Resveratrol nanoparticles are neuroprotective in a model of multiple sclerosis

Abstract

AbstractPurposeOptic neuritis is the most common clinical manifestation of multiple sclerosis. Axonal damage and neuronal loss lead to permanent neurological disability in patients and its animal model, experimental autoimmune encephalomyelitis (EAE). Presently, treatments of this condition aim to reduce inflammation without showing any neuroprotection. Resveratrol is a natural polyphenol found in red wine with neuroprotective effects but poor solubility in water. Thus, a novel nanoparticle formulation of resveratrol was developed and assessed in a mouse model of EAE.MethodsResveratrol nanoparticles (RNs) were formulated using a thin rehydration technique and assessed for stability with spectrophotometric techniques. C57/BL6 mice were immunized with the myelin oligodendroglial glycoprotein peptide. From EAE induction, mice were treated daily for 30 days by oral gavage of RNs (n = 6), vehicle (n = 5) or unconjugated resveratrol (UnRSV); n = 6). Mice were assessed for EAE signs daily and for visual function weekly by optokinetic responses (OKR). Optic nerve and spinal cord inflammation were assessed by hematoxylin and eosin (H&E). Retinal ganglion cells were immunostained with Brn3a.ResultsResveratrol nanoparticles (RNs) containing >10 mg/ml resveratrol were stable over 3 months with an encapsulation efficiency >70%. 16.9 mg/kg RNs reduced the EAE clinical score at day 30 compared to 16.9 mg/kg vehicle (1.4 ± 0.4 versus 3.0 ± 0.4, p < 0.05) whereas up to 100 mg/kg UnRSV did not lead to reduction of EAE scores. OKR, optic nerve inflammation and spinal cord inflammation were not significantly modified by oral administration of RNs. 16.9 mg/kg RNs reduced RGC loss compared to 16.9 mg/kg vehicle (347 ± 12 versus 172 ± 12 cells/standardized field, p < 0.0001). Importantly, to get a similar reduction, at least 100 mg/kg of UnRSV were needed suggesting that RNs increase resveratrol bioavailability.ConclusionsResveratrol nanoparticles (RNs) increase resveratrol solubility and bioavailability. They show neuroprotection by reducing RGC loss. However, as previously reported for resveratrol, these nanoparticles do not have any anti‐inflammatory effect.