digitoxigenin β-cellobiosyl-(1→4)-α-L-thevetoside, 17α-digitoxigenin β-gentiobiosyl-(1→4)-α-L-thevetoside, 17α-tanghanigenin β-D-glucos-3-ulosyl-(1→4)-α-L-thevetoside, 17α-neriifolin, 17α-solanoside, 17βH-deacetyltanghinin, 17βH-neriifolin, 17βH-tanghinigenin thevetoside, cerberalignan A–N, cardenolide, (-)-carinol, cerberin, cerberic acid, cerberidol, cerberinic acid, cerbinal, cerdollaside, cerlcaside A, cerleaside B, clitorin, cyclocerberidol, (+)-cycloolivil, D-cycloolivil, deacetyltanghinin, digitoxigenin β-D-gentiotriosyl-(1→4)-α-L-thevetoside, epoxycerberiol, gentiobiosyl thevetoside, glucosyl thevetoside, L-carinol, manghaslin, neriifolin, nicotiflorin, olivil, ruitn, solanoside, tanghinin, tanghinigenin α-L-acofrioside, tanghiningenin thevetoside, theviridoside, theveside, thevetin B. [5][6][7][8][9][10]

Plant Part Used

Leaves, bark, seeds. [3][5][11]

Traditional Use

In Madagascar the bark is considered a laxative while the roots, barks and leaves are purgatives. [3]

The barks, leaves and milky sap of C. manghas are eaten by Filipinos to induce vomiting or purging [11]. The Chinese collects the bark and leaves all year round and used the decoction for constipation [5].

The flowers are used to treat haemorrhoids. [3]

Filipinos and Chinese make use of oil extracted from the seeds in external applications for treatment of skin diseases and as topical anaesthetic [11]. Certain parts of tropical Asia used C. manghas seeds to treat scabies, hair tonic and as fish poison [3].

Preclinical Data

Pharmacology

Antioxidant activity

Olivil, (-)-carinol and (+)-cycloolivil compounds isolated from C. manghas showed antioxidant activities. [6]

Cytotoxic activity

Cardenolide compounds isolated from C. manghas roots were active antiploriferative and antioestrogenic principles against human colon cancer cell line (Col2) and the Ishikawa cell lines. [7]

Cardenolide compounds isolated from C. manghas seeds also exhibited cytotoxic activities against oral human epidermoid carcinoma (KB), human breast cancer cell (BC) and human small cells lung cancer (NCI-H187). [8]

A phenylpropionic acid derivatives namely cerberic acid A isolated from the C. manghas  bark showed weak cytotoxic activitiy against HepG2, MCF-7 and HeLa cell lines. [10]

C. manghas seeds produced cardiac glycosides which are effective in arresting cell cycle and induce apoptosis in human hepatocellular carcinoma HepG2 cells. GHSC-74 was found to induce S and G2 phase arrest of cell cycle and triggering apoptosis via mitochondrial disruption including both caspase-dependent and –independent pathways, and ROS generation. GHSC-73 also behave in similar manner i.e. inhibiting cell growth of HepG2 cells through caspase-dependent and –independent apoptosis pathways. In the case of neriifolin there was evidence that it reduced the viability of HepG2 cells by inducing S and G2/M phase arrest of the cell cycle, and stimulate apoptosis resulting in activation of caspase-3, -8 and -9 and up-regulate expression of Fas and FasL proteins. [12][13][14][15]

Tanghinigenin, a cardiac glycoside from the C. manghas seeds was able to reduce the viability of human promyelocytic leukemia HL-60 cells. The stimulation resulted in a series of intracellular events which includes activation of caspase-3, -8, and -9 and up-regulation of Fas and FasL protein level. [16]

Toxicity

No documentation

Clinical Data

No documentation.

Dosage

No documentation.

Poisonous Management

Toxic parts

Seeds, leaves [3][17]

Toxin

Cardenolisde compounds including cerebrin, 17β-neriifolin, deacetyltanghinin, tanghinin, 2’-O-acetyl-cerleaside A, cerberoside and odollin cerberin. [3][17]

Risk management

C. manghas contains the cardiac glycoside cerberin which blocks normal electrical impulses throughout the body including the heart. It interferes with the exchange of sodium and potassium in and out of nerve and muscle cells. The sap from this tree is irritant to the skin and eyes. Dusts from raking the leaves can irritate the nose and throat, while inhaling smoke from burning trees can cause poisoning. [3]

Ingestion on C. manghas seeds could produce cardiotoxicity similar to oleander poisoning manifested by hyperkalaemia, bradycardia and AV nodal conduction block. The leaves are substantially less toxic than the seeds. [17]

The reported cases of intoxication by neriifolin via ingestion of coconut crab are rather disturbing. Precaution should be taken of eating coconut crab especially those harvested or caught in areas where C. manghas is endemic. The coconut crab is a favorite dish amongst local Chinese population in Malaysia. [18]

Poisonous clinical findings

There was a report of suicidal poisoning by ingestion of the seeds which resulted in cardiac toxicity. In Sri Lanka between 2001 and 2003 there were seven recorded death attributed to cardenolide poisoning due to suicidal ingestion of C. manghas fruits. These individuals showed the typical signs of poisoning due to cardenolide i.e cardiac dysrhythmias and hyperkalaemia. Death was due to inadequate facilities found in Batticaloa Teaching Hospital to handle the poisoning. [19][20]

In New Caledonia two patient died from consumption of Birgus latro (coconut crab). They presented with gastrointestinal symptoms, major bradycardia and marked hypotension with subsequent asystolia. They had significant hyperkalaemia suggestive of digitaline-like intoxication. Postmortem analysis of their blood, C. manghas fruit kernel and the crab’s gut found a common element in them i.e. neriifolin. It was concluded that the intoxication was due to neriifolin which was transmitted through the coconut crab. [18]

Management

No documentation.

Line drawing

109

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

References

  1. The Plant List. Ver1.1. Cerbera manghas L. [homepage on the Internet]. c2013 [updated 2012 Mar 23; cited 2016 Jun 28]. Available from: http://www.theplantlist.org/tpl1.1/record/kew-37166
  2. Khanh TC. Cerbera manghas L. 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. 154.
  3. Lemmens RHMJ. Cerbera mangas L. In: 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. 161–162.
  4. 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. 194.
  5. Guo J, Kimura T, But PPH, Sung CK, editors. International collation of traditional and folk medicine: Northeast Asia Part IV. Singapore: World Scientific, 2001; p. 89–90.
  6. Lee SK, Mbwambo ZH, Chung H, et al. Evaluation of the antioxidant potential of natural products. Comb Chem High Throughput Screen. 1998 Apr; 1(1):35-46.
  7. Chang LC, Gills JJ, Bhat KP, et al. Activity-guided isolation of constituents ofCerbera manghas with antiproliferative and antiestrogenic activities. Bioorg Med Chem Lett. 2000 Nov 6; 10(21):2431-2434.
  8. Cheenpracha S, Karalai C, Rat-A-Pa Y, Ponglimanont C, Chantrapromma K. New cytotoxic cardenolide glycoside from the seeds of Cerbera manghas. Chem Pharm Bull (Tokyo). 2004;52(8):1023-1025.
  9. Zhang XP, Liu MS, Zhang JQ, Kang SL, Pei YH. Chemical constituents from the bark of Cerbera manghas. J Asian Nat Prod Res. 2009;11(1):75-78.
  10. Zhang XP, Liu MS, Pei YH, Zhang JQ, Kang SL. Phenylpropionic acid derivates from the bark of Cerbera manghas. Fitoterapia. 2010;81(7):852-854.
  11. Scott S, Thomas C. Poisonous plants of paradise: First aid and medical treatment of injuries from Hawai'i's plants. Honolulu, Hawaii: University of Hawai'i Press, 2000; p. 37–40.
  12. Feng B, Huang CG, Chen RH, Guo YW, Jiao BH. 2'-Epi-2'-O-acetylthevetin B induces apoptosis partly via Ca(2+)-mediated mitochondrial pathway in human hepatocellular carcinoma HepG2 cells. Cell Biol Int. 2009; 33(9):918-925.
  13. Feng B, Guo YW, Huang CG, Li L, Chen RH, Jiao BH. 2'-epi-2'-O-Acetylthevetin B extracted from seeds of Cerbera manghas L. induces cell cycle arrest and apoptosis in human hepatocellular carcinoma HepG2 cells. Chem Biol Interact. 2010;183(1):142-153.
  14. Feng B, Guo YW, Huang CG, Li L, Jiao BH. β-d-Glucosyl-(1-4)-α-l-thevetosides of 17β-digitoxigenin from seeds of Cerbera manghas L. induces apoptosis in human hepatocellular carcinoma HepG2 cells. Exp Toxicol Pathol. 2012;64(5):403-410.
  15. Zhao Q, Guo Y, Feng B, Li L, Huang C, Jiao B. Neriifolin from seeds of Cerbera manghas L. induces cell cycle arrest and apoptosis in human hepatocellular carcinoma HepG2 cells. Fitoterapia. 2011 Jul;82(5):735-741.
  16. Wang GF, Guo YW, Feng B, Li L, Huang CG, Jiao BH. Tanghinigenin from seeds of Cerbera manghas L. induces apoptosis in human promyelocytic leukemia HL-60 cells. Environ Toxicol Pharmacol. 2010;30(1):31-36.
  17. Barceloux DG. Medical toxicology of natural substances: Foods, fungi, medicinal herbs, plants and venomous animals. Hoboken, New Jersey: John Wiley & Sons; 2012.
  18. Maillaud C, Lefebvre S, Sebat C, et al. Double lethal coconut crab (Birgus latro L.) poisoning. Toxicon. 2010 Jan;55(1):81-86.
  19. Eddleston M, Haggalla S. Fatal injury in eastern Sri Lanka, with special reference to cardenolide self-poisoning with Cerbera manghas fruits. Clin Toxicol (Phila). 2008;46(8):745-748.
  20. Tsai YC, Chen CY, Yang NI, Yang CC. Cardiac glycoside poisoning following suicidal ingestion of Cerbera manghas. Clin Toxicol (Phila). 2008;46(4):340-341.