Carnosol and melatonin co-treatment attenuates neuroinflammation and oxidative stress in experimental autoimmune...

Neurodegenerative diseases such as multiple sclerosis (MS) involve neuronal loss and functional impairment driven by inflammation and oxidative stress. Carnosol and melatonin are recognized for their anti-oxidative properties and potential to support remyelination. This study assessed the combined therapeutic effect of Carnosol and melatonin in the experimental autoimmune encephalomyelitis (EAE) model.

EAE was induced in 28 female C57BL/6 mice, which were divided into four groups: Control, Carnosol (50 mg/kg), melatonin (10 mg/kg), and combination treatment. From day 9 post-immunization (DPI), clinical signs were scored daily. On day 30, spinal cord, liver, and spleen samples were collected. Histological and immunofluorescence staining evaluated inflammation and remyelination. Serum oxidative markers, malondialdehyde (MDA), PC, and 8-hydroxy-2'-deoxyguanosine (8-OHdG), were measured by enzyme-linked immunosorbent assay (ELISA). Gene expression of nuclear factor erythroid 2-related factor 2 (Nrf2), nuclear factor-kappa B (NF-κB), interleukin (IL)-10, IL-17, Heme oxygenase 1 (HO-1), and NAD(P)H quinone dehydrogenase 1 (NQO1) was analyzed by real-time reverse transcription polymerase chain reaction (RT-PCR).

Co-treatment with Carnosol and melatonin markedly improved clinical scores, reduced central nervous system (CNS) inflammation, and increased remyelination. Serum levels of MDA, PC, and 8-OHdG were significantly lowered. Spinal cord analysis revealed upregulated Nrf2 and downregulated NF-κB. Spleen samples showed elevated IL-10 and reduced IL-17. In the liver, HO-1 and NQO1 expression were highest in the combination group.

Combined Carnosol and melatonin treatment demonstrates compelling potential to counteract inflammation and oxidative stress while promoting remyelination, supporting its further investigation as a therapeutic strategy for MS.