A new ginger extract characterization: Immunomodulatory, antioxidant effects and differential gene expression

Abstract

Ginger (Zingiber officinale) is commonly consumed as spice or herbal medicine with anti-inflammatory, antioxidant, and anticancer properties. It is rich of many bioactive constituents, mainly gingerols and shogaols. Although the bioactive constituents have been identified, the molecular mechanisms of ginger action are still limited, and the related signalling pathways not completely defined. Here, we used a simple ethanol/freeze-drying method to obtain a new ginger extract (GE), which was chemically characterised by Folin-Ciocalteu, antioxidant ORAC and HPLC assays. At cellular level, anti-inflammatory/antioxidant properties of GE, in addition to the commercial [6]-gingerol, were evaluated using RAW264.7 murine macrophages. Cell viability tests verified the non-toxic doses of GE and [6]-gingerol, and the glutathione assay confirmed the antioxidant property of GE. By quantitative PCR, we analysed the differential expression of various genes in LPS-treated cells, after GE/[6]-gingerol pre-treatments. The genes belonged to different categories: immune signalling, pro-/anti-inflammatory cytokines, pro-/anti-antioxidant enzymes, hallmarks of macrophage polarization and endoplasmic reticulum stress response. Results showed that pre-treatment with two doses of GE reduced the LPS-induced expression of TLR4, MyD88, Rel-A, IL-1α, IL-6, TNF-α, IL-10, iNOS and TRIB3 genes to varying degrees, whereas increased Jun, Light/Tnfsf14, HO-1 and Arg-1 gene expression. No effect was found on MIF expression in LPS-induced cells after GE pre-treatments. These results also suggested that GE pre-treatment promotes the expression of specific markers of macrophage polarization in LPS-stimulated cells, with a trend to activate an anti-inflammatory M2 phenotype. Further analyses will broaden the understanding of the role of individual GE components in cellular inflammation/immunomodulation.