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Record Number

464

PROSEA Handbook Number

12(1): Medicinal and poisonous plants 1

Taxon

Trichosanthes L.

Protologue

Sp. pl. 2: 1008 (1753); Gen. pl. ed. 5: 439 (1754).

Family

CUCURBITACEAE

Chromosome Numbers

x = 11; Trichosanthes cucumerina: 2n = 22, Trichosanthes tricuspidata: 2n = 44

Major Taxa and Synonyms

Major species Trichosanthes kirilowii Maxim.

Vernacular Names

Malaysia: timun dendang, timun gagak (Peninsular).

Origin and Geographic Distribution

Trichosanthes comprises some 40 species and is found from Pakistan, India and Sri Lanka to the Himalayas, Burma (Myanmar), Indo-China, China, Japan, Thailand, throughout Malesia, towards northern and eastern Australia and into the Pacific east to Fiji. Some 15 species are present within the Malesian region. Fossil evidence proves the presence of Trichosanthes in Eurasia during the Miocene and Eocene.

Uses

Various Trichosanthes species are used for a wide array of medicinal purposes. The best known of these include application as a cooling agent, as diuretic, as galactagogue, as a hypoglycaemic, and in the treatment of various skin complaints. The fruits of several Trichosanthes species, e.g. those of Trichosanthes ovigera and of cultivated forms of Trichosanthes cucumerina are eaten as a vegetable.

Production and International Trade

Snake gourd (Trichosanthes cucumerina) is mainly grown in home gardens for own consumption or for the local market. The wild Trichosanthes are collected and consumed locally only.

Properties

The importance of Trichosanthes kirilowii has increased due to the discovery of its activity against human immunodeficiency virus (HIV). The active proteins, trichosanthin (a mixture of 4-5 antigenic proteins), and TAP-29 (Trichosanthes anti-HIV protein, a 29 kDa protein), have been isolated from the roots. Both proteins exhibit anti-HIV activity in a similar way, as measured by assays for syncytium formation, p24 expression, and HIV reverse transcriptase activity. However, they differ significantly in cytotoxicity: trichosanthin demonstrates a dose-dependent toxic effect on host cells, but TAP-29 does not. Furthermore, trichosanthin is reported to inactivate eukaryotic ribosomes via its N-glycosidase activity; it is also a potent inhibitor of protein synthesis in a reticulocyte-lysate assay. Two other proteins, karasurin-B and karasurin-C have also been isolated from the tubers of Trichosanthes kirilowii var. japonica. Both karasurins had strong ribosome-inactivating activities, revealed by in vitro inhibition of translation in the rabbit reticulocyte system.
The traditional use of Trichosanthes kirilowii as an abortifacient has led to extensive studies. In a study in which the water extract of the roots at a dose of 0.2 mg/person was administered intramuscular to 2500 pregnant patients, the percentage of labour-induction was 96% in late-term pregnancy, and 71% in mid-term pregnancy. Drug recipes containing whole roots of Trichosanthes kirilowii were also found to be active. However, precautions are recommended, because of the risk of death as a complication. The compounds responsible for the abortifacient activity are trichosanthin, 'BETA'-trichosanthin, 'ALFA'-kirilowin and 'BETA'-kirilowin. Furthermore, 'BETA'-trichosanthin isolated from the tubers of Trichosanthes ovigera, was found to be about twice as potent as trichosanthin from Trichosanthes kirilowii in inducing mid-term abortion in mice.
The proteins 'ALFA'-kirilowin and 'BETA'-kirilowin, isolated from the seeds of Trichosanthes kirilowii, have very similar biological activities as the other trichosanthins. They were found to inhibit protein synthesis in a cell-free system, to suppress [3H]-thymidine incorporation into mouse melanoma cells, and to induce abortion in mice. 'BETA'-Kirilowin, with an ID50 of about 1.8 ng/ml, inhibits the cell-free translation system.
A type-1 ribosome-inactivation protein, designated as TK-35, has been purified from suspension cultures of stem sections of Trichosanthes kirilowii transformed by Agrobacterium rhizogenes. In a protein translation inhibition assay, TK-35 had an IC50 value of 2.45 nM and was able to release the rRNA N-glycosidase diagnostic fragment from rabbit reticulocytes.
The polysaccharide fraction from the rhizomes of Trichosanthes kirilowii showed marked anti-tumour and cytotoxic activities together with immunopotentiating effects. The latter effects were evidenced by an increase in the number of circulating leucocytes and peritoneal exudate cells, and recovery from reduced antibody formation in mice.
In vitro cytotoxicity tests with trichosanthin showed that it selectively injured choriocarcinoma and melanoma cells. Under experimental conditions, the marked decrease in secretion of human chorionic gonadotropin and progesterone by choriocarcinoma cells after treatment with the proteins could be mainly attributed to the loss of cells. A structural, electrophoretic, variant of karasurin isolated from Trichosanthes kirilowii roots strongly inhibited the growth of BeWo cells (a human choriocarcinoma cell line) in vitro.
Furthermore, human peripheral blood-derived monocytes and macrophages were found highly sensitive to trichosanthin; the mixture suppressed lymphocyte proliferation (ID50 about 1.7 µg/ml). Human T and macrophage cell-lines were more sensitive (ID50 < 0.9 µg/ml) to trichosanthin compared with B and myeloid cell-lines. These findings suggest that this selective cytotoxicity towards human macrophages and/or monocytes may be implicated in trichosantin's anti-HIV activity and, furthermore, that the selective killing of leukaemia-lymphoma cells by trichosanthin merits evaluation for possible use to treat some forms of lymphoma and leukaemia.
At non-cytotoxic concentrations (10-1000 ng/ml for splenocytes, and 10-100 ng/ml for macrophages), karasurin-A from the roots of Trichosanthes kirilowii inhibited the lymphocyte proliferation induced by lipopolysaccharide, concanavalin A or phytohaemagglutinin, and nitric oxide production induced by lipopolysaccharide. It has also been suggested that karasurin-A has immunosuppressive activity in vitro. Trichosanthin increased the secretion of the enzymes glutamate-pyruvatetransaminase, lactate dehydrogenase and isocitrate dehydrogenase by isolated rat hepatocytes into the culture medium. This hepatotoxic effect appeared to be concentration-dependent. Trichosanthin furthermore produced adverse effects on prenatal development of mice, both in vitro and in vivo.
'ALFA'-Trichosanthin, isolated from fresh tubers of Trichosanthes kirilowii, showed no lipogenic activity in rat cells, nor did it affect the fasting plasma-glucose levels in mice, or testosterone and corticosterone production in isolated rat cells.
The immunotoxin trichokirin conjugated to a monoclonal antibody directed against the Thy 1.2 antigen, selectively killed leukaemia cells expressing this Thy 1.2 antigen. In in vivo application it is reported to be more advantageous than ricin A-chain immunotoxins. 2-Iminothiolane-trichosanthin conjugated to Hepama-1, which is a monoclonal antibody directed against human hepatoma, proved to be a potent and quite specific agent against hepatoma.
Bryonolic acid isolated from transformed cultures of hairy roots of Trichosanthes kirilowii var. japonica exhibited cytotoxic effects against human and animal tumour cell-lines in vitro, which were independent of the cell type. Normal cells, such as rat hepatocytes, were less sensitive to bryonolic acid than tumour cells. A so-called DNA ladder was detected in bryonolic acid-treated HL-60RG cells, indicating that apostosis may be the cause of cell death triggered by bryonolic acid.
Anti-inflammatory activity of Trichosanthes kirilowii was investigated against ear inflammation in mice induced by tetradecanoylphorbol-13-acetate (TPA). The active constituents, isolated from the seeds, were identified as 3-epikarounidiol (= D:C-friedo-oleana-7,9(11)-diene-3'BETA',29-diol), 7-oxoisomultiflorenol (= 7-oxo-D:C-friedo-olean-8-en-3'BETA'-ol), 3-epibryonolol (= D:C-friedo-olean-8-ene-3'ALFA',29-diol), and 7-oxo-10'ALFA'-cucurbitadienol and its acetyl- and 24-dihydro-derivatives karounidiol (= D:C-friedo-oleana-7,9(11)-diene-3'ALFA',29-diol) and 7-oxodihydrokarounidiol (= 7-oxo-D:C-friedo-olean-8-ene-3'ALFA',29-diol) which are all triterpenes. Furthermore, at 2 mmol/mouse, karounidiol markedly suppressed the promoting effect of TPA (1 mg/mouse) on skin tumour formation in mice following initiation with 7,12-dimethylbenz[a]anthracene (50 mg/mouse).
The 50% ethanol extracts of the whole fruit, as well as of the seeds of Trichosanthes kirilowii administered orally, exhibited anti-inflammatory and analgesic activity. The anti-inflammatory activity was investigated against vascular permeability in mice induced by acetic acid, carrageenin-induced oedema, and granuloma formation in rats induced by cotton pellets; the analgesic activity against writhing symptoms in mice.
Seed extracts of many Trichosanthes species show potent haemagglutinating activity. Data on haemagglutination inhibition show that Me-'BETA'D-galactose is the best monosaccharide inhibitor of the galactose-specific lectin present in the seeds of cultivated Trichosanthes cucumerina. A lectin isolated from the root tuber of Trichosanthes kirilowii agglutinated rabbit erythrocytes. Studies of carbohydrate-binding specificity demonstrated that agglutination was strongly inhibited by lactose and D-galactose. The galactose-binding lectin from root tubers of Trichosanthes kirilowii stimulated the incorporation of D-(3-3H)-glucose into lipids in rat epididymal adipocytes, but did not inhibit lipolysis.
A decoction of dried tubers of Trichosanthes kirilowii exhibited antihyperglycaemic activity. The ethanolic extract of Trichosanthes cucumerina, when administered orally to rats in 250 mg/kg doses failed to lower blood sugar levels, or to depress the peak value after a glucose load. Five glycans, trichosans A, B, C, D and E, isolated from Trichosanthes kirilowii roots, showed hypoglycaemic actions in normal mice. The main glycan, trichosan A, also exhibited activity in alloxan-induced hyperglycaemic mice.
The hypolipidemic activity of the pectin from cultivated Trichosanthes cucumerina was investigated by feeding male Sprague-Dawley rats a diet containing 5% pectin. Levels of serum cholesterol, phospholipids in the liver and fatty acids in the blood fell significantly.
The chloroform extract of roots of Trichosanthes cucumerina showed significant antibacterial activity against Pseudomonas aeruginosa; its activity against Staphylococcus aureus, however, was not significant. Seeds extracts of cultivated Trichosanthes cucumerina resulted in high mortality of the nematodes Meloidogyne incognita and Rotylenchulus reniformis.

Adulterations and Substitutes

Momordica may be a potential substitute for Trichosanthes, due to quite similar properties, such as antihyperglycaemic and cytotoxic activities.

Description

Annual or perennial, monoecious or dioecious, climbing or trailing herbs. Tendrils adjacent to the petiole insertion, simple or 2-5-fid. Leaves alternate, petiolate; blade simple and unlobed to palmately 3-9-lobed or rarely palmately compound; stipules absent. Flowers axillary, unisexual, actinomorphic; calyx with a long, narrow tube and 5 entire to dentate lobes; corolla funnel-shaped, white or greenish-white, deeply 5-lobed, lobes fimbriate with long hairs. Male flowers in usually bracteate racemes or rarely solitary; stamens 3, inserted on the corolla tube, filaments short, free, anthers free or united, one 1-locular and two 2-locular; pistillode 3-parted, filiform. Female flowers solitary or rarely in racemes; staminodes absent; ovary inferior, 3-carpellate but 1-celled with 3 placentas and many ovules, style 1, with 3, entire to bifid stigmas. Fruit a fleshy, indehiscent berry (pepo), globose to long spindle-shaped. Seeds often compressed and elongated.

Growth and Development

Flowering of Trichosanthes cucumerina commences about 5 weeks after sowing. The flowers open in the evening or early morning. Anthers shed their pollen several days before complete flower anthesis; stigmas are receptive from a few hours before anthesis to a few hours after. Trichosanthes flowers are pollinated by insects. The often brightly coloured fruits are eaten by monkeys but especially by large crows which thus disperse the seeds.

Other Botanical Information

Within the subfamily Cucurbitoideae, Trichosanthes belongs to the tribe Trichosantheae, an Old World tribe of 10 genera characterized by elongated hypanthia in both male and female flowers. Trichosanthes is still rather poorly known taxonomically, but a revision is in preparation. Reports from the Malesian region of Trichosanthes bracteata (Lamk) Voigt are erroneous and may concern three widespread, related species: Trichosanthes pubera Blume, Trichosanthes quinquangulata and Trichosanthes tricuspidata. True Trichosanthes bracteata is from continental Asia.

Ecology

Most Trichosanthes species are climbers of open forest, forest margins and thickets, at low to medium altitudes. They are fairly drought resistant, although Trichosanthes cucumerina does not tolerate dry soil.

Propagation and planting

Trichosanthes cucumerina is propagated by seed, requiring 4-6 kg/ha. Seed can be sown in a nursery and seedlings transplanted at the 2-true-leaf stage but usually the seed is directly sown in planting holes or on ridges 1-1.5 m apart, with 60-75 cm between plants. Seeds are soaked in water to hasten germination; under favourable conditions germination takes place within a week. Tuber-bearing Trichosanthes has been propagated vegetatively, but no details are available.

In Vitro Production of Active Compounds

In in vitro culture hairy roots of Trichosanthes kirilowii were successfully induced by infection with Agrobacterium rhizogenes strain R1601, yielding 8.16 mg trichosanthin per g fresh weight. A recombinant Trichosanthes kirilowii trypsin inhibitor analogue with the same activity as the natural one has been successfully synthesized, yielding 2 mg/l. Recombinant 'ALFA'-trichosanthin with concentration-dependent inhibition of protein synthesis in vitro has been synthesized.

Husbandry

For fruit production (e.g. Trichosanthes cucumerina) plants are trellised or otherwise supported so that the fruits can hang down.

Diseases and Pests

The most serious diseases of Trichosanthes cucumerina are downy mildew (Pseudoperonospora cubensis) and anthracnose (Colletotrichum lagenarium). Repeated spraying with fungicides, e.g. maneb, can control both diseases.
The major pests of Trichosanthes cucumerina are leaf beetles (Aulacophora vinula, Copa occidentalis and Lagria villosa) and root-knot nematodes (Meloidogyne spp.).

Harvesting

For consumption as vegetable, fruits are picked 12-20 days after fruit set. For seed production, fruits are harvested when fully ripe and have attained full size.

Yield

From dried tubers of Trichosanthes kirilowii 0.16% of pure trichosanthin has been obtained after cation-exchange perfusion chromatography for only 10 minutes.

Genetic Resources and Breeding

Germplasm collections of Trichosanthes cucumerina are available in the Philippines (NPGRL-IPB, Los Baños), India (Kerala Agricultural University, Trichur, Kerala), Nigeria (NACGRAB, Ibadan), Russia (the Vavilov Institute of Plant Industries, St Petersburg) and the United States (Department of Horticultural Sciences, Cornell University, New York).

Prospects

Several compounds from Trichosanthes show interesting pharmacological activities, e.g. cytotoxic (anti-tumour), anti-inflammatory and anti-HIV. As lead-compounds, they may have potential in research and development of future medicines. Although extracts of the roots of Trichosanthes kirilowii are reported to be abortifacient, this activity must be considered too toxic to be applied, as death may occur as a complication.

Literature

Akihisa, T., Yasukawa, K., Kimura, Y., Takido, M., Kokke, W.C.M.C. & Tamura, T., 1994. Five D:C-friedo-oleanane triterpenes from the seeds of Trichosanthes kirilowii Maxim. and their anti-inflammatory effects. Chemical and Pharmaceutical Bulletin 42(5): 1101-1105.
Chan, W.Y., Ng, T.B., Wu, P.J. & Yeung, H.W., 1993. Developmental toxicity and teratogenicity of trichosanthin, a ribosomeinactivating protein in mice. Teratogenesis, Carcinogenesis and Mutagenesis 13(2): 47-57.
Gildemacher, B.H., Jansen, G.J. & Chayamarit, K., 1993. Trichosanthes L. In: Siemonsma, J.S. & Kasem Piluek (Editors): Plant Resources of South-East Asia No 8. Vegetables. Pudoc Scientific Publishers, Wageningen, the Netherlands. pp. 271-274.
Kumagai, M.H. et al., 1993. Rapid, high-level expression of biologically active 'ALFA'-trichosanthin in transfected plants by an RNA viral vector. Proceedings of the National Academy of Sciences 90(2): 427-430.
Lee-Huang, S. et al., 1991. TAP 29: an antihuman immunodeficiency virus protein from Trichosanthes kirilowii that is nontoxic to intact cells. Proceedings of the National Academy of Sciences 88(1b): 6570-6574.
Ng, T.B., Chan, W.Y. & Yeung, H.W., 1992. Proteins with abortifacient ribosome inactivating immunomodulatory antitumor and anti AIDS activities from Cucurbitaceae plants. General Pharmacology 23(4): 575-590.
Qiu, D.Y., Zhu, G. & Zhu, Z.Q., 1996. Study on production of trichosanthin from the hairy roots of Trichosanthes kirilowii Maxim. Acta Botanica Sinica 38(6): 439-443.
Rugayah & de Wilde, W.J.J.O., 1997. Trichosanthes L. (Cucurbitaceae) in Java. Blumea 42(2): 471-482.
Shaw, P.C., Chan, W.L., Yeung, H.W. & Ng, T.B., 1994. Trichosanthin - A protein with multiple pharmacological properties. Life Sciences 55(4): 253-262.
Tsao, S.W., Ng, T.B. & Yeung, H.W., 1990. Toxicities of trichosanthin and 'ALFA'-momorcharin, abortifacient proteins from Chinese medicinal plants, on cultured tumor cell lines. Toxicon 28(10): 1183-1192.

Author(s)

M.S.M. Sosef, E. Boer & N. Bunyapraphatsara

Trichosanthes borneensis
Trichosanthes cucumerina
Trichosanthes kirilowii
Trichosanthes ovigera
Trichosanthes quinquangulata
Trichosanthes tricuspidata
Trichosanthes villosa
Trichosanthes wawrae

Correct Citation of this Article

Sosef, M.S.M., Boer, E. & Bunyapraphatsara, N., 1999. Trichosanthes L.. In: de Padua, L.S., Bunyapraphatsara, N. and Lemmens, R.H.M.J. (Editors): Plant Resources of South-East Asia No 12(1): Medicinal and poisonous plants 1. PROSEA Foundation, Bogor, Indonesia. Database record: prota4u.org/prosea

Selection of Species

The following species in this genus are important in this commodity group and are treated separatedly in this database:
Trichosanthes borneensis
Trichosanthes cucumerina
Trichosanthes kirilowii
Trichosanthes ovigera
Trichosanthes quinquangulata
Trichosanthes tricuspidata
Trichosanthes villosa
Trichosanthes wawrae

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