Inhibition of wild-type human immunodeficiency virus and reverse transcriptase inhibitor-resistant variants by Phyllanthus amarus.
Substantial progress has been made in research on natural products which effectively inhibit HIV-1 replication. Many active compounds were isolated from traditionally used medicinal plants including Phyllanthus species. This study shows that aqueous as well as alcohol-based Phyllanthus amarus extracts potently inhibit HIV-1 replication in HeLa CD4(+) cells with 50% effective concentration (EC(50)) values ranging from 0.9 to 7.6 microg/ml. A gallotannin enriched fraction showed enhanced activity (0.4 microg/ml), and the purified gallotannins geraniin and corilagin were most active (0.24 microg/ml). HIV-1 replication was also blocked in CD4(+) lymphoid cells with comparable EC(50) values. Applying a cell-based internalization assay, we could demonstrate 70-75% inhibition of virus uptake at concentrations of 2.5 microg/ml for the water/alcohol extract and geraniin. In addition, a concentration-dependent inhibition of HIV-1 reverse transcriptase (RT) could be demonstrated in vitro. The 50% inhibitory concentration (IC(50)) values varied from 1.8 to 14.6 microg/ml. The ability to inhibit replication of a variety of RT inhibitor-resistant HIV-1 strains points to the potential of P. amarus extracts, as natural products, in the chemotherapy of HIV infections.
CMI-Centers for Medical Innovation AG, Fraunhofer Str 15, 82152 Martinsried, Germany. frank.notka@klinik.uni-regensburg.de
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D015704:CD4 Antigens; D024882:Drug Resistance, Viral; D019665:Euphorbiaceae / Q000737:chemistry; D005960:Glucosides / Q000302:isolation & purification / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D015498:HIV-2 / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D047348:Hydrolyzable Tannins / Q000494:pharmacology; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D010946:Plants, Medicinal; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D013634:Tannins / Q000302:isolation & purification / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014779:Virus Replication / Q000187:drug effects
D015704:CD4 Antigens; D005960:Glucosides; D047348:Hydrolyzable Tannins; D010936:Plant Extracts; D018894:Reverse Transcriptase Inhibitors; D013634:Tannins; C024603:Geraniin; C049096:corilagin