Monday, October 14, 2019

Phyllanthus niruri L. (Meniran Hijau)

HERBAL
MEDICINAL 




PHYLLANTHUS
(Phyllanthus niruri L.) +
MENIRAN HIJAU



by

RETTODWIKART THENU, S.Pd







PHYLLANTHUS
(Phyllanthus niruri L.) + Euphorbiaceae


COMMON NAMES


Bhoomi amalaki                                 India
Bhui amla                             Bangladesh
Bhui-amla                             India
Bhuianvalah                        India
Bhuimy-amli                        East Indies
Bhuin-amla                          Pakistan
Bhumyamalaki                   India
Cane peas senna                                 West Indies
Carry-me seed                      Fiji
Carry-me seed                      West Indies
Chamber bitters                   West Indies
Chancapiedra                      Peru
Chickweed                            West Indies
Creole senna                         Virgin Islands
Daun marisan                      East Indies
Derriere-dos                          Haiti
Deye do                                 Haiti
Elrageig                                  Sudan
En bas                                    West Indies
Eruption plant                      Papua-New Guinea
Gale-o-wind                          Bimini
Gale wind grass                    Fiji
Gale-wind grass West          Indies
Graine en bas fievre            French Guiana
Hurricane weed                    West Indies
Jar amla                                Fiji
Jar-amla                                India
Kizha nelli                             India
Mapatan                               Papua-New Guinea
Mimosa                                                 West Indies
Niruri                                      Pakistan
Para-parai mi                       Paraguay
Pei                                           Admiralty Islands
Phyllanto                               Brazil
Pombinha                             East Indies
Querba pedra                       Brazil
Quinine weed                        West Indies
Sampa-sampalukan           Philippines
Sasi                                         Papua-NewGuinea
Se                                            Papua-New Guinea
Shka-nin-du                          Mexico
Viernes santo                        Puerto Rico
Ya-tai-bai                              Thailand
Verba de san pablo             Philippines


Common Names (Duke, J. A et al., 2009)
Adhyana (Sanskrit [1 of ~36]; KAB); Arranca Pedras (Por.; AVP; RAI); Arrebenta Pedras (Brazil; Por.; AVP; MPB); Azulejo (Cuba; AVP); Bahupatri (Sanskrit; ADP); Barbascao (Ven.; AVP); Bhonya Anmali (Guj.; ADP); Bhui Amala (Nepal; NPM); Bhuiamla (Ben.; Urdu; KAP); Bhuiaola (Oriya; KAB); Bhuiavala (Mar.; KAB); Bhuinanvalah (Dec.; KAB); Bhumiamla (Yunani.; KAP); Bhumyamalaki (Nepal; Sanskrit; ADP; AH2; KAP); Bhuyi Avla (Hindi; KAP); Carillo (Nic.; AVP); Cane Peas (Eng.; RAI); Cane Senna (Eng.; RAI);  Carry-Me-Seed (Eng.; RAI); Chamber Bitter (Jam.; JFM); Chanca Piedra (Ecu.; Peru; Sp.; BEJ; LOR; MDD); Chhotaki Dahigola (Tharu; NPM); Ciurelo (Mex.; AVP); Creole Senna (Eng.; RAI); De Dou (Haiti; AHL); Derriere Dos (Haiti; AVP); Des Dos (Haiti; AHL); En Bas Feuilles (Guad.; Mart.; AVP); En Bas Feuilles Blanc (Guad.; Mart.; AVP); Erva Pombinha (Brazil; Por.; AUS; AVP); Feuilles la Fievre (Haiti; AHL); Filanto Urinario (Sp.; AVP); Filantro Urinario (Ma.; JFM); Fly Roost (Eng.; NPM); Gabellon (Col.; AVP); Gale of Wind (Fla.; Usa.; AUS; AVP); Gale-Wind Grass (Eng.; RAI); Garbanzo (Col.; AVP); Graine en Bas Feuille (Creole; Guy.; GMJ); Graines en Bas (Guad.; Mart.; AVP); Graines Sur Dos (Haiti; AVP); Guinda (Sal.; AVP); Herbe du Chagrin (Fr.; KAB); Hierba Pombo (Brazil; MPG); Hurricane Weed (Eng.; RAI); Jangli Amla (Hindi; KAP); Jaramla (Hindi; KAB); Jobitillo (Pan.; AVP); Kaimadgene (Palikur; GMJ); Kidachimikanso (Japan; KAP); Kilanelli (Tam.; KAB); Kiranelligida (Kan.; KAB); Kizharelli (Tam.; KAP); Kizhkkayinelli (Mal.; KAB); Kunaparu (Guiana; AVP); Lavandero (Ven.; AVP); Lenteja (Arg.; AVP); Lloron (Cuba; AVP); Makantowe (Shipibo/Conibo; MD2); Mala (Sanskrit; KAB); Malcoc (Arg.; AVP); Malva Pedra (Brazil; MPB); Mehukaetnipussemnak (Palikur; GMJ); Nelausirika (Tel.; KAB); Niruri (Eng.; Fla.; Fr.; Ocn.; Sin.; AH2; AUS; KAB; KAP); Panatela (Mex.; AVP); Para Paray Mi (Par.; AVP); Perico (Dor.; AVP); Perla (Col.; AVP); Peronillo del Pasto (Sp.; AVP); Petit Tamarin Blanc (Fr.; AVP); Phyllantee Diuretique (St. Bart.; AVP); Phyllanthus (Eng.; Scn.; AH2; CR2); Piedra con Piedra (Peru; SOU); Pimienta (Sal.; AVP); Pimientilla (Sal.; AVP); Pittawaku (Sin.; KAB; KAP); Quebra Pedra (Por.; AVP); Quinilla del Tahuampa (Peru; AVP); Quinine Creole (Fr. Guy.; AVP); Quinine Pays (Haiti; AVP); Quinine Weed (Eng.; RAI); Quininito (Dor.; AHL); Quinino Criollo (Dor.; AVP); Quinino del Pobre (Pr.; Sp.; AVP); Quinquina du Pays (Haiti; AHL); Rockbush (Jam.; AVP); Sacha Foster (Peru; Sp.; LOR; MDD); Santa Maria (Ma.; JFM); Sarandi Blanco (Uru.; AVP); Seaside Laurel (Jam.; AVP); Seed on the Leaf (Wi.; JAD); Semilla en las Hojas (Ma.; JFM); Snap Plant (Jam.; AVP); Sotlugi Kshanate (Piro; RAR); Stonebreaker (Eng.; DAV); Sulfate Pays (Haiti; AVP); Ta Ma La (Tibet; KAP); Tamalaki (Sanskrit; OFF); Viernes Santo (Col.; Pr.; AVP); Yaquillo (Pr.; AVP); Yerba de la Nina (Cuba; AUS; AVP); Yerba de Quinino (Sp.; AVP); Ye Xia Zhu (Pin.; AH2); Yiwayi Sili (Wayapi; GMJ); Yoloba (Sudan; AVP); Zhen Zhu Cao (Pin.; AH2).

Notes: (Duke, J. A et al., 2009 )
P. amarus, P. debilis, P. fraternus and P. niruri are confused in the field and in the literature and in this account too (true confession). The Fleming et al. (1998) entries were under “black catnip” as P. amarus, with the warning “may be confused with Phyllanthus urinaria, P. niruri, P. debilis, and P. fraternus (PH2). Kapoor (1990) and MPI data were applied to P. fraternus. Kirtikar and Basu data (as KAB) to P. niruri L. Gupta (1995) lumped the species amarus, carolinianus, debilis, humilis, and niruri. Taylor (2005) aggregated activities for P. amarus, P. niuriri, and P. sellowianus. Morton treats P. lathyroides as synonym of P. niruri (JFM). Blaschek et al. (1998) recognized P. amarus and P. niruri among the similar species. McGuffin et al. (2000) give the name Phyllanthus as the standardized common name for P. fraternus, P. niruri, and P. urinaria, and maintain P. amarus under the scn Phyllanthus amarus (ocn. = “carry-me-seed”). Manandhar (2002) subsumes P. niruri under P. amarus. Austin (2004) chimes in that “The plant of choice in most, if not all, of the Americas is now P. niruri.” Yaniv and Bachrach (2005) try to straighten us out. These several similar species are aggregated hopelessly in the data below. DNA sequencing has resolved “the long lasting insecurity about the correct taxonomic assignment of Phyllanthus amarus and P. niruri.”
On the basis of sequence analysis obtained from two independent markers of P. amarus, P. niruri, and 8 taxonomically related species, it was possible to characterize P. amarus by species-specific mutations … “ P. fraternis and P. abnormis … are related most closely to P. amarusP. niruri is not genetically linked with P. amarus.” … P. debilis, P. tenellus and P. urinaria are clearly separate species (YAB). I first learned this Amazonian plant far from the Amazon, in Belize and some of the West Indian islands where its English name was “seed on the leaf.” There, matter of fact everywhere I have seen it, it has acquired some very positive folklore. Famed ethnobotanist R. E. Schultes says in his The Healing Forest (Schultes and Raffauf, 1990), as do all our Explorama guides and ACEER workers, that the plant is called “chanca piedras,” which means “stonebreaker.” The guides here say that it helps gravel and kidney stones, drunk as a tea, until you feel as if the stones have passed. Famous explorer Nicole Maxwell had picked that up, long before I got to Amazonian Peru, just when Peter Jenson and Margarita Smith were launching what is now the famous Explorama Camp, more than 30 years ago. Nicole noted then that the “stone-breaker” is quite effective in eliminating kidney stones and gallstones. Still, I like what naturopathic physician Leslie Taylor (2005) says: “It is yet another perfect example that Mother Nature is infinitely a better chemist; the natural herb [whichever species, JAD] continues to work better than any other man-made chemically altered (and patentable) extracts.” An Ayurvedically inclined German physician correspondent heard my taxonomic lamentations and offered the following, returning to Germany from India, “Hello Dr. Duke, back from India I remember your discussion on Phyllantus niruri and amarus. It became very clear that they are not synonyms. Phyllanthus amarus has much more bitter substances and is for that reason more effective in treatment of liver and gall diseases.” And Swerdlow (2000), on the last page of this National Geographic issue, was kind enough to call me one of the world’s leaders in the quest for new medicines from old plants. And he was kind enough to mention that I’m the author of The Green Pharmacy and Herbs of the Bible: 2000 Years of Plant Medicine. More important, he described medicine Nobel Prize winner Baruch Blumberg’s intense work on infectious viral diseases. Hoping to treat people who had already contracted hepatitis B, he studied Phyllanthus amarus, an Asian species used to treat jaundice, and found chemicals therein which disrupted the development of the virus. He then concluded with my comment that chicoric acid, a compound in the weed chicory, shows promise at disrupting the AIDS virus (Swerdlow, 2000).


BOTANICAL DESCRIPTION (Ross, I. A. 2004)
A herb of the EUPHORBIACEAE family that grows up to 60 cm. The plant is bitter in taste, the leaves are small, green, and short-petioled with a thin and glaucous under surface. The flowers are unisexual, monoecious, minute, greenish and inconspicuous, short-stalked and borne in pairs in the axils of the leaves. The fruit is a capsule, globose, slightly depressed at the top with 6  enervations. In the roots, the secondary growth starts very early and is well pronounced. There is a distinct cambium. No starch grains, mineral crystals or latex vessels are seen in either the root or stem.

DESCRIPTIONS (Handayani, V and  Nurfadillah. 2014)
Tumbuhan : Terna semusim, tumbuh tegak, tinggi 38 cm, tidak berbulu, tangkainya berwarna hijau, tumbuh liar di tempat-tempat yang lembab, di sepanjang jalan dan di antara rerumputan dalam jumlah yang banyak.
Daun (Folium): Tunggal, berbentuk jorong (ovalis), ujung (apex) tumpul (obtusus), pangkal (basis) membulat (rotundatus), susunan tulangnya bertulang menyirip (penninervis), tepi (margo) rata (integer), permukaan daun licin (laevis), panjang 9 mm dan lebar 4 mm, berwarna hijau muda.
Batang (Caulis): Basah, berbentuk bulat (teres), permukaan batang licin (laevis), arah tumbuh batang tegak lurus (erectus), cara percabangan monopodial, berwarna hijau muda, tinggi 24 cm
Akar (Radix): Termasuk sistem perakaran tunggang, bercabang, berwarna putih kekuningan.

ORIGIN AND DISTRIBUTION (Ross, I. A. 2004)
The plant originated in India, usually occurring as a winter weed throughout the hotter parts; now widespread throughout the tropics and subtropics in sandy regions during rainy seasons.

GEOGRAPHICAL DISTRIBUTION (Paithankar et al., 2011)
It is a field weed which is found proliferating throughout tropical and subtropical regions of Asia, America, and China. The genus Phyllanthus (L) Murr. comprises from 600 to 700 species with minor distinguishing features among them. Phyllanthus niruri is an annual herb which grows in the wild after first showers of monsoon in Jharkhand, Bihar, Chhattisgarh, etc. states of India. However, it has also been reported to grow commonly in coastal areas. In Indian states it usually grows during second week of June and starts bearing fruits up to mid July or August. It remains in the wild up to the end of the rainy season. However, under safe conditions it can grow and survive upto mid-winter.

P. amarus, P. debilis, P. fraternus and P. niruri are confused in the field and in the literature, and in this account too (true confession). The PH2 entries were under “black catnip” as P. amarus, with the warning “may be confused with Phyllanthus urinaria, P. niruri, P. debilis, and P. fraternus” (PH2). MPI data were applied to P. fraternus, KAB data to P. niruri L. HH3 recognized P. amarus and P. niruri among the similar species (Duke, J. A et al., 2002 )

TRADITIONAL MEDICINAL USES (Ross, I. A. 2004)
Admiralty Islands. Hot water extract of dried bark and leaves is taken orally for acute venereal disease. The extract (500 ml) is taken twice daily for up to 6 monthsPN061 .
Argentina. The plant is used as an emmenagogue by the rural populacePN016.
Bimini. Hot water extract of the entire plant is taken orally to reduce fevers and as a laxati vePN052 .
Brazil. Decoction of dried root is taken orally for jaundice. Decoction of dried seeds is taken orally for diabetes. Hot water extract of dried fruit is taken orally for diabetes. Infusion of dried leaves and stems is taken orally to treat kidney and bladder calculi. Infusion of the dried entire plant administered orally, is used to dissolve kidney and bladder stones, and for renal diseasesPN08o.
Dominican Republic. Hot water extract of leaves is taken orally as a popular fever remedyPN084.
East Africa. Hot water extract of the aerial parts is taken orally as a diureticPN089.
East Indies. Hot water extract of the entire plant is taken orally for menstrual troubles/ complaints and diabetes, as a purgative and tonicPN09O.
Fiji. Decoction of dried leaves and roots is taken orally for fever and for good health. Dried entire plant, ground in buttermilk is taken orally for jaundice. Fresh leaf juice is used externally for cuts and bruises. For eye diseases, the juice is mixed with castor oil and applied to the eye. Infusion of dried leaves is taken orally for dysentery and diarrhea. Infusion of the green root is taken orally to treat heavy menstrual flowPNon.
French Guiana. Hot water extract of leaves is taken orally as a cholagoguePNo17.
Haiti. Decoction of dried leaves is taken orally or used in bath for fever, and orally for indigestionPN077 . Hot water extract of dried entire plant is taken orally as a spasmolytic and for feverPN058.
India. Decoction of the dried aerial parts is taken orally for diarrheaPN025 and jaundiceN065. Fresh plant juice is taken orally for genitourinary disordersPN07o. The fruit is used externally for tubercular ulcers, scabies and ringwormPN03O. Hot water extract of dried entire plant is taken orally, as a diureticPN021 , for gonorrhea, urogenital tract infectionsPN042, diabetesPNOlo, jaundicePN094,PN06\ leucorrheaPN045 and asthma, in Ayurvedic medicinePN068. Hot water extract of dried leaves is taken orally for diabetes. Hot water extract of fresh shoots is taken orally for dysentery and jaundicePN042 . Hot water extract of leaves is taken orally as a stomachicPN03O, for menorrhagiaPN°07 and intermittent feverPNo87. Water extract of roots is taken orally as a galactagogueNoo6.
Malaysia. Hot water extract of leaves is taken orally after a miscarriage and as an emmenagogueNOO7.
Mexico. Hot water extract of dried leaves is an emetic when taken as a strong teaPN091.
Papau-New Guinea. Fresh leaf and root juices are taken orally for venereal diseases. Decoction of dried entire plant is taken orally to treat venereal diseasesPN043. For malaria, the decoction is taken orally and used to bathe the patient. For tuberculosis, a single dose of the decoction is taken orallyPN067. Decoction of dried leaf is taken orally as a treatment for diarrhea. A cupful of the decoction is taken dailyPN027.
Peru. Hot water extract of dried entire plant is taken orally as a diuretic, for gallstones and renal calculiPN079.
Philippines. Decoction of dried entire plant is used as a bath for newborns. It is believed to remove disease-causing elements from the skin. Orally, the decoction is used for coughs in infantsPN069. Hot water extract of the entire plant is taken orally as an emmenagogueNOO1,PNOO5.
Puerto Rico. Hot water extract of leaf and stem is taken orally for feversPNOO4.
Sudan. Hot water extract of dried leaves is taken orally as an analgesicPN060.
Tanzania. Hot water extract of fresh entire plant is taken orally for gonorrheaPNOll.
Thailand. Hot water extract of the entire plant is taken orally as an antipyreticPN093. Hot water extract of the dried aerial parts is taken orally as a diuretic and antipyretic, and for malariaPN031. Hot water extract of dried entire plant is taken orally as an anti-inflammatory agentPN092 .
Virgin Islands. Hot water extract of the plant is taken orally to increase the appetitePN08l .
West Indies. Hot water extract of roots, together with hot water extract of Citrus aurantifolia roots, is taken orally to increase appetite. Hot water extract of the entire plant is taken orally, for malaria and malarial fever. Water extract of the leaves and roots is taken orally for diabetes, and as a diureticPNOl3,PNo88.

WORLDWIDE TRADITIONAL MEDICINAL USES (Paithankar et al., 2011)
Hot water extract of the entire plant is administered orally, to reduce fevers, and as a laxative (Halberstein et al., 1978). Decoction of dried leaves and roots is taken orally for fever, and for good health. Dried entire plant, grounded in buttermilk is administered orally for jaundice. Fresh leaf juice is used externally for cuts and bruises. For eye diseases the juice is mixed with castor oil and applied to the eye. Infusion of dried leaves is administered orally for dysentery and diarrhea. Infusion of green root is taken orally to treat heavy menstrual periods (Singh et al., 1986). Hot water extract of leaves is administered orally as a cholagogue (Duke et al., 1975). Decoction of dried leaves is taken orally for or used in bath for fever, and orally for indigestion (Weninger et al., 1986). Hot water extract of dried entire plant is administered orally as a spasmolytic and is also against fever (Weninger et al., 1982). Fresh plant juice is taken orally for genito urinary disorders (Sahu et al., 1984). The fruit is used externally for tubercular ulcers, scabies and ringworm (Chauhan et al., 1977). Hot water extract of dried entire plant is administered orally for diabetes (Jain et al 1967). For asthma in ayurvedic medicine (Sircar et al 1984). Fresh leaf juice or fresh root juice are taken orally for venereal diseases. Decoction of dried entire plant is administered orally to treat venereal diseases (Holdsworth et al., 1989). Decoction of dried leaf when taken orally is a treatment for diarrhea. A cupful of leaf decoction is drunk daily (Holdsworth et al., 1992). Decoction of dried entire plant is used as a bath for newborns. It is believed to remove diseasecausing elements from the skin. Orally the decoction is used for coughs in infants (Velazco et al., 1980). Hot water extract of commercial sample of the entire plant, is administered orally as an antipyretic (Mokkhasmit et al., 1971). Hot water extract of dried aerial parts administered orally is used as a diuretic, as an antipyretic, and for malaria (Kitisin et al 1952). Hot water extract of dried entire plant is administered orally as an anti-inflammatory agent (Wasuwat et al., 1967). Hot water extract of the plant is taken orally to increase the appetite (Oakes et al 1958). Hot water extract of roots together with hot water extract of Citrus aurantifolia roots is taken orally to increase appetite. Hot water extract of entire plant administered orally, is taken for malarial fever. The plant is boiled and the tea taken. Water extract of the leaves and roots is taken orally for diabetes, and as a diuretic (Asprey et al., 1955).

CHEMICAL CONSTITUENTS
(ppm unless otherwise indicated)


H-Epi-catechin: Rt CultPN020
H-Epi-catechin-3-gallate: Rt CultPN020
H-Epi-gallocatechin: Rt CultPN020
H-Epi-gallocatech i n-3-0-gallate: Rt Cu ItPN020
H-Limonene: Lf EO 4.S%PN083
H-Nor-serurinine: PIPN082
(+)-Catechin: Rt CultPN020
(+)-Gallocatechin: Rt CultPN020
4-Hydroxy-lintetralin: Lf 200PN013,PN011
4-Hydroxy-sesamin: PIPN029
4-Methoxy-nor-securinine: Aer, Lf, Rt, StPN065
2,3-dimethoxy-iso-lintetralin: Lf 2PN013
24-lsopropyl cholesterol: Aer 18PNo33
Ascorbic acid: Lf 0.41 %PN032
Astragalin: LfPN031,PN041
Beta sitosterol: LfPN002
Corilagin: PI 7PN040
Cymene: Lf EO 11 %PN083
Demethylenedioxy niranthin: Lf 2PN013
Dotriacontanoic acid: Aer 6SPN033
Ellagic acid: PI 108_972PN038,PN040,PN021
Eriodictyol-7 -O-alpha-L -rhamnoside: RtPN030
Estradiol: PI 3PN050
Fisetin-41-0-beta-D-glucoside: PI 400PN063
Gallic acid: Rt CultPN020, PI 2.7_27PN040,PN038
Geranin: PI 0.23%PN038
Hinokinin: PIPN014
Hydroxy niranthin: Lf 4PNOll
Hypophyllanthin: PIPN008,
Lf 0.05_0.17%PN087,PN013,PN002, AerPN089
Iso-lintetralin: PI 3.4PN014
Iso-quercitri n: LfPN031,PN041
Kaempferol-4-0-alpha-L-rhamnoside: RtPN030
Linnanthin: Lf 2PN013
Linoleic acid: Sd oil 21 %PN057
Linolenic acid: Sd oil 51.4%PN057
Lintetralin: Lf 5_1SPN014,PN013, AerPN033
Lupeol acetate: RtPN009,PN054
Lupeol: RtPN009,PN054
Niranthin: Lf 9_430PN013,PN002, AerPN033
Nirphyllin: Aer 7PN012
Nirtetralin: PIPN014,PN056, Lf 9_930PN013,PN002
Nirurin: PI 400PN066
Nirurine: Aer 39.8PN076
Nirurinetin: PIPN066
Nor-securinine: RtPN030
Phyllanthenol: Aer 20PN015
Phyllanthenone: Aer 8PN015
Phyllantheol; Aer 15PN015
Phyllanthin: Aer 400PN074, Lf 1100-32S0PN081 ,PN087
Phyllanthine: Rt, Lf, StPN065
Phyllanthus: PIPN042
Phyllester: Aer 12PNo33
Phyllnirurin: Aer 6PN012
Phyllochrysine: Lf, StPN055
Phylltetri n: AerPN033
Phyltetralin: PIPN056, Lf 0.14%PN013
Quercetin: LfPN031,PN041, PIPN063
Quercitrin: LfPN031,PN041, PIPN063
Repandusinic acid A: PIPN021
Repandusinic acid: PI 0.12%PN019
Ricinoleic acid: Sd oil 1.2%PN039
Rutin: PIPN063, LfPN031,PN041
Salicylic acid methyl ester: Lf EOPN083
Seco-4-hydroxy-lintetralin: Lf 20PNOll
Trans-phytol: PIPN049
Triacontan-1-al: Aer 60PN074
Triancontan-1-ol: Aer 560PNo74



PHRMACOlOCICAl ACTIVITIES AND CLINICAL TRIALS (Ross, I. A. 2004)

Aldose reductase inhibition. Ethanol (70%) extract of dried entire plant was active, lClo 1.0 mcg/mlPN040.
Analgesic activity. Methanol extract of dried callus tissue, administered intraperitoneally to mice at a concentration of 10.0 mg/kg, was active vs acetic acid-induced writhing and formalin-induced pedal edema. At 50.0 mg/kg, the extract was inactive vs tail flick response to radiant heatPN026. Ethanol/water (1: 1) extract of dried entire plant, administered intragastrically to male mice at a dose of 50 mg/kg, was active. The extract, administered intraperitoneally to male mice at a dose of 0.3 mg/kg, was also active. In both cases, antinociceptive effects were demonstrated using 5 different models of nociceptionPN028.
Angiotensin-converting enzyme inhibition. Chromatographic fraction of dried entire plant, at a concentration of 100.0 mcg/ ml, was activePN038.
Antibacterial activity. Water extract of fresh entire plant, at a concentration of 1.0% on agar plate, was inactive on Neisseria gonorrheaPNOll. Saline extract of leaves, at a concentration of 10% on agar plate, was active on Pasteurella pestis and Staphylococcus aureus, and inactive on Escherichia coliPN086. Chloroform extract of dried leaves, at a concentration of 1.0 gm/ml on agar plate, was inactive on Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. The methanol extract was active on Staphylococcus aureus, and inactive on Bacillus subtilis, Escherichia coli, and Pseudomonas aeruginosaPN060 .
Antidiarrheal activity. Ethanol/water (1: 1) extract of the dried aerial parts, at a concentration of 300 mg, was inactive for antidiarrheal activity on both guinea pig and rabbit ileums vs Escherichia coli-Inte Rotoxin-induced diarrheaPN025.
Antifungal activity. Petroleum ether extract of whole plant produced antifungal activity on Helminthosporium sativa. The leaf extract produced antifungal activity on Alternaria alternata, and had no activity on Curvalaria lunataPN051.
Antihepatotoxic activity. Hexane extract of dried aerial parts, at a concentration of 1.0 mg/ml in cell culture, was active on rat hepatocytes, results significant at P < 0.01 level vs CCl4-induced hepatotoxicity. The extract was inactive vs galactosamine-induced toxicityPN074. Dried entire plant, administered by gastric intubation to sheep at a dose of 1.0 gm/kg, was active. The animals were dosed daily for 10 days after receiving the hepatotoxic paracetamol. A mixture of Andrographis paniculata, Phyllanthus niruri, and Solanum nigrum was used. Changes induced by toxin were ameliorated by treatment. Changes included anemia, leukocytosis with neutrophilia and lymphopenia, increased coagulation, decreased glucose, cholesterolemia, hypotriglyceridemia jaundice and elevation of AST and ALTPN024. Powdered dried entire plant, administered by gastric intubation to rats at a dose of 200.0 mg/kg, was active on liver homogenate vs ethanol-treated rats dosed for 45 days. Triglyceride, cholesterol and phospholipid contents in fatty liver were reduced to normallevelsPNo36. Water extract of dried leaves, administered by gastric intubation to rats at a concentration of 2.0 ml/kg, was active. The activity was as effective as pretreatment vs CCl4-induced hepatotoxicityPN075.
Antihypercholesterolemic activity. Dried entire plant, in the ration of rats, was active. Fatty liver was induced with alcohol. The plant material reduced the increased deposition of triglycerides, cholesterol and phospholipids in the liver, heart and kidney that resulted from alcohol treatmenrPN078 .
Antihyperglycemic activity. Water extract of dried entire plant, administered by gastric intubation to rats, was active vs alloxan-induced hyperglycemiaPN042.
Antihyperlipemic activity. Water extract of dried entire plant, in the ration of rats, was active. Fatty liver was induced with alcohol. The plant material reduced the increased deposition of triglycerides, choles terol and phospholipids in the liver, heart, and kidney that resulted from the alcohol treatmentPN018.
Antimalarial activity. Ethanol extract of the entire plant produced more than 60% inhibition of Plasmodium falciparum growth, in vitro, at a test concentration of 6 microgram/ mIPN096. The ethanolic, dichloromethane and lyophilized aqueous extracts of the whole plant were evaluated for its antimalarial activity in vivo, in 4-day, suppressive assays against Plasmodium berghei ANKA in mice. No toxic effect of mortality was observed in the mice treated, orally, as a single dose of 500 mg/kg body weight, or as the same dose given twice weekly for 4 weeks. No significant lesions were observed, by eye or during histopathological examinations, in the hearts, lungs, spleens, kidneys, livers, large intestines or brains of any mouse. At a dose of 200 mg/kg, the ethanolic and dichloro-methane extracts produced significant chemosuppressions of parasitaemia, when administered orallyPNo91.
Antimutagenic activity. Water extract of dried leaves, administered by gastric intubation to mice at a dose of 10.0 ml/kg, was active vs nickle-induced clastogenicityPNoJ8.
Antipyretic activity. Ethanol/water (1: 1) extract of the entire plant, administered by gastric intubation to rabbits at variable dosage levels, was inactive vs yeast-induced pyrexiaPN09J.
Antispasmodic activity. Ethanol/water (1:1) extract of the entire plant was active on guinea pig ileum vs ACh- and histamineinduced spasmsPNOOJ.
Antitumor activity. Ethanol/water (1: 1) extract, administered intraperitoneally to mice, was active on LEUK (Friend VirusSolid) pNooJ. Ethanol (95%) and water extracts of dried aerial parts, at doses of 100.0 mg/kg, were inactive on Sarcoma 180(ASC)pNo44.
Anti-urolithiasis effect. The aqueous extract of the plant, in vitro, exhibited a potent and effective non-concentration- dependent inhibitory effect on a model of CaOx crystal endocytosis by Madin-Darby canine kidney cells. The response was present even at very high (pathologic) CaOx concentrations and no toxic effect was detectedPN095.
Antiviral activity. Ethanol (95%) extract of dried aerial parts was active on hepatitis B virus. Antiviral activity was measured in serum of patients who were positive for the hepatitis B virusPNo46. Water extract of the dried entire plant, administered to woodchucks at a dose of 9.0 mg/animal, was active vs hepatitis in long-term chronic carriers of woodchuck hepatitis. No effect was seen in either experimental or control animals. When experimental animals were later switched to intraperitoneal administration, two of them showed a drop in antigen titer (two others died of unrelated causes). No control animals showed any effectsPN094. Water extract of the dried entire plant, administered by gastric intubation to woodchucks, was active on woodchuck hepatitis virus. Biological activity reported has been patentedPNo35. Water extract of the dried entire plant, administered intraperitoneally to woodchucks at a concentration of9.0 mg/ animal, was active vs hepatitis in recently infected woodchucks. Three out of 4 experimental animals showed elimination of woodchuck hepatitis surface antigen and woodchuck hepatitis DNA polymerize after n days. They remained negative for 300 days. Control animal did not show any change. Water extract of the dried entire plant, administered intraperitoneally to woodchucks at a concentration of 9.0 mg/ animal, was active vs hepatitis in long-term chronic carriers of woodchuck hepatitis. Titer of woodchuck hepatitis surface antigen was lowered relative to untreated controls. Half of a ml of the extract was given once a weekPN094 . Water extract of dried entire plant (plants cultivated in USA), tested on hepatitis virus in cell culture, was inactive vs hepadnavirus DNA polymerase, ICso 381.0 and 410.0 mcg/mIPNOJ8. Ethanol (95%) extract of fresh entire plant, tested on Tobacco Mosaic virus in cell culture, was equivocal. The viral inhibitory activity was 7%PN022. Fresh leaf and fresh root extracts, at a concentration of 4.0%, were active on Peanut Mosaic virus, Tobacco Mosaic virus and Tobacco Ring Spot virusPN073.
Cardiotoxic activity. Ethanol/water (1: 1 ) extract of the entire plant, administered intravenously to dogs at variable concentrations, was inactivePN09J.
Chromosome aberration inhibition. Water extract of dried fruit and leaf, administered by gastric intubation to mice at a dose of 685.0 mg/kg, was active vs chromosome damage induced by lead nitrate and aluminum sulphate in bone marrow chromosomes. Dosing was for 7 daysPN041.
Chronotropic effect (positive). Ethanol/ water (1: 1) extract of the entire plant, administered to dogs intravenously at variable dosages, was inactivePN093 .
Cytotoxic activity. Ethanol/water (1: 1) extract of entire plant, in cell culture, was inactive on CA-9KB, EDso> 20.0 mcg/mlPNoo3.
DNA polymerase inhibition. Water extract of dried entire plant, at a concentration of 50.0 mg/ml, was active vs activity of woodchuck hepatitis virus DNA polymerase; 50.0 mg/ml produced 25% inhibition. Methanol and water extracts, a variable dosages, were also active. The biological activity reported in these studies has been patentedPNOJ'.
Hepatitis B surface antigen inactivation. Water extract of dried entire plant, at a concentration of 0.2 mg/ml, was active on hepatitis virus vs reaction of woodchuck hepatitis surface antigen with hepatitis B (Human) antibody. A concentration of 0.63 mg/ ml was active on hepatitis B virus vs reaction of hepatitis B surface antigen with hepatitis B antibodyfN094. Water and methanol extracts of the dried entire plant, at vari- able concentrations, were active. The biological activity reported has been patentedPN015. Water extract of dried leaves, was active. Hepatitis B surface antigen inactivation was assayed, ICso 650 ng/ml. The methanol extract was also active, IC,o 1.2 mcg/ml. Water extract of dried leaves was active. Hepatitis B surface antigen inactivation was assayed, I Cso 3.30 mcg/mlPN023. Chloroform extracrPNOl9 and water extracrPN034 of dried leaves, stem and dried roots, at a concentration of 2.0%, were active.
Hypoglycemic activity. Water extract ofthe dried entire plant, administered orally to rabbits at a dose of 10.0 mg/kg, was inactive. A drop in blood sugar of 15 mg relative to inerttreated control indicated positive resultsPNOIO.
Hypotensive activity. Ethanol/water (1: 1) extract of the entire plant, administered intravenously to dogs at variable dosage levels, was inactivePN093.
Molluscicidal activity. Ethanol (95%) extract of dried stem, at a concentration of 250.0 ppm, was inactive on Biomphalaria pfeifferi and Bulinus truncatus. Petroleum ether extract, at a concentration of 25.0 ppm, was active on Biomphalaria pfeifferi and Bulinus truncatusPN062.
Nematocidal activity. Decoction of bark, at a concentration of 1.0 mg/ml, was active on T oxacara canisPN048.
Reverse transcriptase inhibition. Water extract of the dried entire plant was active on HIV -1 virus, IOso 50.0 mcg/mlPN021 .
Spasmolytic activity. Methanol extract of dried callus tissue, at a concentration of 320.0 mcg/ml, was inactive on guinea pig ileum vs ACh-induced contractionsPN026.
Toxicity assessment (quantitative). Ethanol/ water (1: 1) extract of the entire plant, administered orally to mice, tolerated a maximum dose of 1.0 gm/kgPNOOJ. Water extract of the dried entire plant, at a dose of 0.1 meg/animal, was inactive. No weight loss was found 7 days after treatment with the extractPN094.

PHARMACOLOGICAL AND BIOLOGICAL ACTIVITY (Paithankar et al., 2011)
Hepatoprotective Effect  Hepatitis B is one of the major diseases inflicting human population. Conventional treatment with interferon – alpha is very expensive and has many serious side effects. Alternative herbal medicine using extracts of Phyllanthus niruri and Phyllanthus urinaria have been reported to be effective against Hepatitis B and other viral infections. A study reports quantitative determination of the anti viral effect of these herbs in well-defined in vitro systems (Meixa et al., 1995). Phyllanthus niruri has been reported to exhibit marked antihepatitis B virus surface antigen activity in in-vivo and in-vitro studies. Infectious hepatitis is due to the inability of the bodies’ immune system to eliminate the virus from the liver cells: hence the “carrier state”. An infection with the virus is documented by detectable levels of various viral antigens in the blood, including HbaAg (the surface antigen of the virus) as well as antibodies to the core of virus (HBc antibodies). In one study, 37 patients with chronic viral hepatitis B were treated with a daily dose of 600mg of Phyllanthus niruri for 30 days. 59% of the patients lost the HBsAg two weeks after the end of the treatment. Furthermore, none of the cases followed for up to 9 months had any symptoms of HBsAg. The authors postulated that Phyllanthus niruri might inhibit proliferation of the virus by inhibiting replication of the genetic material of the virus (Thyagarajan et al., 1988). Hepatoprotective effect of an ayurvedic medicine; herbal preparation HPN – 12 (containing Glycirrhiza glabr, Pichorhiza kurroa, Berberis aristata, Piper longum, Phyllanthus niruri, Solanum dulcamara, Zingiber officinale, Curculigo orchioides, Elettaria cardamomum, Tinospora cordifolia, Desmodium trifolium and Sacchrum officinarum) orally administered to male albino rats at 1ml/100g body weight was found to be effective against liver damage (Latha et al., 1999). Animals with Carbon Tetrachloride induced hepatopathy were treated with catliv (contains extracts of Swertia chirata, Eclipta alba, Fumaria vaillanti, Picorrhiza kurroa, Andrographis paniculata and Phyllanthus niruri) at 25ml twice daily orally for six days starting at 48 hours after administration of Carbon tetrachloride. On basis of result obtained it was concluded that the ingredients in catliv, effectively helped in regeneration of hepatic cells and is an effective liver tonic for calves (Pradhan et al., 2001). Research in Japan and India in the 1980's has demonstrated the liver -healing properties of Phyllanthus niruri. The primary compounds responsible are phyllanthin, hypophyllanthin and triacontanal. Glycosides found in Phyllanthus niruri demonstrated Aldose reductase (AR) inhibitory activity in studies conducted by a Japanese research group in 1988 and 1989 (Shimizu et al., 1989).
HIV Replication Inhibition  Aqueous extract of Phyllanthus niruri is reported to have inhibitory effect on human immunodeficiency virus. The investigation examines the anti-HIV effects of the alkaloidal extract of Phyllanthus niruri in human cell lines. The inhibitory effect on HIV replication was monitored in terms of inhibition of virus induced cytopathogenecity in MT-4 cells. The alkaloidal extract of Phyllanthus niruri showed suppressing activity on strains of HIV-1 cells cultured on MT-4 cell lines. The CC50 for the extract was found to be 279.85µgmL-1 whereas the EC50 was found to be 20.98µgmL-1. Interestingly the Selectivity Index (SI) was found to be 13.34, which showed a clear selective toxicity of the extract for the viral cells. The alkaloidal extract of Phyllanthus niruri was thus found to exhibit sensitive inhibitory response on cytopathic effects induced by both the strains of human immunodeficiency virus on human MT-4 cells in the tested concentrations (Naik et al., 2003). Extracts of five medicinal plants: Aristolochia indica, Cassia occidentalis, Phyllanthus niruri, Withania somnifera and Tinospora cordifolia were administered to 10 HIV infected patients for a period of six months to one year. The clinical status of the patient and their CD4 cell counts were periodically monitored. The results indicate that in seven of the ten patients, their CD4 count increased and the patients remained either asymptomatic or their clinical well being improved. There was no change in the CD4 cell count in one of the patient and the other two progressed to full blown AIDS (Natarraj et al., 2000).
Lipid Lowering Activity  Lipid lowering activity of Phyllanthus niruri alcoholic extracts in triton induced hyperlipidaemia was examined in rats. It was observed that administration of triton in rat caused increase in serum cholesterol by 3.5 fold, phospholipid 2 fold and triglyceride 1.2 fold. Administration of Phyllanthus niruri at the dose of 200mg/kg simultaneously with triton lowered the level of total cholesterol, phospholipid and triglyceride by 27, 25 and 24 percent respectively. In an experiment with cholesterol fed rats, Phyllanthus niruri at a dose of 100 mg/kg lowered the elevated level of low-density lipoprotein lipids in hyperlipidemic and drug fed animals. (Chandra et al., 2000)
Anti-Diabetic Activity  An alcoholic extract of Phyllanthus niruri was found to reduce significantly the blood sugar in normal rats and in alloxan diabetes rats. In normal rats, administration of Phyllanthus niruri 200mg/kg body weight reduced the blood sugar by 34.5 percent and to 47.4 percent at the concentration of 1000mg/kg by weight at 1 hour. However at 6th hour, values are almost similar to normal value. Continuous administration of the drug produced significant reduction in normal blood sugar in rats, which on 15th day was also found to reduce the blood sugar in alloxan diabetic rats. In short term experiment, drug was found to reduce the blood sugar at 4th hour by 6.07 percent at dose level of 200mg/kg by weight and 18.7 percent at concentration of 1000mg/kg by weight. Continuous administration of drug produced significant reduction in blood sugar in alloxan diabetic rats. On 15th day values were almost similar to normal in the group taking 1000 mg/kg by weight. Plant extract did not produce any toxicity as seen from liver and kidney function test and in hematological parameters. The results indicate potential antidiabetic action of Phyllanthus niruri. (Raphael et al., 2000).
Anti-Malarial Activity  The ethanolic, dichloromethane and lyophilized aqueous extracts of Cassia occidentalis root bark, Morinda morindoides leaves and whole plants of Phyllanthus niruri were evaluated for their antimalarial activity in vivo, in 4-day, suppressive assays against Plasmodium berghei ANKA in mice. No toxic effect or mortality was observed in mice treated, orally, with any of the extracts as a single dose, of 500 mg/kg body weight, or as the same dose given twice weekly for 4 weeks (to give a total dose of 4 g/kg). No significant lesions were observed, by eye or during histopathological examinations, in the hearts, lungs, spleens, kidneys, livers, large intestines or brains of any mouse. At doses of 200 mg/kg, all the ethanolic and dichloromethane extracts produced significant chemosuppressions of parasitaemia (of > 60% for C. occidentalis root bark and Phyllanthus niruri whole plant, and of 30% for M. morindoides leaves) when administered orally. The most active ethanolic extract, that of Phyllanthus niruri, reduced parasitaemia by 73%. The dichloromethane extracts of M. morindoides and Phyllanthus niruri produced similar reductions (74% and 72% chemosuppression, respectively), whereas that of C. occidentalis was slightly less active (60% chemosuppression). Each lyophilized aqueous extract was less active than the corresponding ethanolic extract (Neraliya et al., 2004).
Activity against Filarial Mosquito (Culex quinquefasciatus) Eighteen plants were evaluated for juvenile hormone analogue activity against Culex quinquefasciatus. Of these acetone extracts of 8 plants namely Commelina benghalensis, Ageratum conyzoides, Achyranthus aspera, Sida acuta, Euphorbia pulcherrina, Rivinia humilis, Ruellia tuberosa and Phyllanthus niruri possessed significant juvenile hormone activity. The LC50 values of 5 most active plants namely Phyllanthus niruri, Amaranthus spinosus, Antegonon leptopus, Corchorus aestuans, Corchorus benghalensis were determined to be 13, 16, 17, 17, 14ppm respectively (Calixto et al., 1984).
Anti-spasmodic activity Research done in Brazil at the Federal University of Santa Catarina in 1984 on Phyllanthus niruri revealed an alkaloid (phyllanthoside) in the leaves and stem with strong antispasmodic activity. It served as a relaxing agent for smooth muscles and they concluded that its spasmolytic action probably accounted for the efficacy of Phyllanthus niruri in expelling stones (Grewal, 1984).
Analgesic activity Methanol extract of dried callus tissue at a concentration of 10mg/kg, administered intraperitonially to mice was active vs. acetic acid induced writhin and vs. formalin – induced pedal edema. The extract, at 50mg/kg was inactive vs tail flick response to radiant heat. Ethanol/ water (1:1) extract of dried entire plant at a dose of 50mg/kg, administered intragastric to male mice was active. The extract also administered intraperitonially to male mice at a dose of 0.3mg/kg was active. In both cases antinociceptive effects were demonstrated using 5 different models of nociception (Santos et al., 1994).
Chromosome Aberration Inhibition Water extract of dried fruit and leaves, at a dose of 685.0 mg/kg, administered to mice by gastric incubation was active vs. chromosome damage induced by lead nitrate and aluminium sulphate in bone marrow chromosomes. Dosing was for 7 days (Holdsworth et al., 1982).


PHARMACOLOGICAL ACTIVITIES OF PHYLLANTHUS AMARUS
(Danladi S, Idris MA, and Umar II. 2018)
Antidiabetic activity  Ethanolic extract of Phyllanthus niruri was found to have significant antidiabetic activity in insulin-dependent diabetes mellitus rat, but showed no effect on non–insulin-dependent diabetes mellitus rat [18] . Additionally, the ethanol extract was found to lower lipid profiles (decrease in plasma cholesterol, triglycerides, Low density lipoprotein cholesterol, very low density lipoprotein cholesterol and atherogenic index, while there is increase in high-density lipoprotein cholesterol) in both insulin-dependent diabetes mellitus and non– insulindependent diabetes mellitus animals [18] . Concordantly, a one week study carried out on non-insulin dependent diabetic patients using aqueous extract of aerial parts of Phyllanthus amarus showed that, it is not effective in lowering both fasting blood glucose and postprandial blood glucose level in untreated non-insulin dependent diabetic patients [19]. Aqueous extract of Phyllanthus niruri demonstrated significant hypoglycemic activity in streptozotocininduced diabetic rats [20]. Relatedly,the methanol extract of the plant has also been found to reduce blood sugar level in alloxan-induced diabetic rats [21] .
Hyperlipidemic activity  Scientific studies have shown that Phyllanthus niruri has antihyperlipidemic effect. It was also reported that the aqueous extract exhibited antihyperlipidemic activity [20]. Hydro-alcoholic extract of leaves of Phyllanthus amarus was also found to have antihyperlipidemic potential in hyperlipidemic rats [22]. Additionally, phyllantrin which is a bioactive compound of Phyllanthus niruri was administered for twelve weeks to mice co-fed with High Fat Diet (HFD); there was protection against HFD induced weight gain and adiposity, reduced mRNA expression of adipogenic genes and increased expression of lipolytic genes in white adipose tissue, reduced liver triglyceride accumulation, restoration of HFD induced serum lipid disturbances as well as reduced serum triglycerides and free fatty acids in HFD fed mice [23] . The lipid-lowering activity of Phyllanthus niruri was found to be mediated through inhibition of hepatic cholesterol biosynthesis, enhanced catabolism of LDL, increased faecal bile acids excretion and activation of LCAT and tissue lipases [24] .
Hyperuricemic effect  It was reported that the methanol extract of the leaves of Phyllanthus niruri exhibited anti hyperuricemic activity in hyperuricemic rats. Lignans isolated from Phyllanthus niruri (Phyllanthin, hypophyllanthin, phyltetralin and niranthin) were also found to increase the urinary excretion of uric acid in hyperuricemic rat. Therefore, the uricosuric effect of this plant may be the attributed mechanism of anti hyperuricemic action [25] .
Lithiasis  Phyllanthus niruri has shown inhibitory effect against calcium oxalate crystal growth and aggregation in human urine. This medicinal plant exhibited antiurolithic activity in both in vitro and in vivo studies [6] . The aqueous extract of Phyllanthus niruri inhibits the growth of the matrix calculus as well as decrease the number of stone satellites in Wistar rats [26]. Oral administration of Phyllanthus niruri extract by calcium stone forming patients reduced urinary calcium in hypercalciuric patients [27] .
Nephroprotective effect of Phyllanthus amarus  The aqueous extract of Phyllanthus amarus at doses of 200 mg and 400 mg/kg/day for 14 days, were found to protect against the nephrotoxic effect of paracetamol and gentamicin in rat, by maintaining the level of blood urea nitrogen and serum creatinine within the normal range compared to control group [1]. In another study, the ethanol extract of the leaves of the plant was investigated for its nephroprotective activity against gentamicin induced nephrotoxicity in rats. Co-administration of the extract with gentamicin prevented kidney and improved all nephrotoxic parameters (physical, urinary and blood) observed [28]. The extracts of Phyllanthus amarus prepared by dissolving the leaves in olive oil for fourteen and seven days were tested for their ability to protect the kidney against cisplatin induced nephrotoxicity. The study revealed significant decrease
Antiplasmodial activity Ethanolic extract of Phyllanthus niruri was found to have potential anti plasmodial activity in vitro by inhibition of the developmental stage of trophozoite to schizonts [7] . Similar in vitro study also showed that the callus extract and intact Phyllanthus niruri extract inhibited the development of trophozoites to schizonts (developmental stage of Plasmodium falciparum) in a dose-dependent manner. The anti plasmodial activity of extract of Phyllanthus niruri (whole plant) exhibited a higher anti plasmodial activity than all calli and intact fresh apical stem extracts [30] . It was reported that the water extraction of Phyllanthus niruri gives better results of antiplasmodial activities than ethanolic extraction and only leaves and stems parts of the plant were active in vitro against plasmodium [31]. 1-O-galloyl-6-O-luteoylR-D-glucose isolated from the Phyllanthus niruri was found to have inhibitory effect against Chloroquine-susceptible P. falciparum strain in vitro [32]. Chloroform/ethanol extract of Phyllanthus niruri showed significant inhibition of P. falciparum growth at different concentrations [33] .
Antinematodal activity Two compounds isolated from Phyllanthus amarus, 8-(3-methyl-but2–enyl)-2-phenyl chroman-4-one and 2-(4-hydroxyphenyl)-8-(3- methyl-but-2–enyl)-chroman-4-one were found to have antinematodal activity against Meloidegyne incognita and Rotelenchulus reniformis [34] .
Antibacterial activity Phyllanthus amarus has broad spectrum antibacterial activity on both gram positive and gram negative bacteria. A study carried out on different bacterial isolates; Bacillus stearothermophilus, Staphylococcus aureus, Bacillus subtilis, Micrococcus leuteus, Salmonella typhi, Enterobacter aerogens, Proteus mirabilis, and Proteus vulgaris revealed that P. amarus showed the least MIC on all bacteria tested [35]. Similarly, the methanolic extract of Phyllanthus amarus was found to have potent inhibitory effect against drugresistant pathogenic gram-negative bacteria; Shigella spp., E. coli, V. cholerae, S. aureus, S. typhimurium, P. aeruginosa, B. subtilis, Klebsiella and Streptococcus sp. in a dose-dependent manner [36] .
Hepatoprotective effect The Protein isolate of Phyllanthus niruri indicates hepatoprotective effect against acetaminophen-induced toxicity [37]. Another study also showed that the aqueous extract of Phyllanthus niruri inhibited paracetamol induced hepatotoxicity in mice [38]. Similarly, fishes pretreated with Phyllanthus niruri extract were protected against paracetamol-induced hepatotoxicity when compared to control [39]. It was also reported that a protein isolated from Phyllanthus niruri protects against oxidative damage of hepatocytes induced by carbon tetrachloride [40]. Both aqueous and methanol extracts of Phyllanthus niruri have been demonstrated to possess hepatoprotective effect [41] . The extract of Phyllanthus amarus was also found to increase hepatic cell function [16] . Similarly, another study reported the hepatoprotective effect of Phyllanthus amarus in ethanol-induced hepatotoxicity and the effect was comparable to standard hepatoprotective drug silymarin. The hepatoprotective effect of the extract was associated with its antioxidant activity [42] . Phyllanthus amarus extract and phyllanthin isolated from the aerial part of the plant were found to protect the human hepatoma HepG2 Cell line against carbon tetrachloride induced hepatotoxicity. Phyllanthin demonstrated the hepatoprotective effect at a lower dose compared to Phyllanthus amarus extract and the effect was in a dose-dependent manner [43]. Combination of ethanolic extract of Phyllanthus amarus and silymarin gives synergistic hepatoprotective activity against carbon tetrachloride-induced hepatotoxicity. The effect was associated with higher concentration of phyllanthin. A combination of silymarin with ethanol extract provided higher hepatoprotective activity than when combined with aqueous extract [44]
Effect on Viral Infections It was reported that the extract of Phyllanthus amarus in an in vitro study inhibited DNA polymerase in Hepatitis B virus (HBV) and Woodchuck hepatitis virus (WHV). Also, in vivo study shows that the extract of Phyllanthus amarus has effect against Hepatitis B virus in infected human [45]. Another study revealed that the extract blocked enzymes that play an important role in the reproduction of hepatitis B virus [46]. Oral administration of Phyllanthus amarus was found to decrease the mortality rate and significantly increase the survival of hepatocellular carcinoma harboring animals [47]. It was also reported that an aqueous extract of Phyllanthus niruri inhibits endogenous DNA polymerase of hepatitis B virus and binds to the surface antigen of hepatitis B virus in vitro. The extract also inhibits woodchuck hepatitis virus DNA polymerase and binds to the surface antigen of WHV in vitro [48] .It was reported that the alkaloidal extract of Phyllanthus niruri inhibited the growth of both HIV-1 and HIV-2 strains cultured on human MT-4 cells [46]. Similarly, the water alcoholic extract of Phyllanthus amarus was found to be a potent inhibitor of HIV-1 replication in HeLaCD4+ and also inhibited the RT inhibitor-resistant HIV strains. The inhibitory effect of Phyllanthus amarus against HIV strain was both in vitro and in vivo [49, 50] . Niruriside, a novel compound isolated from Phyllanthus niruri exhibited anti-HIV activity. It was found to exert inhibitory effect against the binding of REV protein to RRE RNA with an IC50 value of 3.3 µM [51] .
Effect on Reproductive system Methanol extracts of the leaves of Phyllanthus amarus lead to a decrease in sperm motility and count of male guinea pigs in a dosedependent manner. The effect was comparable to the observed effects of Vitamin E on sperm parameters [52] . The ethanolic extract of Phyllanthus amarus significantly affected the litter size and weight of Wistar albino rats at birth in a dose-dependent manner [8] . The alcohol extract of a whole plant of Phyllanthus amarus was found to show reversible antifertility effect in female mice [53]. Similarly, Phyllanthus amarus when given orally to male albino mice induced gradual inhibition of fertility potential with a decline in epididymal sperm profiles. However, the antifertility effect was reversible upon withdrawal of medicinal plant [54] . The methanolic extract of Phyllanthus amarus leaves caused significant increase in the level of testosterone of male Guinea pigs in a dose- and time- dependent manner. It also caused changes in the levels of Leutenizing (LH) and Follicle stimulating (FSH) hormones. These changes caused by Phyllanthus amarus were comparable to the changes caused by vitamin E on Leutenizing (LH) and Follicle stimulating (FSH) hormones. [4] .
Effect on Cardiovascular System It was reported that methyl brevifolincarboxylate (MB) isolated from the leaves of Phyllanthus niruri L. exerted vasorelaxant effect on the aortic rings of rat. It also antagonised the vasoconstriction effect of Norepinephrine [55]. MB was also found to have potent inhibitory effect against platelet aggregation; the effect was comparable to known inhibitor of platelet aggregation adenosine [3] . In a recent study, the aqueous extract of Phyllantus amarus was tested for its cardioprotective property against high-fructose (HF) diet induced cardiac damage in Wistar rats; the aqueous extract prevented the increase in levels of cardiac and aortic lipids i.e., total lipids, triglycerides, total cholesterol and free fatty acids and decreased phospholipids after co-administration with the HF for sixty days [56]. Yao et al. (2018) compared the diuretic effect of the ethanolic fraction of the plant (EEPA) to that of a standard drug (frusemide); the diuretic effect of EEPA was comparable to the standard with an additional benefit of not promoting kaliuresis. Furthermore, the diuretic activity was attributed, at least in part, to the involvement of prostaglandins [57] .
Analgesic, Anti-inflammatory and antiulcer activity Studies have shown that extract of Phyllanthus amarus has an antiinflammatory effect; and that it is effective in preventing persistent neuropathic pain, as well as prevent both ipsilateral and contralateral persistent nociception [58]. Another study showed that P. niruri exhibited potent systemic antinociceptive actions against two models of neurogenic pain [59] . Similarly, methanol extract of Phyllanthus amarus significantly inhibited gastric lesions induced by intragastric administration of absolute ethanol. Aqueous and methanol extracts of Phyllanthus amarus were found to have anti-inflammatory activity [60]
Radioprotective effect It was also reported that Phyllanthus amarus improved antioxidant activity in liver and blood of irradiated mice [61]. Similarly, Phyllanthus amarus prevented the genotoxic effect of radiation on mice chromosome, and it prevented the intestine from radiation induced damages as evident by decreased peroxidation level of intestinal membrane and elevated antioxidant system [62] .
Cancer and cytotoxicity Phyllanthus amarus offers protection against chemical carcinogenesis. It was reported that the aqueous extract of Phyllanthus amarus significantly inhibited hepatocarcinogenesis induced by Nnitrosodiethylamine (NDEA) in a dose-dependent manner in male Wistar rats [63] . Phyllanthus amarus extract was also found to have significant activity against chemically induced tumour. Inhibition of cell cycle regulation, topoisomerase II, P450 enzymes as well as antioxidant activity may contribute to the overall activity of the extract against carcinogenesis induced in animals and this may be relevant to human cancer as well [64]. It was reported that the extract of Phyllanthus amarus inhibited the mutagenicity produced by direct acting mutagens. It also inhibited the activation and mutagenicity of 2-acetaminofluorene (2-AAF), which in turn declined the mutagenesis and possibly carcinogenic potential. Oral administration of Phyllanthus extract was found to significantly inhibit urinary mutagenicity produced in rats by benzo- pyrene [65]. The study showed that the methanol extract of Phyllanthus amarus has Chemopreventive activity against N-methyl N’-nitro-N-nitrosoguanidine (MNNG) induced stomach cancer in Wistar rats [66]. The aqueous extract of Phyllanthus amarus has also demonstrated anti-mutagenic and antigenotoxic properties as indicated by the extracts ability to protect against the mutagenic effects of 2-aminofluorene, 2-aminoanthracene, 4-nitroquinoline-1-oxide, N-ethyl-N-nitro-nitrosogua- nidine, 2- nitrofluorene and sodium azide in test bacteria. In addition, the extract antagonizes DNA damage caused by DMN in hamster liver [67] .
Effect of Phyllanthus amarus on metabolizing enzymes (CYP P450 3A Family) Phyllanthus amarus significantly inhibits the Metabolism of CYPA5 and CYPA7 enzymes which are essential enzymes responsible for phase 1 drug metabolism. Co-administration of Phyllanthus amarus with orthodox drugs that are completely metabolized by CYP3A Family can lead to therapeutic failure, drug interaction and adverse effect since it will interferes with it metabolism [68]. Another study showed that CYP1A2, CYP2C9, CYP2D6 AND CYP3A4 enzymes were inhibited by aqueous extract of Phyllanthus amarus similarly human and rat glutathione S-transferases (GSTS) liver cytosolic enzyme was strongly inhibited by Phyllanthus amarus [69] . Similarly, in in vitro study it was also found out that the extract of Phyllanthus amarus significantly inhibited CYP1A1, CYP1A2, CYP2B1/2, CYP2E1, CYP 1A, 2A, 2B, 2D and 3A enzymes activity, while in in vivo study indicated the activity of P450 enzymes after phenobarbitone administration elevated but oral administration of Phyllanthus amarus was found to reduce the activity [70]. The effect of Phyllanthus amarus extract on the pharmacokinetic profile of midazolam has been studied and found to interfere with CYP3A4, thereby increasing the blood level of the drug [71]. The mean maximum concentration (Cmax), time to reach maximum concentration (Tmax), area under curve (AUC0-8), and elimination half-life (T1/2) (2.9-, 1.6-, 2.8-, and 1.4-fold, respectively) were all increased when compared to control group receiving a single oral dose of midazolam [71] .

TOXICITY STUDY (Danladi S, Idris MA, and Umar II. 2018)
Toxicity study of aqueous extract of Phyllanthus amarus showed that the extract can cause anaemia because it is associated with decrease in the red blood cell (RBC) count, packed cell volume (PCV), haemoglobin concentration (Hb) level of alanine aminotransferase (ALT); but there is an increase in the white blood cell (WBC) count, levels of aspartate aminotransferase (AST), total conjugated bilirubin, total protein and albumin. The extract also causes a decrease in body weight of laboratory animal. Histopathology study has shown that the kidney, liver and testes are affected by the plant; these showed the toxic potential of the plant [72]. The fractions of Phyllanthus amarus obtained from chromatographic separation showed that the plant has toxic effect on blood products [73]. Single oral dose and sub-acute toxicity study of Phyllanthus amarus showed that the medicinal plant is non-toxic with an LD50 > 5 g/kg; which is a clear indication that it is safe, but associated with slight cytotoxic effect to the human adenocarcinoma cell line [75].
The difference between this study and that of Adedapo et al. (2005a72 & b)73 may be as a result of variation in experimental condition and procedure. However, Singh et al. (2016) reported an LD50 of 2590.984 mg/Kg bw in Swiss albino mice model in laboratory condition when administered with aqueous extract of the plant. Doses above 2500 mg/Kg bw demonstrated a statistically signification elevation of urea level and histopathological changes were observed; with no significant increase in creatinine level [76] . Another study showed that alcohol extract of the whole plant was not toxic as it displayed no effect on blood cell counts, Hb levels and serum biochemical parameters. Moreover, the body weights of test animals were affected by the extract [53, 54] .

Antioxidant  (Danladi S, Idris MA, and Umar II. 2018)
Phyllanthus niruri showed significant improvement of body antioxidant activities in both insulin and non-insulin dependent diabetes mellitus animals [18]. A protein isolated from Phyllanthus niruri has also been showed to act as radical scavenger, thereby scavenging the free radicals released by the toxic effect of carbon tetrachloride in hepatocytes. The hepatoprotective effect of Phyllanthus niruri may be associated with it action at cellular level by reducing oxidative stress as a radical scavenger and promoting antioxidative defense mechanism of the cells [40] . In vitro antioxidant assay showed that the plant is an effective radical scavenger [62] . High phenolic content of Phyllanthus amarus showed a strong correlation with its antioxidant activity. Phyllanthus amarus has a high antioxidant activity because of its several phenolic constituents and it inhibits chromium (VI) induced oxidative toxicity to MDAMB-435S human breast carcinoma cells [76]. Similarly, it was also reported that Phyllanthus amarus has a strong free radical scavenging The Journal of Phytopharmacology 345 activity and ferric reducing property; its strong free radical scavenging activity is associated with its high phenolic content. The methanol extract of dried Phyllanthus amarus has lower antioxidant property compared to fresh sample [77] . Phyllanthus amarus was found to have effective in vivo antioxidant activity as seen by its ability to inhibit carbon tetrachloride induce lipid peroxidation in rat liver; while in vitro antioxidant activity showed that the plant has high radical scavenging activity [41] . Phyllanthin was reported to have higher radical scavenging capacity than Phyllanthus amarus, as indicated by its higher antioxidant activity than Phyllanthus amarus [43] . Phyllanthus amarus demonstrated antioxidant activities as indicated by its ability to increase the activities of enzymic and non-enzymic antioxidants and reduce malondialdehyde levels [20]. The methanol extract of Phyllanthus amarus was found to possess potential antioxidant activity as evident by its ability to inhibit lipid peroxidation and scavenge hydroxyl and superoxide radicals in vitro [21]. Aqueous extract of Phyllanthus niruri exhibited high free radical scavenging, inhibition of reactive oxygen and lipid peroxidation [39] . Phyllanthus amarus alleviated oxidative stress induced by nimesulide in the liver as evident by the outcome of post-treatment; with Phyllanthus amarus rapidly restoring most of the Nimesulideinduced oxidative changes compared to those obtained by the selfrecovery of liver [78].


RECENT FINDINGS (Krishnamurthy, K. H. 2014)
The dried leaves contain 0.4 per cent of a toxic bitter principle named phyllanthine (after the generic name) and this is the chief medically active substance of the plant. It is found to be poisonous to fish and frogs. In frogs, it causes depigmentation of the skin although this is regained after about 20 hours. The leaves are very rich in potassium, considered to be responsible for its powerful diuretic effect — the basis for its most celebrated use in jaundice.
The stem contains saponin, a detergent or cleaning substance. A decoction from the stem and leaves is used to dye cotton threads black; in fact, this decoction is so black that it is sometimes used in place of ink. An alcoholic extract of leaves and roots exhibit anti-bacterial activity against micrococcus pyrogenes, the pus causing bacteria and Escherichia coli.

Description: https://www.namahjournal.com/pic/phyl2.jpg
Micrococcus pyrogenes

USES IN TRADITIONAL MEDICINE
1. Gastro-intestinal system
It is used for relieving many afflictions of the abdomen, such as dyspepsia, colic, diarrhoea and dysentery.
a.       An infusion of young tender shoots can be effectively given against chronic dysentery.
b.       The leaves are also boiled in water and the liquid drunk to arrest acute gripping pains in the stomach.
c.        The most important medicinal value of the plant lies in its sure use against jaundice. For this purpose, a tolā of fresh juice from the ground root is given in the early morning along with milk. This is to be taken twice a day, once in the morning and then before bedtime.
d.       Gargling with a cold extract of leaves will cure sores and inflammations in the mouth (mukha pak).
e.        Sprue Sprue is a chronic, chiefly tropical disease, characterised by diarrhoea, emaciation, and anaemia, caused by defective absorption of nutrients from the intestinal tract. Giving some tender leaves of the plant, along with the seeds of methi (fenugreek), will set right this chronic and longstanding disorder.
f.        Edema A decoction from the whole plant mitigates morbid swellings, due to the retention of fluids in the body or dropsy (jalodara), by inducing profuse urine flow.

2. Skin
a.       The roots and leaves are pulverised and made into a paste along with rice water and applied externally as a poultice to lessen morbid swellings and ulcers.
b.       The milky juice from the plant is a good application against offensive and foul smelling sores. It is also found to be effective for difficult and painful tumours.
c.        A poultice, made from the leaves with salt, cures scabby afflictions and this poultice (without salt, to avoid burning) can also be applied on open lesions and bruises.
d.       An application of the poultice prepared from its leaves cures itching, aberrations and eczema.
e.        A decoction from the roots is used as a cooling reagent for the scalp.

3. Genito-urinary problems
The plant increases the quantity of urine and also removes burning associated with its flow. Because of this, it is recommended against gonorrhoea as well. In brief, the plant is very effective for all diseases of the urinary tract, ranging from the kidney to outflow of urine.
a.       In cases of new gonorrhoea, administration of a spoon of fresh juice from the plant, along with sugar and jira, considerably mitigates any pain in urination.
b.       In the Konkan region, the root is ground down with rice water (conjee) and given as a remedy for menorrhagia or excessive menstrual flow.
c.        In the Gold Coast of Africa, the leaves are pounded and used to cure gonorrhoea.
d.       A paste from the entire plant is applied externally to reduce morbid swellings of the breasts.
e.        The juice from fresh roots is taken internally along with milk as a galactagogue (i.e. promoting milk formation in lactating women).

4. Fever
a.       A liquid decoction from the root and leaves is very bitter but a favourite and efficient remedy amongst the natives of Porto Rico in the West Indies for the cure of intermittent fevers. The expected paroxysm (i.e. the climax stage) of such a fever can be prevented by its use. The dose is two drachms in the morning when onset is feared. An infusion of roots and leaves is a good tonic and also a diuretic when taken in repeated doses.
b.       A decoction from the whole plant is given against malarial fever. After administration, the stools become normal and sweating commences. The patient secures sleep. Any enlargement of liver and spleen, which often accompanies longstanding fever, subsides and slowly the incidence of intermittent attacks stops.
c.        Intermittent fever A paste is prepared by grinding its tender leaves along with black pepper. A pellet is made from it, the size of a nutmeg (jayphal) and given for all intermittent fevers including malaria.

5. Eyes When mixed with oil, the juice from the plant is useful against inflamed eyes.
Description: Phyllanthus niruri, Linn. Phyllanthus maderaspatensis, Linn.
Phyllanthus niruri, Linn. Phyllanthus maderaspatensis, Linn.
Description: Phyllanthus niruri, Linn. Phyllanthus maderaspatensis, Linn.
Phyllanthus urinaria, Linn. Phyllanthus simplex, Retz

ACTIVITIES  (Duke, J. A et al., 2009)
Abortifacient (f; RAI); Aldose-Reductase-Inhibitor (1; MPG; RAI; 60P); Amebicide (1; ZUL); Analgesic (f1; DAV; DAW; MBC; RAI); Anthelmintic (1; ZUL); Antialcoholic (1; KEB); Antibabesial (1; X15844943); Anticancer (1; KAB; PHM9:26); Antifertility (1; RAI); Antigenotoxic (1; PHM9:26); Antihepatomic (1; KEB); Antihepatotoxic (1; DAV; TRA); Antihyperuricemic (1; X16953466); Antiinflammatory (f1; RAI); Antileukemic (1; KAB); Antimutagenic (1; PHM9:26; RAI); Antioxidant (1; X16718736); Antiplasmodial (1; X15844943); Antiseptic (1; MPI; PH2; WOI); Antispasmodic (1; DAV; KAB; MPI; RAI; TRA); Antiulcer (f1; JFM; RAI); Antiviral (1; KEB; PH2; RAI; SKY; TRA); Aperitive (f; DAV; DAW); Astringent (f; KAB; SKJ); Bactericide (1; HH2; RAI; TRA; WOI; ZUL); Bitter (1; KAB; MPI; PH2); Carminative (f; DAV; DAW; RAI); Chemopreventive (f1; RAI); Cholagogue (f; GMJ); Contraceptive (1; PR15:265); Deobstruent (f; ADP; MPB; RAI; SKJ); Depurative (f; JFM); Diaphoretic (f; MPB); Digestive (f; DAV; DAW; RAI); Diuretic (f1; DAW; HHB; JFM; KAB; SKJ; TRA; WOI); DNA-Polymerase-Inhibitor (1; SKY); Emetic (f; MPG); Emmenagogue (f; DAV; DAW; NPM); Febrifuge (1; DAV; MPI; RAI; SKJ; TRA); Fungicide (1; ZUL); Gastroprotective (1; RAI); Hepatoprotective (f1; KAB; KEB; MBC; RAI; X16718736); HIV-RTInhibitor (1; KEB); Hypocholesterolemic (1; MPG; RAI); Hypoglycemic (= >Tolbutamide) (1; DAV; KAB; KEB; MPI; RAI; TRA); Hypotensive (1; MBC; RAI; X8786163); Hypotriglyceridemic (1; RAI); Hypouricemic (f1; JFM; X16953466); Immunostimulant (1; X16252911); Lactagogue (f; ADP; KAP; WOI); Laxative (f1; DAV; DAW; KAB; RAI); Litholytic (f1; DAV; RAI; X16896689); Myorelaxant (1; RAI); Natriuretic (1; MPB; RAI); Piscicide (1; JFM; WOI); Protein-Kinase-Inhibitor (1; HH2); Protisticide (1; ZUL); Radioprotective (1; RAI); Refrigerant (f; KAB); RT-Inhibitor (1; RAI); Sedative (f; 60P); Stomachic (f; DAW; SKJ); Tonic (f; DAV; DAW; KAB); Uricosuric (1; MBC); Uterorelaxant (1; RAI); Vasorelaxant (1; X16394535); Vermifuge (f; DAV; DAW; RAI); Vulnerary (f; KAB).

INDICATIONS (Phyllanthus) — (Duke, J. A et al., 2002 )
Description: Cara Membuat Ramuan Daun MeniranAcne (f; JFM); Alcoholism (1; KEB); Ameba (1; ZUL); Amenorrhea f; 60P); Anorexia (f; DAV); Ascites (f; PH2); Bacteria (1; HH2; TRA; WOI; ZUL); Biliousness (f; JFM); Blackhead (f; JFM); Blennorrhagia (f; DAV); Calculus (f; JFM); Cancer (1; JLH; KAB; MPI); Cancer, abdomen (f; JLH); Cancer, colon (f; JLH); Colic (f; DAV; JFM; PH2; WOI); Conjunctivosis (f; HH3); Constipation (f; DAV; KAB; KAP; PH2); Cramp (1; DAV; KAB; MPI; PH2; TRA); Debility (f; HH3); Dermatosis (f; JFM; KAP); Diabetes (f; DAV; JFM; KAB; KEB; MPI; PH2); Diarrhea (f; PH2; WOI); Dropsy (f; DAV; MPI; SKJ); Dysentery (f; DAV; MPI; PH2; SKJ); Dyspepsia (f; MPI; WOI); Dysuria (f; JFM; KAP); Edema (f; JFM; KAP; MPI; SKJ); Enterosis (f; JFM; JLH); Escherichia (1; HH3); Fever (1; DAV; HHB; KAB; MPI; PH2; SKJ;
TRA); Flu (f; DAV); Fungus (1; MPI; ZUL); Gallstone (f; HH3); Gastrosis (f; HHB; JFM; PH2); Gonorrhea (f; HH3; MPI; SKJ); Gout (f; JFM); Gravel (f; JFM; 60P); Hepatosis (2; KEB; MPI; SKY); Herpes (1; HH3); High Cholesterol (1; 60P); HIV (1; ABS); Hyperglycemia (1; DAV; KAB; KEB; MPI; TRA); Hyperuricemia (f; JFM); Infection (1; MPI; PH2; ZUL); Infertility (f; PH2); Insomnia (f; 60P); Itch (f; DAV; KAP); Jaundice (2; DEP; HHB; HH3; KEB; MPI; SKY); Leukemia (1; KAB; MPI); Malaria (f; DAV; DEP; KAB; HH3; PH2); Menorrhagia (f; KAP; MPI); Mycosis (1; MPI; ZUL); Nephrosis (f; DAV; JFM); Nervousness (f; 60P); Ophthalmia (f; KAP; MPI; PH2; WOI); Ovary (f; JFM); Pain (f; DAV); Parasite (1; ZUL); Prostatosis (f; DAV); Prolapse (f; JFM); Pulmonosis (f; 60P); Ringworm (1; ZUL); Scabies (1; DEP; KAB; PH2; ZUL); Snakebite (f; HH3); Sore (f; DEP; MPI; PH2; WOI); Staphylococcus (1; HH3; 60P); Stomachache (f; DAV); Stone (f; HH3); Swelling (f; KAB; MPI; SKJ); Tachycardia (f; PH2); Tenesmus (f; DAV); Tumor (f; JLH); Ulcer (f; JFM; SKJ; 60P); Urogenitosis (f; DEP; KAB; MPI; PH2); UTI (f; SKJ); Vaginosis (f; DAV); VD (f; KAB; HH3); Virus (1; HH3; KAB; KEB; PH2; SKY; TRA); Womb (f; JFM); Worm (1; DAV; ZUL); Wound (f; PH2).

DOSAGES (Phyllanthus) — (Duke, J. A et al., 2002 )
900–2700 mg plant powder/day/3 months (SKY); 10 plants/liter water (PH2); 3–6 g powdered herb (KAP);
14–28 ml tea (KAP); 2–6 ml extract (1:2) (KEB).

DOSAGES (Duke, J. A et al., 2009 )
FNFF = X.
Not considered a food. 3–6 g powdered herb (KAP); 14–28 ml tea (KAP);  900–2,700 mg plant powder/day for 3 mos (SKY); 10 plants/l water (PH2); 1–3 cups weekly for prevention, 3–4 cups/day to expel stones (RAI);  2–3 g capsule/tablet 2×/day (RAI); 2–6 ml extract (1:2) (KEB).
v  Amazonians use for alopecia, amenorrhea, cancer, colic, colitis, constipation, • diabetes, dysentery, dyspepsia, edema, enterosis, fever, flu, gallstones, gas, gonorrhea, itch, jaundice, kidney stones, malaria, nephrosis, oliguria, pain, proctosis, spasms, stomachache, vaginitis, and worms (DAV; RAI; SAR).
v  Ayurevdics use for menorrhagia and oliguria (KAB).
v  Bahamans use for bacterial infection, cold, constipation, fever, flu, and high blood sugar (RAI). \
v  Brazilians use for albuminuria, arthrosis, biliousness, bladder • stones, cancer, catarrh, cholecocystosis, colic, cystosis, diabetes, dyspepsia, dysuria, edema, enterosis, fever, flu, gallstones, gas, gastrosis, gonorrhea, gout, hepatosis, high blood pressure, hyperuricemia, inflammation, jaundice, kidney stones, malaria, nephrosis, obesity, oliguria, pain, proctosis, prostatitis, spasms, stomachache, and uterosis, (MPB; RAI).
v  Cubans use P. niruri for biliousness, diabetes, dysentery, fever, malaria, and oliguria (AUS).
v  Haitians use for colic, colitis, dyspepsia, enterosis, fever, flu, gas, malaria, spasm, stomachache, and oliguria (RAI).
v  Nepalese apply leaf juice to cuts, inflammation, pimples, swelling, and wounds (NPM).
v  Puerto Ricans use tincture as diuretic tonic in malaria with splenic and hepatic ails (KAB).
v  Yunani use plant for dysentery, gastrosis, and sores, the fruits for bruises, ringworm, scabies, and tubercular sores (KAB).

STONE LEAF INGREDIENTS FOR SKIN AND FACE (Jamuin. Com. 2017)
This is the benefits and ways to make meniran leaf concoctions for the face and diseases in the body. Generally used as herbal ingredients are all parts of the plant, including roots and leaves. Fresh plants are usually aerated in the shade before drying. Meniran plant concoction is usually in the form of a decoction that feels bitter, rather sour and cool. Bitter taste due to the content of Filantin, hypophilantin, and potassium salt.
According to Sri Yuliani and Hernani from Balitro (Research Institute for Spices and Medicines), Ministry of Health Republic of Indonesia 1985, herbs and benefits of meniran leaves are efficacious as menstrual decay, phlegm decay or as a cough medicine, urine decay and appetite enhancer. This plant contains alkaloids, saponins, glycosides, flavonoids, tannins, and other medicinal compounds. Other researchers also mentioned that meniran contained phylanthin, hypfilantin, potassium, and tannin compounds.
In China, this plant is known as Zhen Zhu Cao. Benefits of meniran leaf herbs are used to cure inflammation of the kidneys, urinary tract infections, menstrual decay, cure dysentery, increase appetite of children, phlegm decay, herbal medicines for diabetes mellitus and mouth ulcers.
Tannin compounds are very influential as antidiarrheal drugs, potassium is a diuretic and kidney stone decay. The following is a simple herbal concoction to cure several diseases:
1. Treatment of festering wounds, including pimples or inflammation of the facial skin. Festerous wounds are usually accompanied by symptoms of fever and heat, the skin around the wound swells, when the wound is pressed will produce pus.
o    Take half a handful of meniran leaves and grind until smooth.
o    After that stir with salt water as much as one tablespoon.
o    Put this paste on a festering wound or pimple.
o    For festering wounds must be bandaged so that the paste does not come off.
o    This paste is used twice a day. Treatment of other skin diseases by pulverizing the leaves of meniran, then put on the affected skin.
2. Relieve urination, dieuretics, and gout.
o    Take 4 to 5 branches of meniran leaves. Plus the leaves of Mustache Cat (Orthosiphon Grandiflora) with the same dose.
o    Boil both of them into water as much as 220 ml to 110 ml.
o    This herbal concoction is taken 2 times a day.
3. Treatment of gastric inflammation by boiling meniran leaves by three quarters of a handful.
o    Boil in three cups of water to make three quarters.
o    Strain and drink the concoction water mixed with pure honey, measuring three quarters of a glass for one drink, do it three times a day.
4. Treatment of malaria, take half a handful of meniran leaves and boil in 3 cups of water until it becomes one and a half cups. This herb is taken half a glass, 3 times a day.
5. Treatment of gonorrhea.
o    Take three-quarters of a handful of meniran leaves, boil in water as much as four cups to make three quarters.
o   This mixture is filtered, and mixed with a little sugar before drinking three times a day.

DOWNSIDES (Duke, J. A et al., 2009)
Not covered (AHP; KOM; PNC). “No health hazards or side effects are known in conjunction with the proper administration of designated therapeutic dosages” (PH2). None reported (SKY). Taylor (2005), reflecting on reports of abortifacient and antifertility effects, cautions against use during pregnancy and advises cardiac and diabetic patients to consult their practitioner before taking. Phyllanthus amarus potentially toxic (X16317655). As of July 2007, the FDA Poisonous Plant Database listed seven titles alluding to toxicity of this species.

EXTRACTS (Duke, J. A et al., 2009)
Alcoholic extracts bactericidal to Escherichia coli and Micrococcus pyogenes (WOI). Protein fraction of P. niruri hepatoprotective against oxidative stress in mice (X16718736). Lignans hepatoprotective in vitro (KEB). Of three lignans (phyllanthin, hypophyllanthin, and phyltetralin) phyllanthin proved hypouricemic, comparable to allopurinol, benzbromarone, and probenecid (X16953466). Aqueous extracts (with repandusinic acid A) inhibit HIV reverse transcriptase in vitro. Aqueous extracts comparable to tolbutamide as oral hypoglycemic (ZUL). LD50 dry aqueous whole plant extract 3,300 mg/kg ipr mus (HH3). Methyl brevifolincarboxylate, from the leaves of P. niruri, exhibited vasorelaxant effect on rat aortic rings (X16394535). Arabinogalactan from aqueous plant extracts stimulated superoxide anion production in peritoneal macrophages of mice without interfering with the nitric oxide pathway (X16252911). “P. niruri has been widely used against jaundice in Indian traditional medicine. Various classes of chemical constituents, such as lignans, flavonoids, triterpenoids, tannins, and alkaloids, were isolated from this plant. Its aqueous extract has been reported to inhibit DNA polymerase of hepatitis B and woodchuck hepatitis viruses, the avian myeloblastosis virus reverse transcriptase (AMV-RT), and human immunodeficiency virus type-1 reverse transcriptase (HIV-1-RT)” (X8991954). That’s over my head too but means that the tea contains chemicals that might prove useful at taming several viruses, even the HIV virus.

CONTRAINDICATIONS, INTERACTIONS, AND SIDE EFFECTS (Duke, J. A et al., 2002)
Not covered (AHP; KOM; PNC). “Hazards and/or side effects not known for proper therapeutic dosages” (PH2). None reported (SKY).

EXTRACTS (Duke, J. A et al., 2002)
Alcoholic extracts bactericidal to Escherichia coli and Micrococcus pyogenes (WOI). Lignans are hepatoprotective in vitro (KEB). Aqueous extracts (with repandusinic acid A) inhibit HIV-RT in vitro. Aqueous extracts are comparable to tolbutamide as oral hypoglycemic (ZUL). LD50 dry aqueous whole plant extract 3300 mg/kg ipr mouse (HH3). (Duke, J. A et al., 2002)


REFERENCE

Danladi S*, Idris MA, Umar II. 2018. Review on pharmacological activities and phytochemical constituents of Phyllanthus niruri (Amarus). The Journal of Phytopharmacology 2018; 7(3): 341-348 Online at: www.phytopharmajournal.com  ISSN 2320-480X JPHYTO 2018; 7(3): 341-348 May- June Received: 09-03-2018 Accepted: 26-04-2018 © 2018, All rights reserved
Duke, J. A. with Mary Jo Bogenschutz-Godwin, Judi duCellier, Peggy-Ann K. Duke. 2002.  Handbook of Medicinal Herbs 2nd Ed. CRC Press LLC. USA.
Duke, J.A., Godwin,M.J.B., Ottesen, A.R. 2009. Duke's Handbook of Medicinal Plants of Latin America. CRC Press Taylor & Francis Group.
Handayani, V and Nurfadillah. PHARMACOGNOSTIC STUDY OF GREEN MENIRAN (Phyllanthus niruri L.) and RED MENIRAN HERBA (Phyllanthus urinaria L.) Indonesian Journal of Fitofarmaka, Vol 1 No.1; virsaichafarmasi@yahoo.com 1) Faculty of Pharmacy, Indonesian Muslim University Makassar
Jamuin 2017. How to Make Meniran Leaf Remedy for Skin and Face. JAMUIN Pustaka Herba, Indonesian Herbal Medicine. JAMUIN Herbal Library, Indonesian Herbs https://www.jamuin.com/2017/04/how-making-food-dream-meniran-for.html. Entertaining 4/09/2017
Krishnamurthy, K. H.  2014. Bhūmī āmalakī, Phyllanthus. Medicinal plants THE JOURNAL OF INTEGRAL HEALTH NAMAH Journal ; Volume 22 Issue 3 15th October 2014.
Paithankar V. V., Raut K. S., Charde R. M., Vyas J. V. Vidyabharati  2011. Review Article Phyllanthus Niruri: A magic Herb.  Research in Pharmacy 1(4) : 1-9, 2011 ISSN : 2231-539X www.researchinpharmacy.com 2011.  college of Pharmacy, Amravati Email.ID : vivekp62@gmail.com  Paithankar et al. / Research in Pharmacy 1(4) : 1-9, 2011
Ross, I. A. 2004. Medicinal Plants of the World Vol. 1. Chemical Constituents, Traditional and Modern Medical Uses. Human Press. Totowa, New Jersey.



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