Medicinal plant Combretum leprosum mart ameliorates motor, biochemical and molecular alterations in a Parkinson's disease model induced by MPTP

Abstract

Ethnopharmacological relevance: Combretum leprosum is a popular medicinal plant distributed in north and northeastern regions of Brazil. Many different parts of this plant are used in traditional medicine to treat several inflammatory diseases. Parkinson's disease (PD) is a disorder associated with inflammatory toxic factors and the treatments available provide merely a delay of the neurodegeneration.

Aim of the study: We investigated the potential neuroprotective properties of the C. leprosum ethanolic extract (C.l.EE) in a murine model of PD using the toxin 1-methyl-4 phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP).

Materials and methods: The mice were split into four groups: V/S (vehicle/saline), E/S (extract/saline), V/M (vehicle/MPTP) and E/M (extract/ MPTP). Mice received MPTP (30mg/kg, i.p.) or vehicle (10ml/kg, i.p.) once a day for 5 consecutive days and vehicle (10ml/kg) or C.l.EE (100mg/kg) orally by intra-gastric gavage (i.g.) during a 14-d period, starting 3 days before the first MPTP injection. All groups were assessed for behavioural impairments (amphetamine-induced locomotor activity and muscle strength), dopamine content in striatum using high performance liquid chromatography (HPLC), tyrosine hydroxylase (TH) and dopamine transporter (DAT) gene expressions using qPCR.

Results: Animals were injected with d-amphetamine (2mg/kg) and the activity was recorded. Amphetamine-induced hyperlocomotion was observed in all groups; however animals treated with MPTP showed exacerbated hyperlocomotion (approximately 3 fold increase compared to control groups). By contrast, mice treated with MPTP that received C.l.EE exhibited attenuation of the hyperlocomotion and did not differ from control groups. Muscle strength test pointed that C.l.EE strongly avoided muscular deficits caused by MPTP (approximately 2 fold increase compared to V/M group). Dopamine and its metabolites were measured in the striatum. The V/M group presented a dopamine reduction of 80%. On the other hand, the E/M group exhibited an increase in dopamine and its metabolites levels (approximately 3 fold increase compared to V/M group). Tyrosine hydroxylase (TH) and dopamine transporter (DAT) gene expressions were significantly reduced in the V/M group (60%). Conversely, C.l.EE treatment was able to increase the mRNA levels of those genes in the E/M group (approximately 2 fold for TH and DAT).

Conclusions: These data show, for the first time, that C. leprosum ethanolic extract prevented motor and molecular changes induced by MPTP, and partially reverted dopamine deficit. Thus, our results demonstrate that C.l.EE has potential for the treatment and prevention of PD.

Keywords: Combretum Leprosum; MPTP; Neuroinflammation; Parkinson's disease; Phytotherapeutic medicines.