Prophylactic effects of cucurbitacin B in the EAE Model of multiple sclerosis by adjustment of STAT3/IL-23/IL-17 axis and improvement of neuropsychological symptoms.

ABSTRACT

Multiple sclerosis (MS) is an autoimmune disease that affects the central nervous system. Although remarkable progress has been made in treating MS, current therapies are less effective in protecting against the progression of the disease. Since cucurbitacins have shown an extreme range of pharmacological properties, in this study, we aimed to investigate the prophylactic effect of cucurbitacin B (CuB) in the experimental MS model. Experimental autoimmune encephalomyelitis (EAE) induced by subcutaneous immunization of MOG35-55 in C57BL/6 mice. CuB interventions (0.5 and 1 mg/kg, i.p.) were performed every other day from the first day of EAE induction. Assessment of clinical scores and motor function, inflammatory responses, and microglial activation were assessed by qRT-PCR, western blotting, and immunohistochemical (IHC) analyses. CuB (1 mg/kg) significantly decreased the population of CD45+ (P < 0.01), CD11b+ (P < 0.01) and CD45+/CD11b+ (P < 0.05) cells in cortical lesions of EAE mice. In addition, activation of STAT3 (P < 0.001), expression of IL-17 A and IL-23 A (both mRNA and protein), and transcription of Iba-1 significantly decreased. On the contrary, CuB (1 mg/kg) significantly increased the transcription of MBP and Olig-2. Furthermore, a significant decrease in the severity of EAE (P < 0.05), and an improvement in motor function (P < 0.05) and coordination (P < 0.05) were observed after treatment with a high dose of CuB. Our results suggest that CuB may have a wide-ranging effect on autoimmune responses in MS via a reduction in STAT3 activation, microgliosis, and adaptation of the IL-23/IL-17 axis. Further studies are needed to investigate the exact effect of CuB in glial cells and its efficiency and bioavailability in other neuroinflammatory diseases.