Citation

Abstract: Background: Multiple sclerosis (MS), is a debilitating neurological disease that currently
has various treatments, like disease-modifying therapies, monoclonal antibodies, corticosteroids, and
hormonal derivatives. Melatonin has several actions, like regulating circadian rhythms, which are
usually used for insomnia. This scoping review aimed to explore the efficacy of melatonin, both as a
standalone treatment and in conjunction with other drugs, in the management of MS in animal models.

Methods: We searched PubMed, Web of Science, EMBASE, and Google Scholar using (“melatonin”
OR “melatonin receptor”) AND (“multiple sclerosis”) AND (“animal”). Animal studies that evaluated
the effects of melatonin on the development, progression, and outcomes of MS were included. Human
studies and other types of studies like case reports were excluded. We used narrative synthesis for
reporting the results. Results: Overall, 21 studies were included, conducted on mice (n = 15) and rats
(n = 6). Mostly, studies reported that melatonin led to normal circadian rhythms in animals. Melatonin
in doses of both 50 and 100 mg/kg were useful in nociception latency. Melatonin in combination with
other drugs like H-89, diisopropylamine dichloroacetate, gibberellins, and IFN-1β improved outcomes,
while there was not improved cognition in combination with mesenchymal stem cells. In some tests,
male subjects showed significantly better responses. There were controversial results regarding the
effects of melatonin on cytokines, but overall, it led to a reduction in proinflammatory cytokines.

Conclusions: Melatonin overall demonstrated favorable outcomes regarding oxidative stress, antiinflammation, and cytokine levels across various doses. It is recommended conducting systematic reviews
and meta-analyses with a larger number of primary studies to provide more comprehensive insights.