AIM OF THE STUDY: 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. MATERIALS AND 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. CONCLUSION: 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.
AIM OF THE STUDY: 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. MATERIALS AND 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. CONCLUSION: 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.
Authors: Luis Villacorta; Jifeng Zhang; Minerva T Garcia-Barrio; Xi-lin Chen; Bruce A Freeman; Yuqing E Chen; Taixing Cui Journal: Am J Physiol Heart Circ Physiol Date: 2007-04-27 Impact factor: 4.733
Authors: Deepak Poudyal; Phuong Mai Le; Tia Davis; Anne B Hofseth; Alena Chumanevich; Alexander A Chumanevich; Michael J Wargovich; Mitzi Nagarkatti; Prakash S Nagarkatti; Anthony Windust; Lorne J Hofseth Journal: Cancer Prev Res (Phila) Date: 2012-01-31