American ginseng preferentially suppresses STAT/iNOS signaling in activated macrophages.
OBJECTIVE
Ginseng has been used as general tonic for thousands of years in Asia and becomes a popular herbal medicine all over the world. However, the cellular and molecular mechanisms underlying its benefit effects are less explored. Thus, we investigated the effect of a crude extract from Panax quinquefolius (American ginseng) on suppression of pro-inflammatory responses in macrophages with a focus on signal transducer and activator of transcription (STAT) signaling.


METHODS
The crude extract of American ginseng that was supplied by the National Research Council of Canada, Institute for National Measurement Standards (NRCC-INMS) was freshly solvated in Dulbecco's Modified Eagle Medium (DMEM) prior to each experiment. RAW264.7 cells, a murine macrophage cell line, were exposed to lipopolysaccharide (LPS) to induce inflammatory responses such as expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2). Proteins were measured by Western blot and mRNA expression was determined by quantitative real-time PCR (Q-PCR). Activator protein 1 (AP-1)-, nuclear factor-kappaB (NF-kappaB)- and STAT-mediated transcriptional activities were investigated using luciferase reporter constructs.


RESULTS
American ginseng inhibited LPS-induced iNOS expression; however, it did not affect LPS-induced COX2 expression. While American ginseng had no impact on LPS-induced activation of AP-1 or NF-kappaB pathways, it dramatically inhibited LPS-induced activation of STAT signaling. Moreover, American ginseng and AG490, an inhibitor of STAT cascade, synergistically suppressed the LPS-induced iNOS expression.


CONCLUSIONS
American ginseng selectively inhibits the expression of iNOS via suppression of STAT cascade but not NF-kappaB and AP-1 pathways in inflamed macrophages. Such a preferential suppression of STAT/iNOS cascade by American ginseng might have therapeutic potential for inflammatory diseases with over-activation of iNOS.
Ichikawa
Tomonaga
T
Department of Cell Biology and Anatomy, University of South Carolina, Columbia, SC 29208, USA.
Li
Jinqing
J
Nagarkatti
Prakash
P
Nagarkatti
Mitzi
M
Hofseth
Lorne J
LJ
Windust
Anthony
A
Cui
Taixing
T
D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D002460:Cell Line; D017931:DNA Primers; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008262:Macrophage Activation / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000187:drug effects; D052247:Nitric Oxide Synthase Type II / Q000187:drug effects* / Q000378:metabolism; D005894:Panax / Q000737:chemistry*; D010936:Plant Extracts / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D050791:STAT Transcription Factors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
D017931:DNA Primers; D016328:NF-kappa B; D010936:Plant Extracts; D050791:STAT Transcription Factors; D052247:Nitric Oxide Synthase Type II