Lee Min J, Choi Jong H, Lee Sung J, Cho Ik-Hyun
Department of Science in Korean Medicine and Brain Korea 21 Plus Program, Graduate School, Kyung Hee UniversitySeoul, South Korea.
Department of Convergence Medical Science, College of Korean Medicine, Kyung Hee UniversitySeoul, South Korea.
Front Pharmacol. 2017 Apr 18;8:192. doi: 10.3389/fphar.2017.00192. eCollection 2017.
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.
东方医学三黄四神汤(SHSST)传统上用于东亚地区治疗高血压及其并发症。然而,关于其在治疗多发性硬化症(MS)等慢性炎症性疾病方面的潜在价值却知之甚少。在本研究中,我们调查了SHSST在治疗髓鞘少突胶质细胞糖蛋白诱导的实验性自身免疫性脑脊髓炎(EAE)中是否具有有益作用。结果发现,用SHSST进行发病期治疗可减轻EAE小鼠脊髓中的神经症状以及脱髓鞘和神经胶质细胞活化。SHSST还减弱了促炎细胞因子(白细胞介素-1β和肿瘤坏死因子-α)、趋化因子(调节活化正常T细胞表达和分泌因子、单核细胞趋化蛋白-1以及巨噬细胞炎性蛋白-1α)、诱导型一氧化氮合酶和环氧合酶-2的mRNA或蛋白表达,这与EAE小鼠脊髓中核因子-κB和丝裂原活化蛋白激酶信号通路的下调相一致。有趣的是,SHSST的保护作用与EAE小鼠脊髓中Th1细胞数量减少和Treg细胞数量增加有关。综上所述,我们的研究结果首次表明,SHSST可通过抑制Th1细胞反应和上调Treg细胞反应,在较宽的治疗时间窗内延迟或减轻EAE。此外,我们的研究结果足以支持进一步研究将SHSST作为包括MS在内的慢性自身免疫性疾病的治疗方法。