Multiple sclerosis (MS) is a poorly understood disease mechanistically. MOG35-55 peptide induced experimental autoimmune encephalomyelitis (EAE) is a broadly used model to study MS. Using this model we have earlier shown that the antioxidant tempol or the small molecule inhibitor of p38 SB203580 can effectively prevent EAE progression. This effect was mediated by means of regulating immune inflammation, signaling by the p38MAPK-SGK1 pathway, and oxidative stress. However, there is a need to test drugs that can be used in pharmacological intervention of EAE. Given that nordihydroguaiaretic Acid (NDGA) has been shown to possess anti-oxidant activity and capacity of antagonizing autoimmune inflammation, we tested the effect of NDGA in ameliorating EAE in the current study. NDGA showed significant beneficial effect against EAE with both anti-inflammation and antioxidant activity. NDGA could weaken the immune inflammation at least partly by inhibiting the oxidant stress-p38MAPK-SGK1 pathway representing a target for putative pharmacological intervention. (C) 2018 IUBMB Life