Icariin ameliorates the progression of experimental autoimmune encephalomyelitis by down-regulating the major inflammatory signal pathways in a mouse relapse-remission model of multiple sclerosis

Abstract

This study aimed at investigating whether treatment with icariin (ICA) could modulate the progression of experimental autoimmune encephalomyelitis (EAE) and its potential mechanisms in SJL/J mice. Female SJL/J mice were immunized with PLP139-151 peptide to induce relapse-remitting EAE and the immunized mice were treated with vehicle alone (EAE) or ICA (12.5 or 25 mg/body weights) by gavage daily for 42 days. Compared with the control, the EAE mice developed relapse-remitting EAE and reduced body weights (15.76 ± 0.61 vs. 17.60 ± 0.98 g on day 13; 17.35 ± 0.44 vs. 18.46 ± 0.66 g on day 26), accompanied by severe inflammation with many microglia infiltrates and obvious demyelination in the spinal cord tissues. Conversely, ICA treatment significantly reduced the clinical scores (on day 13, 1.00 ± 0.16 and 1.10 ± 0.33 for ICA 12.5 and 25 mg/kg group, respectively vs. 1.62 ± 0.41 in the EAE group; on day 26, 0.50 ± 0.23 and 0.40 ± 0.24 for ICA 12.5 and 25 mg/kg group, respectively, vs. 1.56 ± 0.29 in the EAE group), mitigated the body weight reduction, spinal cord inflammation and demyelination in EAE mice (pathological scores of 2.33 ± 0.82 and 1.11 ± 0.57 for ICA 12.5 and 25 mg/kg, respectively; vs. 4.78 ± 1.13, P < 0.0001). Furthermore, ICA treatment significantly mitigated the EAE-increased iNOS, TNF-α, CD206 and TGF-β1, but further reduced IL-10 mRNA transcripts in the brain mice. More importantly, ICA treatment significantly mitigated the inflammation-related NF-κB, AKT, ERK1/2, p38, c-Jun and MEK phosphorylation in the brain of EAE mice. ICA treatment ameliorates the progression of EAE by down-regulating the major inflammation-related signal pathways in mice.