Abstract
Ceramide plays an important role in the myelination process; thus, the ceramide biosynthetic pathway could be considered a potential target in managing multiple sclerosis (MS). Fingolimod, an approved drug for MS, is considered a standard modulator of the ceramide biosynthetic pathway in the experimental model of MS. Ursolic acid (UA) exhibited neuroprotective activity in Cuprizone (CPZ)-induced animal model of MS. However, the protective activity of UA is yet to be established in the experimental model of MS. Therefore, the objective of the study was to evaluate the effect of UA (50, 100, and 200 mg/kg; p.o.) on the level of expression of ceramide synthase 2 (CS2), sphingomyelin synthase 1 (SMS1) and serine palmitoyl transferase 1 (SPTLC1) in CPZ-induced animal model of MS. CPZ (6 mg/kg; p.o.) was administered for 30 days once daily to male Swiss Albino mice to induce MS. CPZ significantly caused a decrease in the number of squares crossed in Open field, decrease in the muscular strength in Kondziela’s inverted screen, decrease in the ratio between open to closed arm in elevated plus maze, and decrease in the number of head dip in hole board tests in the animals. Further, CPZ increased the levels of reactive oxygen species, GFAP, and Iba-1 and decreased the levels of MBP, NeuN, and Olig2 in mice cortex. Interestingly, CPZ increased the levels of CS2 and SPTLC1, and decreased the level of SMS1 in mice cortex. UA (100 and 200 mg/kg) significantly attenuated CPZ-induced behavioural, biochemical and molecular parameters in the animals. Thus, UA could be a potential therapeutic alternative in the management of MS. Further, the biomarkers of ceramide biosynthetic pathway such as CS2, SMS1, and SPTLC1 could be potential therapeutic targets in the management of MS.