Phyllanthus amarus has anti-inflammatory potential by inhibition of iNOS, COX-2, and cytokines via the NF-kappaB pathway.
OBJECTIVE
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.
Kiemer
Alexandra K
AK
Department of Pharmacy, Center of Drug Research, University of Munich, Butenandtstr. 5-13, 81377 Munich, Germany. alexandra.kiemer@cup.uni-muenchen.de
Hartung
Thomas
T
Huber
Christian
C
Vollmar
Angelika M
AM
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D051546:Cyclooxygenase 2; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000097:blood; D015232:Dinoprostone / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052247:Nitric Oxide Synthase Type II; D029803:Phyllanthus / Q000737:chemistry*; D010936:Plant Extracts / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases; D051381:Rats; D017207:Rats, Sprague-Dawley; D018808:Transcription Factor AP-1 / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D016328:NF-kappa B; D010936:Plant Extracts; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C496318:Nos2 protein, rat; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone