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Euphorbia peplus L.

Protologue
Sp. pl. 1: 456 (1753).
Family
Euphorbiaceae
Chromosome number
2n = 16
Vernacular names
Petty spurge, radium weed, cancer weed, milkweed, wartweed, radium plant (En). Euphorbe omblette, herbe de lait, esule ronde, euphorbe des vignes, reveille-matin des vignes, euphorbe des jardins (Fr). Leitaria, ésula redonda, trovisco (Po).
Origin and geographic distribution
Euphorbia peplus originates from Europe, temperate Asia and northern Africa, and is now widespread in temperate, subtropical and tropical regions of the world. In tropical Africa it occurs from Sudan, Eritrea and Somalia south to Zimbabwe, and also in Réunion and Mauritius.
Uses
Euphorbia peplus is one of a number of plants in the Euphorbiaceae family that has attracted attention as a home remedy for skin cancer, particularly basal cell carcinomas. The milky latex is toxic and irritant and is widely known as a therapeutic agent for the removal of warts and sun-spots on the skin. The plant is also used for its expectorant, anthelmintic, antipyretic and anti-inflammatory activities. In Mauritius a leaf decoction is taken to treat diarrhoea and dysentery.
In Europe and Australia the latex is used in local medicine against corns and waxy growths, and an infusion of the aerial parts is taken to treat asthma, catarrh and as a purgative. In Saudi Arabia an infusion of the aerial parts is applied for the lowering of blood pressure. Euphorbia peplus was widely used in the Ukraine in the 1990s as a treatment for cancer of the stomach, liver and uterus.
The latex causes irritation of the skin, eyes and mucous membranes. Due to the toxicity of the latex, it is advised to use the plant topically only.
Production and international trade
Euphorbia peplus is grown in Australia for extraction of its anti-cancer compounds, but quantities are unknown.
Properties
Euphorbia peplus latex yields mostly diterpenes of the jatrophane, pepluane and ingenane types. Jatrophane and pepluane diterpenes are non-inflammatory, whereas ingenane diterpenes, including ingenol 3-angelate (PEP005) and ingenol, are responsible for the irritant and tumour-promoting properties of the latex. Of the pepluane esters, pepluanone showed significant anti-inflammatory activity in vivo on carrageenan-induced rat paw oedema. Of the ingenane compounds, 5-deoxyingenol, 20-deoxyingenol 3-O-angelate and ingenol 20-O-octanoate exhibited strong inflammatory activities on mice skin, but less strong and more prolonged than several phorbol esters of related Euphorbia species. In addition to these diterpenes, the latex contains the triterpenoids obtusifoliol, cycloartenol, 24-methylenecycloartanol, and the 24-acyclic triterpene alcohol, peplusol, the steroids cholesterol, campesterol, stigmasterol, β-sitosterol, 28-isofucosterol, the flavonoids quercetine, quercetin-3-galactoside, kaempferol, kaempferol-3-galactoside and rhamnetin-3-galactoside, tannins and anthraquinones. From air-dried powdered whole plants simiarenone, nepehinol, alangidiol, cycloartenone, cycloartenol, 24-methylenecycloartanol, obtusifoliol and stigmastanol were isolated. The epicuticular leaf wax contains large amounts of pentacyclic triterpenoids in addition to the common lipid wax constituents: alkanes, wax esters, aldehydes, primary alcohols and fatty acids. Most of the triterpenoids were triterpenols, as well as their acetates, fatty acid esters and the corresponding ketones.
The most active compound is a hydrophobic diterpene ester, ingenol 3-angelate (PEP005), an irritant compound, which possesses topical anti-tumour activity against human cancer cell lines grown as subcutaneous tumours in mice. It has given more than 90% complete responses on different skin cancers in a Phase II clinical trial. The LD90 for PEP005 for a panel of tumour cell lines was 180–220 μM. PEP005 thus emerges as a potential new topical anti-skin cancer agent that has a novel mode of action involving plasma membrane and mitochondrial disruption, primary necrosis and potent activation of protein kinase C. PEP005 also has potent antileukaemic effects, inducing apoptosis in myeloid leukaemia cell lines. It also had powerful inhibitory activity against a wide range of other tumours tested, including breast cancer cells. In preclinical studies it was also shown to have activity against human melanoma xenografts in mice. The intellectual property on the use of ingenane, jatrophane and pepluane type diterpenes, which are being used as anti-neoplastic differentiation control agents, is the subject of several patent applications.
Several diterpenes exhibited a pronounced or moderate anti-herpes virus effect (IC50 of 2.5–8.3 μg/ml) in vitro. The observed HSV-2 inhibitory activities were not associated with virucidal effects.
A crude chloroform extract and hot water extract of the aerial parts showed significant molluscicidal activity against Biomphalaria alexandrina and Bulinus truncatus. An acetone extract showed larvicidal activity against the mosquito Culex pipiens. A methanolic leaf extract inhibited the growth of Aspergillus flavus, and also inhibited the production of aflatoxins ( 73–100%), with greater inhibition at higher concentrations.
Experimental feeding of Euphorbia peplus caused blood-stained faeces and excessive salivation in calves. Lactating goats, which fed on the aerial parts mixed with their usual green fodder, showed symptoms of general poisoning; the main toxic effects were seen in the heart, lung and liver. Histopathological examinations revealed that the primary toxic effects originated from degenerative changes in parenchymal and endothelial cells. The milk of the goats fed on Euphorbia peplus, consumed by their offspring, caused poisoning and even death, with signs similar to those observed in the adults. The toxicity is caused by ingenane type diterpenes.
Description
Monoecious, annual, erect herb up to 30 cm tall, glabrous, with latex in aerial parts. Leaves alternate in lower part of the stem, opposite in upper part, simple and entire; stipules absent; petiole up to 1 cm long; blade obovate, up to 2.5 cm × 1.5 cm, base cuneate, apex rounded. Inflorescence an axillary or terminal cyme consisting of clusters of flowers, each cluster called a ‘cyathium’, in 3-branched umbels; branches up to 3.5 cm long; bracts similar to the leaves, sessile; cyathia almost sessile, c. 1 mm × 1 mm, with a cup-shaped involucre, lobes rounded, minute, margin hairy; glands 4, transversely oblong, c. 0.5 mm long, with 2 horns up to 1 mm long, each involucre containing 1 female flower surrounded by male flowers. Flowers unisexual; male flowers sessile, bracteoles linear, fringed, perianth absent, stamen c. 1 mm long; female flowers with pedicel c. 3 mm long in fruit, ovary superior, glabrous, 3-celled, styles 3, c. 0.5 mm long, spreading. Fruit a deeply 3-lobed capsule c. 2 mm in diameter, base truncate, with fleshy longitudinal ridges, 3-seeded. Seeds oblong-ovoid, c. 1.5 mm × 1 mm, warty, reddish brown becoming grey; caruncle c. 0.3 mm in diameter.
Other botanical information
Euphorbia comprises about 2000 species and has a worldwide distribution, with at least 750 species occurring in continental Africa and about 150 species in Madagascar and the Indian Ocean islands. Euphorbia peplus belongs to section Esula, a group of annual or perennial herbs characterized by absence of stipules, cyathia in axillary and terminal umbel-like cymes, leafy or deltoid bracts, 4 involucral glands, entire or with 2 horns, fruits exserted on reflexed pedicel and seeds with a caruncle. Several other species from this section are medicinally used, 3 of them are mentioned hereafter.
Euphorbia cyparissioides Pax occurs from Nigeria east to Ethiopia and throughout east and southern Africa. In East Africa root powder is eaten with porridge as a strong purgative.
Euphorbia petitiana A.Rich. occurs in Ethiopia and Yemen. In Ethiopia an infusion of the aerial parts is taken as an anthelmintic. Euphorbia ugandensis Pax & K.Hoffm. occurs in Kenya, Uganda and Tanzania. In Kenya the Maasai people take a leaf infusion as an emetic to treat colds and cough.
Growth and development
Euphorbia peplus can be found flowering throughout the year if enough water is available. The plant develops rapidly as it matures in 12–14 weeks.
Ecology
Euphorbia peplus occurs in disturbed localities, gardens, pavements, waste places and pastures, from sea-level up to 1500 m altitude. It prefers shaded localities.
Propagation and planting
The seeds of Euphorbia peplus are small (about 1700 per g) and have a germination rate of more than 70%.
Management
In Australia Euphorbia peplus is grown in small plots for latex production. As the plants can be easily killed by herbicides, and because they do not spread beyond shade, the risk that it will become an invasive weed is small. It is potentially suitable for large-scale agricultural production.
Diseases and pests
Rust and other fungal diseases may become a problem of Euphorbia peplus in the maturing stages. It can also be attacked by viruses and is a host of cabbage whitefly (Aleyrodes proletella), a possible reservoir of cabbage black ring virus.
Harvesting
If enough water is available throughout the year, Euphorbia peplus grows and produces seeds all year round and can be harvested for latex or seed whenever the need arises.
Yield
In Australia the fresh plant yield of Euphorbia peplus is 1–1.5 kg/m2, and latex yield is 100–300 mg/kg freshly harvested plant parts.
Handling after harvest
In Africa the latex of Euphorbia peplus is usually used fresh; in Australia active compounds are extracted industrially.
Genetic resources
Euphorbia peplus has a very large area of distribution, has a short life cycle and produces many seeds. Therefore, there is no risk of genetic erosion.
Breeding
There are currently no breeding programmes of Euphorbia peplus to increase the amount of diterpenes in the latex.
Prospects
Several of the active compounds of Euphorbia peplus are good candidates to be developed into anticancer drugs considering the promising pharmacological studies and clinical trials results. As the active compounds are complex molecules, they have not yet been chemically produced, and can only be obtained directly from the plant. More research into large-scale production and mechanisation of cultivation and latex extraction is needed.
Major references
• Carter, S. & Leach, L.C., 2001. Euphorbiaceae, subfamily Euphorbioideae, tribe Euphorbieae. In: Pope, G.V. (Editor). Flora Zambesiaca. Volume 9, part 5. Royal Botanic Gardens, Kew, Richmond, United Kingdom. pp. 339–465.
• Challacombe, J.M., Suhrbier, A., Parsons, P.G., Jones, B., Hampson, P., Kavanagh, D., Rainger, G.E, Morris, M., Lord, J.M., Le, T.T.T., Hoang Le, D. & Ogbourne, S.M., 2006. Neutrophils are a key component of the antitumor efficacy of topical chemotherapy with ingenol-3-angelate. Journal of Immunology 177(11): 8123–8132.
• Corea, G., Fattorusso, E., Lanzotti, V., di Meglio, P., Maffia, P., Grassia, G., Ialenti, A. & Ianaro, A., 2005. Discovery and biological evaluation of the novel naturally occurring diterpene pepluanone as antiinflammatory agent. Journal of Medicinal Chemistry 48(22): 7055–7062.
• Davis, C. & Parsons, P., 2002. Growing Milkweed, a plant with prospective anticancer properties. A review of the medicinal potential of members of the Euphorbiaceae family. Report for the Rural Industries Research and Development Corporation, Kingston, Australia. 17 pp.
• Gillespie, S.K., Zhang, X.D. & Hersey, P., 2004. Ingenol 3-angelate induces dual modes of cell death and differentially regulates tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis in melanoma. Molecular Cancer Therapy 3: 1651–1658.
• Green, A.C. & Beardmore, G.L., 1988. Home treatment of skin cancer and solar keratoses. Australasian Journal of Dermatology 29(3): 127–130.
• Hampson, P., Chahal, H., Khanim, F., Hayden, R., Mulder, A., Assi, L.K., Bunce, C.M. & Lord, J.M., 2005. PEP005, a selective small-molecule activator of protein kinase C, has potent antileukemic activity mediated via the delta isoform of PKC. Blood 106(4): 1362–1368.
• Hemmers, H., Gülz, P.G. & Marner, F.J., 1988. Triterpenoids in epicuticular waxes of three European Euphorbia species. Zeitschrift für Naturforschung Section C, Biosciences 43(11–12): 799–805.
• Nawito, M., Ahmed, Y.F., Zayed, S.M. & Hecker, E., 1998. Dietary cancer risk from conditional cancerogens in produce of livestock fed on species of spurge (Euphorbiaceae). II. Pathophysiological investigations in lactating goats fed on the skin irritant herb Euphorbia peplus and in their milk-raised kids. Journal of Cancer Research and Clinical Oncology 124(3–4): 179–185.
• Ogbourne, S.M., Suhrbier, A., Jones, B., Cozzi, S-.J., Boyle, G.M., Morris, M., McAlpine, D., Johns, J., Scott, T.M., Sutherland, K.P., Gardner, J.M., Le Thuy, T.T., Lenarczyk, A., Aylward, J.H. & Parsons, P.G., 2004. Antitumor activity of 3-ingenyl angelate: plasma membrane and mitochondrial disruption and necrotic cell death. Cancer Research 64: 2833–2839.
Other references
• Beentje, H.J., 1994. Kenya trees, shrubs and lianas. National Museums of Kenya, Nairobi, Kenya. 722 pp.
• Burkill, H.M., 1994. The useful plants of West Tropical Africa. 2nd Edition. Volume 2, Families E–I. Royal Botanic Gardens, Kew, Richmond, United Kingdom. 636 pp.
• Corea, G., Fattorusso, E., Lanzotti, V., Motti, R., Simon, P.-N., Dumontet, C. & Di Pietro, A., 2004. Jatrophane diterpenes as modulators of multidrug resistance. Advances of structure-activity relationships and discovery of the potent lead pepluanin A. Journal of Medicinal Chemistry 47(4): 988–992.
• Giner, J.L., Berkowitz, J.Z. & Andersson, T., 2000. Nonpolar components of the latex of Euphorbia peplus. Journal of Natural Products 63(2): 267–269.
• Gayar, F.H., Shazli, A.Y. & Abbassy, M.A., 1971. Toxicity of Euphorbia peplus L. (Euphorbiaceae) to insects. Zeitschrift für Angewandte Entomologie 68(1): 56–63.
• Gurib-Fakim, A., Guého, J. & Bissoondoyal, M.D., 1996. Plantes médicinales de Maurice, tome 2. Editions de l’Océan Indien, Rose-Hill, Mauritius. 532 pp.
• Hartwell, J.L., 1970. Plants used against cancer. A survey. Lloydia 33: 97–194.
• Hasan, H.A.H. & Abdel Mallek, A.Y., 1994. Inhibitory effect of aqueous leaf extracts of some plants on growth and aflatoxin production by Aspergillus flavus. Dirasat Series B, Pure and Applied Sciences 21(3): 215–219.
• Hohmann, J., Evanics, F., Berta, L. & Bartok, T., 2000. Diterpenoids from Euphorbia peplus. Planta Medica 63(3): 291–294.
• Hohmann, J., Günther, G., Vasas, A., Kálmán, A. & Argay, G., 1999. Isolation and structure revision of pepluane diterpenoids from Euphorbia peplus. Journal of Natural Products 62(1): 107–109.
• Hohmann, J., Vasas, A., Günther, G., Dombi, G., Blazsó, G., Falkay, G., Máthé I. & Jerkovich, G., 1999. Jatrophane diterpenoids from Euphorbia peplus. Phytochemistry 51(5): 673–677.
• Jakupovic, J., Morgenstern, T., Bittner, M. & Silva, M., 1998. Diterpenes from Euphorbia peplus. Phytochemistry 47(8): 1601–1609.
• Jansen, P.C.M., 1981. Spices, condiments and medicinal plants in Ethiopia, their taxonomy and agricultural significance. Agricultural Research Reports 906. Centre for Agricultural Publishing and Documentation, Wageningen, Netherlands. 327 pp.
• Lotfy, H.S. & Abdel Gawad, M.A., 2000. Molluscicidal effect of some local plants against Lymnaea cailliaudi. Egyptian Journal of Agricultural Research 78(1): 311–319.
• Mucsi, I., Molnar, J., Hohmann, J. & Redei, D., 2001. Cytotoxicities and anti-herpes simplex virus activities of diterpenes isolated from Euphorbia species. Planta Medica 67(7): 672–674.
• Neuwinger, H.D., 2000. African traditional medicine: a dictionary of plant use and applications. Medpharm Scientific, Stuttgart, Germany. 589 pp.
• Rizk, A.M., Hammouda, F.M., El-Missiry, M.M., Radwan H.M. & Evans, F.J., 1985. Biologically active diterpene esters from Euphorbia peplus. Phytochemistry 24(7): 1605–1606.
• Scott, A.J., 1982. Hernandiacées. In: Bosser, J., Cadet, T., Guého, J. & Marais, W. (Editors). Flore des Mascareignes. Familles 153–160. The Sugar Industry Research Institute, Mauritius, l’Office de la Recherche Scientifique Outre-Mer, Paris, France & Royal Botanic Gardens, Kew, Richmond, United Kingdom. 4 pp.
• Shoeb, H.A., El-Eman, M.A. & Osman, N.S., 1982. The molluscicidal activity of Euphorbiaceae Euphorbia peplus. Egyptian Journal of Bilharziasis 9(1): 41–54.
Sources of illustration
• Ross-Craig, S., 1970. Drawings of British plants. Part XXVI. Euphorbiaceae. G. Bell and Sons Ltd, London, United Kingdom. pl. 34–47.
Author(s)
A.T. Tchinda
Institut de Recherches Médicales et d’Etudes des Plantes Médicinales (IMPM), Ministère de la Recherche Scientifique et de l’Innovation, B.P. 6163, Yaoundé, Cameroun


Editors
G.H. Schmelzer
PROTA Network Office Europe, Wageningen University, P.O. Box 341, 6700 AH Wageningen, Netherlands
A. Gurib-Fakim
Faculty of Science, University of Mauritius, Réduit, Mauritius
Associate editors
C.H. Bosch
PROTA Network Office Europe, Wageningen University, P.O. Box 341, 6700 AH Wageningen, Netherlands
M.S.J. Simmonds
Royal Botanic Gardens, Kew, Richmond, Surrey TW9 3AB, United Kingdom
R. Arroo
Leicester School of Pharmacy, Natural Products Research, De Montfort University, The Gateway, Leicester LE1 9BH, United Kingdom
A. de Ruijter
PROTA Network Office Europe, Wageningen University, P.O. Box 341, 6700 AH Wageningen, Netherlands
General editors
R.H.M.J. Lemmens
PROTA Network Office Europe, Wageningen University, P.O. Box 341, 6700 AH Wageningen, Netherlands
L.P.A. Oyen
PROTA Network Office Europe, Wageningen University, P.O. Box 341, 6700 AH Wageningen, Netherlands
Photo editor
A. de Ruijter
PROTA Network Office Europe, Wageningen University, P.O. Box 341, 6700 AH Wageningen, Netherlands

Correct citation of this article:
Tchinda, A.T., 2008. Euphorbia peplus L. In: Schmelzer, G.H. & Gurib-Fakim, A. (Editors). Prota 11(1): Medicinal plants/Plantes médicinales 1. [CD-Rom]. PROTA, Wageningen, Netherlands.
Distribution Map naturalized


1, plant habit; 2, cyathium; 3, seed.
Redrawn and adapted by Achmad Satiri Nurhaman



flowering plant
obtained from
Plants of Hawaii


flowering plant
obtained from
J. De Laet


top of flowering plant
obtained from
malezasdemexico


top of flowering and fruiting stem
obtained from
J. De Laet


top of flowering and fruiting stem
obtained from
J. De Laet


seeds
obtained from
C. Ritchie