多发性硬化症(MS)是一种自身免疫介导的中枢神经系统(CNS)慢性炎症性脱髓鞘疾病,对治疗提出了重大挑战。目前,据信,炎症和神经保护性反应性星形胶质细胞,以及其他常驻中枢神经系统细胞和免疫细胞,有助于MS的病理生理学。在我们的研究中,我们发现异甘草素(ILG),一种生物活性的查尔酮化合物,实验性自身免疫性脑脊髓炎(EAE)的临床评分显着降低了44%(P<0.05)。此外,ILG使脊髓炎症和脱髓鞘的病理评分显著降低61%和65%,分别(两者P<0.0001)。此外,ILG在体内影响CD4、Th1、Th17和Treg细胞的群体。更重要的是,ILG显著增进EAE中星形胶质细胞的活化(P<0.0001)。此外,ILG治疗间接抑制炎性反应性星形胶质细胞并促进神经保护性反应性星形胶质细胞。它降低了脾脏的TNFα水平,IL1α,C1qa,IL1β,和IL17A增加95%(P<0.001),98%(P<0.01),46%(P<0.05),97%(P<0.001),和60%(P<0.001),分别。它也降低了TNFα的CNS水平,IL1α,C1qa,IL1β,和IL17A下降了53%(P<0.05),88%(P<0.05),64%(P<0.01),57%(P<0.05),和60%(P<0.001),分别。这些结果表明ILG通过抑制促炎细胞因子的分泌而发挥免疫调节作用。因此,ILG抑制炎症反应性星形胶质细胞,促进神经保护性反应性星形胶质细胞,减轻炎症和改善EAE。这些发现为ILG在MS防治中的应用提供了理论依据和支持。
Multiple sclerosis (MS) is an autoimmune-mediated chronic inflammatory demyelinating disease of the central nervous system (CNS) that poses significant treatment challenges. Currently, it is believed that inflammatory and neuroprotective reactive astrocytes, along with other resident CNS cells and immune cells, contribute to the pathophysiology of MS. In our study, we found that isoliquiritigenin (ILG), a bioactive chalcone compound, significantly reduces the clinical scores of experimental autoimmune encephalomyelitis (EAE) by 44 % (P < 0.05). Additionally, ILG significantly decreases the pathological scores of spinal cord inflammation and demyelination by 61 % and 65 %, respectively (both P < 0.0001). Furthermore, ILG affects the populations of CD4, Th1, Th17, and Treg cells in vivo. More importantly, ILG significantly promotes the activation of astrocytes in EAE (P < 0.0001). Additionally, ILG treatment indirectly inhibits inflammatory reactive astrocytes and promotes neuroprotective reactive astrocytes. It reduces spleen levels of TNFα, IL1α, C1qa, IL1β, and IL17A by 95 % (P < 0.001), 98 % (P < 0.01), 46 % (P < 0.05), 97 % (P < 0.001), and 60 % (P < 0.001), respectively. It also decreases CNS levels of TNFα, IL1α, C1qa, IL1β, and IL17A by 53 % (P < 0.05), 88 % (P < 0.05), 64 % (P < 0.01), 57 % (P < 0.05), and 60 % (P < 0.001), respectively. These results indicate that ILG exerts an immunoregulatory effect by inhibiting the secretion of pro-inflammatory cytokines. Consequently, ILG inhibits inflammatory reactive astrocytes, promotes neuroprotective reactive astrocytes, alleviates inflammation and improves EAE. These findings provide a theoretical basis and support for the application of ILG in the prevention and treatment of MS.