Ursolic acid derivatives improved clinical signs of experimental autoimmune encephalomyelitis by modulating central nervous system inflammation.

The immunopathogenesis of multiple sclerosis (MS) involves the activation of T lymphocytes, leading to progressive axonal loss and brain atrophy. Ursolic acid (AU) has been widely used as an herbal medicine, with the ability to inhibit the production and secretion of cytokines and may influence the differentiation of CD4 + helper cells. In this study, we aimed to investigate the immunomodulatory effects of ursolic acid derivatives (methyl 3β-hydroxyurs-12-en-28-oate (AUD1) and methyl 3β-acetoxyurs-12-en-28-oate (AUD2)) in a model of experimental autoimmune encephalomyelitis (EAE). EAE was induced by subcutaneous immunization of myelin oligodendrocyte glycoprotein peptide (MOG_35-55) in C57BL/6 mice. On the 15th day post-induction (dpi), the mice were treated with AU, AUD1, or AUD2 (50 mg/kg intraperitoneally per day) for six days. Clinical signs were monitored until 21 dpi, and parameters were assessed in the spinal cord, lymph nodes, and brain at 21 dpi. The results showed that both derivatives similarly attenuated the clinical signs of EAE and reduced inflammation and demyelination in the spinal cord. In addition, they reduced the number of pro-inflammatory cells in the brain, the level of IL-1β, TNF, and IFN-γ in the spinal cord, and, in the periphery, promoted the regulation of pro-inflammatory cells. In conclusion, regulating cells in the periphery and reducing the number of pro-inflammatory cells in the CNS, with AUD1 and AUD2, culminated in the efficacy of the clinical parameters presented in EAE, suggesting a therapeutic potential for treating MS.