A Standardized Extract of <i>Zingiber officinale</i> Roscoe Regulates Clinical and Biological Outcomes in Two Different EAE Mouse Models

<b>Background/Objectives</b>: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system characterized by demyelination and neuronal damage. Current MS therapies are unsatisfactory, and new therapies are encouraged. A correlation between nutritional intake and MS has been speculated. Supplementation of approved immunomodulatory therapy with herbal medicines possessing antioxidant and anti-inflammatory activities could provide benefits to MS patients. Ginger is one of the most widely consumed dietary supplements in the world, commonly used in traditional medicine. Studies demonstrated that ginger may also be beneficial in the management of neurodegenerative diseases. The aim of this study is to investigate the MS therapeutic potential of ginger. <b>Methods</b>: A standardized <i>Zingiber officinale</i> Roscoe extract (ZOE) was orally administered for 14 days. Two experimental autoimmune encephalomyelitis (EAE) models in mice were used. The PLP_139-151-EAE relapsing-remitting model and MOG_35–55-EAE chronic model. Clinical score, von Frey, hot plate, and rotarod tests were used for behavioral tests. ELISA and Western blotting were used to measure cytokines levels. Evans Blue content was determined spectrophotometrically. <b>Results</b>: ZOE attenuated motor disability and pain hypersensitivity in both models had no effect on body weight loss. ZOE reduced the blood–brain barrier (BBB) permeability in the PLP-EAE models and reduced levels of circulating cytokines (Il-6, IL-17) in the MOG-EAE model. ZOE attenuated spinal cytokines overexpression in both models. <b>Conclusions</b>: ZOE improves EAE symptoms and attenuates the proinflammatory response in both models, representing a promising nutraceutical support to the conventional therapeutic approach to MS.