Multiple sclerosis (MS) is a chronic autoimmune and degenerative disease of the central nervous system, and conventional treatments have limited efficacy or side effects.
Ghrelin, a 28-amino
acid octanoylated
peptide, has been reported to have
neuroprotective effects, including anti-oxidation, anti-
inflammation, and anti-apoptosis. Pyroptosis, also called inflammatory cell death, is triggered by overly active
inflammasomes and accompanied by the production of numerous
cytokines. As immune dysfunction is primarily involved in the pathogenesis of MS, this study aimed to explore the
therapeutic effects and precise functional mechanisms of
ghrelin against the
nod-like receptor protein 3 (NLRP3)
inflammasome and pyroptosis in
experimental autoimmune encephalomyelitis (EAE). Sprague Dawley rats were immunized with guinea pig spinal cord homogenates and
pertussis toxin to develop an EAE model. All rats were randomly divided into four groups: normal control group, EAE group, EAE +
ghrelin group, and
ghrelin control group. EAE rats showed abnormal behavioral scores and
body weight changes. Histologic analysis displayed severe inflammatory infiltration and
demyelination in the brain and spinal cord of EAE rats.
Ghrelin treatments potently restored these abnormal changes. In addition, the
ghrelin-treated EAE group showed significantly downregulated expression of inflammatory
cytokines. The expression of
proteins involved in the NLRP3 signaling pathway and pyroptosis was decreased as well. We also found that the anti-inflammatory effect of
ghrelin was associated with inhibition of nuclear factor (NF)-κB activation. Compared with rats in the healthy control group, rats in the
ghrelin control group did not show statistically significant changes in histologic examinations, pro-inflammatory
cytokines production, or molecules involved in the NLRP3 signaling pathway, which indicated that
ghrelin induced no side effects in the animals of our study. Our findings provide more insight into the use of
ghrelin as a novel candidate for MS.