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

Min J Lee,Sung J Lee,Ik-Hyun Cho,Jong H Choi

doi:10.3389/fphar.2017.00192

Abstract

Oriental medicine Samhwangsasim-tang (SHSST) has traditionally been used in East Asia to treat hypertension and its complications. However, little is known about its potential value regarding the treatment of chronic inflammatory diseases such as multiple sclerosis (MS). In this study, we investigated whether SHSST has a beneficial effect in treating myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (EAE). Onset-treatment with SHSST was found to alleviate neurological symptoms as well as demyelination and glial activation in the spinal cords from the EAE mice. The SHSST also attenuated the mRNA or protein expression of pro-inflammatory cytokines (interleukin-1beta and tumor necrotic factor-alpha); chemokines (RANTES, monocyte chemotactic protein-1, and macrophage inflammatory protein-1alpha); inducible nitric oxide synthase; and cyclooxygenase-2 in correspondence with the down-regulation of the nuclear factor-kappa B and mitogen-activated protein kinases signal pathways in the spinal cords from EAE mice. Interestingly, the protective effect of the SHSST was related to a decreased number of Th1 cells and an increased number of Treg cells in spinal cords from EAE mice. Taken together, our finding firstly suggested that SHSST could delay or mitigate EAE with a wide therapeutic time-window by suppressing Th1 cell responses and upregulating Treg cell responses. Also, our findings are strong enough to warrant further investigation of SHSST as a treatment for chronic autoimmune diseases including MS.

Highlights

Multiple sclerosis (MS) is a chronic and demyelinating inflammatory disorder of the central nervous system (CNS), which typically presents in adults who are 20 to 45 years of age (Frohman et al, 2006; Axisa and Hafler, 2016)
Mean body weight was found to have decreased in inverse proportion to the clinical score in mice from the EAE group, while the trend toward declining body weight was significantly blocked in mice from EAE + SHSST group, as compared to EAE group (Figures 3A,B)
Since an imbalance in the subsets of CD4+ T cells was found in the EAE model and MS patients (Dittel, 2008; Hoglund and Maghazachi, 2014; Dendrou et al, 2015), we investigated the population of Th1 (CD4+/IFN-γ+), Th2 (CD4+/IL-4+), Th17 (CD4+/IL-17+), and Treg (CD4+/forkhead box P3 (Foxp3)+) cells in the spinal cord

Summary

Introduction

Multiple sclerosis (MS) is a chronic and demyelinating inflammatory disorder of the central nervous system (CNS), which typically presents in adults who are 20 to 45 years of age (Frohman et al, 2006; Axisa and Hafler, 2016). MS patients still get drugs to combat relapses and to slow the disease: anti-inflammatory medications (corticosteroids), interferon and interferon-beta, mitoxantrone, natalizumab, an alternative treatment method, such as acupuncture, bee sting, etc. The mechanism responsible for demyelination has been under intense study, the complete pathogenesis of MS and innovative medication for MS remain to be determined

Results

Discussion

Conclusion