Bioactivity-guided identification and cell signaling technology to delineate the immunomodulatory effects of Panax ginseng on human promonocytic U937 cells.
BACKGROUND
Ginseng is believed to have beneficial effects against human diseases, and its active components, ginsenosides, may play critical roles in its diverse physiological actions. However, the mechanisms underlying ginseng's effects remain to be investigated. We hypothesize some biological effects of ginseng are due to its anti-inflammatory effects.


METHODS
Human promonocytic U937 cells were used to investigate the immunomodulatory effects of ginseng following TNF-alpha treatment. A global gene expression profile was obtained by using genechip analysis, and specific cytokine expression was measured by quantitative RT-PCR and ELISA. HPLC was used to define the composition of ginsenosides in 70% ethanol-water extracts of ginseng. Activation of signalling kinases was examined by Western blot analysis.


RESULTS
Seventy percent ethanol-water extracts of ginseng significantly inhibited the transcription and secretion of CXCL-10 following TNF-alpha stimulation. Nine ginsenosides including Rb1, Rb2, Rc, Rd, Re, Rf, Rg1, Rg3 and Rh1 were identified in our extract by HPLC. Seven out of nine ginsenosides could significantly inhibit TNF-alpha-induced CXCL-10 expression in U937 cells and give comparable inhibition of CXCL-10 transcription to those with the extract. However, the CXCL-10 suppressive effect of individual ginsenosides was less than that of the crude extract or the mixture of ginsenosides. The CXCL-10 suppression can be correlated with the inactivation of ERK1/2 pathways by ginseng.


CONCLUSIONS
We showed ginseng suppressed part of the TNF-alpha-inducible cytokines and signalling proteins in promonocytic cells, suggesting that it exerts its anti-inflammatory property targeting at different levels of TNF-alpha activity. The anti-inflammatory role of ginseng may be due to the combined effects of ginsenosides, contributing in part to the diverse actions of ginseng in humans.
Cytokine Biology Group, Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, PR China. dcwlee@hku.hk
Davy C W
DC
Lee
Cindy L H
CL
Yang
Stanley C C
SC
Chik
James C B
JC
Li
Jian-hui
JH
Rong
Godfrey C F
GC
Chan
Allan S Y
AS
Lau
D054357:Chemokine CXCL10 / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003470:Culture Media; D004789:Enzyme Activation / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation / Q000187:drug effects; D036145:Ginsenosides / Q000032:analysis / Q000494:pharmacology; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D016209:Interleukin-8 / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D005894:Panax / Q000737:chemistry*; D010936:Plant Extracts / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D020298:U937 Cells
D054357:Chemokine CXCL10; D003470:Culture Media; D036145:Ginsenosides; D007155:Immunologic Factors; D016209:Interleukin-8; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; D020928:Mitogen-Activated Protein Kinases