Novel Phloroglucinol Derivative Compound 21 Protects Experimental Autoimmune Encephalomyelitis Rats <i>via</i> Inhibiting Th1/Th17 Cell Infiltration

Abstract

Multiple Sclerosis (MS) is a chronic autoimmune disease characterized by inflammatory infiltration and demyelination in the central nervous system (CNS). Among all the factors that are involved in the immunological mechanisms of MS, T helper 1 (Th1) cells and T helper 17 (Th17) cells play a critical role. Compound 21, a novel phloroglucinol derivative, has shown remarkable effects on protecting myelin damage in our previous study. However, whether it has effects on MS remains unclear. In this study, the experimental autoimmune encephalomyelitis (EAE) rat model was established to mimic the pathological process of MS and to evaluate the neuroprotective effect of Compound 21. The results illustrated that Compound 21 treatment notably attenuated the neurological deficits, immune infiltration and demyelination of EAE rats. Mechanistic investigation revealed that Compound 21 treatment reduced the population of Th1/Th17 cells and inhibited their infiltration into the CNS. Further study found that the inhibition of Th1/Th17 cell infiltration was related to the direct suppression of Th1/Th17 cell differentiation and inhibition of pro-inflammatory microglial cells. Collectively, all these results proved that Compound 21 treatment suppressed infiltrated Th1/Th17 cells to alleviate the demyelination of EAE rats, suggesting its potential role as a novel candidate for MS treatment. Funding Statement: This investigation was supported by grants from National Sciences Foundation of China (81630097, 81773718), CAMS Innovation Fund for Medical Sciences (No. 2016-I2M-3-011), CAMS The Fundamental Research Funds for the Central Universities (2018RC350002), National Major Scientific and Technological Special Project for “Significant New Drugs Development” during the Thirteenth Five-year Plan Period (2018ZX09711001-003-005, 2018ZX09711001-008-005, 2018ZX09711001-003-020). Declaration of Interests: The authors declare no competing financial or other interests. Ethics Approval Statement: All the animal experiments were carried out according to the guidelines of the Beijing Municipal Ethic Committee for the care and use of laboratory animals.