Neuroprotective effects of lignan 7-hydroxymatairesinol (HMR/lignan™) in a rodent model of Parkinson's disease

Abstract Objective Parkinson's disease (PD) is neurodegenerative disease characterized by loss of dopaminergic neurons in the Substantia Nigra pars compacta (SNc). The pro-inflammatory response can occur early in the disease, contributing to the nigrostriatal degeneration. Identification of the new molecules which are able to slow down the degenerative process associated with PD, represents one of the main interests. Recently, natural polyphenols, especially lignans, have raised much attention for their anti-inflammatory, antioxidant and estrogenic activity on peripheral level. The aim of this study was to evaluate the central effects of chronic treatment with lignan 7-hydroxymatairesinol (HMR/lignan™) on neurodegenerative, neuroinflammatory processes and motor deficits induced by a unilateral intrastriatal injection of 6-hydroxydopamine (6-OHDA) in rats, in order to evaluate the potential neuroprotective properties of this compound. Methods Sprague–Dawley male rats underwent lignan (10mg/Kg) or vehicle treatment (per os) for 4 weeks starting from the day of 6-OHDA injection. The degree of nigrostriatal damage was evaluated by immunohistochemistry. Moreover, we performed a quantitative and qualitative assessment of neuroinflammatory process, including phenotypic polarization of microglia and astrocytes. The motor performance was assessed by behavioral tests. Results We demonstrated that chronic treatment with HMR/lignan™ was able to slow down the progression of degeneration of striatal dopaminergic terminals in rat model of PD, with a consequent improvement in motor performance. Nevertheless, the anti-inflammatory effect of HMR/lignan™ observed in SNc was not sufficient to protect dopaminergic cells bodies. Conclusion These results suggest intriguing properties of HMR/lignan™ at neuroprotective and symptomatic levels in the context of PD.