9^th World Biomarkers Congress

Pharmacological approaches to inhibit brain acute infl ammation may represent important strategies for the control of autoimmune diseases. Multiple sclerosis (MS) is a chronic, infl ammatory, demyelinating and autoimmune disease of the central nervous system (CNS). Cucurbitacin B (CuB), an oxygenated tetracyclic triterpenoid compound extracted from Cucurbitaceae plant species, is a bioactive agent by disruption of microtubule polymerization and inhibition of JAK/STAT signaling. However, there has been little information about impact of CuB on MS treatment. In this research, for the fi rst time we examine eff ects of CuB (specifi c STAT3 blocker), in experimental autoimmune encephalomyelitis (EAE) mouse model of MS. EAE was induced by subcutaneous immunization of MOG35-55 in 8-week-old C57BL/6 mice. CuB was administered at diff erent doses (0.25, 0.5 and 1 mg/kg body weight/day/i.p) from the fi rst day of the experiment. Infl ammatory responses were examined using qRT-PCR, western blot and immunohistochemistry (IHC) analysis of specifi c markers such as p-STAT3, IL17A, IL-23A, CD11b and CD45. CuB reduced STAT3 activation, leukocyte traffi  cking, and also IL-17/IL-23 immune axis in this model. Treated mice with lower doses of CuB exhibited a considerable depletion in the EAE clinical score which correlated with decreased expression of IL-17, IL-23 and infi ltration of CD11b+ and CD45+ cells into the CNS. Our in vivo results suggest that STAT3 inhibition by CuB will be an eff ective and new approach for the treatment of neuro-infl ammatory disease such as MS.