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PubMed2006

Can Phyllanthus niruri affect the efficacy of extracorporeal shock wave lithotripsy for renal stones? A randomized, prospective, long-term study.

PURPOSE: Phyllanthus niruri is a plant used in Brazilian folk medicine for the treatment of urolithiasis. We assessed the efficacy of P. niruri after extracorporeal shock wave lithotripsy for renal stones. MATERIALS AND METHODS: We prospectively evaluated 150 patients with renal stones that were as large as 25 mm and composed of calcium oxalate. All patients received 1 to 3 extracorporeal shock wave lithotripsy sessions by Dornier Lithotriptor S. After treatment 78 of 150 patients (52%) underwent therapy with Uriston, a P. niruri extract (2 gm daily) for at least 3 months (group 1). Otherwise 72 of 150 patients (48%) were used as a control group (group 2). No significant difference in stone size between the 2 groups was found. Stone clearance was assessed after 30, 60, 90 and 180 days by abdominal x-ray and ultrasound scan. RESULTS: Stone-free rate (stone-free defined as the absence of any stone or residual fragments less than 3 mm) was 93.5% in group 1 and 83.3% in group 2 (p = 0.48) at the end point of the followup (180 days). For lower caliceal stones (56 patients) the stone-free rate was 93.7% in the treatment group and 70.8% in the control group (p = 0.01). Re-treatment need for group 1 was 39.7% and for group 2 it was 43.3% (p = 0.2). No side effects were recorded with extracorporeal shock wave lithotripsy or P. niruri therapy. CONCLUSIONS: Regular self-administration of P. niruri after extracorporeal shock wave lithotripsy for renal stones results in an increased stone-free rate that appears statistically significant for lower caliceal location. Its efficacy and the absolute lack of side effects make this therapy suitable to improve overall outcomes after extracorporeal shock wave lithotripsy for lower pole stones.

Adult↗
PubMed2004

Phyllanthus urinaria induces the Fas receptor/ligand expression and ceramide-mediated apoptosis in HL-60 cells.

Phyllanthus urinaria (P. urinaria), a widely used herb medicine, was tested for the anticancer effect on human myeloid leukemia cells in this study. The water extract of P. urinaria induced the apoptosis of HL-60 cells as demonstrated by morphological change, DNA fragmentation and increased caspase-3 activity. However, normal human peripheral mononuclear cells remained viable under the same treatment. The P. urinaria-induced apoptosis of HL-60 cells was associated with the increased Bax gene expression and decreased Bcl-2 gene expression. In addition, the gene expressions of Fas receptor and Fas ligand, but not p53, were also induced in HL-60 cells dose- and time-dependently. The inhibitor of ceramide synthase, fumonisin B1, completely suppressed the apoptosis induced by P. urinaria and this inhibitory effect of fumonisin B1 could be eliminated by the addition of ceramide. It indicated that the activity of ceramide synthase is critical for the P. urinaria-induced apoptosis in HL-60 cells. The P. urinaria-induced apoptosis in HL-60 cells is mediated through a ceramide-related pathway.

Antineoplastic Agents, Phytogenic↗
PubMed2005

Chemoprotective activity of an extract of Phyllanthus amarus against cyclophosphamide induced toxicity in mice.

The effect of 75% methanolic extract of the plant Phyllanthus amarus (P. amarus) was studied against cyclophosphamide (CTX) induced toxicity in mice. Administration of CTX (25 mg/kg b.wt, i.p.) for 14 days produced significant myelosuppression as seen from the decreased WBC count and bone marrow cellularity. Administration of P. amarus extract at doses 250 and 750 mg/kg b.wt significantly reduced the myelosuppression and improved the WBC count, bone marrow cellularity as well as the number of maturing monocytes. CTX treatment also reduced the activity of glutathione system and increased the activity of phase I enzyme that metabolize CTX to its toxic side products. P. amarus administration was found to decrease the activity of phase I enzyme. Administration of P. amarus also increased the cellular glutathione (GSH) and glutathione-S-transferase (GST), thereby decreasing the effect of toxic metabolites of CTX on the cells. Administration of P. amarus did not reduce the tumor reducing activity of CTX. In fact, there was a synergistic action of CTX and P. amarus in reducing the solid tumors in mice. Results indicated that administration of P. amarus can significantly reduce the toxic side effects of CTX and is not interfering with the antitumor efficiency of CTX.

Animals↗
PubMed2003

Phyllanthus urinaria triggers the apoptosis and Bcl-2 down-regulation in Lewis lung carcinoma cells.

Phyllanthus urinaria (P. urinaria), a widely used herb medicine, was tested for the anticancer effect in its water extract for the first time. The water extract of P. urinaria significantly decreased the number of Lewis lung carcinoma cells in a dose-and time-dependent manner as determined by MTT assay. However, the water extract of P. urinaria did not exert any cytotoxic effect on normal cells such as endothelial cells and liver cells. Result from flow cytometry revealed a dose-dependent increase of dead cells 24 hours after treating Lewis lung carcinoma cells with P. urinaria extract. The anticancer activity of P. urinaria extract was due to the apoptosis induced in Lewis lung carcinoma cells, which was demonstrated by DNA fragmentation analysis and increased caspase-3 activity. The apoptosis triggered by P. urinaria extract in Lewis lung carcinoma cells was associated with the down-regulation of Bcl-2 gene expression, but not with p53, p21 and Bax. Furthermore, the partial inhibition of P. urinaria-induced apoptosis in Lewis lung carcinoma cells by pretreatment with cyclosporin A, a mitochondria permeability transition pore inhibitor, suggesting that P. urinaria extract induced the apoptosis of Lewis lung carcinoma cells, at least in part, through a mitochondria-associated intrinsic pathway.

Animals↗
PubMed2003

Lignans from Phyllanthus urinaria.

Chemical investigation on the aerial and the root parts of Phyllanthus urinaria L. culminated in the isolation of four lignans, namely 5-demethoxyniranthin, urinatetralin, dextrobursehernin, urinaligran, together with nine known lignans. Their structures, including the absolute stereochemistry, were elucidated by spectral analysis (NMR and CD) and chemical correlation.

Circular Dichroism↗
PubMed2003

Phyllanthus amarus has anti-inflammatory potential by inhibition of iNOS, COX-2, and cytokines via the NF-kappaB pathway.

BACKGROUND/AIMS: Phyllanthus amarus is a herbal medicine traditionally applied in the treatment of viral hepatitis. Aim of this study was to investigate potential anti-inflammatory properties of standardized P. amarus extracts concerning a potential influence of P. amarus on endotoxin-induced nitric oxide synthase (iNOS), cyclooxygenase (COX-2), and cytokine production in vivo and in vitro. METHODS: Investigations were performed in rat Kupffer cells (KC), in RAW264.7 macrophages, in human whole blood, and in mice. Cells were stimulated with lipopolysaccharides (LPS) in the presence or absence of P. amarus extracts (hexane, EtOH/H(2)O), mice were treated with galactosamine/LPS as a model for acute toxic hepatitis. Nitrite was measured by Griess assay, prostaglandin E(2) (PGE(2)) by radioimmunoassay, and cytokines by enzyme-linked immunosorbent assay. iNOS and COX-2 were determined by Western blot, activation of NF-kappaB and AP-1 by EMSA. RESULTS: P. amarus EtOH/H(2)O and hexane extracts showed an inhibition of LPS-induced production of NO and PGE(2) in KC and in RAW264.7. The extracts also attenuated the LPS-induced secretion of tumor necrosis factor (TNF-alpha) in RAW264.7 as well as in human whole blood. Both extracts reduced expression of iNOS and COX-2 and inhibited activation of NF-kappaB, but not of AP-1. P. amarus inhibited induction of interleukin (IL)-1beta, IL-10, and interferon-gamma in human whole blood and reduced TNF-alpha production in vivo. CONCLUSIONS: This work shows that standardized extracts of P. amarus inhibit the induction of iNOS, COX-2, and TNF-alpha. Therefore, we report for the first time an anti-inflammatory potential of this traditionally employed herbal medicine both in vitro and in vivo.

Animals↗
PubMed2002

Antitumour and anticarcinogenic activity of Phyllanthus amarus extract.

Aqueous extract of Phyllanthus amarus (P. amarus) treatment exhibited potent anticarcinogenic activity against 20-methylcholanthrene (20-MC) induced sarcoma development and increased the survival of tumour harboring mice. The extract administration (p.o) was also found to prolong the life span of Dalton's Lymphoma Ascites (DLA) and Ehrlich Ascites Carcinoma (EAC) bearing mice and reduced the volume of transplanted solid tumours. The extract inhibited aniline hydroxylase, a P-450 enzyme. The concentration required for 50% inhibition (IC(50)) was found to be 540 microg/ml. The extract was found to inhibit DNA topoisomerase II of Saccharomyces cerevisiae mutant cell cultures and inhibited cell cycle regulatory enzyme cdc25 tyrosine phosphatase (IC(50-25) microg/ml). Antitumour and anticancer activity of P. amarus may be related with the inhibition of metabolic activation of carcinogen as well as the inhibition of cell cycle regulators and DNA repair.

Aniline Hydroxylase↗
PubMed2002

Lipid lowering activity of Phyllanthus niruri in hyperlipemic rats.

The lipid lowering activity (LLA) of Phyllanthus niruri has been studied in triton and cholesterol fed hyperlipemic rats. Serum lipids were lowered by P. niruri extract orally fed (250 mg/kg b.w.) to the triton WR-1339 induced hyperlipemic rats. Chronic feeding of this drugs (100 mg/kg b.w.) in animals simultaneously fed with cholesterol (25 mg/kg b.w.) for 30 days caused lowering in the lipids and apoprotein levels of VLDL and LDL in experimental animals. The LLA of this drug is mediated through inhibition of hepatic cholesterol biosynthesis, increased faecal bile acids excretion and enhanced plasma lecithin: cholesterol acyltransferase activity.

Administration, Oral↗
PubMed2002

Validation of a LC method for the analysis of phenolic compounds from aqueous extract of Phyllanthus niruri aerial parts.

A reversed-phase high-performance liquid chromatographic separation and quantitative method using a phosphoric acid-acetonitrile gradient was developed to analyze phenolic compounds present in aqueous extract from the aerial parts of Phyllanthus niruri. The chromatographic method was validated for linearity, precision and accuracy for both reference substance (gallic acid) and for three well resolved peaks from P. niruri aqueous extract. Both calibration curves were linear with correlation coefficients higher than 0.999. The reproducibility for the three peaks ranged from 2.3% to 4.6% and the accuracy for gallic acid in the aqueous extract was 103%. The method allowed the complete resolution of three peaks, one of them was identified by diode array detection as gallic acid. The analysis of the botanic morphological elements of the aerial parts from P. niruri showed that the leaves have a higher amount of phenolic compounds than the branches.

Chromatography, High Pressure Liquid↗
PubMed2002

Antimutagenic mechanisms of Phyllanthus orbicularis when hydrogen peroxide is tested using Salmonella assay.

Phyllanthus orbicularis is a medicinal plant, endemic to Cuba, whose aqueous extract has proven antiviral properties and antimutagenic activities against aromatic amines and hydrogen peroxide. In addition, this plant extract presents antioxidant activity. In this paper, using the Salmonella assay with the experimental approaches of co-incubation, pre- and post-treatments, it is shown that the P. orbicularis extract protects bacterial cells from oxidative damage and mutation by some intracellular mechanism, irrespective of its antioxidant activity.

Antimutagenic Agents↗
PubMed2001

Screening of triterpenoids isolated from Phyllanthus flexuosus for DNA topoisomerase inhibitory activity.

DNA topoisomerases (Topos) are enzymes that play a crucial role in DNA metabolism events such as replication, transcription, recombination, and chromosome segregation at mitosis. Thus, Topo inhibitors could be expected to have antitumor effects. Naturally occurring lupane- and oleanane-type triterpenoids isolated from the bark of Phyllanthus flexuosus were screened for human Topos I and II inhibitory activities. Olean-12-en-3 beta,15 alpha-diol (1), olean-12-en-3 beta,15 alpha,24-triol (3), lupeol (4), and betulin (6) were found to be selective catalytic inhibitors of human Topo II activity with IC(50) values in the range of 10-39 microM.

Antineoplastic Agents, Phytogenic↗
PubMed2005

Anti-babesial and anti-plasmodial compounds from Phyllanthus niruri.

Bioassay-guided fractionation of boiled aqueous extracts from the whole plant of Phyllanthus niruri led to the isolation of 1-O-galloyl-6-O-luteoyl-alpha-d-glucose (1), with IC(50) values of 4.7 microg/mL against Babesia gibsoni and 1.4 microg/mL against Plasmodium falciparum in vitro. The known compounds beta-glucogallin (2), quercetin 3-O-beta-d-glucopyranosyl-(2-->1)-O-beta-d-xylopyranoside (3), beta-sitosterol, and gallic acid were also isolated. Structures of these compounds were elucidated on the basis of their chemical and spectroscopic data.

Animals↗
PubMed2005

Xylans from the medicinal herb Phyllanthus niruri.

Phyllanthus niruri is a well-known medicinal herb that is widely used in Asia, Africa, and South America. The characterization of two purified polysaccharides from the whole plant has been investigated. Methylation analysis and (13)C NMR spectroscopy showed the chemical structure of two xylans. A hot 15% aqueous KOH fraction yielded a linear beta-(1-->4)-linked xylan, and 2% aqueous KOH afforded a complex acidic heteroxylan, with a (1-->4)-linked beta-Xylp main chain, substituted by rhamnose, arabinose, and 4-O-methylglucuronic acid side chains. These contained nonreducing end-units of arabinose, xylose, galactose, glucose, and nonmethylated glucuronic acid.

Brazil↗
PubMed2005

Bioactive constituents of the leaves of Phyllanthus polyphyllus var. siamensis.

A dichloromethane extract of the leaves of Phyllanthus polyphyllus var. siamensis afforded two new monoacetylated triterpene arabinosides (1 and 2) and 15 known compounds. The structures of the new compounds were elucidated on the basis of spectroscopic data interpretation. The isolates and some chemical transformation products were evaluated biologically, and the presence of an arabinosyl moiety among the hederagenin glycosides evaluated was found to be important for the modulation of cytotoxic activity against cancer cells.

Antineoplastic Agents, Phytogenic↗
PubMed2006

Lignans from cell suspension cultures of Phyllanthus niruri, an Indonesian medicinal plant.

Cell suspension cultures of Phyllanthus niruri were used to study the lignan profiles and biosynthesis. Suspension cultures yielded two lignans: the new cubebin dimethyl ether (1) and urinatetralin (2), a new lignan from P. niruri, but reported earlier from P. urinaria. This is the first report of cell suspension cultures of P. niruri that successfully produce lignans. Feeding 0.5 mM ferulic acid or 0.5 mM caffeic acid, being early precursors of lignan biosynthesis, resulted in an increase up to 0.7 mg g(-1) DW of 1 (control value 0.1 mg g(-1) DW) and up to 0.3 mg g(-1) DW of 2 (control value 0.2 mg g(-1) DW). Comparison of the lignan profiles of cell suspensions, callus cultures, aerial plant parts, roots, and seeds showed significant differences.

Caffeic Acids↗
PubMed2002

The effect of Phyllanthus niruri on urinary inhibitors of calcium oxalate crystallization and other factors associated with renal stone formation.

OBJECTIVE: To evaluate the effect of an aqueous extract of Phyllanthus niruri (Pn), a plant used in folk medicine to treat lithiasis, on the urinary excretion of endogenous inhibitors of lithogenesis, citrate, magnesium and glycosaminoglycans (GAGs). MATERIALS AND METHODS: The effect of chronic (42 days) administration of Pn (1.25 mg/mL/day, orally) was evaluated in a rat model of urolithiasis induced by the introduction of a calcium oxalate (CaOx) seed into the bladder of adult male Wistar rats. The animals were divided into four groups: a sham control (16 rats); a control+Pn (six); CaOx+water instead of Pn (14); and CaOx+Pn (22). Plasma and urine were collected after 42 days of treatment for biochemical analysis and the determination of urinary excretion of citrate, magnesium and GAGs. The animals were then killed and the calculi analysed. RESULTS: The creatinine clearance or urinary and plasma concentrations of Na+, K+, Ca2+, oxalate, phosphate and uric acid were unaffected by Pn or the induction of lithiasis. Treatment with Pn strongly inhibited the growth of the matrix calculus and reduced the number of stone satellites compared with the group receiving water. The calculi were eliminated or dissolved in some treated animals (three of 22). The urinary excretion of citrate and magnesium was unaffected by Pn treatment. However, the mean (sd) urinary concentration of GAGs was significantly lower in rats treated with CaOx+Pn, at 5.64 (0.86) mg/g creatinine, than when treated with CaOx + water, at 11.78 (2.21) mg/g creatinine. In contrast, the content of GAGs in the calculi was higher in the CaOx + Pn rats, at 48.0 (10.4) g/g calculus, than in the CaOx + water group, at 16.6 (9.6) g/g calculus. CONCLUSION: These results show that Pn has an inhibitory effect on crystal growth, which is independent of changes in the urinary excretion of citrate and Mg, but might be related to the higher incorporation of GAGs into the calculi.

Animals↗
PubMed2003

Antifungal, antiprotozoal, cytotoxic and piscicidal properties of Justicidin B and a new arylnaphthalide lignan from Phyllanthus piscatorum.

Using activity against Candida albicans as a lead, the bioactivity-guided fractionation of the dichloromethane extract of Phyllanthus piscatorum led to the isolation of the arylnaphthalide lignan justicidin B (1), which was found to be present in high amounts, and a new C-11 hydroxylated derivative that we named piscatorin (2). We provide evidence that justicidin B (1) is the main active principle of P. piscatorum, showing the same biological effects that were found for the raw extracts. Justicidin B inhibited the growth of the pathogenic fungi Aspergillus fumigatus (MIC > or = 1 microg/mL), Aspergillus flavus (MIC > or = 12 microg/mL), and Candida albicans (MIC > or = 4 microg/mL), but was not effective against Cryptococcus neoformans and Blastoschizomyces capitatus. Justicidin B also exhibited strong activity against the trypomastigote form of Trypanosoma brucei rhodesiense (IC50 = 0.2 microg/mL) and moderate activity against Trypanosoma cruzi (IC50 = 2.6 microg/mL). Testing against Plasmodium falciparum showed only weak activity. This is the first report on the in vitro fungicidal and antiprotozoal effects of justicidin B. In addition, both compounds exhibited a non-specific cytotoxicity in neoplastic and primary cell cultures. No antibacterial effects were detected. Both compounds were piscicidal against zebra fish and it is shown for the first time that piscatorin (2) and justicidin B (1) are the piscicidal principles of P. piscatorum, exhibiting a potency that is comparable to rotenone.

Animals↗
PubMed2004

Potential anti-tumor promoting activity of lupane-type triterpenoids from the stem bark of Glochidion zeylanicum and Phyllanthus flexuosus.

Four known lupane-type triterpenoids, glochidonol (1), glochidiol (2), lup-20(29)-ene-1beta,3beta-diol (3) and glochidone (3) were isolated from the stem bark of Glochidion zeylanicum. Previously, lupeol (5), lup-20(29)-ene-3beta,24-diol (6) and betulin (7) were isolated from the stem bark of Phyllanthus flexuosus. This study reports the assays of these lupane-type triterpenoids: all isolates 1-7 and synthetic analogues, glochidonyl acetate (1a), lup-20(29)-ene-1,3-dione (1b) and lup-20(29)-ene 3beta,24-diacetate (6a) were tested for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol 13-acetate (TPA). Among them, the effects of compounds 2 (IC50 = 290 mol ratio/32 pmol TPA) and 3 (IC50 = 300) were stronger than the others. In addition, compound 2 exhibited a strong inhibitory effect on mouse skin tumor promotion in an in vivo mouse two-stage carcinogenesis test.

9,10-Dimethyl-1,2-benzanthracene↗