Korean Red Ginseng and Ginsenoside-Rb1/-Rg1 Alleviate Experimental Autoimmune Encephalomyelitis by Suppressing Th1 and Th17 Cells and Upregulating Regulatory T Cells

Abstract

The effects of Korean red ginseng extract (KRGE) on autoimmune disorders of the nervous system are not clear. We investigated whether KRGE has a beneficial effect on acute and chronic experimental autoimmune encephalomyelitis (EAE). Pretreatment (daily from 10 days before immunization with myelin basic protein peptide) with KRGE significantly attenuated clinical signs and loss of body weight and was associated with the suppression of spinal demyelination and glial activation in acute EAE rats, while onset treatment (daily after the appearance of clinical symptoms) did not. The suppressive effect of KRGE corresponded to the messenger RNA (mRNA) expression of proinflammatory cytokines (tumor necrosis factor-α [TNF-α] and interleukin [IL]-1β), chemokines (RANTES, monocyte chemotactic protein-1 [MCP-1], and macrophage inflammatory protein-1α [MIP-1α]), adhesion molecules (intercellular adhesion molecule-1 [ICAM-1], vascular cell adhesion molecule-1 [VCAM-1], and platelet endothelial cell adhesion molecule [PECAM-1]), and inducible nitric oxide synthase in the spinal cord after immunization. Interestingly, in acute EAE rats, pretreatment with KRGE significantly reduced the population of CD4(+), CD4(+)/IFN-γ(+), and CD4(+)/IL-17(+) T cells in the spinal cord and lymph nodes, corresponding to the downregulation of mRNA expression of IFN-γ, IL-17, and IL-23 in the spinal cord. On the other hand, KRGE pretreatment increased the population of CD4(+)/Foxp3(+) T cells in the spinal cord and lymph nodes of these rats, corresponding to the upregulation of mRNA expression of Foxp3 in the spinal cord. Interestingly, intrathecal pretreatment of rats with ginsenosides (Rg1 and Rb1) significantly decreased behavioral impairment. These results strongly indicate that KRGE has a beneficial effect on the development and progression of EAE by suppressing T helper 1 (Th1) and Th17 T cells and upregulating regulatory T cells. Additionally, pre- and onset treatment with KRGE alleviated neurological impairment of myelin oligodendrocyte glycoprotein(35-55)-induced mouse model of chronic EAE. These results warrant further investigation of KRGE as preventive or therapeutic strategies for autoimmune disorders, such as multiple sclerosis.

Potential involvement of glycogen synthase kinase (GSK)-3β in a rat model of multiple sclerosis: evidenced by lithium treatment

“…Thus, the blockage of GSK-3 signaling may be a therapeutic strategy for neuroprotection in CNS disease [14]. Furthermore, GSK-3 signaling is involved in the activation of adhesion molecules, including vascular cell adhesion molecule 1 (VCAM-1), in cultured endothelial cells [1516], which are important for T-cell migration in EAE [217]. …”

Oriental Medicine Samhwangsasim-tang Alleviates Experimental Autoimmune Encephalomyelitis by Suppressing Th1 Cell Responses and Upregulating Treg Cell Responses

“…Lumbar spinal cords were removed, fixed using 4% PFA for a day, incubated overnight in 30% sucrose solution, and then cut into 10-μm thick by previously described (Lee et al, 2016a,b). The sections were stained with luxol fast blue (LFB) and counterstained by hematoxylin to evaluate demyelination and immune cell infiltration, respectively.…”

Oriental Medicine Woohwangchungsimwon Attenuates Kainic Acid-Induced Seizures and Neuronal Cell Death in the Hippocampus

“…The immunohistochemistry was carried out as previously described [22][23][24] using rabbit anti-ionized calcium binding adaptor molecule-1 (Iba-1) (1:2000; Wako) or rabbit-active (cleaved) caspase-3 antibody (1:1000; Cell Signaling Technology) antibodies. A semiquantitative histological evaluation for Iba-1 antibody (40· magnified microscope field) was conducted and scored blindly by two observers using the following scale: resting microglia, mildly activated microglia, and moderately activated microglia.…”

“…The primer sequences of mouse interleukin (IL)-1b, IL-6, tumor necrosis factor (TNF)-a, cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) were previously described. 22,23 Expression levels of each gene were normalized to that of GAPDH.…”

“…[22][23][24] Briefly, the membranes were blocked and probed overnight with rabbit anti-iNOS (1:500, Sigma) at 4°C and were then incubated with the appropriate secondary antibody conjugated to horseradish peroxidase at room temperature for 1 hour. A signal was developed using an ECL Kit (Santa Cruz Biotechnology) and was visualized with a super cooled-CCD camera system using a gel image analysis program.…”