Bioactivity-guided identification and cell signaling technology to delineate the immunomodulatory effects of Panax ginseng on human promonocytic U937 cells

Davy Cw Lee,Stanley Cc Chik,James Cb Li,Cindy Lh Yang,Jian-Hui Rong,Allan Sy Lau,Godfrey Cf Chan

doi:10.1186/1479-5876-7-34

Davy Cw Lee, Stanley Cc Chik + Show 5 more

Open Access

https://doi.org/10.1186/1479-5876-7-34

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Abstract

BackgroundGinseng 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.MethodsHuman promonocytic U937 cells were used to investigate the immunomodulatory effects of ginseng following TNF-α 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.ResultsSeventy percent ethanol-water extracts of ginseng significantly inhibited the transcription and secretion of CXCL-10 following TNF-α 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-α-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.ConclusionWe showed ginseng suppressed part of the TNF-α-inducible cytokines and signalling proteins in promonocytic cells, suggesting that it exerts its anti-inflammatory property targeting at different levels of TNF-α 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.

Highlights

Ginseng is believed to have beneficial effects against human diseases, and its active components, ginsenosides, may play critical roles in its diverse physiological actions
Immunomodulatory effects of Panax ginseng extract (PGSE) on U937 cells stimulated by tumour necrosis factor-α (TNF-α) To investigate the immunomodulatory activity of ginseng, U937 cells were treated with PGSE and followed by TNFα stimulation
Following the sequential treatment of PGSE and TNF-α, we found that 102 upregulated genes and 64 downregulated genes were repeatedly shown in the gene list of two analyses

Summary

Introduction

Ginseng is believed to have beneficial effects against human diseases, and its active components, ginsenosides, may play critical roles in its diverse physiological actions. Ginseng roots contain multiple active constituents including ginsenosides, polysaccharides, peptides, polyacetylenic alcohols and fatty acids that have been shown to have different effects on carbohydrate and lipid metabolism as well as on the function of neuroendocrine, immune, cardiovascular and central nervous systems in humans [1,2]. Previous studies have shown that ginseng and its active components are potent immunomodulators. Their immunomodulatory effects are mostly due to its regulation of cytokine production and phagocytic activities of monocytes/macrophages and dendritic cells, as well as activation of T- and B- lymphocytes [3,4,5,6,7,8]. A polysaccharide extract from ginseng, enhances the phagocytic activity of macrophages in mice infected with Staphylococcus aureus [9]. The ginseng root extract stimulates the inducible nitric oxide synthase (iNOS) activity in RAW264.7 murine macrophages [10]

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