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Phyllanthus urinaria L.

Protologue
Sp. pl. 2: 982 (1753).
Family
Euphorbiaceae (APG: Phyllanthaceae)
Chromosome number
2n = 26, 48, 52
Vernacular names
Common leaf-flower, shatterstone, chamber bitter (En). Kikilé, petit tamarin rouge, curanellie rouge, urinaire de Malabar (Fr).
Origin and geographic distribution
Phyllanthus urinaria is probably native to Asia and has spread as a weed throughout the tropics. It also occurs in tropical Africa and the Indian Ocean islands, but it is not common there.
Uses
Sap of leafy twigs or a twig decoction is drunk in Côte d’Ivoire and DR Congo to treat pain in the side. In Côte d’Ivoire and Nigeria a paste of fresh crushed leaves and kaolin in water is drunk and applied to the body to treat convulsions, colic, constipation and urethral discharges. In Nigeria a plant decoction is drunk and plant ash in water is applied as ear drops to treat earache. The bitter leaves are eaten to treat hiccup and cough. In DR Congo a decoction of young shoots or roots is taken to treat dysentery, malaria and typhoid fever. A decoction of the whole plant is taken to fight jaundice and gonorrhoea and is topically applied as a poultice to treat skin problems such as ulcers, sores, swelling and itch. In Madagascar, Réunion and Mauritius a plant decoction is drunk as a diuretic and purgative to treat diarrhoea, painful urination, syphilis and liver problems, and also to treat fever. In Madagascar a stem or leaf infusion is taken to treat asthma and bronchitis and is externally applied to treat parasitic skin diseases. In Rodrigues a leaf infusion is taken to treat cough.
Worldwide, Phyllanthus urinaria is used as a diuretic and purgative to treat a wide variety of uro-genital disorders, diarrhoea and diabetes, as a bitter tonic and to treat fever, including malaria. In Asia extracts are also widely used against hepatitis B infections. Externally, crushed plant parts or an infusion are applied to treat ulcers, sores and tumours. In India the crushed plant is used as fish poison.
Production and international trade
Dried Phyllanthus urinaria plant parts or extracts are sold on the internet. Dried herbs are sold at US$ 70 (2.3 kg) to US$ 1100 (22.7 kg). Seeds are sold at US$ 3 (60 seeds) to US$ 40 (1000 seeds).
Properties
The chemical composition and pharmacology of Phyllanthus urinaria have been subject to many investigations. The following chemical constituents have been found: lignans (e.g. phyllanthin, phyltetralin, hypophyllanthin, urinatetralin, dextrobuschernin, 5-demethyoxynirathin and urinaligran), ellagitannins (e.g. corilagin, geraniin, hippomanin A, phyllanthusin F and G, repandinin B and phyllanthusiin U), terpenoids (e.g. β-amyrin, lupeol acetate and β-sitosterol), flavonoids (quercetin, astragalin, quercitrin, rhamnocitrin, isoquercitrin, kaempferol, daucosterol, triacontanol and rutin), phenolic compounds (e.g. caffeic acid, ellagic acid, gallic acid, methylester dehydrochebulic acid, methyl brevifolincarboxylate, hexacosanoic acid, brevifolin, brevifolin carboxylic acid, pyrogallol, n-octadecane, methylgallate, trimethyl-3,4-dehydrochebulate, 1,3,4,6-tetra-O-galloyl-β-d-glucose) and waxes (montanoic acid methyl ester, triacontanol).
Phyllanthus urinaria has been found to inhibit in-vitro DNA polymerase of the hepatitis B virus and other hepatitis-DNA-viruses, such as the woodchuck hepatitis virus. Aqueous extracts have significant antiviral effects and a protective effect on liver cells. It was found that ellagic acid, isolated from the plant, showed significant antihepatotoxic activity. Triacontanol showed hepatoprotective properties, e.g. against galactosamine-induced cytotoxicity in rat hepatocytes. The lignan phyllanthin showed protective activity in rat hepatocytes against cytotoxicity induced by CCl4 and galactosamine. However, phyllanthin has also been reported to be toxic to the nervous system and liver. In a double-blind placebo-controlled study of Phyllanthus urinaria for the treatment of chronic hepatitis B no delayed virological or biochemical response was shown at 24 weeks after the cessation of treatment. An acetone extract was found to suppress herpes simplex virus (HSV). Several bioactive compounds were isolated from the extract. Hippomanin A and geraniin were found to inhibit only HSV-2 and 1,3,4,6-tetra-O-galloyl-β-d-glucose only HSV-1. Derivatives of corilagin showed inhibitory activity against Epstein-Barr virus DNA polymerase.
A water extract of Phyllanthus urinaria induced apoptosis and significantly decreased the number of Lewis lung carcinoma cells and human myeloid leukaemia cells (HL-60 cells) in a dose- and time-dependent manner. It did not exert any cytotoxic effect on normal cells. The oral administration of an aqueous alcohol extract to mice caused significant inhibition of tumour development, without toxic effects.
A plant extract containing corilagin showed significant anti-thrombosis activity in rats in a dose-dependent manner due to its inhibition of platelet-neutrophil adhesion. It did not cause serious bleeding side effect as compared with aspirin or urokinase. Corilagin, however, had no influence on rabbit platelet aggregation.
A methanol extract showed significant antioxidant activity in vitro. A correlation between the antioxidant activity and several phenolic compounds, ellagitannins and flavonoids, was observed. Extracts of Phyllanthus urinaria also showed cardioprotective in vitro and antidiabetic effects in streptozotocin-induced diabetic rats. An aqueous alcoholic extract of stems, leaves and roots caused graded contraction in guinea-pig trachea and urinary bladder. It also exhibited potent and long-lasting antinociceptive activity in several pain models in mice, especially when given orally. Gallic acid ethyl ester, isolated from the aerial parts, produced dose-dependent and pronounced systemic, spinal and supraspinal antinociception in mice.
An aqueous extract showed significant in-vitro antiplasmodial activity against a chloroquine-resistant Plasmodium falciparum strain. The n-hexane fraction of an aqueous alcohol extract from leaves, stems and roots exhibited antibacterial activity against Escherichia coli, Proteus vulgaris, Salmonella typhimurium, Shigella flexneri, Klebsiella pneumoniae, Vibrio parahaemolyticus and Staphylococcus aureus.
Callus culture and root culture protocols were developed using single node explants, but callus extracts showed less activity against viral DNA polymerase and reverse transcriptase than extracts from field-grown plants. The compounds β-sitosterol, glochidonol and glochidone were isolated from the callus extracts.
Adulterations and substitutes
Phyllanthus urinaria is similarly medicinally used as Phyllanthus amarus Schumach. & Thonn. and Phyllanthus fraternus G.L.Webster.
Description
Monoecious, annual or short-lived perennial herb, erect or sprawling, up to 60 cm tall, reddish; branchlets (3–)5–13 cm long, flattened, often slightly winged and sparsely hairy. Leaves alternate, distichous and crowded along lateral branchlets, simple, glabrous, sessile; stipules ovate to lanceolate, long-acuminate, those of main stems with auricles at base; blade oblong to elliptical-oblong, 7–12(–20) mm × 3–6(–9) mm, base cuneate to rounded and slightly unequal, apex rounded, often pointed, margins finely toothed. Flowers 1–2 in the axils of leaves, male flowers towards the apex of branchlets, female flowers at the basal part of branchlets, unisexual, regular, 6-merous; pedicel c. 1 mm long; male flowers with obovate perianth lobes c. 1 mm long, disk lobes 6, stamens 3, filaments fused, anthers free; female flowers with triangular-ovate perianth lobes c. 1 mm long, disk cup-shaped, ovary superior, ovoid, warty, 3-celled, styles fused at base into a triangular plate, 2-fid at apex. Fruit a globular capsule 2–2.5 mm in diameter, usually warty, hanging, 6-seeded. Seeds c. 1 mm long, with sharp transverse ridges.
Other botanical information
Phyllanthus is a large genus comprising about 750 species in tropical and subtropical regions, with about 150 species in mainland tropical Africa and about 60 in Madagascar and the Indian Ocean islands.
Phyllanthus urinaria is highly variable. Several other Phyllanthus spp. indigenous to the Indian Ocean islands have similar medicinal uses as Phyllanthus urinaria. A decoction of the leafy twigs of Phyllanthus lanceolatus Poir., a rare species from Mauritius, and of Phyllanthus phillyreifolius Poir., an endangered species from Réunion and Mauritius, is taken as a diuretic and to treat diarrhoea. A leaf or stem bark decoction is taken as a diuretic to treat venereal diseases and pain caused by kidney stones. An infusion of the young leaves of Phyllanthus pervilleanus (Bail.) Müll.Arg., from Comoros and Madagascar, is considered a strong diuretic.
Phyllanthus angavensis (Leandri) Leandri occurs in south-western Madagascar. A stem bark decoction is taken to treat persistent diarrhoea and amoebic dysentery. A root decoction of Phyllanthus melleri Müll.Arg., from central and eastern Madagascar, is drunk to treat fatigue, diarrhoea and amoebic dysentery. Root powder or the crushed roots are applied to abscesses and ulcers. The small fruits are edible and made into a low-quality alcoholic drink. The roots give a low-quality dye for baskets. The branches are used in wickerwork. A root decoction of Phyllanthus mocquerysianus A.DC. from eastern Madagascar is drunk to treat malaria. Phyllanthus tenellus Roxb. occurs naturally in Tanzania, Mozambique, the Indian Ocean islands and Yemen and has been introduced in several countries of the Old and New tropics. In Madagascar preparations of the leaves and stem are taken to treat asthma, bronchitis and parasitic skin diseases. A bark extract is taken as an astringent and a plant extract to treat blenorrhagia. A decoction of the whole plant is used to treat fever in children.
Growth and development
The branching pattern of Phyllanthus urinaria is ‘phyllanthoid’, i.e. the spirally arranged leaves on the main axes are strongly reduced to so-called ‘cataphylls’, which subtend deciduous branchlets with distichous leaves, the branchlets resembling a compound leaf. Flowering and fruiting may occur throughout the year if enough water is available. Seeds are dispersed by water and animals.
Ecology
Phyllanthus urinaria is a common weed of waste places, clearings, gardens and along paths, but is also found in evergreen forest. It grows on well-drained, fertile, sandy soils, sometimes on limestone, often in humid localities or even in marshy ground, up to 1500 m altitude. It prefers full sun, but may grow under partial shade.
Propagation and planting
Phyllanthus urinaria is a prolific seed producer. The seeds can remain dormant for an extended period of time. They germinate massively during the rainy season and the seedlings are very fast growing. Seed requires light to germinate. A germination rate of up to 80% was observed at temperatures of 25–35°C, but germination was poor at 20°C or 40°C. Germination of seed is also poor under moisture stress conditions. Stratification significantly improved the germination of the seeds.
Management
In experiments in the United States soil fertility and soil moisture affected morphology and yield of Phyllanthus urinaria, with plants being more branched and with a higher dry weight under favourable conditions. Differences in soil fertility and soil moisture generally did not affect the in-vitro inhibitory activity on woodchuck virus DNA polymerase.
Phyllanthus urinaria shows a marked preference for calcareous sites in humid tropical areas. In China, warm, well-drained sandy soils and fertilization with N and K are recommended for cultivation.
Diseases and pests
In Indian rice fields Phyllanthus urinaria is a host of the rice root-knot nematode (Meloidogyne graminicola).
Harvesting
Phyllanthus urinaria is usually harvested from the wild. The plant is often uprooted, but sometimes only aerial parts are collected.
Handling after harvest
The harvested plant material is usually washed and used fresh, but it may also be dried and kept in a dry place for future use.
Genetic resources
Phyllanthus urinaria is a widespread weedy species and is not threatened by genetic erosion.
Prospects
Pharmacological research of Phyllanthus urinaria has shown interesting antitumour, antiviral, antioxidant, antithrombosis and antinociceptive activities, and further research is merited. More research is warranted concerning its husbandry and growth conditions for optimal production of active compounds.
Major references
• 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.
• Coode, M.J.E., 1982. Euphorbiacées. 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. 117 pp.
• Fang, S.H., Rao, Y.K. & Tzeng, Y.M., 2008. Anti-oxidant and inflammatory mediator’s growth inhibitory effects of compounds isolated from Phyllanthus urinaria. Journal of Ethnopharmacology 116: 333–340.
• Huang, S.T., Yang, R.C., Lee, P.N., Yang, S.H., Liao, S.K., Chen, T.Y. & Pang, J.H.S., 2006. Anti-tumor and anti-angiogenic effects of Phyllanthus urinaria in mice bearing Lewis lung carcinoma. International Immunopharmacology 6(6): 870–879.
• Kang, E.H., Kown, T.Y., Oh, G.T., Park, W.F., Park, S.I., Park, S.K. & Lee, Y.I., 2006. The flavonoid ellagic acid from a medicinal herb inhibits host immune tolerance induced by the hepatitis B virus-e antigen. Antiviral Research 72(2): 100–106.
• Lee, C.Y., Peng, W.H., Cheng, H.Y., Chen, F.N., Lai, M.T. & Chiu, T.H., 2006. Hepatoprotective effect of Phyllanthus in Taiwan on acute liver damage induced by carbon tetrachloride. American Journal of Chinese Medicine 34(3): 471–482.
• Liao, C.W., Chang, W.F. & Koo, J., 2006. The efficacy test of protection and treatment of a Phyllanthus extract against the chemical-induced liver damage in rat animal-models. Taiwanese Journal of Agricultural Chemistry and Food Science 44(6): 370–381.
• Neuwinger, H.D., 2000. African traditional medicine: a dictionary of plant use and applications. Medpharm Scientific, Stuttgart, Germany. 589 pp.
• Yang, C.M., Cheng, H.Y., Lin, T.C., Chiang, L.C. & Lin, C.C., 2007. Hippomanin A from acetone extract of Phyllanthus urinaria inhibited HSV-2 but not HSV-1 infection in vitro. Phytotherapy Research 21(12): 1182–1186.
• Yang, C.M., Cheng, H.Y., Lin, T.C., Chiang, L.C. & Lin, C.C., 2007. The in vitro activity of geraniin and 1,3,4,6-tetra-O-galloyl-b-d-glucose isolated from Phyllanthus urinaria against herpes simplex virus type 1 and type 2 infection. Journal of Ethnopharmacology 110(3): 555–558.
Other references
• Adjanohoun, E.J., Aké Assi, L., Ali Ahmed, Eymé, J., Guinko, S., Kayonga, A., Keita, A. & Lebras, M. (Editors), 1982. Médecine traditionelle et pharmacopée - Contribution aux études ethnobotaniques et floristiques aux Comores. Agence de Coopération Culturelle et Technique, Paris, France. 217 pp.
• Bharali, R., Tabassum, J. & Azad, M.R., 2003. Chemopreventive action of Phyllanthus urinaria Linn on DMBA-induced skin carcinogenesis in mice. Indian Journal of Experimental Biology 41(11): 1325–1328.
• Catapan, E., Luis, M., Da Silva, B., Moreno, F.N. & Viana, A.M., 2002. Micropropagation, callus and root culture of Phyllanthus urinaria (Euphorbiaceae). Plant Cell, Tissue and Organ Culture 70(3): 301–309.
• Chan, H.L.Y., Sung, J.J.Y., Fong, W.F., Chim, A.M.L., Yung, P.P., Hui, A.Y., Fung, K.P. & Leung, P.C., 2003. Double-blinded placebo-controlled study of Phyllanthus urinaria for the treatment of chronic hepatitis B. Alimentary Pharmacology and Therapeutics 18(3): 339–345.
• Chularojmontri, L., Wattanapitayakul, S.K., Herunsalee, A., Charuchongkolwongse, S., Niumsakul, S. & Srichairat, S., 2005. Antioxidative and cardioprotective effects of Phyllanthus urinaria L. on doxorubicin-induced cardiotoxicity. Biological and Pharmacological Bulletin 28(7): 1165–1171.
• Cruz, A.B., Moretto, E., Cechinel-Filho, V., Niero, R., Montanari, J.L. & Yunes, R.A., 1994. Antibacterial activity of Phyllanthus urinaria. Fitoterapia 65(5): 461–462.
• Gurib-Fakim, A. & Brendler, T., 2004. Medicinal and aromatic plants of Indian Ocean Islands: Madagascar, Comoros, Seychelles and Mascarenes. Medpharm, Stuttgart, Germany. 568 pp.
• Higashino, H., Suzuki, A., Tanaka, Y. & Pootakhna, K., 1992. Hypoglycemic effects of Siamese Momordica charantia and Phyllanthus urinaria extracts in streptozotocin-induced diabetic rats. Nippon Yakurigaku Zasshi 100(5): 415–421.
• Hout, S., Chea, A., Bun, S.S., Elias, R., Gasquet, M., Timon-David, P., Balansard, G. & Azas, N., 2006. Screening of selected indigenous plants of Cambodia for antiplasmodial activity. Journal of Ethnopharmacology 107(1): 12–18.
• Lavergne, R., 2001. Le grand livre des tisaneurs et plantes médicinales indigènes de la Réunion. Editions Orphie, Chevagny sur Guye, France. 522 pp.
• Paulino, N., Pizollatti, M.G., Yunes, R.A., Cechinel-Filho, V., Creczynski-Pasa, T.B. & Calixto, J.B., 1999. The mechanisms underlying the relaxant effect of methyl and ethyl gallates in the guinea pig trachea in vitro: contribution of potassium channels. Naunyn Schmiedeberg’s Archives of Pharmacology 360(3): 331–336.
• Santos, A.R., De Campos, R.O., Miguel, O.G., Cechinel-Filho, V., Yunes, R.A. & Calixto, J.B., 1999. The involvement of K+ channels and Gi/o protein in the antinociceptive action of the gallic acid ethyl ester. European Journal of Pharmacology 379(1): 7–17.
• Shen, B., Yu, J., Wang, S., Chu, E.S., Wong, V.W., Zhou, X., Lin, G., Sung, J.J. & Chan, H.L., 2008. Phyllanthus urinaria ameliorates the severity of nutritional steatohepatitis both in vitro and in vivo. Hepatology 47(2): 473–483.
• Shen, Z.Q., Dong, Z.J., Peng, H. & Liu, J.K., 2003. Modulation of PAI-1 and tPA activity and thrombolytic effects of corilagin. Planta Medica 69(12): 1109–1112.
• van Holthoon, F.L., 1999. Phyllanthus L. In: de Padua, L.S., Bunyapraphatsara, N. & Lemmens, R.H.M.J. (Editors). Plant Resources of South-East Asia No 12(1). Medicinal and poisonous plants 1. Backhuys Publishers, Leiden, Netherlands. pp. 381–392.
• Ueda, M., Asano, M., Sawai, Y. & Yamamura, S., 1999. Leaf-movement factors of nyctinastic plant, Phyllanthus urinaria L. The universal mechanism for the regulation of nyctinastic leaf-movement. Tetrahedron 55(18): 5781–5792.
• Unander, D.W., Webster, G.L. & Blumberg, B.S., 1991. Uses and bioassays in Phyllanthus (Euphorbiaceae): a compilation. 2. The subgenus Phyllanthus. Journal of Ethnopharmacology 34: 97–133.
• Wang, M.X., Cheng, H.W., Li, Y.J., Meng, L.M. & Mai, K., 1995. Herbs of the genus Phyllanthus in the treatment of chronic hepatitis B: observations with three preparations from different geographic sites. Journal of Laboratory and Clinical Medicine 126(4): 350–352.
• Xu, M., Zha, Z.J., Qin, X.L., Zhang, X.L., Yang, C.R. & Zhang, Y.J., 2007. Phenolic antioxidants from the whole plant of Phyllanthus urinaria. Chemistry and Biodiversity 4(9): 2246–2252.
• Zhou, S., Xu, C., Zhou, N., Huang, Y., Huang, L., Chen, X., Hu, Y. & Liao, Y., 1997. Mechanism of protective action of Phyllanthus urinaria L. against injuries of liver cells. Zhongguo Zhong Yao Za Zhi 22(2): 109–111.
Sources of illustration
• Radcliffe-Smith, A., 1986. Euphorbiaceae. In: Nasir, E. & Ali, S.I. (Editors). Flora of Pakistan No 172. National Herbarium, Pakistan Agricultural Research Council, Islamabad and Department of Botany, University of Karachi, Pakistan. 170 pp.
Author(s)
D.M. Mosango
c/o Laboratory of Natural Sciences, Lycée Français Jean Monnet de Bruxelles (LFB), Avenue du Lycée Français 9, 1180 Brussels, Belgium


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:
Mosango, D.M., 2008. Phyllanthus urinaria 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, fruit; 3, seed.
Redrawn and adapted by Achmad Satiri Nurhaman



plant habit
obtained from
L. Allain


fruiting plant
obtained from
J. McMillian


seeds
obtained from
S. Hurst