High molecular weight polysaccharides are key immunomodulators in North American ginseng extracts: Characterization of the ginseng genetic signature in primary human immune cells

Ethnopharmacological relevance: Ginseng (GS) has played a pivotal role in traditional Chinese medicine for thousands of years. Its use has become increasingly popular in North America, in part due to the many claims of its immune-enhancing properties. The immunopharmacology of the North American variety of GS and its extracts is needed to substantiate these claims. Materials and methods: Human peripheral blood mononuclear cells were exposed to different North American GS extracts and microarray analysis was performed. The profile of cytokine response to GS extracts was established by ELISA, and Ingenuity Pathway Analysis was used to identify potential signaling pathways responsible for the transcriptional profile induced by GS. Fractionation of the aqueous and polysaccharide extracts was done to determine the molecular weight of the active immune modulatory ingredient(s). Results: We found that GS induced a transcriptional profile of immunomodulation characterized by a net T(h)1 immune response, with up-regulation of multiple pro-inflammatory cytokines (e.g., IFN-gamma, IL-23A and IL-6) and down-regulation of TGF-beta, IL-13 and the LPS co-receptor CD14. Ingenuity Pathway Analysis (IPA) revealed that the MAPK (ERK-1/2), PI3K, p38 and NF-kappa B cascades were key signaling pathways through which GS may trigger its immunomodulatory action. Furthermore, induction of such an immunomodulatory signature was recapitulated with the high molecular weight polysaccharides found in aqueous and polysaccharide GS extracts. Conclusions: Based on our results, we conclude that high molecular weight polysaccharides in North American GS aqueous and polysaccharide extracts likely trigger the MAPK (ERK-1/2), PI3K, p38 and NF-kappa B signaling pathways in PBMC resulting in the induction of a T(h)1 transcriptional profile. Our results may assist in optimizing GS-mediated immunomodulation and focus the search for compounds in GS extracts with specific immunomodulatory activities. (C) 2012 Elsevier Ireland Ltd. All rights reserved.