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Phyllanthus amarus Schumach. & Thonn.

Protologue
Schumach., Beskr. Guin. pl.: 421 (1827).
Family
Euphorbiaceae (APG: Phyllanthaceae)
Chromosome number
2n = 26, 52
Synonyms
Phyllanthus niruri auct. non L.
Vernacular names
Black catnip, carry me seed, child pick-a-back, gale of wind, Gulf leaf flower, hurricane weed, shatterstone, stone breaker (En). Herbe au chagrin, petit tamarin blanc (Fr).
Origin and geographic distribution
Phyllanthus amarus originates from tropical America and has spread as a weed throughout the tropics and subtropics. In tropical Africa it occurs in most countries. It also occurs throughout the Indian Ocean islands.
Uses
Phyllanthus amarus is widely used as a medicinal plant. An infusion is considered a good tonic, diuretic and antipyretic. A decoction of the aerial parts or only of the leaves is taken to treat gonorrhoea, diarrhoea, dysentery, stomach-ache, pain in the sides, haemorrhoids and absence of menstruation or female sterility. A suppository of the leaf paste is applied to the vagina to treat absence of menstruation and polyps. Leaf sap, mixed with palm oil or not, is applied as ear drops to treat otitis and applied to abscesses, sores and wounds.
In Côte d’Ivoire a plant decoction is taken to facilitate childbirth, to treat oedema and pain caused by fever or a sore throat. In Mali a leaf decoction is drunk to treat jaundice. In Benin a decoction of leafy twigs is drunk to treat palpitations. A root decoction, mixed with other plants or not, is taken to treat colic and rectal prolapse. A decoction of leafy twigs, mixed with other plants, is drunk to treat cough. Leaves mixed with crushed nuts of Cola acuminata (P.Beauv.) Schott & Endl. and water is applied to shingles. A decoction of the aerial parts is drunk to treat candidosis, and sap is applied locally. In Congo and DR Congo the plant sap is drunk to treat diabetes and tachycardia. Ripe fruit is eaten as an anthelmintic. In Kenya a cold leaf maceration is drunk to treat stomach-ache. A plant decoction is drunk to induce vomiting. In Uganda ground aerial parts are applied to snakebites; the ground material in water is also drunk to treat poisoning by snakebites. In the Indian Ocean islands a leaf or plant decoction is taken to treat diarrhoea and abdominal pain and externally applied to treat skin problems. An infusion of the stem and leaves is used as eye drops to treat eye infections.
Throughout the American and Asiatic tropics the medicinal uses are similar as cited for tropical Africa. Furthermore, Phyllanthus amarus, as well as several other closely resembling species, are widely in use as folk medicine in treatment of liver related troubles.
Phyllanthus amarus is said to have sand-binding properties. In West Africa it is used in medico-magical ceremonies.
Production and international trade
Recent research results have increased the demand for Phyllanthus amarus in international markets. According to a survey conducted in India, in 2004–2005 there was a demand of almost 3000 t of fresh Phyllanthus plants, including Phyllanthus amarus. The annual growth rate is estimated at about 10%, and as such Phyllanthus amarus has a bright future.
In South-East Asia Phyllanthus amarus is sometimes cultivated on a small scale and sold on local markets.
Properties
The following chemical constituents have been isolated from Phyllanthus amarus: lignans (e.g. phyllanthin, hypophyllanthin, phyltetralin, nirtetralin, niranthin), ellagitannins (phyllanthusiin D, amariinic acid, elaeocarpusin, repandusinic acid A and geraniinic acid B), flavonoids (quercetin-3-O-glucosides), tannins (geraniin, amariin, gallocatechin, corilagin and 1,6-digalloylglucopyranoside), alkaloids of the quinolizidine type (phyllantine (= methoxy-securinine), securinine, norsecurinine, isobubbialine, epibubbialine), phenolic compounds (gallic acid, ellagic acid, dotriacontanyl docosanoate, triacontanol, oleanolic acid and ursolic acid) and a chroman derivative (4,4,8-trimethoxy chroman). The alkaloid phyllanthine must not be confused with the lignan phyllanthin. The leaves were found to contain the highest amounts of phyllanthin (0.7%) as compared to the whole plant: phyllanthin (0.4%), hypophyllanthin (1.2%), gallic acid (0.4%) and ellagic acid (0.2%).
Phyllanthus amarus extracts were found to significantly inhibit DNA polymerase of the hepatitis B virus and other hepatitis-DNA-viruses, such as the woodchuck hepatitis virus, together with in-vitro activity against the enzyme reverse-transcriptase of retroviruses. The activity of the extracts in test animals as well as in clinical studies was controversial: both success and failure have been reported. Callus induced from Phyllanthus amarus showed less activity against viral DNA polymerase and reverse transcriptase than extracts from field-grown plants. In a clinical trial, a plant extract had a remarkable effect for chronic viral hepatitis B in recovery of liver function and inhibition of the replication of hepatitis B virus.
Phyllanthin and hypophyllanthin have protective activity in rat hepatocytes against cytotoxicity induced by CCl4 and galactosamine, and it has been suggested that phyllanthin is responsible for antigenotoxic effects reported for the extracts. However, phyllanthin has also been reported to be toxic to the nervous system and liver. A crude extract given orally to rats showed significant liver regenerative effects against alcohol-induced liver cell injury. An ethanolic extract administered orally to mice possessed a potent protective effect against aflatoxin B-1-induced hepatic damage. A crude aqueous extract of in-vitro cultured roots caused a dose-dependent reduction of bovine viral diarrhoea virus with no cytotoxic effect. In another test, extracts of in-vitro grown hairy or adventitious roots showed about 85% inactivation of hepatitis B virus surface antigen. A chroman derivative, 4,4,8-trimethoxy chroman, isolated from the dichloromethane fraction, exhibited very little in-vitro cytotoxicity.
Phyllanthus amarus aqueous extracts show potent anticarcinogenic activity against development of different tumour types. Administration of the extract after tumour development increased survival of rats and mice up to 1 year. An alcoholic extract was found to significantly reduce cytochrome P450 enzymes both in vitro as well as in vivo when orally administered to mice. A hexane extract, the lignans-rich fraction and the lignans nirtetralin, niranthin and phyllanthin exerted cytotoxic effects in 2 human leukaemia cell lines, as well as multidrug resistance reversing properties, mainly due to their ability to synergize with the action of conventional chemotherapeutics. An ethanolic extract showed significant preventive effect against benign prostatic hyperplasia in rats.
Aqueous and alcohol-based extracts potently inhibit HIV-1 replication in human cell lines. A gallotannin enriched fraction showed enhanced activity, and the purified gallotannins geraniin and corilagin were most active. A concentration-dependent inhibition of HIV-1 reverse transcriptase and protease could be demonstrated in vitro. A potent anti-HIV activity was demonstrated in blood of volunteers who had ingested the plant material. A 50% methanol extract, a water extract, as well as isolated corilagin and brevifolin carboxylic acid have demonstrated strong β-glucuronidase inhibitory action. However, phyllanthin and hypophyllanthin were ineffective.
Fresh plant material and a methanol extract showed strong antioxidant activity in various antioxidant assays. A correlation between the antioxidant activity and total phenolic content was observed. Drying of the plant material caused a significant reduction in antioxidant properties. On the other hand, boiling water extracts exhibited significantly stronger antioxidant potentials even from dried plant material due to greater solubility of compounds, breakdown of cellular constituents as well as hydrolysis of tannins. A whole plant extract showed significant radioprotective activity when given orally to mice, by decreasing the damage to intestinal cells, decreasing the lipid peroxidation levels, decreasing the percentage of chromosomal aberrations and by elevating the antioxidant enzymes in the intestine, blood and liver.
Methanol and aqueous extracts inhibited all the phases of inflammation in standardized tests in rats. A hydroalcoholic extract, given intraperitoneally to rats, exhibited pronounced antinociception. Given orally, the extract was less potent. The hexane extract, the lignan-rich fraction and the lignans phyltetralin, nirtetralin and niranthin, but not hypophyllanthin or phyllanthin, inhibited carrageenan-induced rat paw oedema and neutrophil influx. Furthermore, niranthin exhibited anti-inflammatory and anti-allodynic activities. An ethanol and a hexane extract showed significant anti-inflammatory potential in vitro and in vivo in mice.
Aqueous and methanolic extracts of the aerial parts showed antidiabetic activity in mice, rats and rabbits. However, a 1-week treatment with the aqueous extract was incapable of lowering blood glucose in untreated non-insulin dependent diabetic patients. Oleanolic acid, ursolic acid and lupeol isolated from this fraction were shown to inhibit α-amylase.
An aqueous crude extract caused varying degrees of declining fertility when given orally to male mice. An alcohol extract of the whole plant showed significant contraceptive effects in female mice at a dose of 100 mg/kg body weight, when given orally for 30 days.
The antidiarrhoeal and gastrointestinal protective potentials of aqueous extract of Phyllanthus amarus leaves were investigated in mice. An aqueous extract delayed the onset of castor oil-induced diarrhoea in mice. In another experiment with rats, a whole plant extract reduced digestive tract motility and delayed gastric emptying, whereas it caused relaxation of isolated rat fundus and ileum.
Methanolic extracts of leaves, roots and fruits showed significant concentration-dependent antibacterial activity in vitro against a range of gram-positive and gram-negative bacteria; leaf extracts showed the highest activity. A chloroform fraction of the aerial parts showed a significant inhibitory effect against the dermatophytic fungus Microsporum gypseum and against the yeast Candida albicans.
Norsecurinine, isolated from the aerial parts, showed significant activity against spore germination of the crop fungi Alternaria brassicae, Alternaria solani, Curvularia pennisetti, Erysiphe pisi and Helminthosporium frumentacei under glasshouse conditions.
Chloroform and ethanolic extracts of the aerial parts and roots showed significant larvicidal activity against Anopheles stephensi larvae. An ethanolic root extract possessed significant activity against Tribolium castaneum, a pest of stored grain.
Fresh leaves from Phyllanthus amarus plants of Nigerian origin were found to contain high levels of Mn (465 ppm), Cu (21.8 ppm), Zn (75.1 ppm), and NO3 (7,200 ppm). Varying proportions of Fe, Mg, K, Ca and Na were found. The levels of several toxic compounds are high enough to constitute a threat to animals consuming them and the use of the leaves for medicinal purposes should also be monitored.
Adulterations and substitutes
In India a herbal medicine called ‘Bhumyamlaki’ is sold which may be pure Phyllanthus amarus or pure Phyllanthus maderaspatensis L. or a mixture with Phyllanthus fraternus G.L.Webster. It is marketed as a medicine especially for liver troubles.
Description
Monoecious, annual, erect, glabrous herb up to 60 cm tall, reddish; branchlets flattened, often slightly winged and sparsely hairy. Leaves alternate, distichous and crowded along lateral branchlets, simple and entire, sessile; stipules ovate-lanceolate to lanceolate; blade oblong to elliptical-oblong, 7–12(–20) mm × 3–6(–9) mm, base obtuse to rounded and slightly unequal, apex rounded, often pointed. Flowers 1–2 in the axils of leaves, unisexual, pale green, often flushed red; male flowers at the base of branches, other leaf axils with 1 female flower and 1 male flower; pedicel c. 1 mm long; perianth lobes 5(–6), 0.5–1 mm long; male flowers with 5-lobed disk, stamens 3, filaments fused, anthers free; female flowers with cup-shaped, 5-lobed disk, ovary superior, ovoid, warty, 3-celled, styles 3, free, shallowly 2-fid at apex. Fruit an obtusely 3-lobed capsule 2–2.5 mm in diameter, smooth, hanging, 6-seeded. Seeds c. 1 mm long, with 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 other Indian Ocean islands. A subgeneric classification of Phyllanthus is in preparation.
Until 20 years ago taxonomists placed a number of species, including Phyllanthus amarus, under Phyllanthus niruri L. Where the name Phyllanthus niruri has been applied in older literature to African or Asian specimens, usually Phyllanthus amarus is intended, but sometimes also Phyllanthus debilis Klein ex Willd., Phyllanthus fraternus G.L.Webster, Phyllanthus maderaspatensis L. or Phyllanthus rotundifolius Klein ex Willd. Specimens of true Phyllanthus niruri have actually never been confirmed from outside the Americas.
Growth and development
The branching pattern of Phyllanthus amarus is ‘phyllanthoid’, i.e. the spiralled leaves on the main axes are strongly reduced to ‘cataphylls’, which subtend a deciduous branchlet with distichous leaves, the branchlet resembling a compound leaf.
Ecology
Phyllanthus amarus occurs in open localities, waste ground, grassy scrub vegetation and dry deciduous forest, usually on humid, sandy soils, from sea-level up to 1000 m altitude. It is reported as a troublesome weed in pulses, soya bean, groundnut, cereals, sugar cane, cassava, taro, sesame, sunflower and cotton.
Propagation and planting
Seed requires light to germinate. Germination is often less than 50%; germination of freshly harvested seeds is slower than that of older seeds. Scarification by immersion in water at 30°C for 2 hours rendered seeds inviable. Seeds dried to 8% moisture content and treated with turmeric rhizome powder under ambient conditions maintained viability for up to 6 months; untreated seeds stored poorly.
In-vitro propagation can be done by culturing shoot tips, and less successfully by nodal and internodal segments.
Management
In India Phyllanthus amarus is grown as a medicinal crop. The crop duration is 100–300 days. Seeds are mixed with sand and the mixture is broadcast in the field. Sandy loam and black soils with pH 7.5–8 are considered best. The cultivar ‘Navyakrit’ has been developed, which has a high yield of plant material and a high yield of active constituents. About 7.5–10 kg seed/ha is used, and a plant population of 282,500 plants/ha is maintained. The plants are raised without irrigation. One or 2 weedings are considered sufficient. Farm manure is applied as an organic fertilizer. Plant height, leaf area index, dry matter production and yield of the lignans phyllanthin and hypophyllanthin were highest in a field experiment with Phyllanthus amarus treated with poultry manure, the biofertilizer Azospirillum and phosphate-solubilizing bacteria.
Phyllanthus amarus grown in greenhouses at 15°C showed much less inhibitory activity on DNA polymerase of woodchuck hepatitis virus than when grown at 25°C.
Diseases and pests
In India the commercial cultivation of Phyllanthus amarus has led to the outbreak of stem blight caused by Corynespora cassiicola. Phytoplasma-induced yellowing, small leaf development, proliferation of axillary shoots and overall retarded growth of infected plants were found in experimental fields in 1999–2000.
Yield
In India the mutant Phyllanthus amarus line ‘CIM-Jeevan’, produced by γ-radiation, showed a yield of 1–1.2 kg/m2 fresh plant material, compared with about 0.8 kg/m2 of the control. ‘CIM-Jeevan’ also produced a higher phyllanthin (0.7–0.8%) and hypophyllanthin (0.3–0.4%) yield than the control (0.3–0.4% and 0.1–0.2%, respectively). The cultivar ‘Navyakrit’ yields about 1 t/ha dry plants at the end of the rainy season. Each plant yields 20–25 g seed.
Under experimental conditions in Florida, 6– 7-month-old plants reached an average dry weight of about 40 g/plant.
Handling after harvest
Plants are uprooted and dried in the shade.
Genetic resources
Phyllanthus amarus is widespread and common throughout its distribution area and is therefore not threatened by genetic erosion.
Breeding
Although several cultivars have been developed with higher yield and higher concentration of active compounds, more breeding efforts are needed to increase crop yield under different field conditions.
Prospects
Phyllanthus amarus is widely used in local medicine in Africa and Asia. A wealth of research findings have shown interesting antiviral, anti-HIV, anti-inflammatory, antioxidant, antibacterial and antidiabetic activities. More research is needed though, especially well-controlled clinical trials, to evaluate the extracts and the individual compounds. More research is needed as well to improve cultivation methods.
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.
• Kassuya, C.A.L., Silvestre, A., Menezes De Lima, O.Jr, Marotta, D.M., Rehder, V.L.G. & Calixto, J.B., 2006. Antiinflammatory and antiallodynic actions of the lignan niranthin isolated from Phyllanthus amarus - evidence for interaction with platelet activating factor receptor. European Journal of Pharmacology 546(1–3): 182–188.
• Khatoon, S., Raia, V., Rawata, A.K.S. & Mehrotra, S., 2006. Comparative pharmacognostic studies of three Phyllanthus species. Journal of Ethnopharmacology 104(1–2): 79–86.
Other references
• Adedapo, A.A., Abatan, M.O., Akinloye, A.K., Idowu, S.O. & Olorunsogo, O.O., 2003. Morphometric and histopathological studies on the effects of some chromatographic fractions of Phyllanthus amarus and Euphorbia hirta on the male reproductive organs of rats. Journal of Veterinary Science 4(2): 181–185.
• Adeneye, A.A., Amole, O.O. & Adeneye, A.K., 2006. Hypoglycemic and hypocholesterolemic activities of the aqueous leaf and seed extract of Phyllanthus amarus in mice. Fitoterapia 77(7–8): 511–514.
• Ajaiyeoba, E. & Kingston, D., 2006. Cytotoxicity evaluation and isolation of a chroman derivative from Phyllanthus amarus aerial part extract. Pharmaceutical Biology 44(9): 668–671.
• Bhattacharyya, R. & Bhattacharya, S., 2004. Development of a potent in vitro source of Phyllanthus amarus roots with pronounced activity against surface antigen of the hepatitis B virus. In Vitro Cellular and Developmental Biology Plant 40(5): 504–508.
• Chattopadhyay, P., Agrawal, S.S. & Garg, A., 2006. Liver regenerative effect of Phyllanthus amarus L. against alcohol induced liver cell injury in partially hepatectomised albino rats. International Journal of Pharmacology 2(4): 426–430.
• Chezhiyan, N., Saraswathy, S. & Vasumathi, R., 2003. Studies on organic manures, biofertilizers and plant density on growth, yield and alkaloid content of bhumyamalaki (Phyllanthus amarus Schum. & Thonn.). South Indian Horticulture 51(1/6): 96–101.
• Gupta, A.K., Khanuja, S.P.S., Gupta, M.M., Shasany, A.K., Neeraj, J., Verma, R.K., Darokar, M.P., Bagchi, G.D. & Kumar, S., 2003. High herb, phyllanthin and hypophyllanthin yielding variety of bhumyamalaki (Phyllanthus amarus): Cim-Jeevan. Journal of Medicinal and Aromatic Plant Sciences 25(3): 743–745.
• Kumar, K.H.H. & Kuttan, R., 2006. Inhibition of drug metabolizing enzymes (cytochrome P450) in vitro as well as in vivo by Phyllanthus amarus Schum. & Thonn. Biological and Pharmaceutical Bulletin 29(7): 1310–1313.
• Leelarasamee, A., Trakulsomboon, S., Maunwongyathi, P., Somanabandhu, A., Pidetcha, P., Matrakool, B., Lebnak, T., Ridthimat, W. & Chandanayingyong, D., 1990. Failure of Phyllanthus amarus to eradicate hepatitis B surface antigen from symptomless carriers. Lancet 335(8705): 1600–1601.
• Leite, D.F.P., Kassuya, C.A.L., Mazzuco, T.L., Silvestre, A., De Melo, L.V., Rehder, V.L.G., Rumjanek, V.M. & Calixto, J.B., 2006. The cytotoxic effect and the multidrug resistance reversing action of lignans from Phyllanthus amarus. Planta Medica 72(15): 1353–1358.
• Mahat, M.A. & Patil, B.M., 2007. Evaluation of antiinflammatory activity of methanol extract of Phyllanthus amarus in experimental animal models. Indian Journal of Pharmaceutical Sciences 69(1): 33–36.
• Mazumder, A., Mahato, A. & Mazumder, R., 2006. Antimicrobial potentiality of Phyllanthus amarus against drug resistant pathogens. Natural Product Research 20(4): 323–326.
• Notka, F., Meier, G. & Wagner, R., 2004. Concerted inhibitory activities of Phyllanthus amarus on HIV replication in vitro and ex vivo. Antiviral Research 64(2): 93–102.
• Odetola, A.A. & Akojenu, S.M., 2000. Anti-diarrhoeal and gastro-intestinal potentials of the aqueous extract of Phyllanthus amarus (Euphorbiaceae). African Journal of Medicine and Medical Sciences 29(2): 119–122.
• Onocha, P.A., Opegbemi, A.O., Kadri, A.O., Ajayi, K.M. & Okorie, D.A., 2003. Antimicrobial evaluation of Nigerian Euphorbiaceae plants 1: Phyllanthus amarus and Phyllanthus muellerianus leaf extracts. Nigerian Journal of Natural Products and Medicine 7: 9–12.
• Raphael, K.R., Sabu, M.C. & Kuttan, R., 2002. Hypoglycemic effect of methanol extract of Phyllanthus amarus Schum. & Thonn. on alloxan-induced diabetes mellitus in rats and its relation with antioxidant potential. Indian Journal of Experimental Biology 40(8): 905–909.
• Revathi, R., Vanangamudi, K. & Sasthri, G., 2003. Effect of seed treatment and storage container on seed germination and seedling vigour of keelanelli (Phyllanthus amarus(Schum. & Thonn.). Seed Research 31(2): 169–174.
• Sripanidkulchai, B., Tattawasart, U., Laupatarakasem, P., Vinitketkumneun, U., Sripanidkulchai, K., Furihata, C. & Matsushima, T., 2002. Antimutagenic and anticarcinogenic effects of Phyllanthus amarus. Phytomedicine 9(1): 26–32.
• Unander, D.W., Webster, G.L. & Blumberg, B.S., 1995. Usage and bioassays in Phyllanthus (Euphorbiaceae). 4. Clustering of antiviral uses and other effects. Journal of Ethnopharmacology 45: 1–18.
• Wang, X.H., Li, C.Q., Guo, X.B. & Fu, L.C., 2001. A comparative study of Phyllanthus amarus compound and interferon in the treatment of chronic viral hepatitis B. Southeast Asian Journal of Tropical Medicine and Public Health 32(1): 140–142.
Sources of illustration
• 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.
Author(s)
P. Oudhia
SOPAM, 28-A, Geeta Nagar, Raipur, 492001, C.G., India


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:
Oudhia, P., 2008. Phyllanthus amarus Schumach. & Thonn. 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, flowering branch; 2, stem leaf and stipules; 3, part of flowering branchlet; 4, male flower; 5, female flower; 6, fruit; 7, seed.
Source: PROSEA



plant habit CopyLeft EcoPort


inflorescences
obtained from
Botanypictures


fruiting stems
obtained from
Botanypictures


fruiting stem