Purple corn anthocyanins as a nutraceutical approach to control the progression of multiple sclerosis and associated trigeminal pain: role of glial cells

Some dietary components, including anthocyanins (ACNs), are able to prevent chronic diseases through antioxidant, anti-inflammatory, and neuroprotective effects. Our group recently demonstrated the anti-allodynic effect of ACNs from purple corn in an animal model of trigeminal (TG) sensitization, through the inhibition of microglia activation and the production of anti-inflammatory mediators [Magni et al., Front Cell Neurosci 12:378, 2018]. The aim of this work was to verify whether ACN-enriched purple corn can exert beneficial effects on TG pain associated to multiple sclerosis (MS) and on the onset and progression of the disease. Experimental autoimmune encephalomyelitis (EAE) was induced in male Dark Agouti rats by single intradermal injection of MOG1-125 peptide in Incomplete Freund’s Adjuvant (IFA) and sodium acetate [Magni et al., Brain Behav Immun 89:268-280, 2020]. Eleven days before EAE induction rats were assigned to drink water, yellow corn (containing all classes of flavonoids except for ACNs) as control, or purple corn extracts. From day post-immunization 1 to 21: a) rats were weighed daily; b) the development of EAE was evaluated by a scale from 0 to 7, which scores ascending paralysis; c) spontaneous TG pain was evaluated by von Frey test. Fecal samples were collected at significant time points for the analysis of microbiome composition and ACN metabolites. Results show that, thanks to gut ACN metabolism, purple corn positively influences the progression of EAE motor symptoms and protects from associated TG pain, through a mechanism that involves the modulation of glial cell activation, and of pro-/anti-inflammatory mediators and the reduction of purinergic P2X4, P2Y12, and A3 receptors expression, which control glial cell reactivity and are involved in pain transmission. Our findings suggest a possible application of purple corn as a preventive or adjuvant approach to MS and associated symptoms to reduce drug dosage and associated side effects.