Niruriside, a New HIV REV/RRE Binding Inhibitor from <i>Phyllanthus niruri</i>

Qian‐Cutrone, Jingfang; Huang, Stella; Trimble, John J.; Li, Hui; Lin, Pin‐Fang; Alam, Masud; Klohr, Steven E.; Kadow, Kathleen F.

doi:10.1021/np9600560

Cited by 76 publications

(40 citation statements)

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“…Studies with P. niruri have found flavonoids such as quercetin and kaempferol (El-Mekkawy et al, 1995), lignin glycosides called phyllanthostatin A, 1 and 2 (Pettit, Schaufelberger, 1988;Pettit et al, 1990), ellagitannins such as geraniin and furosin (Miguel et al, 1996), niruroidine (Quian-Cutrone et al, 1996), lignans as nirtetralin A and B (Wei et al, 2012) among others.…”

Section: Introductionmentioning

confidence: 99%

“…In addition to alkaloids, other compounds including tannins, flavonoids, phenols, triterpenoids, fatty acids, esters of phthalic acid, lignins such as phyllanthin and hypophyllanthin, and vitamin C have been isolated and characterized in several species of the genus Phyllanthus (Ahmad, Husain, Osman, 1981;Miguel et al, 1996;Quian-Cutrone, 1996;Ueno et al, 1988;Ishimaru et al, 1992;Rajeshkumar et al, 2002;Mahdi et al, 2011;Samali et al, 2012). Studies with P. niruri have found flavonoids such as quercetin and kaempferol (El-Mekkawy et al, 1995), lignin glycosides called phyllanthostatin A, 1 and 2 (Pettit, Schaufelberger, 1988;Pettit et al, 1990), ellagitannins such as geraniin and furosin (Miguel et al, 1996), niruroidine (Quian-Cutrone et al, 1996), lignans as nirtetralin A and B (Wei et al, 2012) among others.…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of (anti)genotoxic activities of Phyllanthus niruri L. in rat bone marrow using the micronucleus test

Queiroz

Matias

Cunha

et al. 2013

Braz. J. Pharm. Sci.

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Phyllanthus niruri L. (Euphorbiaceae), known as "quebra-pedra" (Portuguese for "stonebreaker"), is an herb used for kidney disorders. In light of its frequent use by the population, the present study aimed to investigate the genotoxic, antigenotoxic and cytotoxic activities of a standardized P. niruri extract in bone marrow rats. Three groups of 12 animals were treated daily by gavage over a period of 30 days, with 50, 150 or 250 mg/kg of P. niruri extract aqueous solution. The control group (n = 12) received tap water. At the end of treatment (day 31), groups were divided into two minor subgroups (n=6/group) and received cyclophosphamide (50 mg/kg, i.p.) or saline 0.9% (i.p.). After 24 hours, we evaluated the frequency of micronucleated polychromatic erythrocytes for each animal (MNPCE) at 1000 PCE. Cytotoxicity was evaluated with the PCE/NCE ratio (NEC = normochromatic erythrocytes). General toxicity was assessed during treatment using the parameters of body weight gain, ration and water consumption. The dry extract did not provoke changes in body weight, weight gain, ration and water intake or changes in the frequency of MNPCE or cytotoxicity in bone marrow. We propose that the P. niruri extract used here showed no genotoxic, antigenotoxic and cytotoxic activities under the experimental conditions. Uniterms: Phyllanthus niruri L./genotoxicity. Phyllanthus niruri L./toxicological analysis/experimental study. Medicinal plantas/evaluation.Phyllanthus niruri L. (Euphorbiaceae), conhecida como "quebra-pedra", é uma planta medicinal utilizada frequentemente pela população no tratamento de problemas renais. Foram avaliadas as atividades genotóxicas, antigenotóxicas e citotóxicas de um extrato padronizado dessa espécie em ratos. Três grupos de doze animais foram tratados durante trinta dias, por gavagem, com 50, 150 ou 250 mg/kg/dia de solução aquosa do extrato de P. niruri e um grupo controle (n=12) recebeu água destilada pela mesma via. No final do tratamento os grupos foram divididos em dois subgrupos (6 animais/grupo) e receberam uma dose única de ciclofosfamida (50 mg/kg, i.p.) ou de solução salina 0,9% (i.p.). Após 24 horas, a frequência de eritrócitos policromáticos micronucleados (EPCMN) foi avaliada em 1000 EPC. A citotoxicidade foi avaliada pela relação entre eritrócitos policromáticos e normocromáticos (EPC/ ENC) e a toxicidade geral foi avaliada através dos parâmetros de ganho de peso corporal, consumo de ração e ingestão hídrica. O extrato seco não provocou alterações significativas no peso corporal, ganho de peso e consumo de ração em relação ao grupo controle, nem alterações na frequência de EPCMN ou citotoxicidade em medula óssea. Dessa maneira, pode-se concluir que P. niruri não apresentou atividades genotóxica, antigenotóxica e/ou citotóxica nas condições experimentais executadas. Unitermos INTRODUCTIONMedicinal plants and their preparations have been used to treat several illnesses since the dawn of human history and are one of the foundations for healthcare worldwide (AESGP, 1998;Turolla, 2004;Me...

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Evaluation of (anti)genotoxic activities of Phyllanthus niruri L. in rat bone marrow using the micronucleus test

Queiroz

Matias

Cunha

et al. 2013

Braz. J. Pharm. Sci.

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“…A screening of natural products using an in vitro Rev-RRE binding assay was carried out at Bristol-Myers Squibb. Three novel natural products, one from a plant and two from fungi, were discovered and isolated by bioassay guided fractionation (109,110). The plant metabolite, niruriside, was isolated from Phyllanthus niruri, a plant widely used in Indian traditional medicine.…”

Section: Screening Approachesmentioning

confidence: 99%

Inhibition of the HIV Rev transactivator A new target for therapeutic intervention

Heguy¹

1997

Front Biosci

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The viral transactivator Rev is essential for HIV replication, since it allows the nuclear export of unspliced and partially spliced viral mRNAs that encode the structural proteins. Rev is an RNA binding protein that interacts with a highly structured RNA element, the RRE, found within the envelope sequences. This viral protein also interacts with cellular proteins, termed nucleoporins, and acts as an adaptor between the viral mRNAs and the cellular nuclear export machinery. Both interactions are specific, and required for Rev function. Because of its crucial role in the HIV replication cycle, and its novel mechanism of action, Rev represents an ideal target for therapeutic intervention. This review describes the efforts towards Rev inhibition. Gene therapy approaches, including the expression of trans-dominant mutants and RNA decoys, as well as antisense therapies and small molecule inhibitors of Rev-RRE binding or Rev interaction with the cellular machinery will be discussed. INTRODUCTIONHIV-1, the etiologic agent of Acquired Immunodeficiency Syndrome (AIDS), displays a complex regulation of __________________________________________ Received 6/2/97 Accepted 6/4/97 1 To whom correspondence should be addressed at: Oncogene Science, Inc., 106 Charles Lindbergh Blvd., Uniondale, NY 11553 Tel: 516-222-0023 Fax: 516-222-0114 E-mail: aheguy@oncogene.com viral gene expression during its life cycle. Unlike many "simple" retroviruses (i.e. avian and murine leukemia viruses), which express only three viral genes, the genome of HIV-1 encodes nine genes whose expression patterns are tightly regulated during the HIV-1 replication cycle (Figure 1, for reviews see 1, 2, 3). In the infected host cell, HIV expresses over 20 distinct mRNA species (reviewed in 4). The early stage of regulation of the HIV-1 life cycle is marked by the appearance of the viral regulatory molecules Tat, Rev, and Nef, encoded by the fully spliced 2 kb class of viral mRNAs. The late viral life cycle gene expression is characterized by the cytoplasmic appearance of the 4 kb class of single spliced and 9.2 kb unspliced mRNAs, that encode the proteins required for the assembly of infectious virions. The viral transactivator Rev allows this transition into the late cycle (5, 6), and is therefore essential for viral replication. In effect, proviral mutants that do not express Rev fail to produce structural proteins and therefore cannot form new infectious viral particles (5, 7).Because of its essential role in HIV replication, Rev constitutes an excellent target for therapeutic intervention. Its mode of action and specific interactions with its target RNA and cellular proteins have been extensively studied and elegantly elucidated, and this body of knowledge adds to the attractiveness of Rev as a target. The purpose of this article is to briefly review the latest developments on Rev, and how this knowledge can be used for development of anti-viral strategies, as well as to

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“…The popular uses of Phyllanthus species reported the treatment of dysentery, gonorrhea, urinary discharges, kidney and bladder stones (Unander et al, 1995). Besides its traditional use, other pharmacological properties were also investigated such as hypoglycemic (Hukeri et al, 1988;Navarro et al, 2004), anti-hepatotoxic (Prakash et al, 1995;Naaz et al, 2007), antimalarial (Tona et al, 1999), antinociceptive (Santos et al, 1995), antiinflammatory (Kassuya et al, 2003(Kassuya et al, , 2005(Kassuya et al, , 2006, antiviral (Ogata et al, 1992;Qian-Cutrone et al, 1996), hypolipidemic (Khanna et al, 2002), antihyperuricemic (Murugaiyah & Chan, 2009) and as wound healing (Shanbhag et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Anti-inflammatory, antiallodynic effects and quantitative analysis of gallic acid in spray dried powders from Phyllanthus niruri leaves, stems, roots and whole plant

Couto¹,

Kassuya²,

Calixto³

et al. 2013

Rev. bras. farmacogn.

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Abstract:The anti-inflammatory and antiallodynic effects of spray dried powders starting from leaves, stems, roots, the mixture of leaves and stems, as well as the whole plant aqueous solutions of Phyllanthus niruri L., Phyllanthaceae, were assessed. Gallic acid, used as chemical marker, was quantified by HPLC in the spray dried powders. Carrageenan-induced inflammatory and allodynic responses in the mouse paw were used as pharmacological models. Quantitative and qualitative differences among chemical composition of different herb parts were observed. The oral administration of leaves or leaves plus stems spray dried powders (100 mg/kg) significantly inhibited the carrageenan-induced allodynic effect (42±5 and 54±3%, respectively). Additionally, the spray dried powders of leaves significantly reduced carrageenan-induced paw oedema (35±6%). The spray dried powders of roots, stems, or the mixture of leaves, stems and roots (100 mg/kg, p.o.) did not exhibit antiallodynic or antioedematogenic effect in the same model. In conclusion, differences in the chemical composition of spray dried powders from P. niruri are reflected in their in vivo pharmacological actions. Despite of a direct relationship of anti-inflammatory and antiallodynic effects with the gallic acid content had been observed, especially in the spray dried powders of leaves, the use of spray dried powders of leaves plus stems showed to be more effective, suggesting a synergic effect between their constituents.

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Niruriside, a New HIV REV/RRE Binding Inhibitor from Phyllanthus niruri

Cited by 76 publications

References 23 publications

Evaluation of (anti)genotoxic activities of Phyllanthus niruri L. in rat bone marrow using the micronucleus test

Evaluation of (anti)genotoxic activities of Phyllanthus niruri L. in rat bone marrow using the micronucleus test

Inhibition of the HIV Rev transactivator A new target for therapeutic intervention

Anti-inflammatory, antiallodynic effects and quantitative analysis of gallic acid in spray dried powders from Phyllanthus niruri leaves, stems, roots and whole plant

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