Ip Fanny C F, Ng Yu Pong, Or Terry C T, Sun Peiran, Fu Guangmiao, Li Jessica Y H, Ye Wen-Cai, Cheung Tom H, Ip Nancy Y
Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.
Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.
PLoS One. 2017 Jul 31;12(7):e0182069. doi: 10.1371/journal.pone.0182069. eCollection 2017.
Anemoside A3 (AA3) is a natural triterpenoid glycoside isolated from the root of Pulsatilla chinensis (Bunge) Regel. We previously showed that AA3 exhibits cognitive-enhancing and neuroprotective properties. In the present study, we demonstrated that AA3 modulates inflammatory responses by regulating prostaglandin E receptor 4 signaling. Because prostaglandin E receptor 4 is involved in the pathophysiology of experimental autoimmune encephalomyelitis (EAE), an animal model of human multiple sclerosis (MS), we assessed the beneficial effect of AA3 in EAE mice. AA3 treatment significantly reduced clinical severity and inflammatory infiltrates in the spinal cord of EAE mice. In vitro studies revealed that AA3 inhibited the T cell response toward the encephalitogenic epitope of myelin oligodendrocyte glycoprotein (MOG). AA3 significantly downregulated the expressions of certain Th1 and Th17 cytokines in activated T cells re-stimulated by MOG. Moreover, AA3 inhibited the activation of STAT4 and STAT3, which are the transcription factors pivotal for Th1 and Th17 lineage differentiation, respectively, in activated T cells. Pharmacological analysis further suggested that AA3 reduced Th17 cell differentiation and expansion. In conclusion, AA3 exerts an immunomodulatory effect in EAE, demonstrating its potential as a therapeutic agent for MS in humans.
银莲花皂苷A3（AA3）是从白头翁（Pulsatilla chinensis (Bunge) Regel）根部分离得到的一种天然三萜糖苷。我们之前的研究表明，AA3具有认知增强和神经保护特性。在本研究中，我们证明AA3通过调节前列腺素E受体4信号通路来调节炎症反应。由于前列腺素E受体4参与了实验性自身免疫性脑脊髓炎（EAE）的病理生理过程，EAE是人类多发性硬化症（MS）的动物模型，因此我们评估了AA3对EAE小鼠的有益作用。AA3治疗显著降低了EAE小鼠的临床严重程度和脊髓中的炎性浸润。体外研究表明，AA3抑制T细胞对髓鞘少突胶质细胞糖蛋白（MOG）致脑炎表位的反应。AA3显著下调了由MOG重新刺激的活化T细胞中某些Th1和Th17细胞因子的表达。此外，AA3抑制了STAT4和STAT3的激活，STAT4和STAT3分别是活化T细胞中Th1和Th17谱系分化的关键转录因子。药理学分析进一步表明，AA3减少了Th17细胞的分化和扩增。总之，AA3在EAE中发挥免疫调节作用，证明了其作为人类MS治疗药物的潜力。
