Phyllanthus amarus has anti-inflammatory potential by inhibition of iNOS, COX-2, and cytokines via the NF-κB 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/H2O), 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/H2O and hexane extracts showed an inhibition of LPS-induced production of NO and PGE2 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-a. Therefore, we report for the first time an anti-inflammatory potential of this traditionally employed herbal medicine both in vitro and in vivo. (C) 2002 European Association for the Study of the Liver. Published by Elsevier Science B.V. All rights reserved.