Abstract
This study was aimed to evaluate the effects of celastrol, a natural compound with multiple bioactivities, on multiple sclerosis and optic neuritis (ON) in rat experimental autoimmune encephalomyelitis (EAE). EAE was induced in Sprague Dawley rats using myelin basic protein, and the animals received daily intraperitoneal injections of celastrol or vehicle for 13 days. The EAE rats showed abnormal neurobehavior and inflammatory infiltration and demyelination in the spinal cord. Significantly upregulated mRNA expression of pro-inflammatory cytokines interferon-γ and interleukin-17 and downregulated anti-inflammatory cytokines interleukin-4 were found in the spinal cord of EAE rats. In the study of ON, severely inflammatory responses like in the spinal cord were also seen in the optic nerve, as well as obvious microgliosis. Furthermore, activation of nuclear factor kappa-B and upregulated inducible nitric oxide synthase was observed in the optic nerve. In addition, apoptosis of retinal ganglion cells and dysregulation of apoptotic-associated proteins in the optic nerve were found in EAE rats. Treatment of celastrol potently restored these changes. In most of the indexes, the effects of high dose of celastrol were better than the low dose. Our data conclude that administration of celastrol attenuates multiple sclerosis and ON in EAE via anti-inflammatory and anti-apoptotic effects. These findings provide new pre-clinical evidence for the use of celastrol in treatment of multiple sclerosis.
Highlights
Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative diseases characterized by demyelination in the central nervous system (CNS; Compston and Coles, 2002)
Previous studies have demonstrated that celastrol ameliorated EAE development by suppressing pathogenic Th17 responses and inhibiting inflammatory responses in spinal cord and brain (Abdin and Hasby, 2014; Wang et al, 2015)
Using MPB-induced EAE rats, we found that celastrol attenuated demyelination, inhibited production of pro-inflammatory cytokines and increased production of anti-inflammatory cytokines in spinal cord
Summary
Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative diseases characterized by demyelination in the central nervous system (CNS; Compston and Coles, 2002). The etiology of MS is not completely revealed, but T- and B-cells mediated immune attack is considered to contribute to neuronal damage in the CNS (Lucchinetti et al, 2000; Compston and Coles, 2002). ON is the early diagnostic sign in approximately 20% of MS patients, and about 70% patients develop ON during the course of MS (Sorensen et al, 1999; Toosy et al, 2014; Graham and Klistorner, 2016). Most of patients with monosymptomatic ON eventually develop
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
