A REVIEW ON PHYTOCHEMICAL AND PHARMACOLOGICAL PROPERTIES OF PHYLLANTHUS AMARUS SCHUM. AND THONN.

A REVIEW ON PHYTOCHEMICAL AND PHARMACOLOGICAL PROPERTIES OF PHYLLANTHUS AMARUS SCHUM. AND THONN.

Jyoti Meena^*, R. A. Sharma and Rashmi Rolania

Department of Botany, University of Rajasthan, Jaipur - 302004, Rajasthan, India.

ABSTRACT: Phyllanthus amarus Schum and Thonn herb is in traditional medicine for more than 3000 years. It belongs to a family of Euphorbiaceae and commonly known by the name of carry me seed, stone breaker, gala of wind, etc. It is a branching annual herb of 30 - 60 cm height widely spread throughout tropics and sub-tropics as a weed. Phyllanthus amarus is gaining momentum for its hepatoprotective, anti-carcinogenic, anti-bacterial, anti-viral, anti-inflammatory and more activities as it contains different combinations of secondary metabolites, which render them medicinal properties. The major class of bioactive compounds like alkaloids, flavonoids, lignans, sterols, tannins, triterpenes and volatile oils has been isolated. Lignans like phyllanthin and hypophyllanthin, flavonoids like quercetin were isolated from the leaves of P. amarus. This review is an effort to represent the phytochemicals and their pharmacological properties which constantly addresses a challenge because of a large number of compounds present as a mixture in the extract with trace amounts.

Phyllanthus amarus, Phytochemicals, Pharmacological activity, Traditional uses

INTRODUCTION: The genus Phyllanthus is one of the most important groups of plants traded as a raw herbal drug in India ¹. The genus Phyllanthus of family Euphorbiaceace, consists of approx. 1000 species, spread over tropical and sub-tropical continents like America, Africa, Australia and Asia ^{2, 3}. In India, Phyllanthus amarus is widely distributed as a weed in cultivated and waste lands ⁴. All three major habits i.e., trees, shrubs and herbs are seen amongst the Phyllanthus species. Ravikant et al., have also described southern India to be the genetic hotspot of Phyllanthus species ⁵. Phyllanthus amarus Schum. and Thonn. has a long history of usage by people, because of its rich medicinal values.

Commonly known by the name of Bhumi amla, belongs to a large family of upright or prostrate herbs or shrubs, often with milky acrid juice ⁶. In Unani literature, it is described by the name of ‘Bhuti’ which means Bhum Amlak - Amla of Land ⁷. It plays important role in the development of green medicines which are safer to use and more dependable than costly synthetic drugs with no adverse effects. P. amarus has been described in Ayurveda by the Sanskrit name - Bhoomy-aamlakee, Taamalakee and Bhoodha tree ⁸. P. amarus uses are gaining momentum because of their novel antiviral activity against hepatitis B virus and for several other biological activities such as kidney and gallbladder stones, for cold, flu, tuberculosis, liver diseases, etc ⁹.

Vernacular Names: The plant is known by different vernacular names in the different areas by the local people (Table 1). It is commonly called carry me seed, stone breaker, wind breaker, leaf flower or gale of wind ¹⁰. Phyllanthus means leaf and flower because of its appearance, where flower, fruit and leaf appear to be fused ¹¹.

TABLE 1: NAMES USED WORLDWIDE OF P. AMARUS ARE AS FOLLOWS ^{8, 12}

Botanical Characteristics: Phyllanthus amarus is a branching annual glabrous herb which is 30 - 60 cm high and has slender leaf bearing branchlets, distichous subsessile leaves with elliptic-oblong, obtuse, rounded base (Fig. 1). Flowers are axillary and yellowish, whitish or greenish. Male flowers are in groups of 1 - 3 whereas females are solitary. Fruits are depressed-globose like smooth capsules present underneath the branches and seeds are trigonous, pale brown with longitudinal parallel ribs on the back ¹⁴. Capsules on stalks are 1 - 2 mm long, round, smooth, 2 mm wide six seeds. The plant has explosive seed capsules that propel the seeds some distance from the plant. Seeds are triangular, light brown, 1 mm long with 5 - 6 ribs on the back ^{10, 15}.

FIG. 1: PHYLLANTHUS AMARUS FOUND IN RAJASTHAN IN ITS HABITAT

Distribution: P. amarus is a common pantropical weed that grows well in moist, shady and sunny places. It is widely spread throughout tropics and subtropics ^{11, 16}. The taxonomic revision of genus Phyllanthus by Webster included closely-related genera P. amarus, under the sub-section Swartiziani of the section Phyllanthus. The nomenclature, taxonomic distinctness and close relatives of P. amarus were addressed in detail based on morphology and geographical distribution ^{17 - 19}. It is said to be related to P. abnormis, which is endemic to sandy areas in Texas and Florida of southern USA.

It is, therefore, most likely that Phyllanthus amarus originated in the Caribbean area as a vicarious species of P. abnormis of the southern United States and has spread around the tropics by trading vessels ¹⁷. Among approx. 1000 species of genus Phyllanthus, 53 species are found in India, of which 23 species are endemic. These are distributed throughout the Indian subcontinent, with higher densities in the southern region. Among 53 species of Phyllanthus, 37 are shrubs, 13 are herbs and 3 are trees ²⁰.

Jain et al., 2003 assessed the molecular diversity of P. amarus across India using RAPD (random amplified polymorphic DNA) markers. The genetic variability was assessed across 33 locations covering the states of Tamil Nadu, Karnataka, Maharashtra, Gujarat, Assam, West Bengal, Tripura, Uttar Pradesh, Punjab and Haryana. Intra population variation was larger in accessions from southern India compared to other parts of the country. P. amarus grows wildly in all drier parts of Rajasthan ²¹.

Phytochemical Properties: Phytochemistry is regarded as the heart of herbal therapy and the phytochemical research plays an important role in the development of green medicines, which are safer to use (Table 2). The major class of bioactive compounds like alkaloids, flavonoids, lignans, phenols, tannins, terpenes and volatile oils has been isolated. These bioactive compounds further include their respective phytoconstituents. Alkaloids possess securinine, nor-securinine, epibubbialine, isobubbialine, dihydrosecurinine ^{22, 23}. Flavonoids contain Quercetin, kaempferol, astragalin, quercetin-3-O-glucoside, quercitrin ^{10, 13, 24-26}. Likewise, Tannins include Amarulone, geraniin, amariin, furosin, corilagin, melatonin, phyllanthusin D ^{13, 24, 25}.  Lignans contains important pharmacological activities because of its phyto-constituents such as Phyllanthin, hypo-phyllanthin, 5-dimethoxy-niranthin, nirtetralin, phyltetralin, hinokinin, 4-(3,4-dimethoxy-phenyl)-1-(7-methoxy benzo[1,3]dioxol-5-yl)-2,3-bismethoxymethyl-but --an-1-ol ^{10, 23, 27, 28, 29, 30, 31, 32}. Sterols include Amarosterol A, amarosterol B ³³.  Triterpenes like Phenazine and phenazine derivatives, 2Z, 6Z, 10Z, 14E, 18E, 22E-farnesyl farnesol ^{24, 30} and volatile oils such as Linalool, Phytol ³⁴.

TABLE 2: PHYTOCHEMICALS PRESENT IN P. AMARUS

Ethno-pharmacological Uses: If the selection of plants is made on the grounds of their traditional use, the chance of research success is greater ³⁵. This herb is in traditional medicine for more than 3000 years ³⁶.

• Phyllanthus amarus herb has found its traditional uses in several health problems because of its efficacy in the field of gastrointestinal disorders ³⁷.
• It is used in several female problems such as in leucorrhoea, menorrhagia and mammary abscess and can act as galactagogue ³⁸.
• Fresh leaf paste has the capacity to cure white spots on skin, diabetes, and jaundice ^{39 - 42}.
• Whole plant extract is used in urinary problems, liver disease, dyspepsia, anorexia, constipation and dysentery ^{43, 44}.
• Gonorrhea and syphilis can be treated by a decoction of leaves, sugar and cumin seeds ⁴⁵.
• Treatment of malaria has been successful by amarus whole plant extract ⁴⁶.

It is an ingredient of the most popular formulations of Ayurveda- Chyawanprash, which is consumed at large scale not only in India but also throughout the world because of its anti-inflammatory activity ⁴⁷.

Pharmacological Activities: Plants as a source of new drugs are still poorly explored of all plant species. Only a small percentage has been investigated phytochemically and even a smaller percentage has been properly studied in terms of their pharmacological properties ⁴⁸.

Antioxidant Activity: Methanolic extract of P. amarus was found to have potential antioxidant activity as it could inhibit lipid peroxidation and scavenge hydroxyl and superoxide radicals in- vitro. The amount required for 50% inhibition of lipid peroxide formation was 104 μg/ml and the concentrations needed to scavenge hydroxyl and superoxide radicals were 117 and 19 mg/ml respectively ⁴⁹. Different drying treatments led to a significant reduction (P<0.05) in antioxidant properties of P. amarus methanolic extracts, with microwave drying causing the highest decrease in TPC and antioxidant activity exhibited by the reduction in both radical scavenging activity and FRAP. On the other hand, boiling water extracts appeared to exhibit significantly stronger antioxidant potentials (P<0.05) even in dried plant materials due to greater solubility of compounds, the breakdown of cellular constituents as well as hydrolysis of tannins ⁵⁰.

The antioxidant activity of some of the principal constituents, namely amariin, 1-galloyl-2,3-dehydrohexahydroxydiphenyl (DHHDP)-glucose, repandusinic acid, geraniin, corilagin, phyllanthusiin D, rutin and quercetin 3-O-glucoside were examined for their ability to scavenge free radicals in a range of systems including DPPH, 2,2-azobis-3-ethylbenzthiazoline-6-sulfonic acid (ABTS)/ ferrylmyoglobin, ferric reducing antioxidant power (FRAP) and pulse radiolysis.

The compounds showed significant antioxidant activities with differing efficacy depending on the assays employed. Amariin, repandusinic acid and phyllanthusiin D showed higher antioxidant activity among the ellagitannins and were comparable to the flavonoids, rutin and quercetin 3-O-glucoside ²⁶. P. amarus extracts appear to act as an in vivo natural antioxidant and an effective gastro-protective agent that is as effective as cimetidine. Phyllanthus amarus may also offer protection against toxic effects of alcohol to the liver ⁵¹. Phyllanthin, one of the active lignin present in P. amarus was isolated from the aerial parts, by silica gel column chromatography employing gradient elution with hexane-ethyl acetate solvent mixture.

Characterization of Phyllanthin was done by mass spectrophotometry, UV-visible spectrophotometry, elemental analysis, FTIR, HNMR, CNMR and mass spectral analysis. Free radical scavenging activity of P. amarus extract and phyllanthin was also examined using DPPH assay. The CCl₄ treatment caused a significant decrease in cell viability. It was observed that phyllanthin effectively alleviated the changes induced by CCl4 in a concentration-dependent manner, with much smaller strengths as compared to Phyllanthus amarus extract ⁵².

To study the improved antioxidant status and reduction in the risk of oxidative stress, rats were treated with P. amarus aqueous extract (PAAEt) at a dose of 200 mg/kg body wt/day for 8 weeks along with the assay of lipid peroxidation (LPO), Vitamin C, uric acid and reduced glutathione (GSH) and antioxidant enzymes: Glutathione peroxidase (GPx), catalase (CAT) and superoxide dismutase (SOD). PAAEt treated rats showed a significant decrease in plasma LPO and a significant increase in Plasma Vitamin C, uric acid, GSH levels and GPx, CAT and SOD activities ⁵³.

Using DPPH (1,1-diphenyl-2-picrylhydrazyl) method, free radical scavenging activity was evaluated using in-vitro callus which showed that the methanol extract of P. amarus., contains the highest amount of phenolic compounds and exhibits the greatest antioxidant activity in comparison to other extracts and even more as compared to in-vivo plant extraction ⁵⁴.

Anti-diabetic Activity: The methanolic extract of P. amarus was found to reduce the blood sugar in alloxan diabetic rats by 6% at a dose level of 200 mg/kg body weight and 18.7% reduction in blood sugar ⁴⁹. Anti-diabetic effect of an aqueous and hydroalcoholic extract of P. amarus used in Togo for treating diabetes and many other diseases. Two doses (500 and 1000 mg/kg) of the both extracts were administered orally to diabetic rats. Consequently, aqueous and hydroalcoholic extract of P. amarus decreases significantly blood glucose level after 15 days of administration ⁵⁵. A study by Shetti, oral administration of ethanolic leaf extract (400 mg/kg body weight) for 45 days resulted in significant decline in blood glucose and increase in the activity of glucokinase in the liver of diabetic mice ⁵⁶.

Antimicrobial Activity: Antimicrobials of plant origin have an extremely large therapeutical potential. They are effective in the treatment of infectious diseases, while simultaneously alleviating many of the side effects that are often connected with synthetic antimicrobials ⁵⁷. The effect of nor-securinine, an alkaloid isolated from Phyllanthus amarus was studied against spore germination of some fungi (Alternaria brassicae, Alternaria solani, Curvularia pennisetti, Curvularia sp., Erysiphe pisi, Helminthosporium frumentacei) as well as pea powdery mildew (E. pisi) under glasshouse conditions. The sensitivity of fungi to nor-securinine varied considerably. Nor-securinine was effective against most of the fungi. Pre-inoculation treatment showed greater efficacy than post-inoculation in inhibiting powdery mildew development on pea plants in a glasshouse. Maximum inhibition occurred at 2000 μg/mL ⁵⁸.

Six intestinal organisms were isolated and identified: K. pneumoniae, P. aeruginosa, S. aureus, E. coli, P. mirabilis and E. faecalis. Both agar diffusion and broth dilution methods were used to assay antimicrobial activity against the organisms. Phyllanthus amarus showed bacterio-static action at this concentration because sub-culture yielded growth except on plate of K. pneumoniae. Alcoholic extract of P. amarus showed the maximum zone of inhibition and minimum inhibitory concentration against all the microorganisms. The minimum zone of inhibition and comparatively greater inhibitory concentration were determined in petroleum ether, and the aqueous extract of P. amarus showed less antimicrobial activity against all the experimental strains ⁵⁹. The antimicrobial analysis was carried out using disc diffusion method as described by Boer et al., ¹⁵.

The crude extract and fractions were tested against the Pseudomonas aeruginosa, Escherichia coli, Staphylococcous aureus, and Candida albicans for their antimicrobial and antifungal activities. The results showed that the dichloromethane fraction had activity against all the test organisms with MIC at 100 μg/ml while the hexane, ethyl acetate and aqueous methanol fractions showed no activity against the organisms. The results of the antifungal study showed that the fractions have activity against the organism Candida albicans as the plates did not show growth of any organism after incubation at 37 ͦ C for 21days ⁶⁰. This suggests that the fraction is active against the fungus, Candida albicans. This is in agreement with a previous report by Foo and Wong, 1992 ¹³.

The significant antibacterial activity of ethanol extracts of the P. amarus and P. niruri against E. coli is an indication of their therapeutic potential in the management of UTI. Results obtained in this work agree with the findings of previous authors on the anti-microbial status of P. amarus ^{61 - 63}. The inhibitory activities of P. amarus and P. niruri extracts were the same against four of the five E. coli isolates. It could be suggested that a decoction or an infusion of either of the two herbs could help in the treatment of UTI ⁶⁴.

Anti-viral Activity: Study on 25 compounds isolated from P. amarus, P. multiflorus, P. tenellus and P. virgatus found that niranthin, nirtetralin, hinokinin and geraniin at the non-cytotoxic concentration of 50 μm, suppressed effectively both HBsAg and hepatitis B effective antigen (HbeAg) expression, of these, niranthin showed the best anti-HBsAg activity, while the most potent anti-HBeAg activity was observed with hinokinin ⁶⁵. In-vitro culture of hairy roots of P. amarus induced by Agrobacterium rhizogenes was shown to possess 85% inhibition (in contrast to 15% in the control) in binding of Hepatitis B Surface Antigen (HBsAg) to its antibody (anti-HBs) after 24 h of incubation with HbsAg-positive sera in-vitro at 37 °C ⁶⁶. The aqueous extract of P. amarus showed partial antiviral activity against white spot syndrome virus in shrimp at the concentration of 150 mg/kg of animal body weight for 30 days ⁶⁷. Effect on viral RNA replication was investigated by using Taq Man Real time RT-PCR. P. amarus root extract showed significant inhibition of HCV-NS3 protease enzyme; whereas P. amarus leaves extract showed considerable inhibition of NS5B in the in- vitro assays. Results suggested the possible molecular basis of the inhibitory activity of P. amarus extract against HCV which would help in optimization and subsequent development of specific antiviral agent using P. amarus as a potent natural source ⁶⁸.

Anti-cancer Activity: The methanolic extract of P. amarus hairy roots revealed potent antiproliferative activity in the MCF-7 cells through induction of apoptosis mediated by increased intracellular reactive oxygen species (ROS) in conjunction with decreased mitochondrial membrane potential ⁶⁹. The effects of aqueous extract of the whole plant of P. amarus against Cr (VI)-induced oxidative toxicity in-vitro in MDA-MB-435S human breast carcinoma cells revealed a distinct decline in Cr(VI)-induced cytotoxicity was noticed in MDA-MB-435S cells with an increase in extract dosage. Its phenolic constituents simultaneously may inhibit Cr (VI)-induced oxidative toxicity to MDA-MB-435S cells ⁷⁰.

Phyllanthus amarus was shown to be capable of inducing apoptosis in conjunction with its antimetastastic action, with more than 3-fold increase of caspases-3 and -7, the presence of DNA-fragmentation and terminal deoxynucleotidyl transferase mediated dUTP nick end labeling assay (TUNEL)-positive cells. The ability of Phyllanthus amarus to exert antimetastatic activities is mostly associated to the presence of polyphenol compounds in its extracts ⁷¹.

Anti-venom Activity: Phyllanthus amarus and Andrographis paniculata plant extracts when combined possess potent snake venom neutralizing capacity and could potentially be used for therapeutic purposes in case of snakebite envenomation. Di-herbal plant extracts effectively neutralized the cobra venom induced lethal activity. About 0.24 mg of di-herbal plant extract is able to completely neutralize the lethal activity of 2 LD₅₀ of N. naja venom ⁷².

Fertility Effect:

Fertility in Male: There is a claim on the use of aerial parts of Phyllanthus amarus to improve the fertility in men, by traditional practitioners. Phyllanthus amarus leaf extract causes an increase in the level of Testosterone but has little or no effect on the levels of Leutinizing Hormone (LH) and Follicle Stimulating Hormone (FSH) ⁷³. This increase may be responsible for the enhancement of fertility because the optimum level of Testosterone is required for normal sex drive in adult male and increase in spermatozoa, hence an increase in male fertility ⁷⁴.

Anti-fertility in Female: It was investigated in cyclic adult female mice at a dose of 100 mg/kg body weight for 30 days orally of an alcoholic extract of the whole plant of P. amarus. The results revealed no significant change in absolute body and organ weights and even in general metabolic status. Cohabited females with normal male mice were unable to become pregnant as their cyclicity was affected ⁷⁵. On the other side in the female it has resulted in the abortion of some pregnant female mice. Experiments were designed to test the effect of aqueous extract of P. amarus (AEPA) leaves on implantation and pregnancy. AEPA reduced the time frame for implantation in the treated rats and caused abortion of pregnant rats. Although the aqueous extract of Phyllanthus amarus reduces the time frame for implantation, its abortifacient effect does not support the traditional claim that it can treat sterility ⁷⁶.

Anti-inflammatory Activity: Phyllanthus amarus ethanol, aqueous and hexane extracts showed an inhibition of LPS-induced production of NO and PGE2. The extracts also attenuated the LPS-induced secretion of Tumor necrosis factor (TNF). Both extracts reduced expression of iNOS and COX-2 and inhibited activation of NF-κB, but not of AP-1. P. amarus inhibited induction of interleukin (IL)-1β, IL-10, and interferon-γ in human whole blood and reduced TNF-α production in-vivo ⁷⁷. The effects of methanol extract of P. amarus on different phases of inflammation were examined. Investigations were performed using different phlogistic agents-induced paw edema, carrageenan-induced air-pouch inflammation and cotton pellet granuloma in rats. The methanol extract of Phyllanthus amarus significantly inhibited carrageenan, bradykinin, serotonin and prostaglandin E1-induced paw edema, but failed to inhibit the histamine-induced paw edema. The extract significantly decreased the formation of granuloma tissue in chronic inflammation model ⁷⁸.

TABLE 3: PHARMACOLOGICAL ACTIVITIES REPORTED IN P. AMARUS BY VARIOUS AUTHORS

CONCLUSION: P. amarus is attracting many researchers since many decades because of its potent pharmacological uses, which is discussed above like jaundice, diabetes, syphilis, dysentery, fever, gonorrhea, etc. Every country has their own traditional use of P. amarus but the way of curing disease is almost common everywhere. The extracts of the plant possess various activities like anti-viral, anti-diabetic, anti-hepatoxic, antibacterial, antifungal and anti-inflammatory. This can be of great use for identifying more alternatives to cure different diseases. As this plant grows in tropical and sub-tropical areas, consequently in countries like India, Nigeria and Malaysia, more research work is continued. The aim of this review was to gather the research work undertaken till date in order to provide enough baseline for future works.

ACKNOWLEDGMENT: The authors express their sincere gratitude towards Dr. R. A. Sharma for his supervision. The first author is a recipient of JRF from University Grant Commission, New Delhi.

CONFLICT OF INTEREST: None of the authors of this paper has a financial or personal relationship with other people or organizations that could inappropriately influence or bias the content of the paper.

REFERENCES:

1. Ved DK and Goraya GS: A Text book of demand and supply of medicinal plants in India. NMPB, New Delhi and FRLHT, Bangalore, India, 2008.
2. Unander DW, Webster GL and Blumberg BS: Usage and bioassays in Phyllanthus (Euphorbiaceae)-IV: clustering of antiviral uses and other effects. Journal of Ethno-pharmacology 1995; 45: 1-18.
3. Webster GL: Classification of the Euphorbiaceae. Annals of the Missouri Botanical Garden 1994; 81: 3-32.
4. Joseph B and Raj SJ: An Overview: Pharmacognostic Property of Phyllanthus amarus International Journal of Pharmacology 2011; 7: 40-45.
5. Ravikant G, Srirama R, Senthilkumar U, Ganeshaiah KN and Umashaanker R: Genetic resources of Phyllanthus in Southern India: identification of geographic and genetic hot spots and its implication for conservation. Phyllanthus Species: Scientific Evaluation and Medicinal Applications 2011; 97-118.

6. Lewis W H and Elvin-Lewis P F: A Text Book of Medicinal Botany: Plants affecting Man’s Health. A Wiley-Inter Science Publication, John Wiley and Sons, Second Edition 1977.
7. Husain S, Alam MA, Ahmed S, Quamri A and Khan MA: Hepatoprotective, anticancer and antiviral effects of Bhui Amla in unani medicine: an overview. Journal of Medicinal Plant studies 2014; 2: 50-52.
8. Patel JR, Tripathi P, Sharma V, Chauhan NS and Dixit VK: Phyllanthus amarus: Ethnomedicinal uses, phyto-chemistry and pharmacology: A review. Journal of Ethnopharmacology 2011; 138: 286-313.
9. Unander DW, Herbert HB, Connete JL and Robert TM: Cultivation of and evaluation of variable potentially affecting yield and the inhibition of viral DNA polymerase. Economic Botany 1993; 47: 79-88.
10. Morton J F: Atlas of Medicinal Plants of Middle America. Library of Congress cataloging in Publication Data, Thomas books, 1981:1420.
11. Cabieses F: Apuntes de medicina traditional. La racionalizacion de lo irracional. Notes of traditional medicine. Consejo Nacional de Ciencia y Technologia CONCYTEC Lima-Peru 1993; 414.
12. Council of Scientific and Industrial Research (India): A text book of medicinal plants of India. New Delhi: Publications and Information Directorate, Council of Scientific and Industrial Research, 1988.
13. Foo LY and Wong H: Phyllanthusiin D, Unusual hydrosable tannin from Phyllanthus amarus. Phytochemistry 1992; 31: 711-713.
14. Itoro E, Ukana D and Ekaete D: Phytochemical screening and nutrient analysis of Phyllanthus amarus. Asian Journal of Plant Science and Research 2013; 3: 116-122.
15. Wessels Boer JG, Hekking WHA and Schulz JP: Fa joe kan tak’mi no moi: Inleiding in de flora en vegetatie van Suriname; Deel I en II. Why do say that I am not beautiful: Introduction to the Flora and Vegetation of Suriname; Part I and II. Natuurgids serie B No. 4, Stinasu, Para maribo1976.
16. Nanden-Amattaram T: Medicinale Planten: Tips en simpele recepten voor een goede gezondheid. Medicinal plants and simple recipes for a good health. Paramaribo-Suriname 1998; 18.
17. Webster G L: A monographic study of the west Indian species of Phyllanthus. J. Arnold Arboric. Harv. Univ. 1957; 39: 49-100.
18. Mitra RL and Jain SK: Concept of Phyllanthus niruri (Euphorbiaceae) in Indian Floras. Bull. Bot. Surv. India 1987; 27: 161-176.
19. Chowdhury LB and Rao RR: Taxonomic study of herbaceous species of Phyllanthus (Euphorbiaceae) in India. Phytotaxonomy 2002; 2: 143-162.
20. Balakrishnan N P and Chakrabarty T: A Text Book of The family Euphorbiaceae in India - a synopsis of its profile, taxonomy and bibliography New Delhi: Eastern Book 2007.
21. Jain N, Shasany AK, Sundaresan V, Rajkumar S, Darokar M P, Bagchi GD, Gupta AK, Kumar S and Khanuja SPS: Molecular diversity in Phyllanthus amarus assessed through RAPD analysis. Current Science 2003;85: 1454-1458.
22. Houghton PJ, Woldemariama TZ, Siobhan OS and Thyagarajan SP: Two securinega type alkaloids from Phyllanthus amarus. Phytochemistry 1996; 43: 715-717.
23. Kassuya CA, Silvestre A, Menezes-de-Lima Jr O, Marotta DM, Rehder VL and Calixto JB: Anti-inflammatory and antiallodynic actions of the lignin niranthin isolated from Phyllanthus amarus: Evidence for interaction with platelet activating factor receptor. European Journal of Pharmacology 2006; 546: 182-188.
24. Foo LY: Amarulone, a novel cyclic hydrolyzable tannin from Phyllanthus amarus. Natural Product Letters 1993a; 3: 45-52.
25. Foo LY: Amarinic acid and related ellagitannins from Phyllanthus amarus. Phytochemistry 1995; 39: 217-224.
26. Londhe JS, Devasagayam TP, Foo LY and Ghaskadbi SS: Antioxidant activity of some polyphenol constituents of the medicinal plant Phyllanthus amarus Redox Report 2008; 13: 199-207.
27. Sharma A, Singh RT and Anand S: Estimation of phyllanthin and hypophyllanthin by high performance liquid chromatography in Phyllanthus amarus. Photochemical Analysis 1993; 4: 226-229.
28. Chevallier A: Encyclopedia of Herbal Medicine: Natural Health. Dorling Kindersley Book, USA, Edition 2, 2000: 336.
29. Srivastava V, Singh M, Malasoni R, Shanker K, Verma R K, Gupta MM, Gupta AK, Khanuja SPS: Separation and quantification of lignans in Phyllanthus species by a simple chiral densitometric method. Journal of Separation Science 2008; 31: 47-55.
30. Maciel MAM, Cunha A, Dantas FTNC and Kaiser CR: NMR characterization of bioactive lignans from Phyllanthus amarus Schum and Thonn. Journal of Magnetic Resonance Imaging 2007; 6: 76-82.
31. Huang RL, Huang YL, Ou JC, Chen CC, Hsu FL and Chang C: Screening of 25 compounds isolated from Phyllanthus Species for anti-human hepatitis B virus in- vitro. Phytotherapy Research 2003; 17: 449-453.
32. Singh M, Tiwari N, Shanker K, Verma RK, Gupta AK and Gupta MM: Two new lignans from Phyllanthus amarus. Journal of Asian Natural Products Research 2009; 11: 562-568.
33. Ahmad B and Alam T: Components from whole plant of Phyllanthus amarus Indian Journal of Chemistry, Section B: Organic Chemistry including Medicinal Chemistry 2003; 42: 1786-1790.
34. Moronkola DO, Ogunwande IA, Oyewole IO, Baser KH C, Ozek T and Ozek G: Studies on the volatile oils of Momordica charantia (Cucurbitaceae) and Phyllanthus amarus Schum and Thonn (Euphorbiaceae). Journal of Essential Oil Research 2009; 21: 393-399.
35. Elisabetsky E. and Wannmacher L: The status of ethnopharmacolgy in Brazil. J Ethnopharmacol. 1993; 38 (2-3): 137-43.
36. Verma S, Sharma H and Garg M: Phyllanthus amarus: A review. Journal of Pharmacognosy and Phytohemistry 2014; 3: 18-22.
37. Adegoke AA, Iberi PA, Akinpelu DA and Aiyegoro P: Studies on phytochemical screening and antimicrobial potentials of Phyllanthus amarus against multiple antibiotic resistant bacteria. International Journal of Applied Research in Natural Products 2010; 3: 6.
38. Samuel JK and Andrews B: Traditional medicinal plant wealth of Pachalur and Periyur hamlets Dindigul district, Tamil Nadu. Indian Journal of Traditional Knowledge 2010; 9: 264-270.
39. Muthu C, Ayyanar M, Raja N and Ignacimuthu S: Medicinal plants used by traditional healers in Kancheepuram District of Tamil Nadu, India. Journal of Ethnobiology and Ethnomedicine 2006; 2: 1-10.
40. Ignacimuthu S, Ayyanar M and Sankarasivaraman K: Ethnobotanical study of medicinal plants used by Paliyar tribals in Theni district of Tamil Nadu, India. Fitoterapia 2008; 79: 562-568.
41. Balakrishnan V, Prema P, Ravindran KC and Philip Robinson J: Ethnobotanical studies among villagers from Dharapuram Taluk, Tamil Nadu, India. Global Journal of Pharmacology 2009; 3: 8-14.
42. Rajakumar N and Shivanna MB: Ethno-medicinal application of plants in the eastern region of Shimoga district, Karnataka, India. Journal of Ethnopharmacology 2009; 126: 64-73.
43. Samy RP, Pushparaj PN and Gopalakrishnakone P: A compilation of bioactive compounds from Ayurveda. Bioinformation 2008; 3: 100-110.
44. Kala CP, Dhyani PP and Sajwan BS: Developing the medicinal plants sector in Northern India: challenges and opportunities. Journal of Ethnobiology and Ethnomedicine 2006; 2: 1-15.
45. Upadhyay B, Parveen AK and Dhaker AK: Ethno-medicinal and ethnopharmacological statistical studies of Eastern Rajasthan, India. Journal of Ethnopharmacology 2010; 129: 64-86.
46. Kuppusamy C and Murugan K: In-vitro antimalarial activity of traditionally used Western Ghats plants from India and their interactions with chloroquine against chloroquine resistant Plasmodium falciparum. Parasitology Research 2010; 107: 1351-1364.
47. Kassuya CAL, Leite DFP, De Melo LV, Rehder VLC and Calixto JB: Anti inflammatory properties of extracts, fractions and lignans isolated from Phyllanthus amarus. Planta Medica 2005; 71: 721-726.
48. Mabberley DJ: A Text book of the Plant-Book: A Portable Dictionary of the Vascular Plants. Cambridge University Press, Edition 2,
49. Raphael KR, Sabu MC and Kuttan R: Hypoglycemic effect of methanol extract of Phyllanthus amarus Schum and Thonn. on alloxan induced diabetes mellitus in rats and its relation with antioxidant potential. Indian Journal of Experimental Biology 2002; 40: 905-909.
50. Lim YY and Murtijaya J: Antioxidant properties of Phyllanthus amarus extracts as affected by different drying methods. LWT Food Science and Technology 2007; 40: 1664-1669.
51. Shokunbi OS and Odetola AA: Gastroprotective and antioxidant activities of Phyllanthus amarus extracts on absolute ethanol-induced ulcer in albino rats. Journal of Medicinal Plants Research 2008; 2: 261-267.
52. Krithika R, Mohankumar R, Verma RJ, Shrivastav PS, Mohamad IL, Gunasekaran P and Narasimhan S: Isolation, characterization and antioxidative effect of phyllanthin against CCl₄-induced toxicity in HepG2 cell line. Chemico Biological Interaction 2009; 181: 351-358.
53. Karuna R, Reddy SS, Baskar R and Saralakumari D: Antioxidant potential of aqueous extract of Phyllanthus amarus in rats. Indian Journal of Pharmacology 2009; 41: 64-67.
54. Sen A and Batra A: The study of in-vitro and in-vivo antioxidant activity and total phenolic content of Phyllanthus amarus Schum Thonn: A medicinally important plant. International Journal of Pharmacy and Pharmaceutical Sciences 2013; 5: 942-947.
55. Evi PL and Degbeku K: Antidiabetic Activity of Phyllanthus amarus Schum and Thonn on alloxan induced diabetes in male wistar rats. Journal of Applied Sciences 2011; 11: 2968-2973.
56. Shetti AA, Sanakal RD and Kaliwal BB: Antidiabetic effect of ethanolic leaf extract of Phyllanthus amarus in alloxan induced diabetic mice. Asian Journal of Plant Science and Research 2012; 2: 11-15.
57. Iwu MM, Duncan AR and Okunji CO: New antimicrobials of plant origin. Alexandra: ASHS Press; 1999.
58. Sahni S, Maurya S, Singh UP, Singh AK, Singh VP and Pandey VB: Antifungal activity of nor-securinine against some phytopathogenic fungi. Mycobiology 2005; 33: 97-103.
59. Sen A and Batra A: Determination of antimicrobial potentialities of different solvent extracts of the medicinal plant: Phyllanthus amarus and Thonn. International Journal of Green Pharmacy 2012; 6: 50-56.
60. Okwute Simon KI, Okolo Simon C, Okoh-Esene R and Olajide Olutayo O: Biological and chemical evaluation of the extracts of the leaf of Phyllanthus amarus International Journal of Chem Tech Research 2015; 7: 2347-2354.
61. Alli AI, Ehinmidu JO and Ibrahim YKE: Preliminary phytochemical screening and antimicrobial activities of some medicinal plants used in Ebiraland. Bayero Journal of Pure and Applied Sciences 2011; 4: 10-16.
62. Eldeen IMS, Seow EM, Abdullah R and Sulaiman SF: In vitro antibacterial, antioxidant, total phenolic contents and anti-HIV-1 reverse activities of extracts of seven Phyllanthus South African Journal of Botany 2011; 77: 75-79.
63. Njoroge AD, Anyango B and Dossaji SF: Screening of Phyllanthus species for antimicrobial properties. Chemical Science Journal 2012; 56: 1-11.
64. Gbadamosi IT: Antibacterial attributes of extracts of Phyllanthus amarus and Phyllanthus niruri on Escherichia coli the causal organism of urinary tract infection. Journal of Pharmacognosy and Phytotherapy 2015; 7: 80-86.
65. Huang RL, Huang YL, Ou JC, Chen CC, Hsu FL and Chang C: Screening of 25 compounds isolated from Phyllanthus Species for anti-human hepatitis B virus in- vitro. Phytotherapy Research 2003; 17: 449-453.
66. Bhattacharyya R and Bhattacharya S: 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 Development Biology-Plant 2004; 40: 504-508.
67. Balasubramanian G, Sarathi M, Rajeshkumar S and Sahul Hameed AS: Screening the antiviral activity of Indian medicinal plants against white spot syndrome virus in shrimp. Aquaculture 2007; 263: 15-19.
68. Ravikumar YS, Ray U, Nandhitha M, Perween A, Naika H R, Khanna N and Das S: Inhibition of Hepatitis C virus replication by herbal extract: Phyllanthus amarus as potent natural source. Virus Research 2011; 158: 89-97.
69. Abhyankar G, Suprasanna P, Pandey BN, Mishra KP, Rao KV and Reddy VD: Hairy root extract of Phyllanthus amarus induces apoptotic cell death in human breast cancer cells. Innovative Food Science and Emerging Technologies 2010; 11: 526-532.
70. Guha G, Rajkumar V, Ashok KR and Mathew L: Aqueous extract of Phyllanthus amarus inhibits chromium (VI)-induced toxicity in MDA-MB-435S cells. Food and Chemical Toxicology 2010; 48: 396-401.
71. Lee SH, Jaganath IB, Wang SM and Sekaran SD: Antimetastatic effects of phyllanthus on human lung (A549) and breast (MCF-7) cancer cell lines. PLoS One 2011; 6.
72. Sornakumar RSA, Kunthavai PC and Gnaniah S: Isolation, purification and characterization of active compound from Andrographis paniculata and Phyllanthus amarus Linn. and testing the antivenom activity of the di-herbal extract by in-vitro and in-vivo studies. International Research journal of Pharmacy 2014; 5: 207-211.
73. Obianime AW and Uche FI: The Phytochemical constituents and the effects of methanol extracts of Phyllanthus amarus leaves (kidney stonep lant) on the hormonal parameters of male guinea pigs. Journal of Applied Sciences and Environmental Management 2009; 13: 5-9.
74. Vander A, Sherman J and Luciano D: Human Physiology: The mechanism of body function: McGraw- Hill higher Education. New York USA, Edition 8, 2001: 641-647.
75. Rao MV and Alice KM: Contraceptive effects of Phyllanthus amarus in female mice. Phytotherapy Research 2001; 15: 265-267.
76. Iranloye B, Oyeusi K and Alada A: Effect of aqueous extract of Phyllanthus amarus leaves on implantation and pregnancy in rats. Physiological Society of Nigeria 2010; 25: 63-66.
77. Kiemer AK, Hartung T, Huber C and Vollmar AM: Phyllanthus amarus has anti-inflammatory potential by inhibition of iNOS, COX-2, and cytokines via the NF-κB pathway. Journal of Hepatology 2003; 38: 289-297.
78. Mahat MA and Patil BM: Evaluation of anti-inflammatory activity of methanol extract of Phyllanthus amarus in experimental animal models 2007; 69: 33-36.
    

    ---

    How to cite this article:

    Meena J, Sharma RA and Rolania R: A review on phytochemical and pharmacological properties of Phyllanthus amarus Schum. and Thonn. Int J Pharm Sci Res 2018; 9(4): 1377-86.doi: 10.13040/IJPSR.0975-8232.9(4).1377-86.

    ---

    All © 2013 are reserved by International Journal of Pharmaceutical Sciences and Research. This Journal licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License.

    ---