Multiple sclerosis (MS) is an autoimmune
demyelinating disease of the central nervous system.
Artemisinin (ART) is a natural
sesquiterpene lactone with an endoperoxide bond that is well-known for its anti-inflammatory effects in
experimental autoimmune encephalomyelitis (EAE), the most commonly used animal model of MS.
Tehranolide (TEH) is a novel compound with structural similarity to ART. In this study, we aimed to investigate the ameliorating effect of TEH on EAE development by targeting
proteins and genes involved in this process and compare its effects with ART. Female C57BL/6 mice were immunized with MOG35-55. Twelve days post-immunization, mice were treated with 0.28 mg/kg/day TEH and 2.8 mg/kg/day ART for 18 consecutive days, and the clinical score was measured daily. The levels of pro-inflammatory and anti-inflammatory
cytokines were assessed in mice serum and splenocytes by ELISA. We also evaluated the
mRNA expression level of
cytokines, as well as genes involved in T cell differentiation and myelination in the spinal cord tissue by qRT-PCR. Administration of TEH and ART significantly alleviated EAE signs. A significant reduction in
IL-6 and
IL-17 secretion and
IL-17 and
IL-1 gene expression in spinal cord were observed in the TEH-treated group. ART had similar or less significant effects. Moreover, TGF-β,
IL-4, and
IL-10 genes were stimulated by ART and TEH in the spinal cord, while the treatments did not affect IFN-γ expression. Both treatments dramatically increased the expression of FOXP3, GATA3, MBP, and AXL. Additionally, the T-bet gene was reduced after TEH administration. The compounds made no changes in RORγt,
nestin, Gas6, Tyro3, and
Mertk mRNA expression levels in the spinal cord. The study revealed that both TEH and ART can effectively modulate the genes responsible for
inflammation and myelination that play a crucial role in EAE. Interestingly, TEH demonstrated a greater potency compared to ART and hence may have the potential to be evaluated in interventions for the management of MS.