A Critical Regulation of Th17 Cell Responses and Autoimmune Neuro-Inflammation by Ginsenoside Rg3

Abstract

Among diverse helper T-cell subsets, Th17 cells appear to be pathogenic in diverse autoimmune diseases, and thus, targeting Th17 cells could be beneficial for the treatment of the diseases in humans. Ginsenoside Rg3 is one of the most potent components in Korean Red Ginseng (KRG; Panax ginseng Meyer) in ameliorating inflammatory responses. However, the role of Rg3 in Th17 cells and Th17-mediated autoimmunity is unclear. We found that Rg3 significantly inhibited the differentiation of Th17 cells from naïve precursors in a dendritic cell (DC)–T co-culture system. While Rg3 minimally affected the secretion of IL-6, TNFα, and IL-12p40 from DCs, it significantly hampered the expression of IL-17A and RORγt in T cells in a T-cell-intrinsic manner. Moreover, Rg3 alleviated the onset and severity of experimental autoimmune encephalomyelitis (EAE), induced by transferring myelin oligodendrocyte glycoprotein (MOG)-reactive T cells. Our findings demonstrate that Rg3 inhibited Th17 differentiation and Th17-mediated neuro-inflammation, suggesting Rg3 as a potential candidate for resolving Th17-related autoimmune diseases.

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“… 53 Seven studies were retrieved specifically on the use of Ginseng for EAE. 54 , 55 , 56 , 57 , 58 , 59 , 60 Ginseng can be classified according to their countries of origin: Panax ginseng or Korean Ginseng (人参 rén shēn ), Panax japonicus or Japanese ginseng , Panax notoginseng or Chinese ginseng (三七 sān qī ), Panax quinquefolius or American Ginseng (西洋参 xī yáng shēn ), and Panax vietnamensis or Vietamese ginseng . 61 In general, the plants of the genus Panax have important pharmacological activities attributed to its main active principle, a saponin, known as ginsenoside .…”

“… 58 The ginsenoside Rg3 is one of the most potent anti-inflammatory components of Korean red ginseng (红参 hóng shēn ). 60 Although P. ginseng (人参 rén shēn ) is used in the formulas BZYQT and HQRST , we included in this review other species of ginseng used in controlled clinical trials that treated EAE/MS due to their similar pharmacological properties. We also found seven articles on Glycyrrhizae radix (甘草 gān cǎo ), and its isolates which affected EAE.…”

“…In the study on the influence of the Ginsenoside Rg3 on EAE, small effects on the secretion of IL-6, TNF-α and IL-12p40 from dendritic cells (DCs) were noticed. 60 However, the ginsenoside Rg3 directly downregulated the expression of RORγt in CD4 + T cells which hindered Th17 differentiation from naïve precursors, and consequently alleviated Th17 mediated autoimmunity. 60 Huang Qi glycoprotein (HQGP), an extract of Astragalus membranaceus Bunge (AST 黄芪 huáng qí ) by ammonium sulfate precipitation also delayed the onset and ameliorated the severity of EAE.…”

“… 60 However, the ginsenoside Rg3 directly downregulated the expression of RORγt in CD4 + T cells which hindered Th17 differentiation from naïve precursors, and consequently alleviated Th17 mediated autoimmunity. 60 Huang Qi glycoprotein (HQGP), an extract of Astragalus membranaceus Bunge (AST 黄芪 huáng qí ) by ammonium sulfate precipitation also delayed the onset and ameliorated the severity of EAE. 50 HQGP downregulated IL-6, IL-17, and TNF-α, but increased the expression of IFN-γ.…”

Advances in Ginsenosides

“…In autoimmune diseases, IL-17A-producing CD4 + T cells (Th17) were recognized as critically pathogenic immune cells that mediate tissue inflammation. Park et al demonstrated that ginsenoside Rg3 inhibited Th17 differentiation as well as Th17-mediated neuro-inflammation in a dendritic cell-T co-culture system [9]. The authors suggested that Rg3 could be a potential agent for treating certain autoimmune disorders driven by Th17 cells.…”