1. Antihepatotoxic actions of Formosan plant drugs.

Yang LL, Yen KY, Kiso Y, Hikino H.

2. Effects of an aqueous extract from Phyllantus niruri on calcium oxalate crystallization in vitro.

Barros ME, Schor N, Boim MA.

Urol Res. 2003 Feb;30(6):374-9. Epub 2003 Jan 21. Nephrology Division, Escola Paulista de Medicina, Universidade Federal de Sao Paulo, Sao Paulo, Brazil.

Ann Trop Med Parasitol. 2001 Jan;95(1):47-57.

3. In-vivo antimalarial activity of Cassia occidentalis, Morinda morindoides and Phyllanthus niruri.

Tona L, Mesia K, Ngimbi NP, Chrimwami B, Okond’ahoka, Cimanga K, de Bruyne T, Apers S, Hermans N, Totte J, Pieters L, Vlietinck AJ.

Faculty of Pharmacy, University of Kinshasa, B.P. 212, Kinshasa XI, Democratic Republic of Congo.

Urol Res. 2003 Feb;30(6):374-9. Epub 2003 Jan 21.

4. Effects of an aqueous extract from Phyllantus niruri on calcium oxalate crystallization in vitro.

Barros ME, Schor N, Boim MA.

Nephrology Division, Escola Paulista de Medicina, Universidade Federal de Sao Paulo, Sao Paulo, Brazil.

J Ethnopharmacol. 1987 Jan-Feb;19(1):103-10

5. Antispasmodic effects of an alkaloid extracted from Phyllanthus sellowianus: a comparative study with papaverine.

Calixto JB; Yunes RA; Neto AS; Valle RM; Rae GA

Braz J Med Biol Res, 17: 3-4, 1984, 313-21

6. Isolation and structure (X-ray analysis) of ent-norsecurinine, an alkaloid from Phyllanthus niruri.

Joshi BS; Gawad DH; Pelletier SW; Kartha G; Bhandary K

J Nat Prod, 49: 4, 1986 Jul-Aug, 614-20

7. Antihepatotoxic principles of Phyllanthus niruri herbs.

Syamasundar KV; Singh B; Thakur RS; Husain A; Kiso Y; Hikino H

J Ethnopharmacol, 14: 1, 1985 Sep, 41-4

8. Effects of an extract from Phyllanthus niruri on hepatitis B and woodchuck hepatitis viruses: in vitro and in vivo studies.

Venkateswaran PS; Millman I; Blumberg BS

Proc Natl Acad Sci U S A, 84: 1, 1987 Jan, 274-8

9. Studies on aldose reductase inhibitors from natural products. II. Active components of a Paraguayan crude drug “Para-parai míí,” Phyllanthus niruri.

Shimizu M; Horie S; Terashima S; Ueno H; Hayashi T; Arisawa M; Suzuki S; Yoshizaki M; Morita N

Chem Pharm Bull (Tokyo), 37: 9, 1989 Sep, 2531-2

10. In vitro studies on the effect of certain natural products against hepatitis B virus.

Mehrotra R; Rawat S; Kulshreshtha DK; Patnaik GK; Dhawan BN

ICMR Advance Centre for Pharmacological Research on Traditional Remedies, Central Drug Research Institute, Lucknow.

Indian J Med Res, 92:1990 Apr, 133-8

11. HIV-1 reverse transcriptase inhibitor from Phyllanthus niruri.

Ogata T; Higuchi H; Mochida S; Matsumoto H; Kato A; Endo T; Kaji A; Kaji H
Research Institute for Molecular Genetics, Tsumura & Co., Ibaraki-Ken, Japan.

AIDS Res Hum Retroviruses, 8: 11, 1992 Nov, 1937-44

12. Analgesic effects of callus culture extracts from selected species of Phyllanthus in mice.

Santos AR; Filho VC; Niero R; Viana AM; Moreno FN; Campos MM; Yunes RA; Calixto JB

Department of Pharmacology, Universidade Federal de Santa Catarina, Florianóópolis, Brazil.

J Pharm Pharmacol, 46: 9, 1994 Sep, 755-9

13. [Efficacy of Phyllanthus spp. in treating patients with chronic hepatitis B]

Wang MX; Cheng HW; Li YJ; Meng LM; Mai K

Henan Institute of Medical Sciences, Zhengzhou.

Chung Kuo Chung Yao Tsa Chih, 19: 12, 1994 Dec, 750-1, 764

14. Herbs of the genus Phyllanthus in the treatment of chronic hepatitis B: observations with three preparations from different geographic sites.

Wang M; Cheng H; Li Y; Meng L; Zhao G; Mai K

Henan Institute of Medical Sciences, Henan Medical University, People’s Republic of China.

J Lab Clin Med, 126: 4, 1995 Oct, 350-2

1. Antihepatotoxic actions of Formosan plant drugs.

Yang LL, Yen KY, Kiso Y, Hikino H.

One hundred twenty-nine samples of Formosan plants were screened for antihepatotoxic activity in primary cultured hepatocytes to reveal that 19 and 26 plants exhibited more than 50% inhibition against cytotoxicity produced by carbon tetrachloride and D-galactosamine, respectively. Plants which disclosed significant antihepatotoxic activity in both assay methods are: Wedelia chinense, Mallotus repandus, Phyllantus urinaria, Loranthus parasiticus, Ludwigia octovalvis, Onychium japonicum, Tamarix chinensis and Ampelopsis brevipedunculata.

2. Effects of an aqueous extract from Phyllantus niruri on calcium oxalate crystallization in vitro.

Barros ME, Schor N, Boim MA.

Urol Res. 2003 Feb;30(6):374-9. Epub 2003 Jan 21. Nephrology Division, Escola Paulista de Medicina, Universidade Federal de Sao Paulo, Sao Paulo, Brazil.

Ann Trop Med Parasitol. 2001 Jan;95(1):47-57.

Phyllanthus niruri is a plant used in Brazilian folk medicine for the treatment of urolithiasis. It was previously observed that P. niruri shows no toxicity, potentially increases calculus voiding by stone forming patients and inhibits the endocytosis of calcium oxalate (CaOx) crystals by MDCK cells. In addition, in a rat model of urolithiasis it reduced calculus growth. In the present study, we evaluated the effect of an aqueous extract of P. niruri on CaOx crystallization in vitro. CaOx precipitation was induced by the addition of 0.1 M sodium oxalate to unfiltered urine samples from Wistar rats ( n=14) and normal humans ( n=18) in the presence or absence of P. niruri extract (0.25 mg/ml of urine). The presence of CaOx crystals was evaluated immediately and 24 h later. In vitro crystallization of human urine produced typical mono- and dihydrated CaOx crystals, but only a few typical CaOx crystals were found in rat urine. The presence of P. niruri extract did not inhibit CaOx precipitation and even more crystals were obtained, although they were significantly smaller than those in the control urine. Crystal aggregation observed 24 h after crystallization was also inhibited by P. niruri extract. The results showed an inhibitory effect of P. niruri extract on CaOx crystal growth and aggregation in human urine, suggesting that it may interfere with the early stages of stone formation and may represent an alternative form of treatment and/or prevention of urolithiasis

Phylanthus ‘Chanca Piedra’

3. In-vivo antimalarial activity of Cassia occidentalis, Morinda morindoides and Phyllanthus niruri.

Tona L, Mesia K, Ngimbi NP, Chrimwami B, Okond’ahoka, Cimanga K, de Bruyne T, Apers S, Hermans N, Totte J, Pieters L, Vlietinck AJ.

Faculty of Pharmacy, University of Kinshasa, B.P. 212, Kinshasa XI, Democratic Republic of Congo.

Urol Res. 2003 Feb;30(6):374-9. Epub 2003 Jan 21.

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 actvity 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 Ph. niruri whole plant, and of 30% for M. morindoides leaves) when administered orally. The most active ethanolic extract, that of Ph. niruri, reduced parasitaemia by 73%. The dichloromethane extracts of M. morindoides and Ph. 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.

PMID: 11235553 [PubMed - indexed for MEDLINE]

4. Effects of an aqueous extract from Phyllantus niruri on calcium oxalate crystallization in vitro.

Barros ME, Schor N, Boim MA.

Nephrology Division, Escola Paulista de Medicina, Universidade Federal de Sao Paulo, Sao Paulo, Brazil.

J Ethnopharmacol. 1987 Jan-Feb;19(1):103-10

Phyllanthus niruri is a plant used in Brazilian folk medicine for the treatment of urolithiasis. It was previously observed that P. niruri shows no toxicity, potentially increases calculus voiding by stone forming patients and inhibits the endocytosis of calcium oxalate (CaOx) crystals by MDCK cells. In addition, in a rat model of urolithiasis it reduced calculus growth. In the present study, we evaluated the effect of an aqueous extract of P. niruri on CaOx crystallization in vitro. CaOx precipitation was induced by the addition of 0.1 M sodium oxalate to unfiltered urine samples from Wistar rats ( n=14) and normal humans ( n=18) in the presence or absence of P. niruri extract (0.25 mg/ml of urine). The presence of CaOx crystals was evaluated immediately and 24 h later. In vitro crystallization of human urine produced typical mono- and dihydrated CaOx crystals, but only a few typical CaOx crystals were found in rat urine. The presence of P. niruri extract did not inhibit CaOx precipitation and even more crystals were obtained, although they were significantly smaller than those in the control urine. Crystal aggregation observed 24 h after crystallization was also inhibited by P. niruri extract. The results showed an inhibitory effect of P. niruri extract on CaOx crystal growth and aggregation in human urine, suggesting that it may interfere with the early stages of stone formation and may represent an alternative form of treatment and/or prevention of urolithiasis

5. Antispasmodic effects of an alkaloid extracted from Phyllanthus sellowianus: a comparative study with papaverine.

Calixto JB; Yunes RA; Neto AS; Valle RM; Rae GA

Braz J Med Biol Res, 17: 3-4, 1984, 313-21

Infusions of Phyllanthus sellowianus or P. niruri (Euphorbiaceae) are a popular remedy in Brazil for kidney and bladder stones. This study describes the isolation of an alkaloid from P. sellowianus, denoted ALK-1, and compares its antipasmodic activity with that of papaverine on isolated strips of guinea pig ileum and rat uterus, and rat aorta rings. ALK-1 and papaverine promoted a dose-dependent flattening of the dose-response curves obtained to acetylcholine and histamine on ileum strips and of the dose-response curves to acetylcholine and oxytocin on uterine strips. A non-competitive antagonism of noradrenaline-induced contractions by the P. sellowianus alkaloid was also demonstrated on aortic rings. Whereas the antispasmodic potency (pD’2 values) of papaverine did not depend on the muscle preparation and agonist used, ALK-1 exhibited a greater potency on the ileum strips than on the uterine or aortic preparations. Because of this selective antispasmodic action on the ileum, ALK-1 was equipotent to papaverine on this tissue, but was about 10-fold less potent than papaverine on uterine smooth-muscle. The dose-response curves to CaCl2 obtained for potassium-depolarized uterine strips were shifted to the right by both antispasmodics. Similar pA2 values with slopes not differing from unity -1.0 were obtained from Schild plots of the data, suggesting that competitive antagonism of calcium entry into the cell is a mechanism of action common to both alkaloids. The presence of at least one potent antispasmodic alkaloid in P. sellowianus justifies the popular use of infusions of this plant. Smooth muscle relaxation within the urinary or biliary tract probably facilitates the expulsion of kidney or bladder.

6. Isolation and structure (X-ray analysis) of ent-norsecurinine, an alkaloid from Phyllanthus niruri.

Joshi BS; Gawad DH; Pelletier SW; Kartha G; Bhandary K

J Nat Prod, 49: 4, 1986 Jul-Aug, 614-20

The isolation and structure determination of the alkaloid ent-norsecurinine (4) from Phyllanthus niruri L. is described. The structure and absolute stereochemistry have been confirmed by an X-ray analysis of ent-norsecurinine hydrochloride.

7. Antihepatotoxic principles of Phyllanthus niruri herbs.

Syamasundar KV; Singh B; Thakur RS; Husain A; Kiso Y; Hikino H

J Ethnopharmacol, 14: 1, 1985 Sep, 41-4

Among phyllanthin, hypophyllanthin, triacontanal and tricontanol isolated from a hexane extract of Phyllanthus niruri, phyllanthin and hypophyllanthin protected against carbon tetrachloride- and galactosamine-induced cytotoxicity in primary cultured rat hepatocytes, while triacontanal was protective only against galactosamine-induced toxicity.

8. Effects of an extract from Phyllanthus niruri on hepatitis B and woodchuck hepatitis viruses: in vitro and in vivo studies.

Venkateswaran PS; Millman I; Blumberg BS

Proc Natl Acad Sci U S A, 84: 1, 1987 Jan, 274-8

An aqueous extract of the plant 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 (WHV) DNA polymerase and binds to the surface antigen of WHV in vitro. The extract, nontoxic to mice, was tested for antiviral activity in woodchucks (Marmota monax). In a trial using six long-term WHV-carrier woodchucks, five treated animals showed a faster decrease in woodchuck hepatitis virus surface antigen titer compared to one untreated control. In animals recently infected with WHV, the extract was effective when administered i.p. in three out of four animals in reducing and within 3-6 weeks eliminating both the surface antigen titer and DNA polymerase activity in serum. The treatment was discontinued after 10 weeks, and the treated animals have remained free of detectable markers of WHV for more than 45 weeks. In contrast, three untreated controls remained positive for both markers for WHV. One of the controls died after 8 weeks; the other two controls have remained positive for WHV markers for more than 45 weeks. In a third trial with long-term carriers, test animals treated subcutaneously with the extract for 12 weeks did not respond; but on switching the mode of administration to i.p., two out of the five animals showed a significant decrease in woodchuck hepatitis virus surface antigen titer compared to controls.

9. Studies on aldose reductase inhibitors from natural products. II. Active components of a Paraguayan crude drug “Para-parai míí,” Phyllanthus niruri.

Shimizu M; Horie S; Terashima S; Ueno H; Hayashi T; Arisawa M; Suzuki S; Yoshizaki M; Morita N

Chem Pharm Bull (Tokyo), 37: 9, 1989 Sep, 2531-2

Aldose reductase (AR) inhibitory activity-directed fractionation of the 70% ethanolic extract of Para-parai míí, Phyllanthus niruri, has led to the isolation of three active components, ellagic acid (1), brevifolin carboxylic acid (4) and ethyl brevifolin carboxylate (5). Among them, 1 showed the highest inhibitory activity, being about 6 times more potent than quercitrin, which is a known natural inhibitor of AR.

10. In vitro studies on the effect of certain natural products against hepatitis B virus.

Mehrotra R; Rawat S; Kulshreshtha DK; Patnaik GK; Dhawan BN

ICMR Advance Centre for Pharmacological Research on Traditional Remedies, Central Drug Research Institute, Lucknow.

Indian J Med Res, 92:1990 Apr, 133-8

Picroliv (active principle from Picrorrhiza kurroa), its major components picroside I, catalpol, kutkoside I, kutkoside, andrographolide (active constituent of Andrographis paniculata), silymarin and Phyllanthus niruri extract were tested for the presence of anti hepatitis B virus surface antigen (anti HBs) like activity. HBsAg positive serum samples obtained from hepatitis B virus (HBV) associated acute and chronic liver diseases and healthy HBsAg carriers were used to evaluate the anti-HBs like activity of compounds/extract. The latter were mixed with serum samples and incubated at 37 degrees C overnight followed by HBsAg screening in the Elisa system. A promising anti-HBsAg like activity was noted in picroliv (and its major components) catalpol, P. niruri which differed from the classical viral neutralization. Picroliv also inhibited purified HBV antigens (HBsAg and HBsAg) prepared from healthy HBsAg carriers. The in vitro testing system appears to be a suitable model to identify an agent active against HBV, prior to undertaking detailed studies.

11. HIV-1 reverse transcriptase inhibitor from Phyllanthus niruri.

Ogata T; Higuchi H; Mochida S; Matsumoto H; Kato A; Endo T; Kaji A; Kaji H

Research Institute for Molecular Genetics, Tsumura & Co., Ibaraki-Ken, Japan.

AIDS Res Hum Retroviruses, 8: 11, 1992 Nov, 1937-44

An aqueous extract of Phyllanthus niruri (Euphorbiaceae) inhibited human immunodeficiency virus type-1 reverse transcriptase (HIV-1-RT). The inhibitor against HIV-1-RT in this plant was purified by combination of three column chromatographies, Sephadex LH-20, cellulose, and reverse-phase high-performance liquid chromatography. The inhibitor was then identified by nuclear magnetic resonance (NMR) spectra as repandusinic acid A monosodium salt (RA) which was originally isolated from Mallotus repandus. The 50% inhibitory doses (ID50) of RA on HIV-1-RT and DNA polymerase alpha (from HeLa cells) were 0.05 microM and 0.6 microM, respectively, representing approximately a 10-fold more sensitivity of HIV-1-RT compared with DNA polymerase alpha. RA was shown to be a competitive inhibitor with respect to the template-primer while it was a noncompetitive inhibitor with respect to the substrate. RA as low as 10.1 microM inhibited HIV-1-induced cytopathogenicity in MT-4 cells. In addition, 4.5 microM of RA inhibited HIV-1-induced giant cell formation of SUP-T1 approximately 50%. RA (2.5 microM) inhibited up to 90% of HIV-1 specific p24 antigen production in a Clone H9 cell system.

12. Analgesic effects of callus culture extracts from selected species of Phyllanthus in mice.

Santos AR; Filho VC; Niero R; Viana AM; Moreno FN; Campos MM; Yunes RA; Calixto JB

Department of Pharmacology, Universidade Federal de Santa Catarina, Florianóópolis, Brazil.

J Pharm Pharmacol, 46: 9, 1994 Sep, 755-9

The aim of this study was to evaluate the analgesic effect of the methanolic extract from callus culture of Phyllanthus tenellus, P. corcovadensis and P. niruri in several models of pain in mice. The extracts (medium containing 2,4-dichlorophenoxyacetic acid) of P. corcovadensis, P. niruri and P. tenellus (3-90 mg kg-1, i.p.) caused graded inhibition of abdominal constrictions induced by acetic acid (0.6%), with ID50 (i.e. dose that reduced response of control by 50%) values of about 30, 19 and > 30 mg kg-1, respectively. The extract of callus of Phyllanthus obtained in indole-3-butyric acid and indole-3-acetic acid media (3-90 mg kg-1, i.p.) caused a similar analgesic effect. In the formalin test, the extract of P. tenellus obtained in indole butyric acid medium (3-100 mg kg-1, i.p.) inhibited only the second phase of formalin-induced pain with an ID50 value of about 100 mg kg-1. Both the indole acetic acid and indole butyric acid methanolic extracts of P. tenellus and P. corcovadensis (10-100 mg kg-1, i.p.) dose-dependently inhibited both phases of formalin-induced pain (ID50 values for the second phase were approx. 100 and 52 mg kg-1, respectively). However, the extract of callus from Phyllanthus failed to affect formalin-induced paw oedema, as well as the response to radiant heat in the tail-flick test. In addition, the analgesic effect of morphine, but not the analgesic effects caused by Phyllanthus callus extract, was fully antagonized by naloxone.(ABSTRACT TRUNCATED AT 250 WORDS)

13. [Efficacy of Phyllanthus spp. in treating patients with chronic hepatitis B]

Wang MX; Cheng HW; Li YJ; Meng LM; Mai K

Henan Institute of Medical Sciences, Zhengzhou.

Chung Kuo Chung Yao Tsa Chih, 19: 12, 1994 Dec, 750-1, 764

The efficacy of Phyllanthus amarus produced in india, P. niruri gathered from hainan province and P. urinaria from henan province was assessed in a total of 88 cases of chronic hepatitis B with 11.42 and 35 each. It was shown that P. urinaria had the effect of seroconversion on HBeAg from positive to negative as well as on HBeAb from negative to positive, while the other two herbs had not. In addition none of these three herbs had similar effect on HBsAg.

14. Herbs of the genus Phyllanthus in the treatment of chronic hepatitis B: observations with three preparations from different geographic sites.

Wang M; Cheng H; Li Y; Meng L; Zhao G; Mai K

Henan Institute of Medical Sciences, Henan Medical University, People’s Republic of China.

J Lab Clin Med, 126: 4, 1995 Oct, 350-2

It has been suggested that herbs of the Phyllanthus family may have antiviral activity. We therefore tested the effects of three different Phyllanthus extracts on the serologic status of 123 patients with chronic hepatitis B. Eleven patients received an extract of Phyllanthus amarus (L) provided by S.P. Thyagarajan, Madras, India. Forty-two patients received Phyllanthus niruri (L), gathered from Hainan Province in China, and 35 patients received an extract of Phyllanthus urinaria (L), which had been gathered in Henan Province. Thirty-five control patients received no herbal therapy. The patients receiving Phyllanthus urinaria (L) were both more likely to lose detectable hepatitis B e-antigen from their serum and more likely to seroconvert hepatitis B e-antibody status from negative to positive than were patients given either of the other two preparations. No patient changed status with respect to hepatitis B s-antigen.

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