Attenuation of behavioral deficits and reduction of astrogliosis by limonene complexed with beta-cyclodextrin in an animal model of parkinsonism

Parkinson’s disease (PD) is a neurodegenerative disorder marked by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Research suggests that neuroinflammation significantly contributes to the onset and progression of PD. In this respect, targeting neuroinflammation has emerged as a promising strategy to delay and potentially prevent disease progression. There is growing interest in the therapeutic potential of terpenes for PD treatment, mainly due to their neuroprotective and anti-inflammatory activities. Additionaly, the complexation of terpenes with β-cyclodextrin can enhance the pharmacological properties of these organic compounds. This study evaluated the potential neuroprotective effects of D-limonene complexed (LIM-BCD) or not with β-cyclodextrin (LIM) on a reserpine-induced model of parkinsonism in mice. Male Swiss mice (6-7 months; 40-65 g, n = 54) were administrated every other day with reserpine (RES, 0.1 mg/kg) and daily with LIM (1 mg/kg, p.o.) or LIM-BCD (10 mg/kg, p.o.) for 28 days. Chronic LIM treatment provoked a delay in the onset of catalepsy, protected against memory deficits, and attenuated the RES-induced reduction of tyrosine hydroxylase (TH) immunoreactivity in the dorsal striatum (STRd). Additionally, treatment with LIM-BCD decreased the frequency of oral movements, reduced falls in the rotarod, protected against decreased TH and glial fibrillary acidic protein (GFAP) immunoreactivity in the SNpc. These results suggest that LIM exhibits a neuroprotective effect in RES-induced PD by inhibiting astrocytic activity, and LIM-BCD could represent a novel therapeutic approach for PD. • Limonene (LIM) has a neuroprotective effect on reserpine-induced progressive parkinsonism. • LIM complexed with β-cyclodextrin (LIM-BCD) attenuates astrocyte activity. • LIM-BCD protects against decreased immunoreactivity of tyrosine hydroxylase in the striatum and substantia nigra. • LIM-BCD has therapeutic potential for Parkinson’s disease.