Inflammation and Oxidative Stress in Multiple Sclerosis: Consequences for Therapy Development

Table 4

Antioxidant complementary therapies and their relevance for MS. Complementary antioxidant therapies for MS were reviewed in detail in [144].

Compound	Specification	Antioxidant characteristics	Relevance for MS
Coenzyme Q10	Coenzyme	Energy transfer molecule, cofactor in mitochondrial electron transport chain	Increases SOD and decreases malondialdehyde A in RRMS patients; synthetic analog has no effect on EAE
Curcumin	Natural pigment	ROS, RNS, and peroxyl radical scavenger; it also modulated GSH, catalase, and SOD activities [190]	Decreases EAE clinical severity, demyelination, and inflammation in the spinal cord and IL-12 production by macrophages/microglia through Janus kinase-STAT pathway [191]
Melatonin	Neurohormone	Activates SOD, catalase, and GPx	It increases SOD and GPx levels in erythrocytes of SPMS patients. Its levels negatively correlate with lesion activity. It ameliorates EAE symptoms, blocks Th17 differentiation and promotes Tr1 expansion.
Vitamin A	Essential nutrient (retinoic acid)	Hydrophobic polyene chain quenches singlet oxygen and neutralizes thiyl radicals stabilizing peroxyl radicals [192].	Serum levels are low in MS patients during relapses [193]. It increases TGFbeta and FoxP3 expression in PBMCs in Avonex-treated RRMS patients [194]. Retinoic acid inhibits cytokine production by Th17 cells in EAE [195].
Vitamin C	Essential nutrient (ascorbic acid)	Scavenges ROS and RNS [196]	Serum levels are low in MS patients during relapses [193]. It promotes OLGs generation and remyelination [197].
Vitamin D	Essential nutrient	Inhibits iron-dependent lipid peroxidation [198]	Serum levels are low in MS patients with elevated relapse frequency [199]. It diminishes risk of MS although the therapeutic value is still debated [200].
Vitamin E	Essential nutrient (alpha-tocopherol)	Peroxyl radical scavenger [201]	Serum levels are low in MS patients during relapses [193]. During IFNβ treatment, decreased MRI activity in RRMS patients is associated with higher levels of alpha-tocopherol [202]. It decreases IFNγ production, inflammation, and demyelination in the spinal cord of EAE mice [203].