Articles

Cerbera manghas

Synonyms

Cerbera veneifera (Poir.) Steud., Manghas lactescens Burm, Arbor lactaria Rumph.

Vernacular Names:

English:   Sea Mango, Tanghin, Ordeal Plant
Indonesia:  Bintaro (Java)
China:   Hai Mang Guo
Vietnam:  Cay-muap-sac
India:  Dabur, Dhakur
Hong Kong:  Hoi Mong Gwor
Arabic:  Jubla Hunk
French:  Tanghin [2] [3]

General Information

Description

Cerbera manghas is a member of the Apocynaceae family. It is a shrub or small tree reaching up to 20m high. The bole is glabrous reaching up to 70cm in diameter. The bark is thick, rough, peeling off, with large lenticels, grey to dark brown. All parts oozes white latex. The leaves are arranged spirally in terminal clusters. They are simple and entire with petiole 1.0-1.5cm long. The blade is narrowly obovate, 5-30cm long and 1-8cm wide, cuneate at the base and shortly acuminate at the apex. They have a leathery texture and veins are pinnate with 15-40 pairs of lateral veins. Inflorescence in terminal cymes consist of many flowers. The peduncle is 1.5-12.0cm long; bracts are as long as the sepals, deciduous. The flowers are bisexual, regular, 5-merous and fragrant. The pedicel is 0.5-3.0cm long; sepals are ovate or obovate 1.0-3.5cm x 0.5cm, spreading to recurved; corolla tube funnel-shaped, 1.5-5.5cm long, widened at the apex, pale green with white or pale yellow scales in the throat, hairy inside, lobes obliquely elliptical or obovate, 1.5-3.0cm x 1-2cm, spreading to recurved, white but pink at the base. The stamens are inserted just below the top of the corolla tube, included, and covered by scales of corolla tube. The anthers are sessile. The ovary is superior, globose, and consists of 2 separate carpels. The style is long and slender with pistil head consisting of a 5-ridged basal part, a veil and a cone-shaped apex. The fruit consist of 1 or 2 separate or basally fused, drupe-like, ellipsoid follicles 5-12 cm x 3-7cm, rounded at both ends, dark red when mature. They are indehiscent and usually contain a single seed. The seed is flattened and orbicular in shape and measures 2.5cm in diameter, with a small wing at the apex. [3]

Plant Part Used

Leaves, bark, seeds. [1] [2] [3]

Chemical Constituents

(-)-14-hydroxy-3beta-(3-O-methyl-6-deoxy-alpha-L-glucopyranosyl)-11alpha,12alpha-epoxy 5beta,14beta,17betaH)-card-20(22)-enolide; (-)-14-hydroxy-3beta-(3-O-methyl-6-deoxy-alpha-L-rhamnosyl)-11alpha12alpha-epoxy-(5beta,14beta,17betaH)-card-20 (22)-enolide; (-)-17beta-neriifolin; 3beta-O-(2'-O-acetyl-alpha-L-thevetosyl)-14beta-hydroxy-7-en-5beta-card-20(22)-enolide, (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; 17beta-neriifolin; 17a-cerdollaside; 17a-deacetyltanghinin; 17a-digitoxigenin b-D-gluco-3-ulosyl-(1à4)-a-L-thevetoside; 17a-digitoxigenin b-D-apiosyl-(1à6)-b-D-glucosyl-(1à4)-a-L-thevetosided; 17a-digitoxigenin b-cellobiosyl-(1à4)-a-L-thevetoside, 17a-digitoxigenin b-gentiobiosyl-(1à4)-a-L-thevetoside; 17a-tanghanigenin b-D-glucos-3-ulosyl-(1à4)-a-L-thevetoside; 17a-neriifolin; 17a-solanoside; 17bH-deacetyltanghinin; 17bH-neriifolin; 17bH-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 b-D-gentiotriosyl-(1à4)-a-L-thevetoside; epoxycerberiol; gentiobiosyl thevetoside; glucosyl thevetoside; l-carinol, manghaslin, neriifolin; nicotiflorin; olivil; ruitn; solanoside; tanghinin; tanghinigenin a-L-acofrioside; tanghiningenin thevetoside; theviridoside; theveside; thevetin B. [2] [5] [6] [7] [8] [9]

Traditional Used:

Gastointestinal diseases

The barks, leaves and milky sap of C. manghas are eaten by Filipinos to induce vomiting or purging. The Chinese collects the bark and leaves all year round and used the decoction for constipation. In Madagascar the bark is considered a laxative while the roots, barks and leaves are purgatives. The flowers are used to treat haemorrhoids. [1] [2] [3]

Other uses

Filipinos and Chinese make use of oil extracted from the seeds in external applications for treatment of skin diseases and as topical anaesthetic. Certain parts of tropical Asia used C. manghas to treat scabies, hair tonic and as fish poison. [1] [2] [3]

Pre-Clinical Data

Pharmacology

Antioxidant activity

Three compounds isolated from C. manghas (olivil, (-)-carinol and (+)-cycloolivil) showed antioxidant activities. [5]

 Cytotoxic activity

Three cardenolide compounds isolated from the roots of C. manghas were active antiploriferative and antioestrogenic principles against human colon cancer cell line (Col2) and the Ishikawa cell lines. The compounds were (-)-14-hydroxy-3beta-(3-O-methyl-6-deoxy-alpha-L-rhamnosyl)-11a lpha, 12alpha-epoxy-(5beta,14beta,17betaH)-card-20 (22)-enolide;(-)-14-hydroxy-3beta-(3-O-methyl-6-deoxy-alpha-L-glucopyranosyl)-11alpha,12alpha epoxy-(5beta,14beta,17betaH)-card -20(22)-enolide; cardenolide; (-)-17beta-neriifolin. [6]

Another three cardenolide compounds isolated from the seeds of C. manghas (7,8-Dehydrocerberin, deacetyltanghinin and tanghinin) exhibited cytotoxic activities against oral human epidermoid carcinoma (KB), human breast cancer cell (BC) and human small cells lung cancer (NCI-H187). [7]

From the bark of C. manghas two phenylpropionic acid derivatives were isolated (cerberic acid A and B). Cerberic acid A has weak cytotoxic activitiy against HepG2, MCF-7 and HeLa cell lines. [9]

The seeds of C. manghas produce four cardiac glycosides which are effective in arresting cell cycle and induce apoptosis in human hepatocellular carcinoma HepG2 cells. These compounds are 2'-Epi-2'-O-acetylthevetin B (GHSC-74), β-d-Glucosyl-(1-4)-α-l-thevetosides (GHSC-73), and neriifolin. 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. [10] [11] [12] [13]

Another cardiac glycoside from the seeds of C. manghas, tanghinigenin 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. [14]

Toxicities

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]

The reported cases of intoxication by neriifolin via ingestion of coconut crab are rather disturbing. We should thus be wary 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. [17]

Clinical Data

Clinical Trials

No documentation

Adverse Effects in Human:

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. This is attributed to the presence of a number of cardenolisde compounds including cerebrin, 17b-neriifolin, deacetyltanghinin, tanghinin, 2’-O-acetyl-cerleaside A, cerberoside and odollin. [4]

Used in Certain Conditions

Pregnancy / Breastfeeding

No documentation

Age Limitations

Neonates / Adolescents

No documentation

Geriatrics

No documentation

Chronic Disease Conditions

No documentation

Interactions

Interactions with drugs

No documentation

Interactions with Other Herbs / Herbal Constituents

No documentation

Contraindications

Contraindications

No documentation

Case Reports

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. [15] [16]

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. Post-mortem 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. [17]

Read More

  1) Botanical Info

References

  1. Scott S, Thomas C. Poisonous Plants of Paradise: First Aid and Medical Treatment of Injuries from Hawai’i’s. Plants University of Hawaii Press Honolulu; 2000. p. 37–40.
  2. Kimura T. International Collation of Traditional and Folk Medicine Northeast Asia. Vol 4, Part 4. Singapore: World Scientific Publishing; 2002. p. 89–90.
  3. Schmelzer GH, PROTA Volume 11 : Medicinal Plants 1. Backhuys Publishers Wageningen; 2008. p. 161–162.
  4. Barceloux DG. Medical Toxicology of Natural Substances: Food, Fungi, Medicinal Herbs, Plants, and Venomous Animals. Wiley, John & Sons, Incorporated; 2012.
  5. Lee SK, Mbwambo ZH, Chung H, Luyengi L, Gamez EJ, Mehta RG, Kinghorn AD, Pezzuto JM. Evaluation of the antioxidant potential of natural products. Combinatorial Chemistry & High Throughput Screening. 1998 Apr; 1(1):35-46.
  6. Chang LC, Gills JJ, Bhat KP, Luyengi L, Farnsworth NR, Pezzuto JM, Kinghorn AD. Activity-guided isolation of constituents of Cerbera manghas with antiproliferative and antiestrogenic activities. Bioorganic & Medicinal Chemistry Letters. 2000 Nov 6; 10(21):2431-4.
  7. Cheenpracha S, Karalai C, Rat-A-Pa Y, Ponglimanont C, Chantrapromma K. New cytotoxic cardenolide glycoside from the seeds of Cerbera manghas. Chemical & Pharmaceutical Bulletin (Tokyo). 2004 Aug;52(8):1023-5.
  8. Zhang XP, Liu MS, Zhang JQ, Kang SL, Pei YH. Chemical constituents from the bark of Cerbera manghas. Journal of Asian Natural Products Research. 2009;11(1):75-8.
  9. Zhang XP, Liu MS, Pei YH, Zhang JQ, Kang SL. Phenylpropionic acid derivates from the bark of Cerbera manghas. Fitoterapia. 2010 Oct;81(7):852-4.
  10. 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 Biology International. 2009 Sep; 33(9):918-25.
  11. 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. Chemico-Biological Interactions. 2010 Jan 5;183(1):142-53.
  12. 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. Experimental and Toxicologic Pathology. 2012 Jul;64(5):403-10.
  13. 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):735-41.
  14. 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. Environmental Toxicology and Pharmacology. 2010 Jul;30(1):31-6.
  15. Eddleston M, Haggalla S. Fatal injury in eastern Sri Lanka, with special reference to cardenolide self-poisoning with Cerbera manghas fruits. Clinical Toxicology (Phila). 2008 Sep;46(8):745-8.
  16. Tsai YC, Chen CY, Yang NI, Yang CC. Cardiac glycoside poisoning following suicidal ingestion of Cerbera manghas. Clinical Toxicology (Phila). 2008 Apr;46(4):340-1.
  17. Maillaud C, Lefebvre S, Sebat C, Barguil Y, Cabalion P, Cheze M, Hnawia E, Nour M, Durand F. Double lethal coconut crab (Birgus latro L.) poisoning. Toxicon. 2010 Jan;55(1):81-6.