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Evaluation of Phyllanthus amarus and Phyllanthus maderaspatensis as agents for postexposure prophylaxis in neonatal duck hepatitis B virus infection.

The therapeutic potential of plant extracts of Phyllanthus amarus and Phyllanthus maderas patensis for postexposure prophylaxis against infection by Hepadnaviruses was studied in ducklings infected by the duck hepatitis B virus (DHBV). Forty-four Pekin ducklings were inoculated intraperitoneally with DHBV at 24 hr post-hatch. They were treated by intraperitoneal injection of Phyllanthus amarus (aqueous extract) (100 mg/kg body weight) or Phyllanthus mad eraspatensis (alcoholic extract) (100 mg/kg body weight) for a period of 4 weeks. Infected ducklings treated with saline served as controls. Weekly serum samples obtained before, during, and after treatment were analysed for the presence of DHBV DNA in serum by dot blot hybridisation using alpha 32P-labelled probes. Liver tissue was collected after killing the ducks at various time intervals and was studied for replicative status of the viral DNA and liver histopathology; 17 of 21 ducks were viraemic on completion of treatment with Phyllanthus amarus. At 16 week posttreatment follow-up four of seven animals remained viraemic. Similar results were obtained with Phyllanthus maderaspatensis. There was no alteration in DHBV replication in the liver. No toxicity was observed with this treatment. These observations suggest that Phyllanthus amarus and Phyllanthus maderaspatensis are not useful as therapeutic agents for postexposure prophylaxis against DHBV infection.

Animals↗

Evaluation of anti-hepadnavirus activity of Phyllanthus amarus and Phyllanthus maderaspatensis in duck hepatitis B virus carrier Pekin ducks.

Extracts of the two traditional Indian herbs, Phyllanthus amarus (P. amarus) and Phyllanthus maderaspatensis (P. maderaspatensis), described by others as useful in the treatment of chronic hepatitis B virus infection were studied for antiviral properties on duck hepatitis B virus infection. One hundred and fourteen ducks infected posthatch with the duck hepatitis B virus (DHBV) were divided into groups at three months of age and treated intraperitoneally with the aqueous, butanol, and alcoholic extracts of these two plants at doses of 25, 50, or 200 mg/kg body weight. Saline-treated animals served as controls. In the ducks negative for DHBV in serum after treatment, we observed replicative intermediates in the liver. There was no definite antiviral property observed in the treated ducks.

Animals↗

Uses and bioassays in Phyllanthus (Euphorbiaceae): a compilation. II. The subgenus Phyllanthus.

References to either indigenous uses or the results of controlled assays are numerous for species of Phyllanthus (Euphorbiaceae). These citations have been arranged by subgenus, section, subsection and species and will be published in four parts, including (Part IV) analysis, discussion and conclusions concerning apparent clustering of some uses or effects within taxa. This paper (Part II) covers the subgenus Phyllanthus.

Humans↗

Comparative pharmacognostic studies of three Phyllanthus species.

Different species of Phyllanthus are considered to be very effective hepatoprotective agents in the Indian indigenous systems of medicine and are considered bitter, astringent, stomachic, diuretic, febrifuge, deobstruant and antiseptic. Still ayurvedic practitioners prescribed fresh juice of 'Bhuiamlki' for jaundice. Various species of Phyllanthus are being sold in India under the trade name 'Bhuiamlki'. During market surveillance of herbal drug, it was observed that almost all the commercial samples, either comprise of Phyllanthus amarus Schum & Thonn. or Phyllanthus maderaspatensis Linn. or mixture of Phyllanthus amarus, Phyllanthus fraternus Webster. and Phyllanthus maderaspatensis. Therefore, in this context the detailed pharmacognostical evaluation of all the three species has been carried out with the aim to establish the identification markers of this important hepatoprotective agent (effective in hepatitis B too). The study conclude that all the three species can be differentiated on the basis of macro and microscopic characters, physico-chemical values, HPTLC fingerprint profile, and detection of phyllanthin and hypophyllanthin as marker components. Besides, an interesting conclusion can also be drawn that phyllanthin and hypophyllanthin said to protect hepatocytes against carbon tetrachloride and galactosamine induced toxicity, may not be exclusively responsible for hepatoprotective activity as these are present only in Phyllanthus amarus while Phyllanthus fraternus and Phyllanthus maderaspatensis also possess significant hepatoprotective activity.

Phyllanthus↗

Antinociceptive properties of extracts of new species of plants of the genus Phyllanthus (Euphorbiaceae).

The hydroalcoholic extract (HE) of the four new species of Phyllanthus, given intraperitoneally, produced significant inhibition of acetic acid-induced abdominal constrictions, with mean ID(50) values of 0.3, 1.8, 7.4 and 26.5 mg/kg for Phyllanthus amarus, Phyllanthus orbiculatus, Phyllanthus fraternus and Phyllanthus stipulatus, respectively. In the formalin test, the four species of Phyllanthus, also produced graded inhibition against both phases of formalin-induced licking, being more active in relation of the late phase. The HE of the Phyllanthus species elicited significant inhibition of the capsaicin-induced neurogenic pain, with mean ID(50) values of 8.9, 6.7, >30 and approximately 30 mg/kg for P. amarus, P. fraternus, P. stipulatus and P. orbiculatus, respectively. Given orally all HE of the Phyllanthus species were less potent and efficacious than when given by intraperitoneally. Results of the present study extend previous data and indicate that all extracts of Phyllanthus plants so far studied exhibit pronounced antinociception when assessed in chemical models of nociception, namely acetic acid-induced writhing, and formalin and capsaicin-induced licking.

Abdomen↗

Genus Phyllanthus for chronic hepatitis B virus infection: a systematic review.

To evaluate the efficacy and safety of genus Phyllanthus for chronic hepatitis B virus (HBV) infection we performed a systematic review of randomized clinical trials. Randomized trials comparing genus Phyllanthus vs. placebo, no intervention, general nonspecific treatment, other herbal medicine, or interferon treatment for chronic HBV infection were identified by electronic and manual searches. Trials of Phyllanthus herb plus interferon (IFN) vs. IFN alone were also included. No blinding and language limitations were applied. The methodological quality of trials was assessed by the Jadad scale plus allocation concealment. Twenty-two randomized trials (n=1947) were identified. The methodological quality was high in five double-blind trials and low in the 17 remaining trials. The combined results showed that Phyllanthus species had positive effect on clearance of serum HBsAg (relative risk 5.64, 95% CI 1.85-17.21) compared with placebo or no intervention. There was no significant difference on clearance of serum HBsAg, HBeAg and HBV DNA between Phyllanthus and IFN. Phyllanthus species were better than nonspecific treatment or other herbal medicines for the clearance of serum HBsAg, HBeAg, HBV DNA, and liver enzyme normalization. Analyses showed a better effect of the Phyllanthus plus IFN combination on clearance of serum HBeAg (1.56, 1.06-2.32) and HBV DNA (1.52, 1.05-2.21) than IFN alone. No serious adverse event was reported. Based on this review Phyllanthus species may have positive effect on antiviral activity and liver biochemistry in chronic HBV infection. However, the evidence is not strong due to the general low methodological quality and the variations of the herb. Further large trials are needed.

Adult↗

The chemical composition of Phyllanthus discoideus and its effect on the ruminal ammonia and volatile fatty acid concentration when fed to west African dwarf sheep.

The feeding value of Phyllanthus discoideus (also called Margaritaria discoidea) leaves was evaluated using eight two-year-old West African Dwarf sheep fed natural grass hay. Four of the animals were fistulated ruminally and used for ammonia and volatile fatty acid determination in the fluid. Dried leaves of Phyllanthus discoideus were offered at two levels (25% and 50% of DMI, diets D25% and D50%, respectively) as supplements to the basal hay diet. The CP content of the control, D25% and D50% diets were 11.5, 12.6 and 13.6%, respectively, and their digestible energy amounted to 58.2, 61.1 and 56.9%, respectively. Rumen liquor was sampled one hour before and one, three and five hours after the morning feeding. Sheep fed the control diet had a higher ruminal ammonia concentration than those fed diet D25%. Similarly, ruminal ammonia concentration was higher in sheep fed the control diet than those fed the diet D50%. Five hours after feeding the ruminal ammonia concentration was significantly lower than one hour after feeding. The VFA concentrations in rumen fluid of sheep fed the control diet was inferior to those fed diets D25% and D50%. Sheep fed diet D50% showed significantly higher VFA concentrations than those fed diet D25%. Digestibility of organic matter and digestible energy did not show any significant difference. However, a marginal increase in organic matter digestibility of 3.5% was observed in diet D25% compared with the control diet. There was no significant difference in the N-digestibility in sheep fed the control, D25% and D50% diets. Nevertheless, a marginal improvement in N-digestibility (1.5%) and N-retention (2.7%) was observed with the highest level of Phyllanthus discoideus (D50%). In conclusion, Phyllanthus discoideus appears as a particularly valuable feedstuff because it contains low levels of condensed tannins (12.8 g/kg), high CP content (156 g/kg) and a relatively high GE content (19.3 kJ/g DM). Although the improvement in N-digestibility and N-retention were only marginal the feeding of Phyllanthus discoideus could be justified under extreme shortage of feed resources during dry season. It should also be mentioned that a much more pronounced effect by supplementation with Phyllanthus discoideus could be expected when poor quality grass hay prevalent in West Africa during the dry season is fed. Phyllanthus discoideus could serve as a supplement to poor quality grass at 25% to 50% of supplementation.

Ammonia↗

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

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.

Adult↗

Effects of alkaloidal extract of Phyllanthus niruri on HIV replication.

Phyllanthus niruri has been found to exhibit marked inhibitory effect on hepatitis B virus evident by its exhaustive utility in cases of chronic jaundice. However, till date, research has not been focused on identification and validation of active pharmacophores of Phyllanthus niruri responsible for the reported inhibitory effect of its aqueous extract on anti-human immunodeficiency virus. The present 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 279.85 microgmL(-1) whereas the EC50 was found to be 20.98 microgmL(-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.

Cells, Cultured↗

Efficacy of Phyllanthus amarus for eradication of hepatitis B virus in chronic carriers.

Sixty-five adult asymptomatic chronic carriers of hepatitis B virus were enrolled to the randomized controlled efficacy study of Phyllanthus amarus. Thirty-four received Phyllanthus amarus 600 mg per day for 30 days and 31 received placebo in identical capsules. The conversion rate of HBsAg was 6 per cent in the study group at day 30. When 20 subjects in the Phyllanthus amarus group were given a further 30-day treatment and 22 placebo recipients given Phyllanthus amarus 1,200 mg per day for 30 days, the conversion was observed in 1 (5%) in the higher dose group. Adverse effects were not observed in all patients receiving the plant. The results indicated that Phyllanthus amarus, whole plant except root, grown in the central part of Thailand, given at the studied dosage and duration, had a very minimal effect on eradication of HBsAg from Thai adult asymptomatic chronic carriers.

Adolescent↗

[Experimental study on anti-duck hepatitis B viral effect of Phyllanthus urinaria of different areas and combined therapy with other drugs].

The duck hepatitis B virus model was treated with phyllanthus urinaria of different area and combined with Sophora flavesceus as well as ciprofloxacin once a day for one month, the results indicated: Guangxi and Yunnan Phyllanthus could lower the serum DHBV DNA significantly (P < 0.05), but Chongqing Phyllanthus couldn't. And the amount of serum DHBV DNA rose a week after stopping of Yunnan Phyllanthus. The antiviral effect of Guangxi Phyllanthus combined with ciprofloxacin seems to be strengthened (P < 0.05).

Animals↗

A two-stage clinical trial of Phyllanthus amarus in hepatitis B carriers: failure to eradicate the surface antigen.

BACKGROUND: There have been conflicting data in literature about the value of Phyllanthus amarus in treating hepatitis B virus-related disorders. AIM: To evaluate the role of Phyllanthus amarus in eradication of the virus in hepatitis B carriers. METHODS: Phyllanthus amarus was administered to 30 asymptomatic carriers of hepatitis B surface antigen (HBsAg) in a dosage of 250 to 500 mg thrice daily for 4 to 8 weeks. RESULTS: None of the 30 subjects cleared HBsAg. Phyllanthus amarus was well tolerated, with no clinical side effects or changes in the organ profiles for safety evaluation. CONCLUSION: Phyllanthus amarus is not effective in clearing HBsAg in asymptomatic carriers of the antigen.

Adult↗

Phyllanthus piscatorum, ethnopharmacological studies on a women's medicinal plant of the Yanomamï Amerindians.

The shrub Phyllanthus piscatorum Kunth (Euphorbiaceae) is cultivated by various ethnic groups of the Amazon because of its piscicidal properties. During ethnobotanical fieldwork among the Yanomamï Amerindians in Venezuela we observed that Phyllanthus piscatorum was exclusively cultivated and used by the women. Aerial parts of this herbaceous shrub are employed as fish poison and medicine to treat wounds and fungal infections. In addition, the leaves are used as tobacco substitute. Ethnobotanical data regarding the context of the use of this plant are presented. To validate ethnobotanical information related to its medicinal indications, antimicrobial, and antiprotozoal properties of water, methanol (MeOH) and dichloromethane (DCM) extracts were studied. No activity against Gram-positive bacterial strains but significant activity against the fungi Aspergillus fumigatus, Aspergillus flavus and the yeast Candida albicans were found. All extracts showed weak in vitro activity against Plasmodium falciparum and Trypanosoma brucei rhodesiense. The extracts were further investigated for cytotoxic effects in an in vitro test system with leukemia Jurkat T, HeLa, and human peripheral mononuclear blood cells (PBMCs). During the first 48 h the extracts did not exhibit any cytotoxicity. After 72 h the DCM extract potently inhibited viability of HeLa cells. Although in several communities along the upper Orinoco the cultivation and use of Phyllanthus piscatorum is being lost because of the ongoing acculturation, the traditional medicinal use of Phyllanthus piscatorum might provide an effective and cheap remedy against dermatological diseases linked with Candida albicans infections.

Animals↗

Inhibition of experimental gastric lesion and inflammation by Phyllanthus amarus extract.

Methanolic extract of Phyllanthus amarus Shum & Thonn (Euphorbiaceae) 50, 200, and 1000 mg/kg body weight significantly inhibited gastric lesions, induced by intragastric administration of absolute ethanol (8 ml/kg). Mortality, increased stomach weight, ulcer index, and intraluminal bleeding were reduced significantly by Phyllanthus amarus. Biochemical analysis indicated that reduced glutathione (GSH) of gastric mucosa produced by ethanol administration was significantly elevated by treatment with Phyllanthus amarus extract. Aqueous and methanol extracts of Phyllanthus amarus produced an inhibition of rat paw edema up to 42% compared to control in 3h and continued up to 8h. Anti-oxidant activity of the extract as well as presence of tannins in the extract may be responsible for these observed activities.

Animals↗

Double-blinded placebo-controlled study of Phyllanthus urinaris for the treatment of chronic hepatitis B.

BACKGROUND: Previous studies suggested that Phyllanthus species have an anti-viral effect on hepatitis B, but methodologies have been inadequate. AIMS: This study aimed to investigate the anti-viral effect of Phyllanthus urinaris. METHODS: Chronic hepatitis B patients with positive hepatitis B e-antigen (HBeAg), hepatitis B virus (HBV) DNA > 500 000 copies/mL and elevated alanine transaminase (ALT) were recruited. Patients were randomized into groups of 12 receiving P. urinaris 1, 2 and 3 g three times daily for 6 months or placebo (six cases). The primary endpoint was HBV DNA reduction, and secondary endpoints were HBeAg seroconversion and ALT normalization. RESULTS: On an intention-to-treat analysis there was no difference in log10[HBV DNA] reduction of the Phyllanthus 1-g (0.18 +/- 1.42), 2-g (0.33 +/- 1.08) and 3-g (0.85 +/- 1.30) groups vs. placebo (0.28 +/- 0.85) (P = 0.90, 0.92 and 0.38, respectively) at the end of treatment. The percentage of patients among the placebo, Phyllanthus 1-g, 2-g and 3-g groups undergoing HBeAg seroconversion (0%, 9.1%, 8.3% and 16.7%, respectively) and ALT normalization (0%, 0%, 8.3% and 33.3%) were not significantly different at the end of treatment. No delayed virological or biochemical response was documented at 24 weeks after the cessation of treatment. No serious adverse event was reported. CONCLUSION: P. urinaris treatment for 6 months has no demonstrable anti-viral effect in chronic hepatitis B.

Adult↗

A review of the plants of the genus Phyllanthus: their chemistry, pharmacology, and therapeutic potential.

The plants of the genus Phyllanthus (Euphorbiaceae) are widely distributed in most tropical and subtropical countries, and have long been used in folk medicine to treat kidney and urinary bladder disturbances, intestinal infections, diabetes, and hepatitis B. In recent years, the interest in the plants has increased considerably. Substantial progress on their chemistal and pharmacological properties, as well as a few clinical studies of some Phyllanthus species have been made. This review discusses the current knowledge of their chemistry, the in vitro and in vivo pharmacological, biochemical, and clinical studies carried out on the extracts, and the main active constituents isolated from different species of plants of the genus Phyllanthus. These studies carried out with the extracts and purified compounds from these plants support most of their reported uses in folk medicine as an antiviral, in the treatment of genitourinary disorders, and as antinociceptive agents. However, well-controlled, double-binding clinical trials are lacking. Several compounds including alkaloids, flavonoids, lignans, phenols, and terpenes were isolated from these plants and some of them interact with most key enzymes. Together this data strongly supports the view that the plants belonging to the genus Phyllanthus have potential beneficial therapeutic actions in the management of hepatitis B, nefrolitiase, and in painful disorders.

Alkaloids↗

In vivo studies of a crude extract of Phyllanthus amarus L. in modifying the genotoxicity induced in Vicia faba L. by tannery effluents.

The genotoxic effects of two types of tannery effluent (Raw-to-Wetblue and Wetblue-to-Finish) and the antigenotoxic property of a crude extract of Phyllanthus amarus L. were evaluated using the root meristem of Vicia faba L. as the in vivo test system. The root tip cells were exposed to the tannery effluents at different concentrations for varying durations. Squash preparations were made following Haematoxylin staining procedures. Cytological investigations revealed a duration- and concentration-dependent decrease in mitotic frequency and an increase in chromosomal irregularities. The root meristems pre-treated with effluents for 8 h (Raw-to-Wetblue) and 24 h (Wetblue-to-Finish) which caused the maximum incidence of mitotic anomalies, were then exposed to the crude extract of Phyllanthus amarus (0.25, 0.5, 0.75 and 1%) to study its efficacy modifying genetic damage. It was observed that the root meristems post-treated with Phyllanthus showed a significant reduction in the frequency of chromosomal alterations. However, there was no significant variation in the mitotic frequency. The study suggests that Phyllanthin, a principle of Phyllanthus amarus, is antigenotoxic.

Chromosome Aberrations↗

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

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)

Abdominal Muscles↗