Purple corn anthocyanins protect from the progression of multiple sclerosis and its associated symptoms: A role for glial purinergic receptors?

BACKGROUND Functional foods enriched with specific bioactives are one of the most intriguing approaches to promote and restore health. 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]. In addition, we also demonstrated glial cell activation and an up-regulation of the expression of purinergic receptor subtypes P2X4, P2Y12, and A3 in an animal model of multiple sclerosis (MS) characterized by the early development of TG pain [Magni et al., Brain Behav Immun 89:268-280, 2020]. AIM We aimed at verifying whether ACN-enriched purple corn can be exploited as adjuvant functional food to modify the onset and progression of multiple sclerosis (MS) and of one of its comorbidities, i.e. TG pain, with a specific focus on the involvement of neuroinflammation, glial cells and glial purinergic receptors. MATERIALS AND METHODS Relapsing-remitting experimental autoimmune encephalomyelitis (EAE), the animal model of MS, was induced in male Dark Agouti rats by single intra-dermal injection at the base of the tail of the myelin peptide MOG1-125 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 divided into 3 groups drinking water, yellow corn (containing all classes of flavonoids except for ACNs and used as control), or purple corn extracts (preventive approach). We also add another experimental group in which animals began drinking purple corn extract from the onset of EAE motor symptoms, as a therapeutic strategy. From day post-immunization (DPI) 1 to 21: i) rats were weighed daily; ii) the development of EAE was evaluated by a scale from 0 to 7, based on the degree of ascending paralysis; iii) spontaneous TG pain was evaluated by von Frey test. After sacrifice, CNS tissues were collected for subsequent analyses. RESULTS Results show that preventive administration of 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 receptor expression, which control glial cell reactivity and are involved in pain transmission. Conversely, the therapeutic administration of purple corn extract has no effect on EAE motor symptoms and only partially reduces the development of TG pain, but maintains its ability to reduce neuroinflammation, glial cells activation and P2X4, P2Y12, and A3 receptor expression. DISCUSSION Our results show that the reduction of neuroinflammation and of EAE-induced increase in purinergic receptor expression could contribute to the protective effect of ACNs against the development of motor symptoms of EAE and associated TG sensitization. However, further analyses are needed to explain the only partial effect exerted by the therapeutic administration of the ACN-enriched purple corn extract. CONCLUSION Overall, our findings suggest a possible exploitation of purple corn as a preventive or adjuvant approach to MS and associated symptoms to reduce drug dosage and associated side effects.